@article {pmid38596649, year = {2024}, author = {Zhang, H and Ma, L and Peng, W and Wang, B and Sun, Y}, title = {Association between gut microbiota and onset of type 2 diabetes mellitus: a two-sample Mendelian randomization study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1327032}, pmid = {38596649}, issn = {2235-2988}, abstract = {AIM: Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM.

METHODS: This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (F), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's Q statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis.

RESULTS: The corrected IVW estimates suggested the increased relative abundance of family Oxalobacteraceae (OR = 1.0704) and genus Oxalobacter (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species faecis (OR = 0.9460) had a negative relationship with T2DM. The relationships of class Betaproteobacteria, family Lactobacillaceae, species finegoldii, and species longum with T2DM were also significant according to the IVW results (all P < 0.05).

CONCLUSIONS: GM had a potential causal association with T2DM, especially species faecis, finegoldii, and longum. Further studies are still needed to clarify certain results that are contradictory with previous findings.}, } @article {pmid38586050, year = {2024}, author = {Ho, PY and Huang, KC}, title = {Challenges in quantifying functional redundancy and selection in microbial communities.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.26.586891}, pmid = {38586050}, abstract = {Microbiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grown in vitro are selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.}, } @article {pmid38577200, year = {2024}, author = {Salvadori, M and Rosso, G}, title = {Update on the gut microbiome in health and diseases.}, journal = {World journal of methodology}, volume = {14}, number = {1}, pages = {89196}, pmid = {38577200}, issn = {2222-0682}, abstract = {The Human Microbiome Project, Earth Microbiome Project, and next-generation sequencing have advanced novel genome association, host genetic linkages, and pathogen identification. The microbiome is the sum of the microbes, their genetic information, and their ecological niche. This study will describe how millions of bacteria in the gut affect the human body in health and disease. The gut microbiome changes in relation with age, with an increase in Bacteroidetes and Firmicutes. Host and environmental factors affecting the gut microbiome are diet, drugs, age, smoking, exercise, and host genetics. In addition, changes in the gut microbiome may affect the local gut immune system and systemic immune system. In this study, we discuss how the microbiome may affect the metabolism of healthy subjects or may affect the pathogenesis of metabolism-generating metabolic diseases. Due to the high number of publications on the argument, from a methodologically point of view, we decided to select the best papers published in referred journals in the last 3 years. Then we selected the previously published papers. The major goals of our study were to elucidate which microbiome and by which pathways are related to healthy and disease conditions.}, } @article {pmid38563656, year = {2024}, author = {Zhu, J and Yin, J and Chen, J and Hu, M and Lu, W and Wang, H and Zhang, H and Chen, W}, title = {Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2336877}, doi = {10.1080/19490976.2024.2336877}, pmid = {38563656}, issn = {1949-0984}, abstract = {Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.}, } @article {pmid38562901, year = {2024}, author = {Dilmore, AH and Kuplicki, R and McDonald, D and Kumar, M and Estaki, M and Youngblut, N and Tyakht, A and Ackermann, G and Blach, C and MahmoudianDehkordi, S and Dunlop, BW and Bhattacharyya, S and Guinjoan, S and Mandaviya, P and Ley, RE and Kaddaruh-Dauok, R and Paulus, MP and Knight, R and , }, title = {Medication Use is Associated with Distinct Microbial Features in Anxiety and Depression.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.19.585820}, pmid = {38562901}, abstract = {This study investigated the relationship between gut microbiota and neuropsychiatric disorders (NPDs), specifically anxiety disorder (ANXD) and/or major depressive disorder (MDD), as defined by DSM-IV or V criteria. The study also examined the influence of medication use, particularly antidepressants and/or anxiolytics, classified through the Anatomical Therapeutic Chemical (ATC) Classification System, on the gut microbiota. Both 16S rRNA gene amplicon sequencing and shallow shotgun sequencing were performed on DNA extracted from 666 fecal samples from the Tulsa-1000 and NeuroMAP CoBRE cohorts. The results highlight the significant influence of medication use; antidepressant use is associated with significant differences in gut microbiota beta diversity and has a larger effect size than NPD diagnosis. Next, specific microbes were associated with ANXD and MDD, highlighting their potential for non-pharmacological intervention. Finally, the study demonstrated the capability of Random Forest classifiers to predict diagnoses of NPD and medication use from microbial profiles, suggesting a promising direction for the use of gut microbiota as biomarkers for NPD. The findings suggest that future research on the gut microbiota's role in NPD and its interactions with pharmacological treatments are needed.}, } @article {pmid38559015, year = {2024}, author = {Maghini, DG and Oduaran, OH and Wirbel, J and Olubayo, LAI and Smyth, N and Mathema, T and Belger, CW and Agongo, G and Boua, PR and Choma, SS and Gómez-Olivé, FX and Kisiangani, I and Mashaba, GR and Micklesfield, L and Mohamed, SF and Nonterah, EA and Norris, S and Sorgho, H and Tollman, S and Wafawanaka, F and Tluway, F and Ramsay, M and Bhatt, AS and Hazelhurst, S}, title = {Expanding the human gut microbiome atlas of Africa.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.03.13.584859}, pmid = {38559015}, abstract = {Population studies are crucial in understanding the complex interplay between the gut microbiome and geographical, lifestyle, genetic, and environmental factors. However, populations from low- and middle-income countries, which represent ∼84% of the world population, have been excluded from large-scale gut microbiome research. Here, we present the AWI-Gen 2 Microbiome Project, a cross-sectional gut microbiome study sampling 1,803 women from Burkina Faso, Ghana, Kenya, and South Africa. By intensively engaging with communities that range from rural and horticultural to urban informal settlements and post-industrial, we capture population diversity that represents a far greater breadth of the world's population. Using shotgun metagenomic sequencing, we find that study site explains substantially more microbial variation than disease status. We identify taxa with strong geographic and lifestyle associations, including loss of Treponema and Cryptobacteroides species and gain of Bifidobacterium species in urban populations. We uncover a wealth of prokaryotic and viral novelty, including 1,005 new bacterial metagenome-assembled genomes, and identify phylogeography signatures in Treponema succinifaciens . Finally, we find a microbiome signature of HIV infection that is defined by several taxa not previously associated with HIV, including Dysosmobacter welbionis and Enterocloster sp. This study represents the largest population-representative survey of gut metagenomes of African individuals to date, and paired with extensive clinical biomarkers, demographic data, and lifestyle information, provides extensive opportunity for microbiome-related discovery and research.}, } @article {pmid38553666, year = {2024}, author = {Ma, ZS}, title = {Towards a unified medical microbiome ecology of the OMU for metagenomes and the OTU for microbes.}, journal = {BMC bioinformatics}, volume = {25}, number = {1}, pages = {137}, pmid = {38553666}, issn = {1471-2105}, abstract = {BACKGROUND: Metagenomic sequencing technologies offered unprecedented opportunities and also challenges to microbiology and microbial ecology particularly. The technology has revolutionized the studies of microbes and enabled the high-profile human microbiome and earth microbiome projects. The terminology-change from microbes to microbiomes signals that our capability to count and classify microbes (microbiomes) has achieved the same or similar level as we can for the biomes (macrobiomes) of plants and animals (macrobes). While the traditional investigations of macrobiomes have usually been conducted through naturalists' (Linnaeus & Darwin) naked eyes, and aerial and satellite images (remote-sensing), the large-scale investigations of microbiomes have been made possible by DNA-sequencing-based metagenomic technologies. Two major types of metagenomic sequencing technologies-amplicon sequencing and whole-genome (shotgun sequencing)-respectively generate two contrastingly different categories of metagenomic reads (data)-OTU (operational taxonomic unit) tables representing microorganisms and OMU (operational metagenomic unit), a new term coined in this article to represent various cluster units of metagenomic genes.

RESULTS: The ecological science of microbiomes based on the OTU representing microbes has been unified with the classic ecology of macrobes (macrobiomes), but the unification based on OMU representing metagenomes has been rather limited. In a previous series of studies, we have demonstrated the applications of several classic ecological theories (diversity, composition, heterogeneity, and biogeography) to the studies of metagenomes. Here I push the envelope for the unification of OTU and OMU again by demonstrating the applications of metacommunity assembly and ecological networks to the metagenomes of human gut microbiomes. Specifically, the neutral theory of biodiversity (Sloan's near neutral model), Ning et al.stochasticity framework, core-periphery network, high-salience skeleton network, special trio-motif, and positive-to-negative ratio are applied to analyze the OMU tables from whole-genome sequencing technologies, and demonstrated with seven human gut metagenome datasets from the human microbiome project.

CONCLUSIONS: All of the ecological theories demonstrated previously and in this article, including diversity, composition, heterogeneity, stochasticity, and complex network analyses, are equally applicable to OMU metagenomic analyses, just as to OTU analyses. Consequently, I strongly advocate the unification of OTU/OMU (microbiomes) with classic ecology of plants and animals (macrobiomes) in the context of medical ecology.}, } @article {pmid38549112, year = {2024}, author = {Edwin, NR and Fitzpatrick, AH and Brennan, F and Abram, F and O'Sullivan, O}, title = {An in-depth evaluation of metagenomic classifiers for soil microbiomes.}, journal = {Environmental microbiome}, volume = {19}, number = {1}, pages = {19}, pmid = {38549112}, issn = {2524-6372}, support = {SFI/16/RC/3835//VistaMilk/ ; Ref: 2020019//Teagasc Walsh Scholarship Programme/ ; }, abstract = {BACKGROUND: Recent endeavours in metagenomics, exemplified by projects such as the human microbiome project and TARA Oceans, have illuminated the complexities of microbial biomes. A robust bioinformatic pipeline and meticulous evaluation of their methodology have contributed to the success of these projects. The soil environment, however, with its unique challenges, requires a specialized methodological exploration to maximize microbial insights. A notable limitation in soil microbiome studies is the dearth of soil-specific reference databases available to classifiers that emulate the complexity of soil communities. There is also a lack of in-vitro mock communities derived from soil strains that can be assessed for taxonomic classification accuracy.

RESULTS: In this study, we generated a custom in-silico mock community containing microbial genomes commonly observed in the soil microbiome. Using this mock community, we simulated shotgun sequencing data to evaluate the performance of three leading metagenomic classifiers: Kraken2 (supplemented with Bracken, using a custom database derived from GTDB-TK genomes along with its own default database), Kaiju, and MetaPhlAn, utilizing their respective default databases for a robust analysis. Our results highlight the importance of optimizing taxonomic classification parameters, database selection, as well as analysing trimmed reads and contigs. Our study showed that classifiers tailored to the specific taxa present in our samples led to fewer errors compared to broader databases including microbial eukaryotes, protozoa, or human genomes, highlighting the effectiveness of targeted taxonomic classification. Notably, an optimal classifier performance was achieved when applying a relative abundance threshold of 0.001% or 0.005%. The Kraken2 supplemented with bracken, with a custom database demonstrated superior precision, sensitivity, F1 score, and overall sequence classification. Using a custom database, this classifier classified 99% of in-silico reads and 58% of real-world soil shotgun reads, with the latter identifying previously overlooked phyla using a custom database.

CONCLUSION: This study underscores the potential advantages of in-silico methodological optimization in metagenomic analyses, especially when deciphering the complexities of soil microbiomes. We demonstrate that the choice of classifier and database significantly impacts microbial taxonomic profiling. Our findings suggest that employing Kraken2 with Bracken, coupled with a custom database of GTDB-TK genomes and fungal genomes at a relative abundance threshold of 0.001% provides optimal accuracy in soil shotgun metagenome analysis.}, } @article {pmid38506069, year = {2024}, author = {Li, J and Zheng, G and Jiang, D and Deng, C and Zhang, Y and Ma, Y and Su, J}, title = {Mendelian randomization analysis reveals a causal effect of Streptococcus salivarius on diabetic retinopathy through regulating host fasting glucose.}, journal = {Journal of cellular and molecular medicine}, volume = {28}, number = {7}, pages = {e18200}, doi = {10.1111/jcmm.18200}, pmid = {38506069}, issn = {1582-4934}, support = {KYQD20201001//Scientific Research Foundation for Talents of Wenzhou Medical University/ ; LR19C060001//Natural Science Foundation of Zhejiang Province/ ; 2023M732679//China Postdoctoral Science Foundation/ ; 32200535//National Natural Science Foundation of China/ ; 61871294//National Natural Science Foundation of China/ ; 82172882//National Natural Science Foundation of China/ ; }, abstract = {Diabetic retinopathy (DR) is one of leading causes of vision loss in adults with increasing prevalence worldwide. Increasing evidence has emphasized the importance of gut microbiome in the aetiology and development of DR. However, the causal relationship between gut microbes and DR remains largely unknown. To investigate the causal associations of DR with gut microbes and DR risk factors, we employed two-sample Mendelian Randomization (MR) analyses to estimate the causal effects of 207 gut microbes on DR outcomes. Inputs for MR included Genome-wide Association Study (GWAS) summary statistics of 207 taxa of gut microbes (the Dutch Microbiome Project) and 21 risk factors for DR. The GWAS summary statistics data of DR was from the FinnGen Research Project. Data analysis was performed in May 2023. We identified eight bacterial taxa that exhibited significant causal associations with DR (FDR < 0.05). Among them, genus Collinsella and species Collinsella aerofaciens were associated with increased risk of DR, while the species Bacteroides faecis, Burkholderiales bacterium_1_1_47, Ruminococcus torques, Streptococcus salivarius, genus Burkholderiales_noname and family Burkholderiales_noname showed protective effects against DR. Notably, we found that the causal effect of species Streptococcus salivarius on DR was mediated through the level of host fasting glucose, a well-established risk factor for DR. Our results reveal that specific gut microbes may be causally linked to DR via mediating host metabolic risk factors, highlighting potential novel therapeutic or preventive targets for DR.}, } @article {pmid38497260, year = {2024}, author = {Singh, A and Luallen, RJ}, title = {Understanding the factors regulating host-microbiome interactions using Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {379}, number = {1901}, pages = {20230059}, doi = {10.1098/rstb.2023.0059}, pmid = {38497260}, issn = {1471-2970}, abstract = {The Human Microbiome Project was a research programme that successfully identified associations between microbial species and healthy or diseased individuals. However, a major challenge identified was the absence of model systems for studying host-microbiome interactions, which would increase our capacity to uncover molecular interactions, understand organ-specificity and discover new microbiome-altering health interventions. Caenorhabditis elegans has been a pioneering model organism for over 70 years but was largely studied in the absence of a microbiome. Recently, ecological sampling of wild nematodes has uncovered a large amount of natural genetic diversity as well as a slew of associated microbiota. The field has now explored the interactions of C. elegans with its associated gut microbiome, a defined and non-random microbial community, highlighting its suitability for dissecting host-microbiome interactions. This core microbiome is being used to study the impact of host genetics, age and stressors on microbiome composition. Furthermore, single microbiome species are being used to dissect molecular interactions between microbes and the animal gut. Being amenable to health altering genetic and non-genetic interventions, C. elegans has emerged as a promising system to generate and test new hypotheses regarding host-microbiome interactions, with the potential to uncover novel paradigms relevant to other systems. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.}, } @article {pmid38491556, year = {2024}, author = {Elradi, M and Ahmed, AI and Saleh, AM and Abdel-Raouf, KMA and Berika, L and Daoud, Y and Amleh, A}, title = {Derivation of a novel antimicrobial peptide from the Red Sea Brine Pools modified to enhance its anticancer activity against U2OS cells.}, journal = {BMC biotechnology}, volume = {24}, number = {1}, pages = {14}, pmid = {38491556}, issn = {1472-6750}, abstract = {Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain was selected, modified to improve its anticancer properties, verified to maintain high anticancer properties, and processed for further in-silico prediction of structure and function. The peptide's anticancer properties were then assessed in vitro on osteosarcoma U2OS cells, through cytotoxicity assay (MTT assay), scratch-wound healing assay, apoptosis/necrosis detection assay (Annexin/PI assay), RNA expression analysis of Caspase 3, KI67 and Survivin, and protein expression of PARP1. L929 mouse fibroblasts were also assessed for cytotoxicity treatment. In addition, the antimicrobial activity of the peptide was also examined on E coli and S. aureus, as sample representative species of the human bacterial microbiome, by examining viability, disk diffusion, morphological assessment, and hemolytic analysis. We observed a dose dependent cytotoxic response from peptide treatment of U2OS, with a higher tolerance in L929s. Wound closure was debilitated in cells exposed to the peptide, while annexin fluorescent imaging suggested peptide treatment caused apoptosis as a major mode of cell death. Caspase 3 gene expression was not altered, while KI67 and Survivin were both downregulated in peptide treated cells. Additionally, PARP-1 protein analysis showed a decrease in expression with peptide exposure. The peptide exhibited minimal antimicrobial activity on critical human microbiome species E. coli and S. aureus, with a low inhibition rate, maintenance of structural morphology and minimal hemolytic impact. These findings suggest our novel peptide displayed preliminary ACP properties against U2OS cells, through limited specificity, while triggering apoptosis as a primary mode of cell death and while having minimal impact on the microbiological species E. coli and S. aureus.}, } @article {pmid38486697, year = {2024}, author = {Xiao, QA and Qin, L and Yu, J and Hu, YT and Ai, LF and Wang, DC and Xia, X and Zhang, XL}, title = {The causality between gut microbiome and chronic regional pain: a Mendelian randomization analysis.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1329521}, doi = {10.3389/fmicb.2024.1329521}, pmid = {38486697}, issn = {1664-302X}, abstract = {BACKGROUND: Numerous investigations have underscored the causal effect between chronic pain (CP) and gut microbiota, jointly contributing to the onset and development of widespread CP. Nonetheless, there was still uncertainty about the causal effect between gut microbiota and chronic regional pain (CRP).

METHODS: Genome-wide association study (GWAS) summary data of gut microbial taxa (MiBioGen Consortium: 211 microbiotas and the Dutch Microbiome Project: 207 microbiotas) and eight types of CRP were used to reveal the causal effect between persistent pain in a specific region of the body and gut microbiota. A two-sample bidirectional Mendelian randomization (MR) design was used. In order to ensure the accuracy of the results, multiple sensitivity analyses were employed.

RESULTS: This study uncovered significant causal associations between six gut microbial taxa and three types of CRP (forward: Genus Parabacteroides for general pain; Class Bacteroidia, Order Bacteroidales, and Phylum Bacteroidetes for back pain. Reverse: knee pain for Genus Howardella and Order Coriobacteriales) by forward and reverse MR analysis. These findings had been verified by a rigorous Bonferroni correction. Furthermore, this research identified 19 microbial taxa that exhibited potential correlations with four types of CRP. There are no significant or potential gut microbiotas that were associated with other types of CRP, including fascial pain, stomach or abdominal pain, and hip pain.

CONCLUSION: This two-sample bidirectional MR analysis unveiled the causality between gut microbial taxa and eight CRP conditions. The findings reveal the interplay between CRP and 6 gut microbiotas while also delineating 19 potential specific microbial taxa corresponding to diverse locations of persistent pain.}, } @article {pmid38481313, year = {2024}, author = {Wang, J and Teng, M and Feng, R and Su, X and Xu, K and Wang, J and Wang, G and Zhang, Y and Xu, P}, title = {Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization study.}, journal = {Diabetology & metabolic syndrome}, volume = {16}, number = {1}, pages = {66}, pmid = {38481313}, issn = {1758-5996}, abstract = {BACKGROUND: This study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot's foot.

METHODS: GM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications.

RESULTS: After multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors.

CONCLUSION: Extensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.}, } @article {pmid38474213, year = {2024}, author = {Hong, BY and Driscoll, M and Gratalo, D and Jarvie, T and Weinstock, GM}, title = {Improved DNA Extraction and Amplification Strategy for 16S rRNA Gene Amplicon-Based Microbiome Studies.}, journal = {International journal of molecular sciences}, volume = {25}, number = {5}, pages = {}, doi = {10.3390/ijms25052966}, pmid = {38474213}, issn = {1422-0067}, abstract = {Next-generation sequencing technology has driven the rapid advancement of human microbiome studies by enabling community-level sequence profiling of microbiomes. Although all microbiome sequencing methods depend on recovering the DNA from a sample as a first critical step, lysis methods can be a major determinant of microbiome profile bias. Gentle enzyme-based DNA preparation methods preserve DNA quality but can bias the results by failing to open difficult-to-lyse bacteria. Mechanical methods like bead beating can also bias DNA recovery because the mechanical energy required to break tougher cell walls may shear the DNA of the more easily lysed microbes, and shearing can vary depending on the time and intensity of beating, influencing reproducibility. We introduce a non-mechanical, non-enzymatic, novel rapid microbial DNA extraction procedure suitable for 16S rRNA gene-based microbiome profiling applications that eliminates bead beating. The simultaneous application of alkaline, heat, and detergent ('Rapid' protocol) to milligram quantity samples provided consistent representation across the population of difficult and easily lysed bacteria equal to or better than existing protocols, producing sufficient high-quality DNA for full-length 16S rRNA gene PCR. The novel 'Rapid' method was evaluated using mock bacterial communities containing both difficult and easily lysed bacteria. Human fecal sample testing compared the novel Rapid method with a standard Human Microbiome Project (HMP) protocol for samples from lung cancer patients and controls. DNA recovered from both methods was analyzed using 16S rRNA gene sequencing of the V1V3 and V4 regions on the Illumina platform and the V1V9 region on the PacBio platform. Our findings indicate that the 'Rapid' protocol consistently yielded higher levels of Firmicutes species, which reflected the profile of the bacterial community structure more accurately, which was confirmed by mock community evaluation. The novel 'Rapid' DNA lysis protocol reduces population bias common to bead beating and enzymatic lysis methods, presenting opportunities for improved microbial community profiling, combined with the reduction in sample input to 10 milligrams or less, and it enables rapid transfer and simultaneous lysis of 96 samples in a standard plate format. This results in a 20-fold reduction in sample handling time and an overall 2-fold time advantage when compared to widely used commercial methods. We conclude that the novel 'Rapid' DNA extraction protocol offers a reliable alternative for preparing fecal specimens for 16S rRNA gene amplicon sequencing.}, } @article {pmid38467837, year = {2024}, author = {Bhosle, A and Bae, S and Zhang, Y and Chun, E and Avila-Pacheco, J and Geistlinger, L and Pishchany, G and Glickman, JN and Michaud, M and Waldron, L and Clish, CB and Xavier, RJ and Vlamakis, H and Franzosa, EA and Garrett, WS and Huttenhower, C}, title = {Integrated annotation prioritizes metabolites with bioactivity in inflammatory bowel disease.}, journal = {Molecular systems biology}, volume = {}, number = {}, pages = {}, pmid = {38467837}, issn = {1744-4292}, support = {R24DK110499//HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/ ; }, abstract = {Microbial biochemistry is central to the pathophysiology of inflammatory bowel diseases (IBD). Improved knowledge of microbial metabolites and their immunomodulatory roles is thus necessary for diagnosis and management. Here, we systematically analyzed the chemical, ecological, and epidemiological properties of ~82k metabolic features in 546 Integrative Human Microbiome Project (iHMP/HMP2) metabolomes, using a newly developed methodology for bioactive compound prioritization from microbial communities. This suggested >1000 metabolic features as potentially bioactive in IBD and associated ~43% of prevalent, unannotated features with at least one well-characterized metabolite, thereby providing initial information for further characterization of a significant portion of the fecal metabolome. Prioritized features included known IBD-linked chemical families such as bile acids and short-chain fatty acids, and less-explored bilirubin, polyamine, and vitamin derivatives, and other microbial products. One of these, nicotinamide riboside, reduced colitis scores in DSS-treated mice. The method, MACARRoN, is generalizable with the potential to improve microbial community characterization and provide therapeutic candidates.}, } @article {pmid38340164, year = {2024}, author = {Osborne, C and Gilbert-Parkes, S and Spiers, G and Lamit, LJ and Lilleskov, EA and Basiliko, N and Watmough, S and , }, title = {Global Patterns of Metal and Other Element Enrichment in Bog and Fen Peatlands.}, journal = {Archives of environmental contamination and toxicology}, volume = {}, number = {}, pages = {}, pmid = {38340164}, issn = {1432-0703}, abstract = {Peatlands are found on all continents, covering 3% of the global land area. However, the spatial extent and causes of metal enrichment in peatlands is understudied and no attempt has been made to evaluate global patterns of metal enrichment in bog and fen peatlands, despite that certain metals and rare earth elements (REE) arise from anthropogenic sources. We analyzed 368 peat cores sampled in 16 countries across five continents and measured metal and other element concentrations at three depths down to 70 cm as well as estimated cumulative atmospheric S deposition (1850-2009) for each site. Sites were assigned to one of three distinct broadly recognized peatland categories (bog, poor fen, and intermediate-to-moderately rich fen) that varied primarily along a pH gradient. Metal concentrations differed among peatland types, with intermediate-to-moderately rich fens demonstrating the highest concentrations of most metals. Median enrichment factors (EFs; a metric comparing natural and anthropogenic metal deposition) for individual metals were similar among bogs and fens (all groups), with metals likely to be influenced by anthropogenic sources (As, Cd, Co, Cu, Hg, Pb, and Sb) demonstrating median enrichment factors (EFs) > 1.5. Additionally, mean EFs were substantially higher than median values, and the positive correlation (< 0.40) with estimated cumulative atmospheric S deposition, confirmed some level of anthropogenic influence of all pollutant metals except for Hg that was unrelated to S deposition. Contrary to expectations, high EFs were not restricted to pollutant metals, with Mn, K and Rb all exhibiting elevated median EFs that were in the same range as pollutant metals likely due to peatland biogeochemical processes leading to enrichment of these nutrients in surface soil horizons. The global patterns of metal enrichment in bogs and fens identified in this study underscore the importance of these peatlands as environmental archives of metal deposition, but also illustrates that biogeochemical processes can enrich metals in surface peat and EFs alone do not necessarily indicate atmospheric contamination.}, } @article {pmid38285276, year = {2024}, author = {Fang, M and Liu, W and Wang, Z and Li, J and Hu, S and Li, Z and Chen, W and Zhang, N}, title = {Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study.}, journal = {European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society}, volume = {}, number = {}, pages = {}, pmid = {38285276}, issn = {1432-0932}, support = {81972514//National Natural Science Foundation of China/ ; }, abstract = {PURPOSE: Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica.

METHODS: Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis.

RESULTS: Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation.

CONCLUSION: Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.}, } @article {pmid38284649, year = {2024}, author = {Hayer, SS and Conrin, M and French, JA and Benson, AK and Alvarez, S and Cooper, K and Fischer, A and Alsafwani, ZW and Gasper, W and Suhr Van Haute, MJ and Hassenstab, HR and Azadmanesh, S and Briardy, M and Gerbers, S and Jabenis, A and Thompson, JL and Clayton, JB}, title = {Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2305476}, pmid = {38284649}, issn = {1949-0984}, support = {K01 OD030514/OD/NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; R25 GM141506/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Anti-Bacterial Agents/toxicity ; Callithrix ; Brain-Gut Axis ; *Gastrointestinal Microbiome ; Dysbiosis/microbiology ; Multiomics ; }, abstract = {Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) - a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.}, } @article {pmid38233502, year = {2024}, author = {Chopra, A and Franco-Duarte, R and Rajagopal, A and Choowong, P and Soares, P and Rito, T and Eberhard, J and Jayasinghe, TN}, title = {Exploring the presence of oral bacteria in non-oral sites of patients with cardiovascular diseases using whole metagenomic data.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {1476}, pmid = {38233502}, issn = {2045-2322}, support = {2022.00340.CEECIND//Fundação para a Ciência e a Tecnologia/ ; "Contrato-Programa" UIDB/04050/2020//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {Humans ; *Cardiovascular Diseases ; *Microbiota/genetics ; Bacteria/genetics ; Metagenome ; *Plaque, Atherosclerotic ; }, abstract = {Cardiovascular diseases (CVDs) encompass various conditions affecting the heart and its blood vessels and are often linked with oral microbes. Our data analysis aimed to identify oral bacteria from other non-oral sites (i.e., gut, arterial plaque and cultured blood) that could be linked with CVDs. Taxonomic profiling identified bacteria to the species level and compared with the Human Oral Microbiome Database (HOMD). The oral bacteria in the gut, cultured blood and arterial plaque samples were catalogued, with their average frequency calculated for each sample. Additionally, data were filtered by comparison with the Human Microbiome Project (HMP) database. We identified 17,243 microbial species, of which 410 were present in the HOMD database and further denominated as "oral", and were found in at least one gut sample, but only 221 and 169 species were identified in the cultured blood and plaque samples, respectively. Of the 410 species, 153 were present solely in oral-associated environments after comparison with the HMP database, irrespective of their presence in other body sites. Our results suggest a potential connection between the presence of specific species of oral bacterial and occurrence of CVDs. Detecting these oral bacterial species in non-oral sites of patients with CVDs could help uncover the link between oral health and general health, including cardiovascular conditions via bacterial translocation.}, } @article {pmid38168274, year = {2023}, author = {Liu, R and Wang, Y and Cheng, D}, title = {Micro-DeMix: A mixture beta-multinomial model for investigating the fecal microbiome compositions.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {38168274}, support = {R01 GM145772/GM/NIGMS NIH HHS/United States ; }, abstract = {Extensive research has uncovered the involvement of the human gut microbiome in various facets of human health, including metabolism, nutrition, physiology, and immune function. Researchers often study fecal microbiota as a proxy for understanding the gut microbiome. However, it has been demonstrated that this approach may not suffice to yield a comprehensive understanding of the entire gut microbial community. Emerging research is revealing the heterogeneity of the gut microbiome across different gastrointestinal (GI) locations in both composition and functions. While spatial metagenomics approach has been developed to address these variations in mice, limitations arise when applying it to human-subject research, primarily due to its invasive nature. With these restrictions, we introduce Micro-DeMix, a mixture beta-multinomial model that decomposes the fecal microbiome at compositional level to understand the heterogeneity of the gut microbiome across various GI locations and extract meaningful insights about the biodiversity of the gut microbiome. Moreover, Micro-DeMix facilitates the discovery of differentially abundant microbes between GI regions through a hypothesis testing framework. We utilize the Inflammatory Bowel Disease (IBD) data from the NIH Integrative Human Microbiome Project to demonstrate the effectiveness and efficiency of the proposed Micro-DeMix.}, } @article {pmid38132705, year = {2024}, author = {Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Holliday, R and Brostow, DP and Penzenik, ME and Forster, JE and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Association of homelessness and diet on the gut microbiome: a United States-Veteran Microbiome Project (US-VMP) study.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0102123}, pmid = {38132705}, issn = {2379-5077}, mesh = {Humans ; United States/epidemiology ; *Veterans/psychology ; *Gastrointestinal Microbiome ; *Ill-Housed Persons ; *Microbiota ; Diet ; }, abstract = {Military veterans account for 8% of homeless individuals living in the United States. To highlight associations between history of homelessness and the gut microbiome, we compared the gut microbiome of veterans who reported having a previous experience of homelessness to those from individuals who reported never having experienced a period of homelessness. Moreover, we examined the impact of the cumulative exposure of prior and current homelessness to understand possible associations between these experiences and the gut microbiome. Microbiome samples underwent genomic sequencing and were analyzed based on alpha diversity, beta diversity, and taxonomic differences. Additionally, demographic information, dietary data, and mental health history were collected. A lifetime history of homelessness was found to be associated with alcohol use disorder, substance use disorder, and healthy eating index compared to those without such a history. In terms of differences in gut microbiota, beta diversity was significantly different between veterans who had experienced homelessness and veterans who had never been homeless (P = 0.047, weighted UniFrac), while alpha diversity was similar. The microbial community differences were, in part, driven by a lower relative abundance of Akkermansia in veterans who had experienced homelessness (mean; range [in percentages], 1.07; 0-33.9) compared to veterans who had never been homeless (2.02; 0-36.8) (P = 0.014, ancom-bc2). Additional research is required to facilitate understanding regarding the complex associations between homelessness, the gut microbiome, and mental and physical health conditions, with a focus on increasing understanding regarding the longitudinal impact of housing instability throughout the lifespan.IMPORTANCEAlthough there are known stressors related to homelessness as well as chronic health conditions experienced by those without stable housing, there has been limited work evaluating the associations between microbial community composition and homelessness. We analyzed, for the first time, bacterial gut microbiome associations among those with experiences of homelessness on alpha diversity, beta diversity, and taxonomic differences. Additionally, we characterized the influences of diet, demographic characteristics, military service history, and mental health conditions on the microbiome of veterans with and without any lifetime history of homelessness. Future longitudinal research to evaluate the complex relationships between homelessness, the gut microbiome, and mental health outcomes is recommended. Ultimately, differences in the gut microbiome of individuals experiencing and not experiencing homelessness could assist in identification of treatment targets to improve health outcomes.}, } @article {pmid38127919, year = {2023}, author = {L'Heureux, JE and van der Giezen, M and Winyard, PG and Jones, AM and Vanhatalo, A}, title = {Localisation of nitrate-reducing and highly abundant microbial communities in the oral cavity.}, journal = {PloS one}, volume = {18}, number = {12}, pages = {e0295058}, pmid = {38127919}, issn = {1932-6203}, mesh = {Humans ; *Nitrates/metabolism ; Nitrogen Dioxide ; Mouth/microbiology ; Bacteria ; Saliva/metabolism ; *Microbiota ; Streptococcus ; }, abstract = {The nitrate (NO3-) reducing bacteria resident in the oral cavity have been implicated as key mediators of nitric oxide (NO) homeostasis and human health. NO3--reducing oral bacteria reduce inorganic dietary NO3- to nitrite (NO2-) via the NO3--NO2--NO pathway. Studies of oral NO3--reducing bacteria have typically sampled from either the tongue surface or saliva. The aim of this study was to assess whether other areas in the mouth could contain a physiologically relevant abundance of NO3- reducing bacteria, which may be important for sampling in clinical studies. The bacterial composition of seven oral sample types from 300 individuals were compared using a meta-analysis of the Human Microbiome Project data. This analysis revealed significant differences in the proportions of 20 well-established oral bacteria and highly abundant NO3--reducing bacteria across each oral site. The genera included Actinomyces, Brevibacillus, Campylobacter, Capnocytophaga, Corynebacterium, Eikenella, Fusobacterium, Granulicatella, Haemophilus, Leptotrichia, Microbacterium, Neisseria, Porphyromonas, Prevotella, Propionibacterium, Rothia, Selenomonas, Staphylococcus, Streptococcus and Veillonella. The highest proportion of NO3--reducing bacteria was observed in saliva, where eight of the bacterial genera were found in higher proportion than on the tongue dorsum, whilst the lowest proportions were found in the hard oral surfaces. Saliva also demonstrated higher intra-individual variability and bacterial diversity. This study provides new information on where samples should be taken in the oral cavity to assess the abundance of NO3--reducing bacteria. Taking saliva samples may benefit physiological studies, as saliva contained the highest abundance of NO3- reducing bacteria and is less invasive than other sampling methods. These results inform future studies coupling oral NO3--reducing bacteria research with physiological outcomes affecting human health.}, } @article {pmid38095449, year = {2024}, author = {Arehart, CH and Sterrett, JD and Garris, RL and Quispe-Pilco, RE and Gignoux, CR and Evans, LM and Stanislawski, MA}, title = {Poly-omic risk scores predict inflammatory bowel disease diagnosis.}, journal = {mSystems}, volume = {9}, number = {1}, pages = {e0067723}, pmid = {38095449}, issn = {2379-5077}, support = {K01 HL157658/HL/NHLBI NIH HHS/United States ; }, mesh = {Humans ; *Inflammatory Bowel Diseases/diagnosis ; Metagenomics/methods ; Phenotype ; *Microbiota ; Risk Factors ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by complex etiology and a disrupted colonic ecosystem. We provide a framework for the analysis of multi-omic data, which we apply to study the gut ecosystem in IBD. Specifically, we train and validate models using data on the metagenome, metatranscriptome, virome, and metabolome from the Human Microbiome Project 2 IBD multi-omic database, with 1,785 repeated samples from 130 individuals (103 cases and 27 controls). After splitting the participants into training and testing groups, we used mixed-effects least absolute shrinkage and selection operator regression to select features for each omic. These features, with demographic covariates, were used to generate separate single-omic prediction scores. All four single-omic scores were then combined into a final regression to assess the relative importance of the individual omics and the predictive benefits when considered together. We identified several species, pathways, and metabolites known to be associated with IBD risk, and we explored the connections between data sets. Individually, metabolomic and viromic scores were more predictive than metagenomics or metatranscriptomics, and when all four scores were combined, we predicted disease diagnosis with a Nagelkerke's R[2] of 0.46 and an area under the curve of 0.80 (95% confidence interval: 0.63, 0.98). Our work supports that some single-omic models for complex traits are more predictive than others, that incorporating multiple omic data sets may improve prediction, and that each omic data type provides a combination of unique and redundant information. This modeling framework can be extended to other complex traits and multi-omic data sets.IMPORTANCEComplex traits are characterized by many biological and environmental factors, such that multi-omic data sets are well-positioned to help us understand their underlying etiologies. We applied a prediction framework across multiple omics (metagenomics, metatranscriptomics, metabolomics, and viromics) from the gut ecosystem to predict inflammatory bowel disease (IBD) diagnosis. The predicted scores from our models highlighted key features and allowed us to compare the relative utility of each omic data set in single-omic versus multi-omic models. Our results emphasized the importance of metabolomics and viromics over metagenomics and metatranscriptomics for predicting IBD status. The greater predictive capability of metabolomics and viromics is likely because these omics serve as markers of lifestyle factors such as diet. This study provides a modeling framework for multi-omic data, and our results show the utility of combining multiple omic data types to disentangle complex disease etiologies and biological signatures.}, } @article {pmid38094582, year = {2023}, author = {Luo, Y and Zhou, Y and Huang, P and Zhang, Q and Luan, F and Peng, Y and Wei, J and Li, N and Wang, C and Wang, X and Zhang, J and Yu, K and Zhao, M and Wang, C}, title = {Causal relationship between gut Prevotellaceae and risk of sepsis: a two-sample Mendelian randomization and clinical retrospective study in the framework of predictive, preventive, and personalized medicine.}, journal = {The EPMA journal}, volume = {14}, number = {4}, pages = {697-711}, pmid = {38094582}, issn = {1878-5077}, abstract = {OBJECTIVE: Gut microbiota is closely related to sepsis. Recent studies have suggested that Prevotellaceae could be associated with intestinal inflammation; however, the causal relationship between Prevotellaceae and sepsis remains uncertain. From the perspective of predictive, preventive, and personalized medicine (PPPM), exploring the causal relationship between gut Prevotellaceae and sepsis could provide opportunity for targeted prevention and personalized treatment.

METHODS: The genome-wide association study (GWAS) summary-level data of Prevotellaceae (N = 7738) and sepsis were obtained from the Dutch Microbiome Project and the UK Biobank (sepsis, 1380 cases; 429,985 controls). MR analysis was conducted to estimate the associations between Prevotellaceae and sepsis risk. The 16S rRNA sequencing analysis was conducted to calculate the relative abundance of Prevotellaceae in sepsis patients to explore the relationship between Prevotellaceae relative abundance and the 28-day mortality.

RESULTS: Genetic liability to f__Prevotellaceae (OR, 1.91; CI, 1.35-2.71; p = 0.0003) was associated with a high risk of sepsis with inverse-variance weighted (IVW). The median Prevotellaceae relative abundance in non-survivors was significantly higher than in survivors (2.34% vs 0.17%, p < 0.001). Multivariate analysis confirmed that Prevotellaceae relative abundance (OR, 1.10; CI, 1.03-1.22; p = 0.027) was an independent factor of 28-day mortality in sepsis patients. ROC curve analysis indicated that Prevotellaceae relative abundance (AUC: 0.787, 95% CI: 0.671-0.902, p = 0.0003) could predict the prognosis of sepsis patients.

CONCLUSION: Our results revealed that Prevotellaceae was causally associated with sepsis and affected the prognosis of sepsis patients. These findings may provide insights to clinicians on developing improved sepsis PPPM strategies.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-023-00340-6.}, } @article {pmid38076824, year = {2023}, author = {Schweickart, A and Batra, R and Neth, BJ and Martino, C and Shenhav, L and Zhang, AR and Shi, P and Karu, N and Huynh, K and Meikle, PJ and Schimmel, L and Dilmore, AH and Blennow, K and Zetterberg, H and Blach, C and Dorrestein, PC and Knight, R and , and Craft, S and Kaddurah-Daouk, R and Krumsiek, J}, title = {A Modified Mediterranean Ketogenic Diet mitigates modifiable risk factors of Alzheimer's Disease: a serum and CSF-based metabolic analysis.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, pmid = {38076824}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 AG049638/AG/NIA NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean-ketogenic diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.}, } @article {pmid38051644, year = {2023}, author = {Hou, T and Wang, Q and Dai, H and Hou, Y and Zheng, J and Wang, T and Lin, H and Wang, S and Li, M and Zhao, Z and Chen, Y and Xu, Y and Lu, J and Liu, R and Ning, G and Wang, W and Xu, M and Bi, Y}, title = {Interactive Association Between Gut Microbiota and Thyroid Cancer.}, journal = {Endocrinology}, volume = {165}, number = {1}, pages = {}, doi = {10.1210/endocr/bqad184}, pmid = {38051644}, issn = {1945-7170}, support = {81930021//National Natural Science Foundation of China/ ; SHDC2020CR1001A//Clinical Research Plan of SHDC/ ; 20152508//Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Genome-Wide Association Study ; *Microbiota ; *Thyroid Neoplasms/genetics ; }, abstract = {CONTEXT: The association between the gut microbiota and thyroid cancer remains controversial.

OBJECTIVE: We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer.

METHODS: We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18 340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1 620 354). We performed a bidirectional Mendelian randomization (MR) to investigate the causality from microbiota taxa and metabolism pathways to thyroid cancer and vice versa. We performed a systematic review of previous observational studies and compared MR results with observational findings.

RESULTS: Eight taxa and 12 metabolism pathways had causal effects on thyroid cancer, where RuminococcaceaeUCG004 genus (P = .001), Streptococcaceae family (P = .016), Olsenella genus (P = .029), ketogluconate metabolism pathway (P = .003), pentose phosphate pathway (P = .016), and L-arginine degradation II in the AST pathway (P = .0007) were supported by sensitivity analyses. Conversely, thyroid cancer had causal effects on 3 taxa and 2 metabolism pathways, where the Holdemanella genus (P = .015) was supported by sensitivity analyses. The Proteobacteria phylum, Streptococcaceae family, Ruminococcus2 genus, and Holdemanella genus were significantly associated with thyroid cancer in both the systematic review and MR, whereas the other 121 significant taxa in observational results were not supported by MR.

DISCUSSIONS: These findings implicated the potential role of host-microbiota crosstalk in thyroid cancer, while the discrepancy among observational studies calls for further investigations.}, } @article {pmid38048079, year = {2023}, author = {Fu, P and Wu, Y and Zhang, Z and Qiu, Y and Wang, Y and Peng, Y}, title = {VIGA: a one-stop tool for eukaryotic virus identification and genome assembly from next-generation-sequencing data.}, journal = {Briefings in bioinformatics}, volume = {25}, number = {1}, pages = {}, pmid = {38048079}, issn = {1477-4054}, support = {32370700//National Natural Science Foundation of China/ ; 2022YFC2303802//National Key Plan for Scientific Research and Development of China/ ; }, mesh = {Humans ; High-Throughput Nucleotide Sequencing ; *Colitis, Ulcerative ; *Crohn Disease ; Genome, Viral ; Metagenome ; }, abstract = {Identification of viruses and further assembly of viral genomes from the next-generation-sequencing data are essential steps in virome studies. This study presented a one-stop tool named VIGA (available at https://github.com/viralInformatics/VIGA) for eukaryotic virus identification and genome assembly from NGS data. It was composed of four modules, namely, identification, taxonomic annotation, assembly and novel virus discovery, which integrated several third-party tools such as BLAST, Trinity, MetaCompass and RagTag. Evaluation on multiple simulated and real virome datasets showed that VIGA assembled more complete virus genomes than its competitors on both the metatranscriptomic and metagenomic data and performed well in assembling virus genomes at the strain level. Finally, VIGA was used to investigate the virome in metatranscriptomic data from the Human Microbiome Project and revealed different composition and positive rate of viromes in diseases of prediabetes, Crohn's disease and ulcerative colitis. Overall, VIGA would help much in identification and characterization of viromes, especially the known viruses, in future studies.}, } @article {pmid38047279, year = {2023}, author = {Candeliere, F and Musmeci, E and Amaretti, A and Sola, L and Raimondi, S and Rossi, M}, title = {Profiling of the intestinal community of Clostridia: taxonomy and evolutionary analysis.}, journal = {Microbiome research reports}, volume = {2}, number = {2}, pages = {13}, pmid = {38047279}, issn = {2771-5965}, abstract = {Aim: Clostridia are relevant commensals of the human gut due to their major presence and correlations to the host. In this study, we investigated intestinal Clostridia of 51 healthy subjects and reconstructed their taxonomy and phylogeny. The relatively small number of intestinal Clostridia allowed a systematic whole genome approach based on average amino acid identity (AAI) and core genome with the aim of revising the current classification into genera and determining evolutionary relationships. Methods: 51 healthy subjects' metagenomes were retrieved from public databases. After the dataset's validation through comparison with Human Microbiome Project (HMP) samples, the metagenomes were profiled using MetaPhlAn3 to identify the population ascribed to the class Clostridia. Intestinal Clostridia genomes were retrieved and subjected to AAI analysis and core genome identification. Phylogeny investigation was conducted with RAxML and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) algorithms, and SplitsTree for split decomposition. Results: 225 out of 406 bacterial taxonomic units were ascribed to Bacillota [Firmicutes], among which 124 were assigned to the class Clostridia. 77 out of the 124 taxonomic units were referred to a species, altogether covering 87.7% of Clostridia abundance. According to the lowest AAI genus boundary set at 55%, 15 putative genera encompassing more than one species (G1 to G15) were identified, while 19 species did not cluster with any other one and each appeared to belong to a diverse genus. Phylogenetic investigations highlighted that most of the species clustered into three main evolutive clades. Conclusion: This study shed light on the species of Clostridia colonizing the gut of healthy adults and pinpointed several gaps in knowledge regarding the taxonomy and the phylogeny of Clostridia.}, } @article {pmid38045612, year = {2023}, author = {Brüssow, H}, title = {The human microbiome project at ten years - some critical comments and reflections on "our third genome", the human virome.}, journal = {Microbiome research reports}, volume = {2}, number = {1}, pages = {7}, pmid = {38045612}, issn = {2771-5965}, abstract = {The Human Microbiome Project (HMP) has raised great expectations claiming the far-reaching influence of the microbiome on human health and disease ranging from obesity and malnutrition to effects going well beyond the gut. So far, with the notable exception of fecal microbiota transplantation in Clostridioides difficile infection, practical application of microbiome intervention has only achieved modest clinical effects. It is argued here that we need criteria for the link between microbiome and disease modelled on the links between pathogens and infectious disease in Koch's postulates. The most important question is whether the microbiome change is a cause of the given disease or a consequence of a pathology leading to disease where the microbiome change is only a parallel event without a causal connection to the disease - in philosophical parlance, an epiphenomenon. Also discussed here is whether human virome research is a necessary complement to the microbiome project with a high potential for practical applications.}, } @article {pmid38029073, year = {2023}, author = {Xie, Q and Hu, B}, title = {Effects of gut microbiota on prostatic cancer: a two-sample Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1250369}, pmid = {38029073}, issn = {1664-302X}, abstract = {AIM: Recent observational and small-sample case-control studies have shown a relationship between gut microbiota composition and prostatic cancer (PCa). Nevertheless, the causal association between gut microbiota and PCa is still unclear. Herein, we used the Mendelian randomization (MR) method to explore the potential causal relationship between gut microbiota and PCa.

METHODS: In this two-sample MR study, data were extracted from the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis conducted by the MiBioGen consortium (n = 14,306) and the Dutch Microbiome Project (n = 8,208). Summary statistics for PCa were obtained from the FinnGen consortium release data (n = 95,213). Inverse variance weighted (IVW), MR-Egger, strength test (F), and MR-PRESSO were used to examine the potential causal association between gut microbiota and PCa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables.

RESULTS: IVW estimates suggested that the relative abundance of Akkermansia muciniphila (odds ratio [OR] = 0.7926, 95% confidence interval [CI]: 0.6655-0.9440) and Bacteroides salyersiae (OR = 0.9023, 95% CI: 0.8262-0.9853) were negatively associated with the odds of PCa, while that of Eubacterium biforme (OR = 1.1629, 95% CI: 1.0110-1.3376) was positively associated with the odds of PCa. In addition, we explored these relationships among patients without other cancers and similarly found that the relative abundance of Akkermansia muciniphila, Bacteroides salyersiae, and Eubacterium biforme were linked to PCa (all P < 0.05).

CONCLUSION: Gut microbiota potentially influenced the occurrence of PCa. Our findings may provide some new ideas for researching the methods of PCa prevention. In addition, further studies are needed to explore the causal association and specific underlying mechanisms between gut microbiota and PCa.}, } @article {pmid37973865, year = {2023}, author = {King, AM and Zhang, Z and Glassey, E and Siuti, P and Clardy, J and Voigt, CA}, title = {Systematic mining of the human microbiome identifies antimicrobial peptides with diverse activity spectra.}, journal = {Nature microbiology}, volume = {8}, number = {12}, pages = {2420-2434}, pmid = {37973865}, issn = {2058-5276}, support = {HR0011-15-C-0084//United States Department of Defense | Defense Advanced Research Projects Agency (DARPA)/ ; }, mesh = {Humans ; Antimicrobial Peptides ; *Methicillin-Resistant Staphylococcus aureus ; Escherichia coli ; Peptides/genetics/pharmacology/chemistry ; Bacteria/genetics ; *Microbiota/genetics ; Anti-Bacterial Agents/pharmacology ; }, abstract = {Human-associated bacteria secrete modified peptides to control host physiology and remodel the microbiota species composition. Here we scanned 2,229 Human Microbiome Project genomes of species colonizing skin, gastrointestinal tract, urogenital tract, mouth and trachea for gene clusters encoding RiPPs (ribosomally synthesized and post-translationally modified peptides). We found 218 lanthipeptides and 25 lasso peptides, 70 of which were synthesized and expressed in E. coli and 23 could be purified and functionally characterized. They were tested for activity against bacteria associated with healthy human flora and pathogens. New antibiotics were identified against strains implicated in skin, nasal and vaginal dysbiosis as well as from oral strains selectively targeting those in the gut. Extended- and narrow-spectrum antibiotics were found against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. Mining natural products produced by human-associated microbes will enable the elucidation of ecological relationships and may be a rich resource for antimicrobial discovery.}, } @article {pmid37940997, year = {2023}, author = {Dai, H and Hou, T and Wang, Q and Hou, Y and Zhu, Z and Zhu, Y and Zhao, Z and Li, M and Lin, H and Wang, S and Zheng, R and Xu, Y and Lu, J and Wang, T and Ning, G and Wang, W and Zheng, J and Bi, Y and Xu, M}, title = {Roles of gut microbiota in atrial fibrillation: insights from Mendelian randomization analysis and genetic data from over 430,000 cohort study participants.}, journal = {Cardiovascular diabetology}, volume = {22}, number = {1}, pages = {306}, pmid = {37940997}, issn = {1475-2840}, mesh = {Humans ; *Atrial Fibrillation/diagnosis/epidemiology/genetics ; *Gastrointestinal Microbiome ; Mendelian Randomization Analysis ; Cohort Studies ; *Diabetes Mellitus, Type 2 ; Genome-Wide Association Study ; *Coronary Artery Disease ; }, abstract = {BACKGROUND: Gut microbiota imbalances have been suggested as a contributing factor to atrial fibrillation (AF), but the causal relationship is not fully understood.

OBJECTIVES: To explore the causal relationships between the gut microbiota and AF using Mendelian randomization (MR) analysis.

METHODS: Summary statistics were from genome-wide association studies (GWAS) of 207 gut microbial taxa (5 phyla, 10 classes, 13 orders, 26 families, 48 genera, and 105 species) (the Dutch Microbiome Project) and two large meta-GWASs of AF. The significant results were validated in FinnGen cohort and over 430,000 UK Biobank participants. Mediation MR analyses were conducted for AF risk factors, including type 2 diabetes, coronary artery disease (CAD), body mass index (BMI), blood lipids, blood pressure, and obstructive sleep apnea, to explore the potential mediation effect of these risk factors in between the gut microbiota and AF.

RESULTS: Two microbial taxa causally associated with AF: species Eubacterium ramulus (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.04-1.12, P = 0.0001, false discovery rate (FDR) adjusted p-value = 0.023) and genus Holdemania (OR 1.15, 95% CI 1.07-1.25, P = 0.0004, FDR adjusted p-value = 0.042). Genus Holdemania was associated with incident AF risk in the UK Biobank. The proportion of mediation effect of species Eubacterium ramulus via CAD was 8.05% (95% CI 1.73% - 14.95%, P = 0.008), while the proportion of genus Holdemania on AF via BMI was 12.01% (95% CI 5.17% - 19.39%, P = 0.0005).

CONCLUSIONS: This study provided genetic evidence to support a potential causal mechanism between gut microbiota and AF and suggested the mediation role of AF risk factors.}, } @article {pmid37875417, year = {2023}, author = {Li, J and Yang, Z and Yuan, W and Bao, Z and Li, MD}, title = {Heme metabolism mediates the effects of smoking on gut microbiome.}, journal = {Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco}, volume = {}, number = {}, pages = {}, doi = {10.1093/ntr/ntad209}, pmid = {37875417}, issn = {1469-994X}, abstract = {INTRODUCTION: The number of smokers worldwide increased greatly during the past decades and reached 1.14 billion in 2019, becoming a leading risk factor for human health. Tobacco smoking has wide effects on human genetics, epigenetics, transcriptome, and gut microbiome. Although many studies have revealed effects of smoking on host transcriptome, research on the relationship among smoking, host gene expression, and the gut microbiome is limited.

METHODS: We first explored transcriptome and metagenome profile differences between smokers and non-smokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bi-directional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes.

RESULTS: Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and non-smokers. With smoking as an exposure variable, we identified 272 significant causal relationships between gene expression and gut microbes, among which there were 247 genes that mediate the effect of smoking on gut microbes. Pathway-based enrichment analysis showed that these genes were significantly enriched in heme metabolic pathway, which mainly mediated the changes of Bacteroides finegoldii and Lachnospiraceae bacterium 9_1_43BFAA. Additionally, by performing metabolome data analysis in the Integrated Human Microbiome project (iHMP) database, we verified the correlation between the intermediate products of the heme metabolism pathway (porphobilinogen, bilirubin, and biliverdin) and gut microbiome.

CONCLUSIONS: By investigating the bi-directional interaction between smoking-related host gene expression and gut microbes, this study provided evidence for the mediation of smoking on gut microbes through co-involvement or interaction of heme metabolism.

IMPLICATIONS: By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched non-smokers, we are the first to reveal causal relationships among tobacco smoking, host gene expression and gut microbes. These findings offer insight into how smoking affects gut microbes through host gene expression and metabolism, which highlights the importance of heme metabolism in modulating the effects of smoking on gut microbiome.}, } @article {pmid37874170, year = {2023}, author = {Brostow, DP and Donovan, M and Penzenik, M and Stamper, CE and Spark, T and Lowry, CA and Ishaq, SL and Hoisington, AJ and Brenner, LA}, title = {Food desert residence has limited impact on veteran fecal microbiome composition: a U.S. Veteran Microbiome Project study.}, journal = {mSystems}, volume = {8}, number = {6}, pages = {e0071723}, pmid = {37874170}, issn = {2379-5077}, support = {//U.S. Department of Veterans Affairs (VA)/ ; }, mesh = {Humans ; Food Deserts ; *Veterans/psychology ; *Microbiota ; Feces ; *Gastrointestinal Microbiome ; }, abstract = {Social and economic inequities can have a profound impact on human health. The inequities could result in alterations to the gut microbiome, an important factor that may have profound abilities to alter health outcomes. Moreover, the strong correlations between social and economic inequities have been long understood. However, to date, limited research regarding the microbiome and mental health within the context of socioeconomic inequities exists. One particular inequity that may influence both mental health and the gut microbiome is living in a food desert. Persons living in food deserts may lack access to sufficient and/or nutritious food and often experience other inequities, such as increased exposure to air pollution and poor access to healthcare. Together, these factors may confer a unique risk for microbial perturbation. Indeed, external factors beyond a food desert might compound over time to have a lasting effect on an individual's gut microbiome. Therefore, adoption of a life-course approach is expected to increase the ecological validity of research related to social inequities, the gut microbiome, and physical and mental health.}, } @article {pmid37810788, year = {2023}, author = {Ochoa-Sánchez, M and Acuña Gomez, EP and Ramírez-Fenández, L and Eguiarte, LE and Souza, V}, title = {Current knowledge of the Southern Hemisphere marine microbiome in eukaryotic hosts and the Strait of Magellan surface microbiome project.}, journal = {PeerJ}, volume = {11}, number = {}, pages = {e15978}, pmid = {37810788}, issn = {2167-8359}, mesh = {Animals ; *Eukaryota/genetics ; RNA, Ribosomal, 16S/genetics ; *Microbiota/genetics ; Metagenome ; Fishes/genetics ; Aquatic Organisms/genetics ; Mammals/genetics ; }, abstract = {Host-microbe interactions are ubiquitous and play important roles in host biology, ecology, and evolution. Yet, host-microbe research has focused on inland species, whereas marine hosts and their associated microbes remain largely unexplored, especially in developing countries in the Southern Hemisphere. Here, we review the current knowledge of marine host microbiomes in the Southern Hemisphere. Our results revealed important biases in marine host species sampling for studies conducted in the Southern Hemisphere, where sponges and marine mammals have received the greatest attention. Sponge-associated microbes vary greatly across geographic regions and species. Nevertheless, besides taxonomic heterogeneity, sponge microbiomes have functional consistency, whereas geography and aging are important drivers of marine mammal microbiomes. Seabird and macroalgal microbiomes in the Southern Hemisphere were also common. Most seabird microbiome has focused on feces, whereas macroalgal microbiome has focused on the epibiotic community. Important drivers of seabird fecal microbiome are aging, sex, and species-specific factors. In contrast, host-derived deterministic factors drive the macroalgal epibiotic microbiome, in a process known as "microbial gardening". In turn, marine invertebrates (especially crustaceans) and fish microbiomes have received less attention in the Southern Hemisphere. In general, the predominant approach to study host marine microbiomes has been the sequencing of the 16S rRNA gene. Interestingly, there are some marine holobiont studies (i.e., studies that simultaneously analyze host (e.g., genomics, transcriptomics) and microbiome (e.g., 16S rRNA gene, metagenome) traits), but only in some marine invertebrates and macroalgae from Africa and Australia. Finally, we introduce an ongoing project on the surface microbiome of key species in the Strait of Magellan. This is an international project that will provide novel microbiome information of several species in the Strait of Magellan. In the short-term, the project will improve our knowledge about microbial diversity in the region, while long-term potential benefits include the use of these data to assess host-microbial responses to the Anthropocene derived climate change.}, } @article {pmid37790319, year = {2023}, author = {Jansen, R and Milaneschi, Y and Schranner, D and Kastenmuller, G and Arnold, M and Han, X and Dunlop, BW and , and Rush, AJ and Kaddurah-Daouk, R and Penninx, BW}, title = {The Metabolome-Wide Signature of Major Depressive Disorder.}, journal = {Research square}, volume = {}, number = {}, pages = {}, pmid = {37790319}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; R01 MH108348/MH/NIMH NIH HHS/United States ; R01 AG069901/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; }, abstract = {Major Depressive Disorder (MDD) is an often-chronic condition with substantial molecular alterations and pathway dysregulations involved. Single metabolite, pathway and targeted metabolomics platforms have indeed revealed several metabolic alterations in depression including energy metabolism, neurotransmission and lipid metabolism. More comprehensive coverage of the metabolome is needed to further specify metabolic dysregulation in depression and reveal previously untargeted mechanisms. Here we measured 820 metabolites using the metabolome-wide Metabolon platform in 2770 subjects from a large Dutch clinical cohort with extensive depression clinical phenotyping (1101 current MDD, 868 remitted MDD, 801 healthy controls) at baseline and 1805 subjects at 6-year follow up (327 current MDD, 1045 remitted MDD, 433 healthy controls). MDD diagnosis was based on DSM-IV psychiatric interviews. Depression severity was measured with the Inventory of Depressive Symptomatology self-report. Associations between metabolites and MDD status and depression severity were assessed at baseline and at the 6-year follow-up. Metabolites consistently associated with MDD status or depression severity on both occasions were examined in Mendelian randomization (MR) analysis using metabolite (N=14,000) and MDD (N=800,000) GWAS results. At baseline, 139 and 126 metabolites were associated with current MDD status and depression severity, respectively, with 79 overlapping metabolites. Six years later, 34 out of the 79 metabolite associations were subsequently replicated. Downregulated metabolites were enriched with long-chain monounsaturated (P=6.7e-07) and saturated (P=3.2e-05) fatty acids and upregulated metabolites with lysophospholipids (P=3.4e-4). Adding BMI to the models changed results only marginally. MR analyses showed that genetically-predicted higher levels of the lysophospholipid 1-linoleoyl-GPE (18:2) were associated with greater risk of depression. The identified metabolome-wide profile of depression (severity) indicated altered lipid metabolism with downregulation of long-chain fatty acids and upregulation of lysophospholipids, for which causal involvement was suggested using genetic tools. This metabolomics signature offers a window on depression pathophysiology and a potential access point for the development of novel therapeutic approaches.}, } @article {pmid37747198, year = {2023}, author = {Duan, Z and Fu, J and Zhang, F and Cai, Y and Wu, G and Ma, W and Zhou, H and He, Y}, title = {The association between BMI and serum uric acid is partially mediated by gut microbiota.}, journal = {Microbiology spectrum}, volume = {11}, number = {5}, pages = {e0114023}, pmid = {37747198}, issn = {2165-0497}, abstract = {Obesity is a risk factor for the development of hyperuricemia, both of which were related to gut microbiota. However, whether alterations in the gut microbiota lie in the pathways mediating obesity's effects on hyperuricemia is less clear. Body mass index (BMI) and serum uric acid (SUA) were separately important indicators of obesity and hyperuricemia. Our study aims to investigate whether BMI-related gut microbiota characteristics would mediate the association between BMI and SUA levels. A total of 6,280 participants from Guangdong Gut Microbiome Project were included in this study. Stool samples were collected for 16S rRNA gene sequencing. The results revealed that BMI was significantly and positively associated with SUA. Meanwhile, BMI was significantly associated with the abundance of 102 gut microbial genera, 16 of which were also significantly associated with SUA. The mediation analysis revealed that the association between BMI and SUA was partially mediated by the abundance of Proteobacteria (proportion mediated: 0.94%, P < 0.05). At the genus level, 25 bacterial genera, including Ralstonia, Oscillospira, Faecalibacterium, etc., could also partially mediate the association of BMI with SUA (the highest proportion is mediated by Ralstonia, proportion mediated: 2.76%, P < 0.05). This study provided evidence for the associations among BMI, gut microbiota, and SUA, and the mediation analysis suggested that the association of BMI with SUA was partially mediated by the gut microbiota. IMPORTANCE Using 16S rRNA sequencing analysis, local interpretable machine learning technique analysis and mediation analysis were used to explore the association between BMI with SUA, and the mediating effects of gut microbial dysbiosis in the association were investigated.}, } @article {pmid37719161, year = {2023}, author = {Hayer, SS and Hwang, S and Clayton, JB}, title = {Antibiotic-induced gut dysbiosis and cognitive, emotional, and behavioral changes in rodents: a systematic review and meta-analysis.}, journal = {Frontiers in neuroscience}, volume = {17}, number = {}, pages = {1237177}, pmid = {37719161}, issn = {1662-4548}, support = {K01 OD030514/OD/NIH HHS/United States ; }, abstract = {There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases-PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the study-populations, respectively. Decrease in sociability, social novelty preference, recognition memory and spatial cognition was found in 18.1, 35.3, 26.1, and 62.5 percent of the study-populations, respectively. Only one bacterial taxon (increase in gut Proteobacteria) showed statistically significant association with behavioral changes (increase in anxiety). There were no consistent findings with statistical significance for the potential biomarkers [Brain-derived neurotrophic factor (BDNF) expression in the hippocampus, serum corticosterone and circulating IL-6 and IL-1β levels]. Results of the meta-analysis revealed a significant association between symptoms of negative valence system (including anxiety and depression) and cognitive system (decreased spatial cognition) with antibiotic intake (p < 0.05). However, between-study heterogeneity and publication bias were statistically significant (p < 0.05). Risk of bias was evaluated to be high in the majority of the studies. We identified and discussed several reasons that could contribute to the heterogeneity between the results of the studies examined. The results of the meta-analysis provide promising evidence that there is indeed an association between antibiotic-induced gut dysbiosis and psychopathologies. However, inconsistencies in the implemented methodologies make generalizing these results difficult. Gut microbiota depletion using antibiotics may be a useful strategy to evaluate if and how gut microbes influence cognition, emotion, and behavior, but the heterogeneity in methodologies used precludes any definitive interpretations for a translational impact on clinical practice.}, } @article {pmid37655719, year = {2023}, author = {Corewyn, LC and Kelaita, MA and Nollman, J and Hagnauer, I and Blanco-Peña, K and Lessnau, RG and Clayton, JB and Shields-Cutler, R and Stoos, KB}, title = {Hematology and blood biochemistry in a declining population of mantled howler monkeys (Alouatta palliata palliata) at La Pacifica, Costa Rica.}, journal = {Journal of medical primatology}, volume = {52}, number = {6}, pages = {353-360}, pmid = {37655719}, issn = {1600-0684}, support = {K01 OD030514/OD/NIH HHS/United States ; }, mesh = {Female ; Male ; Animals ; Costa Rica ; *Alouatta ; *Alouatta caraya ; *Hematology ; }, abstract = {BACKGROUND: Alouatta palliata palliata are an ecologically flexible howler monkey subspecies that has recently been relisted as Endangered. Populations are declining through much of the subspecies' range, including at our study site at La Pacifica, Costa Rica. Our objectives were to screen blood hematology and biochemistry samples collected from this wild population to elucidate their baseline health.

METHODS: We collected blood samples from 38 adult individuals from across the study site and analyzed 13 hematology and 14 biochemistry parameters.

RESULTS: Most hematology and blood biochemistry parameter values were similar between males and females. However, mean hemoglobin was significantly lower, and mean white blood cell count was significantly higher in females; and mean calcium and mean creatinine were significantly lower in females compared to males.

CONCLUSIONS: Overall, the La Pacifica population appeared healthy based on the blood parameters analyzed from sampled individuals. Our results were also largely consistent with published data available from other populations of A. p. palliata, and with reference values for captive Alouatta caraya.}, } @article {pmid37644161, year = {2023}, author = {Koo, H and Morrow, CD}, title = {Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {14112}, pmid = {37644161}, issn = {2045-2322}, mesh = {Child ; Humans ; Animals ; Mice ; *Fecal Microbiota Transplantation ; *Clostridioides difficile/genetics ; Tissue Donors ; Bacteroides/genetics ; }, abstract = {Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.}, } @article {pmid37642431, year = {2023}, author = {Farmer, N and Maki, KA and Barb, JJ and Jones, KK and Yang, L and Baumer, Y and Powell-Wiley, TM and Wallen, GR}, title = {Geographic social vulnerability is associated with the alpha diversity of the human microbiome.}, journal = {mSystems}, volume = {8}, number = {5}, pages = {e0130822}, pmid = {37642431}, issn = {2379-5077}, mesh = {Humans ; *Social Vulnerability ; *Microbiota/genetics ; Geography ; Risk Factors ; Public Health ; }, abstract = {As a risk factor for conditions related to the microbiome, understanding the role of SVI on microbiome diversity may assist in identifying public health implications for microbiome research. Here we found, using a sub-sample of the Human Microbiome Project phase 1 cohort, that SVI was linked to microbiome diversity across body sites and that SVI may influence race/ethnicity-based differences in diversity. Our findings, build on the current knowledge regarding the role of human geography in microbiome research, suggest that measures of geographic social vulnerability be considered as additional contextual factors when exploring microbiome alpha diversity.}, } @article {pmid37637212, year = {2023}, author = {Li, W and Mirone, J and Prasad, A and Miolane, N and Legrand, C and Dao Duc, K}, title = {Orthogonal outlier detection and dimension estimation for improved MDS embedding of biological datasets.}, journal = {Frontiers in bioinformatics}, volume = {3}, number = {}, pages = {1211819}, pmid = {37637212}, issn = {2673-7647}, abstract = {Conventional dimensionality reduction methods like Multidimensional Scaling (MDS) are sensitive to the presence of orthogonal outliers, leading to significant defects in the embedding. We introduce a robust MDS method, called DeCOr-MDS (Detection and Correction of Orthogonal outliers using MDS), based on the geometry and statistics of simplices formed by data points, that allows to detect orthogonal outliers and subsequently reduce dimensionality. We validate our methods using synthetic datasets, and further show how it can be applied to a variety of large real biological datasets, including cancer image cell data, human microbiome project data and single cell RNA sequencing data, to address the task of data cleaning and visualization.}, } @article {pmid37637104, year = {2023}, author = {Gois, MFB and Fernández-Pato, A and Huss, A and Gacesa, R and Wijmenga, C and Weersma, RK and Fu, J and Vermeulen, RCH and Zhernakova, A and Lenters, VC and Kurilshikov, A}, title = {Impact of occupational pesticide exposure on the human gut microbiome.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1223120}, pmid = {37637104}, issn = {1664-302X}, abstract = {The rising use of pesticides in modern agriculture has led to a shift in disease burden in which exposure to these chemicals plays an increasingly important role. The human gut microbiome, which is partially responsible for the biotransformation of xenobiotics, is also known to promote biotransformation of environmental pollutants. Understanding the effects of occupational pesticide exposure on the gut microbiome can thus provide valuable insights into the mechanisms underlying the impact of pesticide exposure on health. Here we investigate the impact of occupational pesticide exposure on human gut microbiome composition in 7198 participants from the Dutch Microbiome Project of the Lifelines Study. We used job-exposure matrices in combination with occupational codes to retrieve categorical and cumulative estimates of occupational exposures to general pesticides, herbicides, insecticides and fungicides. Approximately 4% of our cohort was occupationally exposed to at least one class of pesticides, with predominant exposure to multiple pesticide classes. Most participants reported long-term employment, suggesting a cumulative profile of exposure. We demonstrate that contact with insecticides, fungicides and a general "all pesticides" class was consistently associated with changes in the gut microbiome, showing significant associations with decreased alpha diversity and a differing beta diversity. We also report changes in the abundance of 39 different bacterial taxa upon exposure to the different pesticide classes included in this study. Together, the extent of statistically relevant associations between gut microbial changes and pesticide exposure in our findings highlights the impact of these compounds on the human gut microbiome.}, } @article {pmid37630647, year = {2023}, author = {Zhang, F and Zhang, X and Fu, J and Duan, Z and Qiu, W and Cai, Y and Ma, W and Zhou, H and Chen, Y and Zheng, J and He, Y}, title = {Sex- and Age-Dependent Associations between Parabacteroides and Obesity: Evidence from Two Population Cohort.}, journal = {Microorganisms}, volume = {11}, number = {8}, pages = {}, pmid = {37630647}, issn = {2076-2607}, support = {82022044//National Natural Science Foundation of China/ ; }, abstract = {Parabacteroides levels are reported to be low in obese individuals, and this genus has shown an anti-obesity capacity in animal studies. Nevertheless, the relationship between Parabacteroides and obesity in different subpopulations, e.g., with respect to age and sex, and its association with subsequent weight change have rarely been explored. The cross-sectional associations of Parabacteroides genus- and species-level OTU abundance with obesity were explored in the Guangdong Gut Microbiome Project (GGMP), which included 5843 adults, and replicated in the Guangzhou Nutrition and Health Study (GNSH), which included 1637 individuals. Furthermore, we assessed the prospective associations of Parabacteroides and its main OTUs' abundance with the subsequent changes in body mass index (BMI) in the GNSH. We found that Parabacteroides was inversely associated with obesity among females and participants aged 40-69 years in the GGMP and the replicated cohort in the GNSH. After a 3-year follow-up, there was no significant correlation between Parabacteroides and the subsequent changes in BMI. However, Seq4172 (P. johnsonii) showed a negative correlation with subsequent BMI changes in the female and middle-aged (40-69 years) subpopulations. Overall, our results indicate that Parabacteroides have an inverse relationship with obesity and that Seq4172 (P. johnsonii) have a negative association with subsequent changes in BMI among females and middle-aged populations in perspective analyses.}, } @article {pmid37626146, year = {2023}, author = {Singh, S and Singh, S and Lukas, SB and Machado, S and Nouri, A and Calderon, F and Rieke, ER and Cappellazzi, SB}, title = {Long-term agro-management strategies shape soil bacterial community structure in dryland wheat systems.}, journal = {Scientific reports}, volume = {13}, number = {1}, pages = {13929}, pmid = {37626146}, issn = {2045-2322}, mesh = {*Soil ; Triticum ; Carbon Dioxide ; Agriculture ; *Calcinosis ; Carbon ; }, abstract = {Soil microbes play a crucial role in soil organic matter decomposition and nutrient cycling and are influenced by management practices. Therefore, quantifying the impacts of various agricultural management practices on soil microbiomes and their activity is crucial for making informed management decisions. This study aimed to assess the impact of various management systems on soil bacterial abundance and diversity, soil enzyme activities and carbon mineralization potential in wheat-based systems. To accomplish this, soil samples from 0 to 15 cm depth were collected from ongoing long-term field trials in eastern Oregon region under wheat (Triticum aestivum L.)-fallow (WF), WF with different tillage (WT), wheat-pea (Pisum sativum L.) (WP), WF under different crop residue management (CR) and natural undisturbed/unmanaged grassland pasture (GP). These trials consisted of an array of treatments like tillage intensities, nitrogen rates, organic amendments, and seasonal residue burning. This study was a part of the Soil Health Institute's North American Project to Evaluate Soil Health measurements (NAPESHM). Bacterial community structure was determined using amplicon sequencing of the V4 region of 16SrRNA genes and followed the protocols of the Earth Microbiome Project. In addition, extracellular enzyme activities, and carbon mineralization potential (1d-CO2) were measured. Among different trials, 1d-CO2 in WT, WP, and CR studies averaged 53%, 51% and 87% lower than GP systems, respectively. Enzyme activities were significantly greater in GP compared to the other managements and followed similar trend as respiration. We observed higher evenness in GP and higher richness in spring residue burning treatment of CR study. Our results indicated that species evenness is perhaps a better indicator of soil health in comparison to other indices in dryland wheat systems.}, } @article {pmid37619924, year = {2023}, author = {Golovko, G and Khanipov, K and Reyes, V and Pinchuk, I and Fofanov, Y}, title = {Identification of multivariable Boolean patterns in microbiome and microbial gene composition data.}, journal = {Bio Systems}, volume = {233}, number = {}, pages = {105007}, doi = {10.1016/j.biosystems.2023.105007}, pmid = {37619924}, issn = {1872-8324}, abstract = {Virtually every biological system is governed by complex relations among its components. Identifying such relations requires a rigorous or heuristics-based search for patterns among variables/features of a system. Various algorithms have been developed to identify two-dimensional (involving two variables) patterns employing correlation, covariation, mutual information, etc. It seems obvious, however, that comprehensive descriptions of complex biological systems need also to include more complicated multivariable relations, which can only be described using patterns that simultaneously embrace 3, 4, and more variables. The goal of this manuscript is to (a) introduce a novel type of associations (multivariable Boolean patterns) that can be manifested between features of complex systems but cannot be identified (described) by traditional pair-vise metrics; (b) propose patterns classification method, and (c) provide a novel definition of the pattern's strength (pattern's score) able to accommodate heterogeneous multi-omics data. To demonstrate the presence of such patterns, we performed a search for all possible 2-, 3-, and 4-dimensional patterns in historical data from the Human Microbiome Project (15 body sites) and collection of H. pylori genomes associated with gastric ulcers, gastritis, and duodenal ulcers. In all datasets under consideration, we were able to identify hundreds of statistically significant multivariable patterns. These results suggest that such patterns can be common in microbial genomics/microbiomics systems.}, } @article {pmid37569821, year = {2023}, author = {Dong, H and Ming, D}, title = {A Comprehensive Self-Resistance Gene Database for Natural-Product Discovery with an Application to Marine Bacterial Genome Mining.}, journal = {International journal of molecular sciences}, volume = {24}, number = {15}, pages = {}, pmid = {37569821}, issn = {1422-0067}, support = {2019YFA0905700, 2021YFC2102700//the National Key Research and Development Program of China/ ; }, abstract = {In the world of microorganisms, the biosynthesis of natural products in secondary metabolism and the self-resistance of the host always occur together and complement each other. Identifying resistance genes from biosynthetic gene clusters (BGCs) helps us understand the self-defense mechanism and predict the biological activity of natural products synthesized by microorganisms. However, a comprehensive database of resistance genes is still lacking, which hinders natural product annotation studies in large-scale genome mining. In this study, we compiled a resistance gene database (RGDB) by scanning the four available databases: CARD, MIBiG, NCBIAMR, and UniProt. Every resistance gene in the database was annotated with resistance mechanisms and possibly involved chemical compounds, using manual annotation and transformation from the resource databases. The RGDB was applied to analyze resistance genes in 7432 BGCs in 1390 genomes from a marine microbiome project. Our calculation showed that the RGDB successfully identified resistance genes for more than half of the BGCs, suggesting that the database helps prioritize BGCs that produce biologically active natural products.}, } @article {pmid37533836, year = {2023}, author = {Su, Q and Jin, C and Bo, Z and Yang, Y and Wang, J and Wang, J and Zhou, J and Chen, Y and Zeng, H and Chen, G and Wang, Y}, title = {Association between gut microbiota and gastrointestinal cancer: a two-sample bi-directional Mendelian randomization study.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1181328}, pmid = {37533836}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer.

MATERIALS AND METHODS: Summary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses.

RESULTS: We identified potential causal associations between 21 bacterial taxa and GI cancers (values of p < 0.05 in all three MR methods). Among them, phylum Verrucomicrobia (OR: 0.17, 95% CI: 0.05-0.59, p = 0.005) retained a strong negative association with intrahepatic cholangiocarcinoma after the Bonferroni correction, whereas order Bacillales (OR: 1.67, 95% CI: 1.23-2.26, p = 0.001) retained a strong positive association with pancreatic cancer. Reverse MR analyses indicated that GI cancer was associated with 17 microbial taxa in all three MR methods, among them, a strong inverse association between colorectal cancer and family Clostridiaceae1 (OR: 0.91, 95% CI: 0.86-0.96, p = 0.001) was identified by Bonferroni correction.

CONCLUSION: Our study implicates the potential causal effects of specific microbial taxa on GI cancer, potentially providing new insights into the prevention and treatment of GI cancer through specific gut bacteria.}, } @article {pmid37379424, year = {2023}, author = {Seabourn, PS and Weber, DE and Spafford, H and Medeiros, MCI}, title = {Aedes albopictus microbiome derives from environmental sources and partitions across distinct host tissues.}, journal = {MicrobiologyOpen}, volume = {12}, number = {3}, pages = {e1364}, pmid = {37379424}, issn = {2045-8827}, support = {P20 GM125508/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Aedes/microbiology ; *Microbiota ; Life Cycle Stages ; Soil ; Symbiosis ; }, abstract = {The mosquito microbiome consists of a consortium of interacting microorganisms that reside on and within culicid hosts. Mosquitoes acquire most of their microbial diversity from the environment over their life cycle. Once present within the mosquito host, the microbes colonize distinct tissues, and these symbiotic relationships are maintained by immune-related mechanisms, environmental filtering, and trait selection. The processes that govern how environmental microbes assemble across the tissues within mosquitoes remain poorly resolved. We use ecological network analyses to examine how environmental bacteria assemble to form bacteriomes among Aedes albopictus host tissues. Mosquitoes, water, soil, and plant nectar were collected from 20 sites in the Mānoa Valley, Oahu. DNA was extracted and associated bacteriomes were inventoried using Earth Microbiome Project protocols. We find that the bacteriomes of A. albopictus tissues were compositional taxonomic subsets of environmental bacteriomes and suggest that the environmental microbiome serves as a source pool that supports mosquito microbiome diversity. Within the mosquito, the microbiomes of the crop, midgut, Malpighian tubules, and ovaries differed in composition. This microbial diversity partitioned among host tissues formed two specialized modules: one in the crop and midgut, and another in the Malpighian tubules and ovaries. The specialized modules may form based on microbe niche preferences and/or selection of mosquito tissues for specific microbes that aid unique biological functions of the tissue types. A strong niche-driven assembly of tissue-specific microbiotas from the environmental species pool suggests that each tissue has specialized associations with microbes, which derive from host-mediated microbe selection.}, } @article {pmid37331612, year = {2023}, author = {Adelfio, M and Bonzanni, M and Callen, GE and Paster, BJ and Hasturk, H and Ghezzi, CE}, title = {A physiologically relevant culture platform for long-term studies of in vitro gingival tissue.}, journal = {Acta biomaterialia}, volume = {167}, number = {}, pages = {321-334}, pmid = {37331612}, issn = {1878-7568}, support = {R03 DE030224/DE/NIDCR NIH HHS/United States ; }, mesh = {Humans ; *Gingiva/pathology ; *Periodontitis/microbiology/pathology ; Epithelium ; Bacteria ; Biomarkers ; Porphyromonas gingivalis ; }, abstract = {There is a clinical need to understand the etiologies of periodontitis, considering the growing socio-economic impact of the disease. Despite recent advances in oral tissue engineering, experimental approaches have failed to develop a physiologically relevant gingival model that combines tissue organization with salivary flow dynamics and stimulation of the shedding and non-shedding oral surfaces. Herein, we develop a dynamic gingival tissue model composed of a silk scaffold, replicating the cyto-architecture and oxygen profile of the human gingiva, along with a saliva-mimicking medium that reflected the ionic composition, viscosity, and non-Newtonian behavior of human saliva. The construct was cultured in a custom designed bioreactor, in which force profiles on the gingival epithelium were modulated through analysis of inlet position, velocity and vorticity to replicate the physiological shear stress of salivary flow. The gingival bioreactor supported the long-term in vivo features of the gingiva and improved the integrity of the epithelial barrier, critical against the invasion of pathogenic bacteria. Furthermore, the challenge of the gingival tissue with P. gingivalis lipopolysaccharide, as an in vitro surrogate for microbial interactions, indicated a greater stability of the dynamic model in maintaining tissue homeostasis and, thus, its applicability in long-term studies. The model will be integrated into future studies with the human subgingival microbiome to investigate host-pathogen and host-commensal interactions. STATEMENT OF SIGNIFICANCE: The major societal impact of human microbiome had reverberated up to the establishment of the Common Fund's Human Microbiome Project, that has the intent of studying the role of microbial communities in human health and diseases, including periodontitis, atopic dermatitis, or asthma and inflammatory bowel disease. In addition, these chronic diseases are emergent drivers of global socioeconomic status. Not only common oral diseases have been shown to be directly correlated with several systemic conditions, but they are differentially impacting some racial/ethnic and socioeconomic groups. To address this growing social disparity, the development of in vitro gingival model would provide a time and cost-effective experimental platform, able to mimic the spectrum of periodontal disease presentation, for the identification of predictive biomarkers for early-stage diagnosis.}, } @article {pmid37317128, year = {2023}, author = {Bar, K and Litera-Bar, M and Sozańska, B}, title = {Bacterial Microbiota of Asthmatic Children and Preschool Wheezers' Airways-What Do We Know?.}, journal = {Microorganisms}, volume = {11}, number = {5}, pages = {}, pmid = {37317128}, issn = {2076-2607}, abstract = {Asthma is the most chronic pulmonary disease in pediatric population, and its etiopathology still remains unclear. Both viruses and bacteria are suspected factors of disease development and are responsible for its exacerbation. Since the launch of The Human Microbiome Project, there has been an explosion of research on microbiota and its connection with various diseases. In our review, we have collected recent data about both upper- and lower-airway bacterial microbiota of asthmatic children. We have also included studies regarding preschool wheezers, since asthma diagnosis in children under 5 years of age remains challenging due to the lack of an objective tool. This paper indicates the need for further studies of microbiome and asthma, as in today's knowledge, there is no particular bacterium that discriminates the asthmatics from the healthy peers and can be used as a potential biological factor in the disease prevalence and treatment.}, } @article {pmid37254222, year = {2023}, author = {Addison, S and Armstrong, C and Wigley, K and Hartley, R and Wakelin, S}, title = {What matters most? Assessment of within-canopy factors influencing the needle microbiome of the model conifer, Pinus radiata.}, journal = {Environmental microbiome}, volume = {18}, number = {1}, pages = {45}, pmid = {37254222}, issn = {2524-6372}, support = {The Tree Microbiome Project: at the root of climate proofing forests (C04X2002)//Ministry of Business, Innovation and Employment/ ; }, abstract = {The assembly and function of the phyllosphere microbiome is important to the overall fitness of plants and, thereby, the ecosystems they inhabit. Presently, model systems for tree phyllosphere microbiome studies are lacking, yet forests resilient to pests, diseases, and climate change are important to support a myriad of ecosystem services impacting from local to global levels. In this study, we extend the development of model microbiome systems for trees species, particularly coniferous gymnosperms, by undertaking a structured approach assessing the phyllosphere microbiome of Pinus radiata. Canopy sampling height was the single most important factor influencing both alpha- and beta-diversity of bacterial and fungal communities (p < 0.005). Bacterial and fungal phyllosphere microbiome richness was lowest in samples from the top of the canopy, subsequently increasing in the middle and then bottom canopy samples. These differences maybe driven by either by (1) exchange of microbiomes with the forest floor and soil with the lower foliage, (2) strong ecological filtering in the upper canopy via environmental exposure (e.g., UV), (3) canopy density, (4) or combinations of factors. Most taxa present in the top canopy were also present lower in tree; as such, sampling strategies focussing on lower canopy sampling should provide good overall phyllosphere microbiome coverage for the tree. The dominant phyllosphere bacteria were Alpha-proteobacteria (Rhizobiales and Sphingomonas) along with Acidobacteria Gp1. However, the P. radiata phyllosphere microbiome samples were fungal dominated. From the top canopy samples, Arthoniomycetes and Dothideomycetes were highly represented, with abundances of Arthoniomycetes then reducing in lower canopy samples whilst abundances of Ascomycota increased. The most abundant fungal taxa were Phaeococcomyces (14.4% of total reads) and Phaeotheca spp. (10.38%). A second-order effect of canopy sampling direction was evident in bacterial community composition (p = 0.01); these directional influences were not evident for fungal communities. However, sterilisation of needles did impact fungal community composition (p = 0.025), indicating potential for community differences in the endosphere versus leaf surface compartments. Needle age was only important in relation to bacterial communities, but was canopy height dependant (interaction p = 0.008). By building an understanding of the primary and secondary factors related to intra-canopy phyllosphere microbiome variation, we provide a sampling framework to either explicitly minimise or capture variation in needle collection to enable ongoing ecological studies targeted at inter-canopy or other experimental levels.}, } @article {pmid37211280, year = {2023}, author = {Chow, EWL and Pang, LM and Wang, Y}, title = {Impact of the host microbiota on fungal infections: New possibilities for intervention?.}, journal = {Advanced drug delivery reviews}, volume = {198}, number = {}, pages = {114896}, doi = {10.1016/j.addr.2023.114896}, pmid = {37211280}, issn = {1872-8294}, mesh = {Humans ; Antifungal Agents/pharmacology/therapeutic use ; *Mycoses/drug therapy ; Fungi ; *Microbiota ; Bacteria ; }, abstract = {Many human fungal pathogens are opportunistic. They are primarily benign residents of the human body and only become infectious when the host's immunity and microbiome are compromised. Bacteria dominate the human microbiome, playing an essential role in keeping fungi harmless and acting as the first line of defense against fungal infection. The Human Microbiome Project, launched by NIH in 2007, has stimulated extensive investigation and significantly advanced our understanding of the molecular mechanisms governing the interaction between bacteria and fungi, providing valuable insights for developing future antifungal strategies by exploiting the interaction. This review summarizes recent progress in this field and discusses new possibilities and challenges. We must seize the opportunities presented by researching bacterial-fungal interplay in the human microbiome to address the global spread of drug-resistant fungal pathogens and the drying pipelines of effective antifungal drugs.}, } @article {pmid37195998, year = {2023}, author = {Dai, H and Hou, T and Wang, Q and Hou, Y and Wang, T and Zheng, J and Lin, H and Zhao, Z and Li, M and Wang, S and Zhang, D and Dai, M and Zheng, R and Lu, J and Xu, Y and Chen, Y and Ning, G and Wang, W and Bi, Y and Xu, M}, title = {Causal relationships between the gut microbiome, blood lipids, and heart failure: a Mendelian randomization analysis.}, journal = {European journal of preventive cardiology}, volume = {30}, number = {12}, pages = {1274-1282}, doi = {10.1093/eurjpc/zwad171}, pmid = {37195998}, issn = {2047-4881}, mesh = {Humans ; *Gastrointestinal Microbiome ; Mendelian Randomization Analysis ; Bayes Theorem ; Genome-Wide Association Study ; *Heart Failure ; Apolipoproteins B ; Lipids ; Polymorphism, Single Nucleotide ; }, abstract = {AIMS: Studies have linked gut microbiome and heart failure (HF). However, their causal relationships and potential mediating factors have not been well defined. To investigate the causal relationships between the gut microbiome and HF and the mediating effect of potential blood lipids by using genetics.

METHODS AND RESULTS: We performed a bidirectional and mediation Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7738), blood lipids (UK Biobank, n = 115 078), and a meta-analysis of HF (115 150 cases and 1550 331 controls). We applied the inverse-variance weighted estimation method as the primary method, with several other estimators as complementary methods. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal lipids. Six microbial taxa are suggestively associated with HF causally. The most significant taxon was the species Bacteroides dorei [odds ratio = 1.059, 95% confidence interval (CI) = 1.022-1.097, P-value = 0.0017]. The MR-BMA analysis showed that apolipoprotein B (ApoB) was the most likely causal lipid for HF (the marginal inclusion probability = 0.717, P-value = 0.005). The mediation MR analysis showed that ApoB mediated the causal effects of species B. dorei on HF (proportion mediated = 10.1%, 95% CI = 0.2-21.6%, P-value = 0.031).

CONCLUSION: The study suggested a causal relationship between specific gut microbial taxa and HF and that ApoB might mediate this relationship as the primary lipid determinant of HF.}, } @article {pmid37195192, year = {2023}, author = {Wang, J and Pan, Z and Yu, J and Zhang, Z and Li, YZ}, title = {Global assembly of microbial communities.}, journal = {mSystems}, volume = {8}, number = {3}, pages = {e0128922}, pmid = {37195192}, issn = {2379-5077}, support = {32070030//National Natural Science Foundation of China (NSFC)/ ; 2018YFA0900400, 2018YFA0901704//MOST | National Key Research and Development Program of China (NKPs)/ ; ZR2022QC229//Science Foundation for Youths of Shandong Province/ ; 2022M711918//China Postdoctoral Science Foundation/ ; SDCX-ZG-20220201//Postdoctoral Innovation Project of Shandong Province ()/ ; 32201303//National Natural Science Foundation of China (NSFC)/ ; }, mesh = {Animals ; *Bacteria/genetics ; *Microbiota/genetics ; Microbial Interactions ; Genes, Bacterial ; Stochastic Processes ; }, abstract = {Different habitats harbor different microbial communities with elusive assembly mechanisms. This study comprehensively investigated the global assembly mechanisms of microbial communities and effects of community-internal influencing factors using the Earth Microbiome Project (EMP) data set. We found that deterministic and stochastic processes contribute approximately equally to global microbial community assembly, and, specifically, deterministic processes generally play a major role in free-living and plant-associated (but not plant corpus) environments, while stochastic processes are the major contributor in animal-associated environments. In contrast with the assembly of microorganisms, the assembly of functional genes, predicted from PICRUSt, is mainly attributed to deterministic processes in all microbial communities. The sink and source microbial communities are normally assembled using similar mechanisms, and the core microorganisms are specific to different environment types. On a global scale, deterministic processes are positively related to the community alpha diversity, microbial interaction degree and bacterial predatory-specific gene abundance. Our analysis provides a panoramic picture and regularities of global and environment-typical microbial community assemblies. IMPORTANCE With the development of sequencing technologies, the research topic of microbial ecology has evolved from the analysis of community composition to community assembly, including the relative contribution of deterministic and stochastic processes for the formation and maintenance of community diversity. Many studies have reported the microbial assembly mechanisms in various habitats, but the assembly regularities of global microbial communities remain unknown. In this study, we analyzed the EMP data set using a combined pipeline to explore the assembly mechanisms of global microbial communities, microbial sources to construct communities, core microbes in different environment types, and community-internal factors influencing assembly. The results provide a panoramic picture and rules of global and environment-typical microbial community assemblies, which enhances our understandings of the mechanisms globally controlling community diversity and species coexistence.}, } @article {pmid37063923, year = {2023}, author = {Hou, T and Dai, H and Wang, Q and Hou, Y and Zhang, X and Lin, H and Wang, S and Li, M and Zhao, Z and Lu, J and Xu, Y and Chen, Y and Gu, Y and Zheng, J and Wang, T and Wang, W and Bi, Y and Ning, G and Xu, M}, title = {Dissecting the causal effect between gut microbiota, DHA, and urate metabolism: A large-scale bidirectional Mendelian randomization.}, journal = {Frontiers in immunology}, volume = {14}, number = {}, pages = {1148591}, pmid = {37063923}, issn = {1664-3224}, mesh = {Humans ; Docosahexaenoic Acids ; *Gastrointestinal Microbiome ; *Gout/genetics ; Mendelian Randomization Analysis ; Uric Acid ; }, abstract = {OBJECTIVES: Our aim was to investigate the interactive causal effects between gut microbiota and host urate metabolism and explore the underlying mechanism using genetic methods.

METHODS: We extracted summary statistics from the abundance of 211 microbiota taxa from the MiBioGen (N =18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N =7738), gout from the Global Biobank Meta-analysis Initiative (N =1,448,128), urate from CKDGen (N =288,649), and replication datasets from the Global Urate Genetics Consortium (N gout =69,374; N urate =110,347). We used linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) to detect genetic causality between microbiota and gout/urate. Mediation MR and colocalization were performed to investigate potential mediators in the association between microbiota and urate metabolism.

RESULTS: Two taxa had a common causal effect on both gout and urate, whereas the Victivallaceae family was replicable. Six taxa were commonly affected by both gout and urate, whereas the Ruminococcus gnavus group genus was replicable. Genetic correlation supported significant results in MR. Two microbiota metabolic pathways were commonly affected by gout and urate. Mediation analysis indicated that the Bifidobacteriales order and Bifidobacteriaceae family had protective effects on urate mediated by increasing docosahexaenoic acid. These two bacteria shared a common causal variant rs182549 with both docosahexaenoic acid and urate, which was located within MCM6/LCT locus.

CONCLUSIONS: Gut microbiota and host urate metabolism had a bidirectional causal association, implicating the critical role of host-microbiota crosstalk in hyperuricemic patients. Changes in gut microbiota can not only ameliorate host urate metabolism but also become a foreboding indicator of urate metabolic diseases.}, } @article {pmid37017243, year = {2023}, author = {Dilmore, AH and Martino, C and Neth, BJ and West, KA and Zemlin, J and Rahman, G and Panitchpakdi, M and Meehan, MJ and Weldon, KC and Blach, C and Schimmel, L and Kaddurah-Daouk, R and Dorrestein, PC and Knight, R and Craft, S and , }, title = {Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.}, journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association}, volume = {19}, number = {11}, pages = {4805-4816}, pmid = {37017243}, issn = {1552-5279}, support = {R01 AG046171/AG/NIA NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; RF1 AG059093/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; U01 AG061359/AG/NIA NIH HHS/United States ; RF1 AG057452/AG/NIA NIH HHS/United States ; P30 AG072947/AG/NIA NIH HHS/United States ; RF1 AG051550/AG/NIA NIH HHS/United States ; RF1 AG0151550/AG/NIA NIH HHS/United States ; /NH/NIH HHS/United States ; RF1 AG0151550/AG/NIA NIH HHS/United States ; }, mesh = {United States ; Humans ; Adult ; *Alzheimer Disease/metabolism ; Diet, Fat-Restricted ; *Microbiota ; Metabolome/physiology ; Seizures ; Ketone Bodies ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {INTRODUCTION: The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low-fat-diet intervention.

METHODS: Prediabetic adults, either with mild cognitive impairment (MCI) or cognitively normal (CN), were placed on either a low-fat American Heart Association diet or high-fat modified Mediterranean KD (MMKD) for 6 weeks; then, after a 6-week washout period, they crossed over to the alternate diet. We collected stool samples for shotgun metagenomics and untargeted metabolomics at five time points to investigate individuals' microbiome and metabolome throughout the dietary interventions.

RESULTS: Participants with MCI on the MMKD had lower levels of GABA-producing microbes Alistipes sp. CAG:514 and GABA, and higher levels of GABA-regulating microbes Akkermansia muciniphila. MCI individuals with curcumin in their diet had lower levels of bile salt hydrolase-containing microbes and an altered bile acid pool, suggesting reduced gut motility.

DISCUSSION: Our results suggest that the MMKD may benefit adults with MCI through modulation of GABA levels and gut-transit time.}, } @article {pmid36973807, year = {2023}, author = {Zhang, Y and Wang, Y and Tang, M and Zhou, J and Zhang, T}, title = {The microbial dark matter and "wanted list" in worldwide wastewater treatment plants.}, journal = {Microbiome}, volume = {11}, number = {1}, pages = {59}, pmid = {36973807}, issn = {2049-2618}, mesh = {Sewage ; Wastewater ; RNA, Ribosomal, 16S/genetics/analysis ; *Microbiota/genetics ; *Water Purification ; }, abstract = {BACKGROUND: Wastewater treatment plants (WWTPs) are one of the largest biotechnology applications in the world and are of critical importance to modern urban societies. An accurate evaluation of the microbial dark matter (MDM, microorganisms whose genomes remain uncharacterized) proportions in WWTPs is of great value, while there is no such research yet. This study conducted a global meta-analysis of MDM in WWTPs with 317,542 prokaryotic genomes from the Genome Taxonomy Database and proposed a "wanted list" for priority targets in further investigations of activated sludge.

RESULTS: Compared with the Earth Microbiome Project data, WWTPs had relatively lower genome-sequenced proportions of prokaryotes than other ecosystems, such as the animal related environments. Analysis showed that the median proportions of the genome-sequenced cells and taxa (100% identity and 100% coverage in 16S rRNA gene region) in WWTPs reached 56.3% and 34.5% for activated sludge, 48.6% and 28.5% for aerobic biofilm, and 48.3% and 28.5% for anaerobic digestion sludge, respectively. This result meant MDM had high proportions in WWTPs. Besides, all of the samples were occupied by a few predominant taxa, and the majority of the sequenced genomes were from pure cultures. The global-scale "wanted list" for activated sludge contained four phyla that have few representatives and 71 operational taxonomic units with the majority of them having no genome or isolate yet. Finally, several genome mining methods were verified to successfully recover genomes from activated sludge such as hybrid assembly of the second- and third-generation sequencing.

CONCLUSIONS: This work elucidated the proportion of MDM in WWTPs, defined the "wanted list" of activated sludge for future investigations, and certified potential genome recovery methods. The proposed methodology of this study can be applied to other ecosystems and improve understanding of ecosystem structure across diverse habitats. Video Abstract.}, } @article {pmid36966280, year = {2023}, author = {Zhao, Y and Yi, J and Xiang, J and Jia, W and Chen, A and Chen, L and Zheng, L and Zhou, W and Wu, M and Yu, Z and Tang, J}, title = {Exploration of lung mycobiome in the patients with non-small-cell lung cancer.}, journal = {BMC microbiology}, volume = {23}, number = {1}, pages = {81}, pmid = {36966280}, issn = {1471-2180}, mesh = {Humans ; *Mycobiome ; *Carcinoma, Non-Small-Cell Lung ; Fungi/genetics ; *Lung Neoplasms ; Lung ; }, abstract = {As the Human Microbiome Project (HMP) progresses, the relationship between microbes and human health has been receiving increasing attention. A growing number of reports support the correlation between cancer and microbes. However, most studies have focused on bacteria, rather than fungal communities. In this study, we studied the alteration in lung mycobiome in patients with non-small-cell lung cancer (NSCLC) using metagenomic sequencing and qPCR. The higher fungal diversity and more complex network were observed in the patients with NSCLC. In addition, Alternaria arborescens was found as the most relevant fungus to NSCLC, and the enrichment of it in cancerous tissue was also detected. This study proposes that the changes in fungal communities may be closely related to lung cancer, and provides insights into further exploration the relationship between lung cancer and fungi.}, } @article {pmid36943054, year = {2023}, author = {Zhou, C and Wang, Y and Li, C and Xie, Z and Dai, L}, title = {Amelioration of Colitis by a Gut Bacterial Consortium Producing Anti-Inflammatory Secondary Bile Acids.}, journal = {Microbiology spectrum}, volume = {11}, number = {2}, pages = {e0333022}, pmid = {36943054}, issn = {2165-0497}, abstract = {The Integrative Human Microbiome Project and other cohort studies have indicated that inflammatory bowel disease is accompanied by dysbiosis of gut microbiota, decreased production of secondary bile acids, and increased levels of primary bile acids. Secondary bile acids, such as ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. In this study, we screened human gut bacterial strains for bile acid metabolism and designed a consortium of three species, including Clostridium AP sp000509125, Bacteroides ovatus, and Eubacterium limosum, and named it BAC (bile acid consortium). We showed that the three-strain gut bacterial consortium BAC is capable of converting conjugated primary bile acids taurochenodeoxycholic acid and glycochenodeoxycholic acid to secondary bile acids UDCA and LCA in vitro. Oral gavage treatment with BAC in mice resulted in protective effects against dextran sulfate sodium (DSS)-induced colitis, including reduced weight loss and increased colon length. Furthermore, BAC treatment increased the fecal level of bile acids, including UDCA and LCA. BAC treatment enhanced intestinal barrier function, which may be attributed to the increased activation of the bile acid receptor TGR5 by secondary bile acids. Finally, we examined the remodeling of gut microbiota by BAC treatment. Taken together, the three-strain gut bacterial consortium BAC restored the dysregulated bile acid metabolism and alleviated DSS-induced colitis. Our study provides a proof-of-concept demonstration that a rationally designed bacterial consortium can reshape the metabolism of the gut microbiome to treat diseases. IMPORTANCE Secondary bile acids have been reported to be anti-inflammatory, yet it remains to be studied whether introducing selected bacteria strains to restore bile acid metabolism of the gut microbiome can alleviate intestinal inflammation. To address this gap, we designed a consortium of human gut bacterial strains based on their metabolic capacity to produce secondary bile acids UDCA and LCA, and we evaluated the efficacy of single bacterial strains and the bacterial consortium in treating the murine colitis model. We found that oral gavage of the bacterial consortium to mice restored secondary bile acid metabolism to increase levels of UDCA and LCA, which induced the activation of TGR5 to improve gut-barrier integrity and reduced the inflammation in murine colitis. Overall, our study demonstrates that rationally designed bacterial consortia can reshape the metabolism of the gut microbiome and provides novel insights into the application of live biotherapeutics for treating IBD.}, } @article {pmid36929933, year = {2023}, author = {Zou, H and Sun, T and Jin, B and Wang, S}, title = {sBGC-hm: an atlas of secondary metabolite biosynthetic gene clusters from the human gut microbiome.}, journal = {Bioinformatics (Oxford, England)}, volume = {39}, number = {3}, pages = {}, pmid = {36929933}, issn = {1367-4811}, mesh = {Humans ; *Gastrointestinal Microbiome/genetics ; *Microbiota ; Multigene Family ; Biosynthetic Pathways/genetics ; }, abstract = {SUMMARY: Microbial secondary metabolites exhibit potential medicinal value. A large number of secondary metabolite biosynthetic gene clusters (BGCs) in the human gut microbiome, which exhibit essential biological activity in microbe-microbe and microbe-host interactions, have not been adequately characterized, making it difficult to prioritize these BGCs for experimental characterization. Here, we present the sBGC-hm, an atlas of secondary metabolite BGCs allows researchers to explore the potential therapeutic benefits of these natural products. One of its key features is the ability to assist in optimizing the BGC structure by utilizing the gene co-occurrence matrix obtained from Human Microbiome Project data. Results are viewable online and can be downloaded as spreadsheets.

The database is openly available at https://www.wzubio.com/sbgc. The website is powered by Apache 2 server with PHP and MariaDB.}, } @article {pmid36928026, year = {2023}, author = {Seymour, CO and Palmer, M and Becraft, ED and Stepanauskas, R and Friel, AD and Schulz, F and Woyke, T and Eloe-Fadrosh, E and Lai, D and Jiao, JY and Hua, ZS and Liu, L and Lian, ZH and Li, WJ and Chuvochina, M and Finley, BK and Koch, BJ and Schwartz, E and Dijkstra, P and Moser, DP and Hungate, BA and Hedlund, BP}, title = {Hyperactive nanobacteria with host-dependent traits pervade Omnitrophota.}, journal = {Nature microbiology}, volume = {8}, number = {4}, pages = {727-744}, pmid = {36928026}, issn = {2058-5276}, support = {1826734//National Science Foundation (NSF)/ ; 1928924//National Science Foundation (NSF)/ ; 1516679//National Science Foundation (NSF)/ ; }, mesh = {Humans ; *Calcifying Nanoparticles/metabolism ; Bacteria/metabolism ; *Microbiota/genetics ; }, abstract = {Candidate bacterial phylum Omnitrophota has not been isolated and is poorly understood. We analysed 72 newly sequenced and 349 existing Omnitrophota genomes representing 6 classes and 276 species, along with Earth Microbiome Project data to evaluate habitat, metabolic traits and lifestyles. We applied fluorescence-activated cell sorting and differential size filtration, and showed that most Omnitrophota are ultra-small (~0.2 μm) cells that are found in water, sediments and soils. Omnitrophota genomes in 6 classes are reduced, but maintain major biosynthetic and energy conservation pathways, including acetogenesis (with or without the Wood-Ljungdahl pathway) and diverse respirations. At least 64% of Omnitrophota genomes encode gene clusters typical of bacterial symbionts, suggesting host-associated lifestyles. We repurposed quantitative stable-isotope probing data from soils dominated by andesite, basalt or granite weathering and identified 3 families with high isotope uptake consistent with obligate bacterial predators. We propose that most Omnitrophota inhabit various ecosystems as predators or parasites.}, } @article {pmid36910167, year = {2023}, author = {Zhao, J and Rodriguez, J and Martens-Habbena, W}, title = {Fine-scale evaluation of two standard 16S rRNA gene amplicon primer pairs for analysis of total prokaryotes and archaeal nitrifiers in differently managed soils.}, journal = {Frontiers in microbiology}, volume = {14}, number = {}, pages = {1140487}, pmid = {36910167}, issn = {1664-302X}, abstract = {The advance of high-throughput molecular biology tools allows in-depth profiling of microbial communities in soils, which possess a high diversity of prokaryotic microorganisms. Amplicon-based sequencing of 16S rRNA genes is the most common approach to studying the richness and composition of soil prokaryotes. To reliably detect different taxonomic lineages of microorganisms in a single soil sample, an adequate pipeline including DNA isolation, primer selection, PCR amplification, library preparation, DNA sequencing, and bioinformatic post-processing is required. Besides DNA sequencing quality and depth, the selection of PCR primers and PCR amplification reactions arguably have the largest influence on the results. This study tested the performance and potential bias of two primer pairs, i.e., 515F (Parada)-806R (Apprill) and 515F (Parada)-926R (Quince) in the standard pipelines of 16S rRNA gene Illumina amplicon sequencing protocol developed by the Earth Microbiome Project (EMP), against shotgun metagenome-based 16S rRNA gene reads. The evaluation was conducted using five differently managed soils. We observed a higher richness of soil total prokaryotes by using reverse primer 806R compared to 926R, contradicting to in silico evaluation results. Both primer pairs revealed various degrees of taxon-specific bias compared to metagenome-derived 16S rRNA gene reads. Nonetheless, we found consistent patterns of microbial community variation associated with different land uses, irrespective of primers used. Total microbial communities, as well as ammonia oxidizing archaea (AOA), the predominant ammonia oxidizers in these soils, shifted along with increased soil pH due to agricultural management. In the unmanaged low pH plot abundance of AOA was dominated by the acid-tolerant NS-Gamma clade, whereas limed agricultural plots were dominated by neutral-alkaliphilic NS-Delta/NS-Alpha clades. This study stresses how primer selection influences community composition and highlights the importance of primer selection for comparative and integrative studies, and that conclusions must be drawn with caution if data from different sequencing pipelines are to be compared.}, } @article {pmid36838283, year = {2023}, author = {Morrison, AG and Sarkar, S and Umar, S and Lee, STM and Thomas, SM}, title = {The Contribution of the Human Oral Microbiome to Oral Disease: A Review.}, journal = {Microorganisms}, volume = {11}, number = {2}, pages = {}, pmid = {36838283}, issn = {2076-2607}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; }, abstract = {The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.}, } @article {pmid36770726, year = {2023}, author = {Zhang, MN and Xie, R and Wang, HG and Wen, X and Wang, JY and He, L and Zhang, MH and Yang, XZ}, title = {Cepharanthine Alleviates DSS-Induced Ulcerative Colitis via Regulating Aconitate Decarboxylase 1 Expression and Macrophage Infiltration.}, journal = {Molecules (Basel, Switzerland)}, volume = {28}, number = {3}, pages = {}, pmid = {36770726}, issn = {1420-3049}, mesh = {Animals ; Mice ; Humans ; *Colitis, Ulcerative/chemically induced/drug therapy/metabolism ; Macrophages ; Colon/metabolism ; *Benzylisoquinolines/pharmacology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; *Colitis/metabolism ; Mice, Inbred C57BL ; }, abstract = {Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.}, } @article {pmid36675055, year = {2023}, author = {Kustrimovic, N and Bombelli, R and Baci, D and Mortara, L}, title = {Microbiome and Prostate Cancer: A Novel Target for Prevention and Treatment.}, journal = {International journal of molecular sciences}, volume = {24}, number = {2}, pages = {}, pmid = {36675055}, issn = {1422-0067}, mesh = {Male ; Humans ; *Microbiota/physiology ; *Prostatic Neoplasms/therapy/pathology ; *Gastrointestinal Microbiome/physiology ; Prostate/pathology ; Inflammation ; Dysbiosis ; }, abstract = {Growing evidence of the microbiome's role in human health and disease has emerged since the creation of the Human Microbiome Project. Recent studies suggest that alterations in microbiota composition (dysbiosis) may play an essential role in the occurrence, development, and prognosis of prostate cancer (PCa), which remains the second most frequent male malignancy worldwide. Current advances in biological technologies, such as high-throughput sequencing, transcriptomics, and metabolomics, have enabled research on the gut, urinary, and intra-prostate microbiome signature and the correlation with local and systemic inflammation, host immunity response, and PCa progression. Several microbial species and their metabolites facilitate PCa insurgence through genotoxin-mediated mutagenesis or by driving tumor-promoting inflammation and dysfunctional immunosurveillance. However, the impact of the microbiome on PCa development, progression, and response to treatment is complex and needs to be fully understood. This review addresses the current knowledge on the host-microbe interaction and the risk of PCa, providing novel insights into the intraprostatic, gut, and urinary microbiome mechanisms leading to PCa carcinogenesis and treatment response. In this paper, we provide a detailed overview of diet changes, gut microbiome, and emerging therapeutic approaches related to the microbiome and PCa. Further investigation on the prostate-related microbiome and large-scale clinical trials testing the efficacy of microbiota modulation approaches may improve patient outcomes while fulfilling the literature gap of microbial-immune-cancer-cell mechanistic interactions.}, } @article {pmid36655544, year = {2023}, author = {Sun, H and Wang, P and Li, Y}, title = {An integrated microbiome project for charactering microbial diversity in classroom based on virtual simulation experiments.}, journal = {Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology}, volume = {51}, number = {2}, pages = {171-179}, doi = {10.1002/bmb.21706}, pmid = {36655544}, issn = {1539-3429}, mesh = {Humans ; RNA, Ribosomal, 16S/genetics ; *Learning ; Students ; Computational Biology/education ; *Microbiota/genetics ; }, abstract = {Microbiome study requires both molecular techniques and bioinformatics skills, which are challenging for biologists to participate in this growing field. To introduce microbiome concepts and skills to students, a 6-week wet-lab and bioinformatics course for undergraduates was implemented through the project-based learning (PBL) approach. In the saliva microbiome project, students collected their saliva samples, performed DNA extraction and PCR amplification, followed by metagenomic analysis to compare the diversity and abundances of microbes among samples. First, students are required to practice molecular techniques and bioinformatics analysis skills in a virtual simulation lab. To our knowledge, our study is the first one to incorporate a virtual lab into microbiome experience. Then, students applied their recently acquired skills to produce and analyze their own 16S amplicon sequencing data and reported their results via a scientific report. The student learning outcomes show that the Virtual lab can improve students' laboratory techniques and research capabilities. Moreover, a simple pipeline to analyze 16S rRNA gene amplicon sequencing data is introduced in a step-by-step manner that helps students to develop analysis skills. This project can be modified as either a virtual course or a module within another course such as microbiology, molecular biology, and bioinformatics. Our study provides evidence on the positive impact of virtual labs on learning outcomes in undergraduate science education.}, } @article {pmid36612415, year = {2022}, author = {Eggers, S and Bixby, M and Renzetti, S and Curtin, P and Gennings, C}, title = {Human Microbiome Mixture Analysis Using Weighted Quantile Sum Regression.}, journal = {International journal of environmental research and public health}, volume = {20}, number = {1}, pages = {}, pmid = {36612415}, issn = {1660-4601}, support = {T32 HD049311/HD/NICHD NIH HHS/United States ; K99 ES032884/ES/NIEHS NIH HHS/United States ; P30ES023515/ES/NIEHS NIH HHS/United States ; U2CES026555/ES/NIEHS NIH HHS/United States ; }, mesh = {Humans ; Feces ; *Microbiota ; *Gastrointestinal Microbiome ; Obesity ; Body Mass Index ; }, abstract = {Studies of the health effects of the microbiome often measure overall associations by using diversity metrics, and individual taxa associations in separate analyses, but do not consider the correlated relationships between taxa in the microbiome. In this study, we applied random subset weighted quantile sum regression with repeated holdouts (WQSRSRH), a mixture method successfully applied to 'omic data to account for relationships between many predictors, to processed amplicon sequencing data from the Human Microbiome Project. We simulated a binary variable associated with 20 operational taxonomic units (OTUs). WQSRSRH was used to test for the association between the microbiome and the simulated variable, adjusted for sex, and sensitivity and specificity were calculated. The WQSRSRH method was also compared to other standard methods for microbiome analysis. The method was further illustrated using real data from the Growth and Obesity Cohort in Chile to assess the association between the gut microbiome and body mass index. In the analysis with simulated data, WQSRSRH predicted the correct directionality of association between the microbiome and the simulated variable, with an average sensitivity and specificity of 75% and 70%, respectively, in identifying the 20 associated OTUs. WQSRSRH performed better than all other comparison methods. In the illustration analysis of the gut microbiome and obesity, the WQSRSRH analysis identified an inverse association between body mass index and the gut microbe mixture, identifying Bacteroides, Clostridium, Prevotella, and Ruminococcus as important genera in the negative association. The application of WQSRSRH to the microbiome allows for analysis of the mixture effect of all the taxa in the microbiome, while simultaneously identifying the most important to the mixture, and allowing for covariate adjustment. It outperformed other methods when using simulated data, and in analysis with real data found results consistent with other study findings.}, } @article {pmid36566203, year = {2022}, author = {Dang, T and Kumaishi, K and Usui, E and Kobori, S and Sato, T and Toda, Y and Yamasaki, Y and Tsujimoto, H and Ichihashi, Y and Iwata, H}, title = {Stochastic variational variable selection for high-dimensional microbiome data.}, journal = {Microbiome}, volume = {10}, number = {1}, pages = {236}, pmid = {36566203}, issn = {2049-2618}, mesh = {Humans ; Bayes Theorem ; Algorithms ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Metagenomics ; }, abstract = {BACKGROUND: The rapid and accurate identification of a minimal-size core set of representative microbial species plays an important role in the clustering of microbial community data and interpretation of clustering results. However, the huge dimensionality of microbial metagenomics datasets is a major challenge for the existing methods such as Dirichlet multinomial mixture (DMM) models. In the approach of the existing methods, the computational burden of identifying a small number of representative species from a large number of observed species remains a challenge.

RESULTS: We propose a novel approach to improve the performance of the widely used DMM approach by combining three ideas: (i) we propose an indicator variable to identify representative operational taxonomic units that substantially contribute to the differentiation among clusters; (ii) to address the computational burden of high-dimensional microbiome data, we propose a stochastic variational inference, which approximates the posterior distribution using a controllable distribution called variational distribution, and stochastic optimization algorithms for fast computation; and (iii) we extend the finite DMM model to an infinite case by considering Dirichlet process mixtures and estimating the number of clusters as a variational parameter. Using the proposed method, stochastic variational variable selection (SVVS), we analyzed the root microbiome data collected in our soybean field experiment, the human gut microbiome data from three published datasets of large-scale case-control studies and the healthy human microbiome data from the Human Microbiome Project.

CONCLUSIONS: SVVS demonstrates a better performance and significantly faster computation than those of the existing methods in all cases of testing datasets. In particular, SVVS is the only method that can analyze massive high-dimensional microbial data with more than 50,000 microbial species and 1000 samples. Furthermore, a core set of representative microbial species is identified using SVVS that can improve the interpretability of Bayesian mixture models for a wide range of microbiome studies. Video Abstract.}, } @article {pmid36566099, year = {2023}, author = {Mishra, K and Isali, I and Sindhani, M and Prunty, M and Bell, S and Mahran, A and Damiani, G and Ghannoum, M and Retuerto, M and Kutikov, A and Ross, J and Woo, LL and Abbosh, PH and Bukavina, L}, title = {Characterization of Changes in Penile Microbiome Following Pediatric Circumcision.}, journal = {European urology focus}, volume = {9}, number = {4}, pages = {669-680}, doi = {10.1016/j.euf.2022.12.007}, pmid = {36566099}, issn = {2405-4569}, mesh = {United States ; Male ; Infant ; Humans ; Child ; Phylogeny ; *Gastrointestinal Microbiome ; *Microbiota/genetics ; *Mycobiome ; Inflammation ; }, abstract = {BACKGROUND: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome.

OBJECTIVE: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism.

We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project.

We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles.

RESULTS AND LIMITATIONS: Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis.

PATIENT SUMMARY: Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.}, } @article {pmid36557564, year = {2022}, author = {Bruno, A and Fumagalli, S and Ghisleni, G and Labra, M}, title = {The Microbiome of the Built Environment: The Nexus for Urban Regeneration for the Cities of Tomorrow.}, journal = {Microorganisms}, volume = {10}, number = {12}, pages = {}, pmid = {36557564}, issn = {2076-2607}, support = {H43C22000550001//Ministry of Education, Universities and Research/ ; }, abstract = {Built environments are, for most of us, our natural habitat. In the last 50 years, the built-up area has more than doubled, with a massive biodiversity loss. The undeniable benefits of a city providing all the basic needs to a growing population showed longer-term and less obvious costs to human health: autoimmune and non-communicable diseases, as well as antimicrobial resistance, have reached unprecedented and alarming levels. Humans coevolved with microbes, and this long-lasting alliance is affected by the loss of connection with natural environments, misuse of antibiotics, and highly sanitized environments. Our aim is to direct the focus onto the microbial communities harbored by the built environments we live in. They represent the nexus for urban regeneration, which starts from a healthy environment. Planning a city means considering, in a two-fold way, the ecosystem health and the multidimensional aspects of wellbeing, including social, cultural, and aesthetic values. The significance of this perspective is inspiring guidelines and strategies for the urban regeneration of the cities of tomorrow, exploiting the invaluable role of microbial biodiversity and the ecosystem services that it could provide to create the robust scientific knowledge that is necessary for a bioinformed design of buildings and cities for healthy and sustainable living.}, } @article {pmid36534203, year = {2022}, author = {Jesus, HNR and Ramos, JN and Rocha, DJPG and Alves, DA and Silva, CS and Cruz, JVO and Vieira, VV and Souza, C and Santos, LS and Navas, J and Ramos, RTJ and Azevedo, V and Aguiar, ERGR and Mattos-Guaraldi, AL and Pacheco, LGC}, title = {The pan-genome of the emerging multidrug-resistant pathogen Corynebacterium striatum.}, journal = {Functional & integrative genomics}, volume = {23}, number = {1}, pages = {5}, pmid = {36534203}, issn = {1438-7948}, support = {BOL0505/2018//Fundação de Amparo à Pesquisa do Estado da Bahia/ ; BOL0505/2018//Fundação de Amparo à Pesquisa do Estado da Bahia/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CAPES-PROCAD 071/2013//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; CNPq Nº 09/2018//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; CNPq Nº 09/2018//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; CNPq Nº 09/2018//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; MCT/FINEP/CT-INFRA01/2013//Financiadora de Estudos e Projetos/ ; }, mesh = {Humans ; *Corynebacterium ; *Anti-Bacterial Agents ; Phenotype ; Virulence Factors/genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Microbial Sensitivity Tests ; }, abstract = {Corynebacterium striatum, a common constituent of the human skin microbiome, is now considered an emerging multidrug-resistant pathogen of immunocompromised and chronically ill patients. However, little is known about the molecular mechanisms in the transition from colonization to the multidrug-resistant (MDR) invasive phenotype in clinical isolates. This study performed a comprehensive pan-genomic analysis of C. striatum, including isolates from "normal skin microbiome" and from MDR infections, to gain insights into genetic factors contributing to pathogenicity and multidrug resistance in this species. For this, three novel genome sequences were obtained from clinical isolates of C. striatum of patients from Brazil, and other 24 complete or draft C. striatum genomes were retrieved from GenBank, including the ATCC6940 isolate from the Human Microbiome Project. Analysis of C. striatum strains demonstrated the presence of an open pan-genome (α = 0.852803) containing 3816 gene families, including 15 antimicrobial resistance (AMR) genes and 32 putative virulence factors. The core and accessory genomes included 1297 and 1307 genes, respectively. The identified AMR genes are primarily associated with resistance to aminoglycosides and tetracyclines. Of these, 66.6% are present in genomic islands, and four AMR genes, including aac(6')-ib7, are located in a class 1-integron. In conclusion, our data indicated that C. striatum possesses genomic characteristics favorable to the invasive phenotype, with high genomic plasticity, a robust genetic arsenal for iron acquisition, and important virulence determinants and AMR genes present in mobile genetic elements.}, } @article {pmid36453887, year = {2022}, author = {Zhang, W and Han, N and Zhang, T and Qiang, Y and Peng, X and Li, X and Kan, B}, title = {The Spatial Features and Temporal Changes in the Gut Microbiota of a Healthy Chinese Population.}, journal = {Microbiology spectrum}, volume = {10}, number = {6}, pages = {e0131022}, pmid = {36453887}, issn = {2165-0497}, mesh = {Adult ; Humans ; *Gastrointestinal Microbiome/genetics ; RNA, Ribosomal, 16S/genetics ; Cohort Studies ; East Asian People ; *Microbiota ; Feces/microbiology ; }, abstract = {In this study, we aimed to understand the characteristics of the gut microbial composition in a healthy Chinese population and to evaluate if they differed across different regions. In addition, we aimed to understand the changes in the gut microbial composition over time. We collected 239 fecal samples from healthy Chinese adults living in four regions and performed a 1-year time cohort study in a small population in Beijing. The Chinese gut microbiota share 34 core bacterial genera and 39 core bacterial species, which exist in all collected samples. Several disease-related microorganisms (DRMs), virulence factors, and antibiotic resistance genes were found in one or more healthy Chinese samples. Differences in gut microbiota were observed in samples from different regions, locations, individuals, and time points. Compared to other factors, time was associated with a lower degree of change in the gut microbiota. Our findings revealed spatial and temporal changes in the gut microbiota of healthy Chinese individuals. Compared to fecal microbiomes of 152 samples in the publicly released the Human Microbiome Project (HMP) project from the United States, samples in this study have higher variability in the fecal microbiome, with higher richness, Shannon diversity indices, and Pielou evenness indexes, at both the genus and species levels. The microbiota data obtained in this study will provide a detailed basis for further understanding the composition of the gut microbiota in the healthy Chinese population. IMPORTANCE China accounts for approximately 1/5th of the world's total population. Differences in environment, ethnicity, and living habits could impart unique features to the structure of the gut microbiota of Chinese individuals. In 2016, we started to investigate healthy Chinese people and their gut microbiomes. Phase I results for 16S rRNA amplicons have been released. However, owing to the limitations of 16S rRNA amplicon sequencing, the gut microbiome of a healthy Chinese population could not be examined thoroughly at the species level, and the detailed changes in the gut microbiota over time need to be investigated. To address these knowledge gaps, we started a phase II study and investigated the basis for variations in the gut microbiome composition in a healthy Chinese population at the species level using shotgun metagenomics technology. In the phase II study, we also conducted a time scale analysis of fecal samples from healthy Chinese subjects, as a pioneered study, which quantitatively clarified the changes in the gut microbiota at both the spatial and temporal levels and elucidated the distribution pattern of DRMs in healthy Chinese individuals.}, } @article {pmid36446618, year = {2023}, author = {Li, DD and Zhang, Z and Wang, JN and Zhang, P and Liu, Y and Li, YZ}, title = {Estimate of the degradation potentials of cellulose, xylan, and chitin across global prokaryotic communities.}, journal = {Environmental microbiology}, volume = {25}, number = {2}, pages = {397-409}, doi = {10.1111/1462-2920.16290}, pmid = {36446618}, issn = {1462-2920}, mesh = {*Cellulose/metabolism ; Xylans/metabolism ; Chitin/metabolism ; Polysaccharides/metabolism ; *Chitinases ; }, abstract = {Complex polysaccharides (e.g. cellulose, xylan, and chitin), the most abundant renewable biomass resources available on Earth, are mainly degraded by microorganisms in nature. However, little is known about the global distribution of the enzymes and microorganisms responsible for the degradation of cellulose, xylan, and chitin in natural environments. Through large-scale alignments between the sequences released by the Earth Microbiome Project and sequenced prokaryotic genomes, we determined that almost all prokaryotic communities have the functional potentials to degrade cellulose, xylan, and chitin. The median abundances of genes encoding putative cellulases, xylanases, and chitinases in global prokaryotic communities are 0.51 (0.17-1.01), 0.24 (0.05-0.57), and 0.33 (0.11-0.71) genes/cell, respectively, and the composition and abundance of these enzyme systems are environmentally varied. The taxonomic sources of the three enzymes are highly diverse within prokaryotic communities, and the main factor influencing the diversity is the community's alpha diversity index rather than gene abundance. Moreover, there are obvious differences in taxonomic sources among different communities, and most genera with degradation potentials are narrowly distributed. In conclusion, our analysis preliminarily depicts a panorama of cellulose-, xylan-, and chitin-degrading enzymatic systems across global prokaryotic communities.}, } @article {pmid36443458, year = {2022}, author = {Shaffer, JP and Nothias, LF and Thompson, LR and Sanders, JG and Salido, RA and Couvillion, SP and Brejnrod, AD and Lejzerowicz, F and Haiminen, N and Huang, S and Lutz, HL and Zhu, Q and Martino, C and Morton, JT and Karthikeyan, S and Nothias-Esposito, M and Dührkop, K and Böcker, S and Kim, HW and Aksenov, AA and Bittremieux, W and Minich, JJ and Marotz, C and Bryant, MM and Sanders, K and Schwartz, T and Humphrey, G and Vásquez-Baeza, Y and Tripathi, A and Parida, L and Carrieri, AP and Beck, KL and Das, P and González, A and McDonald, D and Ladau, J and Karst, SM and Albertsen, M and Ackermann, G and DeReus, J and Thomas, T and Petras, D and Shade, A and Stegen, J and Song, SJ and Metz, TO and Swafford, AD and Dorrestein, PC and Jansson, JK and Gilbert, JA and Knight, R and , }, title = {Standardized multi-omics of Earth's microbiomes reveals microbial and metabolite diversity.}, journal = {Nature microbiology}, volume = {7}, number = {12}, pages = {2128-2150}, pmid = {36443458}, issn = {2058-5276}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Microbiota/genetics ; Metagenome ; Metagenomics ; Earth, Planet ; Soil ; }, abstract = {Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Earth, informing both microbial and chemical ecology, and provides a foundation and methods for multi-omics microbiome studies of hosts and the environment.}, } @article {pmid36423084, year = {2022}, author = {Ganz, HH and Jospin, G and Rojas, CA and Martin, AL and Dahlhausen, K and Kingsbury, DD and Osborne, CX and Entrolezo, Z and Redner, S and Ramirez, B and Eisen, JA and Leahy, M and Keaton, C and Wong, J and Gardy, J and Jarett, JK}, title = {The Kitty Microbiome Project: Defining the Healthy Fecal "Core Microbiome" in Pet Domestic Cats.}, journal = {Veterinary sciences}, volume = {9}, number = {11}, pages = {}, pmid = {36423084}, issn = {2306-7381}, abstract = {Here, we present a taxonomically defined fecal microbiome dataset for healthy domestic cats (Felis catus) fed a range of commercial diets. We used this healthy reference dataset to explore how age, diet, and living environment correlate with fecal microbiome composition. Thirty core bacterial genera were identified. Prevotella, Bacteroides, Collinsella, Blautia, and Megasphaera were the most abundant, and Bacteroides, Blautia, Lachnoclostridium, Sutterella, and Ruminococcus gnavus were the most prevalent. While community composition remained relatively stable across different age classes, the number of core taxa present decreased significantly with age. Fecal microbiome composition varied with host diet type. Cats fed kibble had a slightly, but significantly greater number of core taxa compared to cats not fed any kibble. The core microbiomes of cats fed some raw food contained taxa not as highly prevalent or abundant as cats fed diets that included kibble. Living environment also had a large effect on fecal microbiome composition. Cats living in homes differed significantly from those in shelters and had a greater portion of their microbiomes represented by core taxa. Collectively our work reinforces the findings that age, diet, and living environment are important factors to consider when defining a core microbiome in a population.}, } @article {pmid36378489, year = {2022}, author = {Gupta, VK and Bakshi, U and Chang, D and Lee, AR and Davis, JM and Chandrasekaran, S and Jin, YS and Freeman, MF and Sung, J}, title = {TaxiBGC: a Taxonomy-Guided Approach for Profiling Experimentally Characterized Microbial Biosynthetic Gene Clusters and Secondary Metabolite Production Potential in Metagenomes.}, journal = {mSystems}, volume = {7}, number = {6}, pages = {e0092522}, pmid = {36378489}, issn = {2379-5077}, support = {R35 GM133475/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Metagenome/genetics ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Computational Biology ; Multigene Family/genetics ; }, abstract = {Biosynthetic gene clusters (BGCs) in microbial genomes encode bioactive secondary metabolites (SMs), which can play important roles in microbe-microbe and host-microbe interactions. Given the biological significance of SMs and the current profound interest in the metabolic functions of microbiomes, the unbiased identification of BGCs from high-throughput metagenomic data could offer novel insights into the complex chemical ecology of microbial communities. Currently available tools for predicting BGCs from shotgun metagenomes have several limitations, including the need for computationally demanding read assembly, predicting a narrow breadth of BGC classes, and not providing the SM product. To overcome these limitations, we developed taxonomy-guided identification of biosynthetic gene clusters (TaxiBGC), a command-line tool for predicting experimentally characterized BGCs (and inferring their known SMs) in metagenomes by first pinpointing the microbial species likely to harbor them. We benchmarked TaxiBGC on various simulated metagenomes, showing that our taxonomy-guided approach could predict BGCs with much-improved performance (mean F1 score, 0.56; mean PPV score, 0.80) compared with directly identifying BGCs by mapping sequencing reads onto the BGC genes (mean F1 score, 0.49; mean PPV score, 0.41). Next, by applying TaxiBGC on 2,650 metagenomes from the Human Microbiome Project and various case-control gut microbiome studies, we were able to associate BGCs (and their SMs) with different human body sites and with multiple diseases, including Crohn's disease and liver cirrhosis. In all, TaxiBGC provides an in silico platform to predict experimentally characterized BGCs and their SM production potential in metagenomic data while demonstrating important advantages over existing techniques. IMPORTANCE Currently available bioinformatics tools to identify BGCs from metagenomic sequencing data are limited in their predictive capability or ease of use to even computationally oriented researchers. We present an automated computational pipeline called TaxiBGC, which predicts experimentally characterized BGCs (and infers their known SMs) in shotgun metagenomes by first considering the microbial species source. Through rigorous benchmarking techniques on simulated metagenomes, we show that TaxiBGC provides a significant advantage over existing methods. When demonstrating TaxiBGC on thousands of human microbiome samples, we associate BGCs encoding bacteriocins with different human body sites and diseases, thereby elucidating a possible novel role of this antibiotic class in maintaining the stability of microbial ecosystems throughout the human body. Furthermore, we report for the first time gut microbial BGC associations shared among multiple pathologies. Ultimately, we expect our tool to facilitate future investigations into the chemical ecology of microbial communities across diverse niches and pathologies.}, } @article {pmid36357382, year = {2022}, author = {Liu, Y and Elworth, RAL and Jochum, MD and Aagaard, KM and Treangen, TJ}, title = {De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {6799}, pmid = {36357382}, issn = {2041-1723}, support = {P01 AI152999/AI/NIAID NIH HHS/United States ; R01 DK128187/DK/NIDDK NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; T32 HL098069/HL/NHLBI NIH HHS/United States ; R01 NR014792/NR/NINR NIH HHS/United States ; T32 HD098068/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; Biomass ; *Microbiota/genetics ; Metagenomics/methods ; Metagenome ; Specimen Handling ; }, abstract = {Computational analysis of host-associated microbiomes has opened the door to numerous discoveries relevant to human health and disease. However, contaminant sequences in metagenomic samples can potentially impact the interpretation of findings reported in microbiome studies, especially in low-biomass environments. Contamination from DNA extraction kits or sampling lab environments leaves taxonomic "bread crumbs" across multiple distinct sample types. Here we describe Squeegee, a de novo contamination detection tool that is based upon this principle, allowing the detection of microbial contaminants when negative controls are unavailable. On the low-biomass samples, we compare Squeegee predictions to experimental negative control data and show that Squeegee accurately recovers putative contaminants. We analyze samples of varying biomass from the Human Microbiome Project and identify likely, previously unreported kit contamination. Collectively, our results highlight that Squeegee can identify microbial contaminants with high precision and thus represents a computational approach for contaminant detection when negative controls are unavailable.}, } @article {pmid36348188, year = {2022}, author = {Rasmussen, N}, title = {René Dubos, the Autochthonous Flora, and the Discovery of the Microbiome.}, journal = {Journal of the history of biology}, volume = {55}, number = {3}, pages = {537-558}, pmid = {36348188}, issn = {1573-0387}, mesh = {Animals ; Humans ; *Microbiota ; *Anthozoa ; Symbiosis ; }, abstract = {Now characterised by high-throughput sequencing methods that enable the study of microbes without lab culture, the human "microbiome" (the microbial flora of the body) is said to have revolutionary implications for biology and medicine. According to many experts, we must now understand ourselves as "holobionts" like lichen or coral, multispecies superorganisms that consist of animal and symbiotic microbes in combination, because normal physiological function depends on them. Here I explore the 1960s research of biologist René Dubos, a forerunner figure mentioned in some historical accounts of the microbiome, and argue that he arrived at the superorganism concept 40 years before the Human Microbiome Project. This raises the question of why his contribution was not hailed as revolutionary at the time and why Dubos is not remembered for it.}, } @article {pmid36288838, year = {2022}, author = {Fransson, E and Gudnadottir, U and Hugerth, LW and Itzel, EW and Hamsten, M and Boulund, F and Pennhag, A and Du, J and Schuppe-Koistinen, I and Brusselaers, N and Engstrand, L}, title = {Cohort profile: the Swedish Maternal Microbiome project (SweMaMi) - assessing the dynamic associations between the microbiome and maternal and neonatal adverse events.}, journal = {BMJ open}, volume = {12}, number = {10}, pages = {e065825}, pmid = {36288838}, issn = {2044-6055}, mesh = {Infant ; Pregnancy ; Infant, Newborn ; Female ; Humans ; Child ; Sweden/epidemiology ; *Premature Birth ; Pregnancy Trimester, Third ; Cohort Studies ; *Microbiota ; }, abstract = {PURPOSE: The Swedish Maternal Microbiome (SweMaMi) project was initiated to better understand the dynamics of the microbiome in pregnancy, with longitudinal microbiome sampling, shotgun metagenomics, extensive questionnaires and health registry linkage.

PARTICIPANTS: Pregnant women were recruited before the 20th gestational week during 2017-2021 in Sweden. In total, 5439 pregnancies (5193 unique women) were included. For 3973 pregnancies (73%), samples were provided at baseline, and for 3141 (58%) at all three timepoints (second and third trimester and postpartum). In total, 38 591 maternal microbiome samples (vaginal, faecal and saliva) and 3109 infant faecal samples were collected. Questionnaires were used to collect information on general, reproductive and mental health, diet and lifestyle, complemented by linkage to the nationwide health registries, also used to follow up the health of the offspring (up to age 10).

FINDINGS TO DATE: The cohort is fairly representative for the total Swedish pregnant population (data from 2019), with 41% first-time mothers. Women with university level education, born in Sweden, with normal body mass index, not using tobacco-products and aged 30-34 years were slightly over-represented.

FUTURE PLANS: The sample and data collection were finalised in November 2021. The next steps are the characterisation of the microbial DNA and linkage to the health and demographic information from the questionnaires and registries. The role of the microbiome on maternal and neonatal outcomes and early-childhood diseases will be explored (including preterm birth, miscarriage) and the role and interaction of other risk factors and confounders (including endometriosis, polycystic ovarian syndrome, diet, drug use). This is currently among the largest pregnancy cohorts in the world with longitudinal design and detailed and standardised microbiome sampling enabling follow-up of both mothers and children. The findings are expected to contribute greatly to the field of reproductive health focusing on pregnancy and neonatal outcomes.}, } @article {pmid36280324, year = {2022}, author = {Gupta, A and Singh, V and Mani, I}, title = {Dysbiosis of human microbiome and infectious diseases.}, journal = {Progress in molecular biology and translational science}, volume = {192}, number = {1}, pages = {33-51}, doi = {10.1016/bs.pmbts.2022.06.016}, pmid = {36280324}, issn = {1878-0814}, mesh = {Humans ; Dysbiosis ; Prebiotics ; *Gastrointestinal Microbiome ; *Microbiota ; *Probiotics ; Bacteria ; *Communicable Diseases ; }, abstract = {Since birth, the human body gets colonized by various communities of symbiotic or commensal microorganisms and they persist till the death of an individual. The human microbiome is comprised of the genomes of microorganisms such as viruses, archaea, eukaryotes, protozoa, and, most remarkably, bacteria. The development of "omics" technologies gave way to the Human Microbiome Project (HMP) which aimed at exploring the collection of microbial genes and genomes inhabiting the human body. Eubiosis, i.e., a healthy and balanced composition of such microbes contributes to the metabolic function, protection against pathogens and provides nutrients and energy to the host. Whereas, an imbalance in the diversity of microorganisms, termed dysbiosis, greatly influences the state of health and disease. This chapter summarizes the impact of gut bacteria on the well-being of humans and highlights the protective role played by the human microbiota during bacterial and viral infections. The condition of dysbiosis and how it plays a role in the establishment of various infections and metabolic disorders such as Clostridioides difficile infection (CFI), inflammatory bowel disease (IBD), cancer, periodontitis, and obesity are described in detail. Further, treatments such as fecal transplantation, probiotics, prebiotics, phage therapy, and CRISPR/Cas system, which target gut microbiota during digestive diseases are also discussed.}, } @article {pmid36274714, year = {2022}, author = {Zheng, Y and Shi, J and Chen, Q and Deng, C and Yang, F and Wang, Y}, title = {Identifying individual-specific microbial DNA fingerprints from skin microbiomes.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {960043}, pmid = {36274714}, issn = {1664-302X}, abstract = {Skin is an important ecosystem that links the human body and the external environment. Previous studies have shown that the skin microbial community could remain stable, even after long-term exposure to the external environment. In this study, we explore two questions: Do there exist strains or genetic variants in skin microorganisms that are individual-specific, temporally stable, and body site-independent? And if so, whether such microorganismal genetic variants could be used as markers, called "fingerprints" in our study, to identify donors? We proposed a framework to capture individual-specific DNA microbial fingerprints from skin metagenomic sequencing data. The fingerprints are identified on the frequency of 31-mers free from reference genomes and sequence alignments. The 616 metagenomic samples from 17 skin sites at 3-time points from 12 healthy individuals from Integrative Human Microbiome Project were adopted. Ultimately, one contig for each individual is assembled as a fingerprint. And results showed that 89.78% of the skin samples despite body sites could identify their donors correctly. It is observed that 10 out of 12 individual-specific fingerprints could be aligned to Cutibacterium acnes. Our study proves that the identified fingerprints are temporally stable, body site-independent, and individual-specific, and can identify their donors with enough accuracy. The source code of the genetic identification framework is freely available at https://github.com/Ying-Lab/skin_fingerprint.}, } @article {pmid36268225, year = {2022}, author = {Khorsand, B and Asadzadeh Aghdaei, H and Nazemalhosseini-Mojarad, E and Nadalian, B and Nadalian, B and Houri, H}, title = {Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn's disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {12}, number = {}, pages = {1015890}, pmid = {36268225}, issn = {2235-2988}, mesh = {Humans ; *Colitis, Ulcerative ; *Crohn Disease/microbiology ; *Gastrointestinal Microbiome/genetics ; Metagenome ; Escherichia coli ; Siderophores ; Lipopolysaccharides ; *Inflammatory Bowel Diseases/microbiology ; Feces/microbiology ; *Escherichia coli Infections ; Sulfur ; Nitrogen ; }, abstract = {OBJECTIVES: A number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.

METHODS: Metagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.

RESULTS: Compared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.

CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.}, } @article {pmid36258167, year = {2022}, author = {Vikramdeo, KS and Anand, S and Pierce, JY and Singh, AP and Singh, S and Dasgupta, S}, title = {Distribution of microbiota in cervical preneoplasia of racially disparate populations.}, journal = {BMC cancer}, volume = {22}, number = {1}, pages = {1074}, pmid = {36258167}, issn = {1471-2407}, support = {CA231925, CA224306/NH/NIH HHS/United States ; CA231925, CA224306/NH/NIH HHS/United States ; }, mesh = {Female ; Humans ; Papillomaviridae/genetics ; RNA, Ribosomal, 16S/genetics ; *Papillomavirus Infections/complications ; Dysbiosis ; *Uterine Cervical Neoplasms/pathology ; *Microbiota/genetics ; *Uterine Cervical Dysplasia/epidemiology ; }, abstract = {BACKGROUNDS: Microbiome dysbiosis is an important contributing factor in tumor development and thus may be a risk predictor for human malignancies. In the United States, women with Hispanic/Latina (HIS) and African American (AA) background have a higher incidence of cervical cancer and poorer outcomes than Caucasian American (CA) women.

METHODS: Here, we assessed the distribution pattern of microbiota in cervical intraepithelial neoplasia (CIN) lesions obtained from HIS (n = 12), AA (n = 12), and CA (n = 12) women, who were screened for CC risk assessment. We employed a 16S rRNA gene sequencing approach adapted from the NIH-Human Microbiome Project to identify the microbial niche in all CIN lesions (n = 36).

RESULTS: We detected an appreciably decreased abundance of beneficial Lactobacillus in the CIN lesions of the AA and HIS women compared to the CA women. Differential abundance of potentially pathogenic Prevotella, Delftia, Gardnerella, and Fastidiosipila was also evident among the various racial groups. An increased abundance of Micrococcus was also evident in AA and HIS women compared to the CA women. The detection level of Rhizobium was higher among the AA ad CA women compared to the HIS women. In addition to the top 10 microbes, a unique niche of 27 microbes was identified exclusively in women with a histopathological diagnosis of CIN. Among these microbes, a group of 8 microbiota; Rubellimicrobium, Podobacter, Brevibacterium, Paracoccus, Atopobium, Brevundimonous, Comamonous, and Novospingobium was detected only in the CIN lesions obtained from AA and CA women.

CONCLUSIONS: Microbial dysbiosis in the cervical epithelium represented by an increased ratio of potentially pathogenic to beneficial microbes may be associated with increased CC risk disparities. Developing a race-specific reliable panel of microbial markers could be beneficial for CC risk assessment, disease prevention, and/or therapeutic guidance.}, } @article {pmid36233254, year = {2022}, author = {Rinaldi, F and Pinto, D and Borsani, E and Castrezzati, S and Amedei, A and Rezzani, R}, title = {The First Evidence of Bacterial Foci in the Hair Part and Dermal Papilla of Scalp Hair Follicles: A Pilot Comparative Study in Alopecia Areata.}, journal = {International journal of molecular sciences}, volume = {23}, number = {19}, pages = {}, pmid = {36233254}, issn = {1422-0067}, support = {private//Giuliani SpA/ ; }, mesh = {Adult ; *Alopecia Areata ; Hair Follicle/pathology ; Humans ; *Microbiota ; Middle Aged ; Scalp/pathology ; Young Adult ; }, abstract = {The role of the microbiome in hair follicle (HF) growth represents a growing field of research. Here, we studied the bacterial population in the scalp hair follicles of subjects with alopecia areata (AA). Two Healthy and two AA subjects, respectively (20−60 years old), were enrolled and studied regarding the microbial community in the subepidermal scalp compartments by means of a 4-mm biopsy punch. Samples were examined by 16S sequencing, histochemical staining (Gram’s method), and transmission electron microscopy (TEM). Bacterial foci were observed in the AA subjects’ follicles with both the two adopted complementary approaches (electron microscopy and Gram staining). Significant (p < 0.05) differences were also found in the three-layer biopsy samples (p < 0.05) regarding the bacterial population. In particular, in the deep epidermis and dermis levels, a significant (p < 0.05) lower abundance of Firmicutes and a higher abundance of Proteobacteria were found in AA samples compared to the healthy control. Firmicutes also showed a significant (p < 0.05) lower abundance in hypodermis in AA subjects. In addition, Enterobacteriaceae and the genera Streptococcus, Gemella, Porphyromonas, and Granulicatella were relatively more abundant in AA groups at the deep epidermis level. The Staphylococcus and Flavobacterium genera were significantly less abundant in AA samples than in controls in all three-layer biopsy samples (p < 0.05). In contrast, Veillonella and Neisseriaceae were relatively more abundant in the healthy control group compared to the AA sample. Therefore, higher alpha diversity was observed in all three-layer biopsy samples of AA patients compared to the control. In conclusion, our data suggest that tAA could be defined as a “hair disease associated with dysregulated microbiome-immunity axis of hair follicles”.}, } @article {pmid36231000, year = {2022}, author = {Prakash, A and Nourianpour, M and Senok, A and Atiomo, W}, title = {Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota.}, journal = {Cells}, volume = {11}, number = {19}, pages = {}, pmid = {36231000}, issn = {2073-4409}, mesh = {Dysbiosis/complications/microbiology ; *Endometrial Neoplasms ; Female ; *Gastrointestinal Microbiome/physiology ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome ; }, abstract = {Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the 'Human Microbiome Project' in 2016. We obtained 200 articles by inputting keywords such as 'gut microbiome', 'gut microbiota', 'gut dysbiosis', 'PCOS', and 'endometrial cancer' into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.}, } @article {pmid36160151, year = {2022}, author = {Aboul Naga, SH and Hassan, LM and El Zanaty, RT and Refaat, M and Amin, RH and Ragab, G and Soliman, MM}, title = {Behçet uveitis: Current practice and future perspectives.}, journal = {Frontiers in medicine}, volume = {9}, number = {}, pages = {968345}, pmid = {36160151}, issn = {2296-858X}, abstract = {Described as early as Hippocrates in his "Third Book of Endemic Diseases," Behçet's Disease (BD), also known as "The Silk Road Disease" following its initial demographics, consists of a triad of recurrent oro-genital ulcers and associated uveitis. Current demographics and rising percentages of patients seen far beyond the Silk Road in Ocular Inflammatory Disease and Uveitis Clinics list BD uveitis as one of the frontliners of non-infectious autoinflammatory eye diseases. Clinical features of BD and juvenile-onset BD are detailed alongside various approaches in classification and suggested algorithms for diagnosis that are outlined in this review. With the ongoing Human Microbiome Project and studies such as the MAMBA study, the role of the human microbiome in BD is highlighted in the pathophysiology of BD to include the current research and literature perspective. Furthermore, with the advancement of recent diagnostic and investigative techniques, especially in the field of Optical Coherence Tomography (OCT), disease-related characteristics are updated to encompass SD, EDI and OCT-angiography characteristics of BD. Having entered the era of biologic therapy, the role of various specific cytokine-blocking biologic drugs, such as TNF-α inhibitors (e.g., adalimumab, infliximab), interferon α-2a inhibitors, IL-6 and IL-1 inhibitors are presented and contrasted alongside the conventional immunosuppressant drugs and the classic old gold standard: corticosteroids (systemic or local). Finally, with the ongoing SARS-CoV-2 pandemic, it was not possible to conclude the review without reviewing the latest evidence-based literature reporting BD morbidity in this era, the observed pattern and treatment recommendations as well as those related to reported post-vaccine complications and emergence of BD.}, } @article {pmid36083529, year = {2022}, author = {de Lima Ferreira, JK and de Mello Varani, A and Tótola, MR and Fernandes Almeida, M and de Sousa Melo, D and Ferreira Silva E Batista, C and Chalfun-Junior, A and Pimenta de Oliveira, KK and Wurdig Roesch, LF and Satler Pylro, V}, title = {Phylogenomic characterization and pangenomic insights into the surfactin-producing bacteria Bacillus subtilis strain RI4914.}, journal = {Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology]}, volume = {53}, number = {4}, pages = {2051-2063}, pmid = {36083529}, issn = {1678-4405}, support = {404651/2018-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 303061/2019-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 133550/2019-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; Finance Code 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 001//Brazilian Microbiome Project/ ; }, mesh = {*Bacillus subtilis/genetics/metabolism ; Phylogeny ; *Peptides, Cyclic/genetics/metabolism ; Lipopeptides ; Operon ; Bacterial Proteins/metabolism ; }, abstract = {Bacillus subtilis is a versatile bacterial species able to produce surfactin, a lipopeptide biosurfactant. We carried out the phylogenomic characterization and pangenomic analyses using available B. subtilis complete genomes. Also, we report the whole genome of the biosurfactant-producing B. subtilis strain RI4914 that was isolated from effluent water from an oil exploration field. We applied a hybrid sequencing approach using both long- and short-read sequencing technologies to generate a highly accurate, single-chromosome genome. The pangenomics analysis of 153 complete genomes classified as B. subtilis retrieved from the NCBI shows an open pangenome composed of 28,511 accessory genes, which agrees with the high genetic plasticity of the species. Also, this analysis suggests that surfactin production is a common trait shared by members of this species since the srfA operon is highly conserved among the B. subtilis strains found in most of the assemblies available. Finally, increased surfactin production corroborates the higher srfAA gene expression in B. subtilis strain RI4914.}, } @article {pmid36047699, year = {2022}, author = {An, U and Shenhav, L and Olson, CA and Hsiao, EY and Halperin, E and Sankararaman, S}, title = {STENSL: Microbial Source Tracking with ENvironment SeLection.}, journal = {mSystems}, volume = {7}, number = {5}, pages = {e0099521}, pmid = {36047699}, issn = {2379-5077}, support = {R35 GM125055/GM/NIGMS NIH HHS/United States ; R01 HG011345/HG/NHGRI NIH HHS/United States ; }, mesh = {*Microbiota ; Algorithms ; Machine Learning ; }, abstract = {Microbial source tracking analysis has emerged as a widespread technique for characterizing the properties of complex microbial communities. However, this analysis is currently limited to source environments sampled in a specific study. In order to expand the scope beyond one single study and allow the exploration of source environments using large databases and repositories, such as the Earth Microbiome Project, a source selection procedure is required. Such a procedure will allow differentiating between contributing environments and nuisance ones when the number of potential sources considered is high. Here, we introduce STENSL (microbial Source Tracking with ENvironment SeLection), a machine learning method that extends common microbial source tracking analysis by performing an unsupervised source selection and enabling sparse identification of latent source environments. By incorporating sparsity into the estimation of potential source environments, STENSL improves the accuracy of true source contribution, while significantly reducing the noise introduced by noncontributing ones. We therefore anticipate that source selection will augment microbial source tracking analyses, enabling exploration of multiple source environments from publicly available repositories while maintaining high accuracy of the statistical inference. IMPORTANCE Microbial source tracking is a powerful tool to characterize the properties of complex microbial communities. However, this analysis is currently limited to source environments sampled in a specific study. In many applications there is a clear need to consider source selection over a large array of microbial environments, external to the study. To this end, we developed STENSL (microbial Source Tracking with ENvironment SeLection), an expectation-maximization algorithm with sparsity that enables the identification of contributing sources among a large set of potential microbial environments. With the unprecedented expansion of microbiome data repositories such as the Earth Microbiome Project, recording over 200,000 samples from more than 50 types of categorized environments, STENSL takes the first steps in performing automated source exploration and selection. STENSL is significantly more accurate in identifying the contributing sources as well as the unknown source, even when considering hundreds of potential source environments, settings in which state-of-the-art microbial source tracking methods add considerable error.}, } @article {pmid35993401, year = {2022}, author = {Wiesmann, C and Lehr, K and Kupcinskas, J and Vilchez-Vargas, R and Link, A}, title = {Primers matter: Influence of the primer selection on human fungal detection using high throughput sequencing.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2110638}, pmid = {35993401}, issn = {1949-0984}, mesh = {DNA, Fungal ; Fungi/genetics ; *Gastrointestinal Microbiome/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Mycobiome/genetics ; }, abstract = {Microbiota research has received an increasing attention for its role in disease development and fungi are considered as one of the key players in the microbial niche. Various sequencing approaches have been applied to uncover the role of fungal community in health and disease; however, little is known on the performance of various primers and comparability between the studies. Motivated by the recent publications, we performed a systematic comparison of the 18S and ITS regions to identify the impact of various primers on the sequencing results. Using four pairs of primers extensively used in literature, fungal community was retrieve from 25 fecal samples, and applying high throughput sequencing; and the results were compared in order to select the most suitable primers for fungal detection in human fecal samples. Considering the high variability between samples, primers described in the Earth microbiome project detected the broadest fungal spectrum suggesting its superior performance in mycobiome research.}, } @article {pmid35973395, year = {2022}, author = {Scricciolo, A and Lombardo, V and Elli, L and Bascuñán, KA and Doneda, L and Rinaldi, F and Pinto, D and Araya, M and Costantino, A and Vecchi, M and Roncoroni, L}, title = {Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {41}, number = {9}, pages = {2025-2030}, doi = {10.1016/j.clnu.2022.07.029}, pmid = {35973395}, issn = {1532-1983}, mesh = {Adult ; *Celiac Disease ; Diet, Gluten-Free ; *Glutens/adverse effects ; Humans ; Proline ; Prolyl Oligopeptidases ; Quality of Life ; }, abstract = {BACKGROUND: A gluten-free diet (GFD) is the main therapy for non-coeliac gluten sensitivity (NCGS). However, the availability of novel enzymes with the ability to digest gluten could represent a therapeutic opportunity for NCGS patients to avoid a GFD.

AIMS: To evaluate the controlled reintroduction of gluten with or without the endopeptidase P1016 in NCGS patients.

METHODS: This is a randomized, double-blind, placebo-controlled monocentric study, Registered under ClinicalTrials.gov Identifier no. NCT01864993. Gluten was reintroduced incrementally over a 3-week period under nutritional control. NCGS patients were randomized into two groups and administered P1016 or placebo during gluten reintroduction. We evaluated symptoms (visual analogue scale, VAS), quality of life (SF-36) and mental health symptoms (SCL-90) on a weekly basis.

RESULTS: We enrolled a total 23 patients who were allocated to a placebo group (n = 11, age 38.4 ± 2.9) or an intervention group (n = 12, age 39.5 ± 3.1). No effect of P1016 on symptoms was found. During gluten reintroduction, patients reported a significant increase in abdominal pain and a worsening of stool consistency. Furthermore, no differences were found between the groups regarding SCL-90 and SF-36 scores.

CONCLUSIONS: Our results demonstrate a lack of effect of P1016 in the management of NCGS patients and the possible reintroduction of gluten.}, } @article {pmid35966676, year = {2022}, author = {Wei, Q and Li, Z and Gu, Z and Liu, X and Krutmann, J and Wang, J and Xia, J}, title = {Shotgun metagenomic sequencing reveals skin microbial variability from different facial sites.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {933189}, pmid = {35966676}, issn = {1664-302X}, abstract = {Biogeography (body site) is known to be one of the main factors influencing the composition of the skin microbial community. However, site-associated microbial variability at a fine-scale level was not well-characterized since there was a lack of high-resolution recognition of facial microbiota across kingdoms by shotgun metagenomic sequencing. To investigate the explicit microbial variance in the human face, 822 shotgun metagenomic sequencing data from Han Chinese recently published by our group, in combination with 97 North American samples from NIH Human Microbiome Project (HMP), were reassessed. Metagenomic profiling of bacteria, fungi, and bacteriophages, as well as enriched function modules from three facial sites (forehead, cheek, and the back of the nose), was analyzed. The results revealed that skin microbial features were more alike in the forehead and cheek while varied from the back of the nose in terms of taxonomy and functionality. Analysis based on biogeographic theories suggested that neutral drift with niche selection from the host could possibly give rise to the variations. Of note, the abundance of porphyrin-producing species, i.e., Cutibacterium acnes, Cutibacterium avidum, Cutibacterium granulosum, and Cutibacterium namnetense, was all the highest in the back of the nose compared with the forehead/cheek, which was consistent with the highest porphyrin level on the nose in our population. Sequentially, the site-associated microbiome variance was confirmed in American populations; however, it was not entirely consistent. Furthermore, our data revealed correlation patterns between Propionibacterium acnes bacteriophages with genus Cutibacterium at different facial sites in both populations; however, C. acnes exhibited a distinct correlation with P. acnes bacteriophages in Americans/Chinese. Taken together, in this study, we explored the fine-scale facial site-associated changes in the skin microbiome and provided insight into the ecological processes underlying facial microbial variations.}, } @article {pmid35913193, year = {2022}, author = {Zheng, X and Dai, X and Zhu, Y and Yang, J and Jiang, H and Dong, H and Huang, L}, title = {(Meta)Genomic Analysis Reveals Diverse Energy Conservation Strategies Employed by Globally Distributed Gemmatimonadota.}, journal = {mSystems}, volume = {7}, number = {4}, pages = {e0022822}, pmid = {35913193}, issn = {2379-5077}, mesh = {Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Bacteria ; Genomics ; *Microbiota/genetics ; }, abstract = {Gemmatimonadota is a phylum-level lineage distributed widely but rarely reported. Only six representatives of Gemmatimonadota have so far been isolated and cultured in laboratory. The physiology, ecology, and evolutionary history of this phylum remain unknown. The 16S rRNA gene survey of our salt lake and deep-sea sediments, and Earth Microbiome Project (EMP) samples, reveals that Gemmatimonadota exist in diverse environments globally. In this study, we retrieved 17 metagenome-assembled genomes (MAGs) from salt lake sediments (12 MAGs) and deep-sea sediments (5 MAGs). Analysis of these MAGs and the nonredundant MAGs or genomes from public databases reveals Gemmatimonadota can degrade various complex organic substrates, and mainly employ heterotrophic pathways (e.g., glycolysis and tricarboxylic acid [TCA] cycle) for growth via aerobic respiration. And the processes of sufficient energy being stored in glucose through gluconeogenesis, followed by the synthesis of more complex compounds, are prevalent in Gemmatimonadota. A highly expandable pangenome for Gemmatimonadota has been observed, which presumably results from their adaptation to thriving in diverse environments. The enrichment of the Na[+]/H[+] antiporter in the SG8-23 order represents their adaptation to salty habitats. Notably, we identified a novel lineage of the SG8-23 order, which is potentially anoxygenic phototrophic. This lineage is not closely related to the phototrophs in the order of Gemmatimonadales. The two orders differ distinctly in the gene organization and phylogenetic relationship of their photosynthesis gene clusters, indicating photosystems in Gemmatimonadota have evolved in two independent routes. IMPORTANCE The phylum Gemmatimonadota is widely distributed in various environments. However, their physiology, ecology and evolutionary history remain unknown, primary due to the limited cultured isolates and available genomes. We were intrigued to find out how widespread this phylum is, and how it can thrive under diverse conditions. Our results here expand the knowledge of the genetic and metabolic diversity of Gemmatimonadota, and shed light on the diverse energy conservation strategies (i.e., oxidative phosphorylation, substrate phosphorylation, and photosynthetic phosphorylation) responsible for their global distribution. Moreover, gene organization and phylogenetic analysis of photosynthesis gene clusters in Gemmatimonadota provide a valuable insight into the evolutionary history of photosynthesis.}, } @article {pmid35879415, year = {2022}, author = {Lopera-Maya, EA and Kurilshikov, A and van der Graaf, A and Hu, S and Andreu-Sánchez, S and Chen, L and Vila, AV and Gacesa, R and Sinha, T and Collij, V and Klaassen, MAY and Bolte, LA and Gois, MFB and Neerincx, PBT and Swertz, MA and , and Harmsen, HJM and Wijmenga, C and Fu, J and Weersma, RK and Zhernakova, A and Sanna, S}, title = {Author Correction: Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.}, journal = {Nature genetics}, volume = {54}, number = {9}, pages = {1448}, doi = {10.1038/s41588-022-01164-2}, pmid = {35879415}, issn = {1546-1718}, } @article {pmid35877716, year = {2022}, author = {Silva, SG and Paula, P and da Silva, JP and Mil-Homens, D and Teixeira, MC and Fialho, AM and Costa, R and Keller-Costa, T}, title = {Insights into the Antimicrobial Activities and Metabolomes of Aquimarina (Flavobacteriaceae, Bacteroidetes) Species from the Rare Marine Biosphere.}, journal = {Marine drugs}, volume = {20}, number = {7}, pages = {}, pmid = {35877716}, issn = {1660-3397}, support = {Fundo Azul program - FA_05_2017_032//Direção-Geral de Política do Mar/ ; EMBRC.PT ALG-01-0145-FEDER-022121//CRESC Algarve 2020 and COMPETE 2020/ ; PTDC/MAR-BIO/1547/2014, UIDB/04565/2020, UIDP/04565/2020, LA/P/0140/2020, UIDB/04326/2020, PD/BD/143029/2018//Fundação para a Ciência e Tecnologia/ ; 22231/01/SAICT/2016//Lisboa2020/ ; }, mesh = {*Anti-Infective Agents/metabolism/pharmacology ; Bacteroidetes/genetics ; *Biological Products/metabolism/pharmacology ; Ecosystem ; *Flavobacteriaceae/genetics ; Humans ; Metabolome ; *Methicillin-Resistant Staphylococcus aureus ; Phylogeny ; }, abstract = {Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the ‘Sponge Microbiome Project’ dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems.}, } @article {pmid35854695, year = {2022}, author = {Therdtatha, P and Shinoda, A and Nakayama, J}, title = {Crisis of the Asian gut: associations among diet, microbiota, and metabolic diseases.}, journal = {Bioscience of microbiota, food and health}, volume = {41}, number = {3}, pages = {83-93}, pmid = {35854695}, issn = {2186-6953}, abstract = {The increase of lifestyle-related diseases in Asia has recently become remarkably serious. This has been associated with a change in dietary habits that may alter the complex gut microbiota and its metabolic function in Asian people. Notably, the penetration of modern Western diets into Asia, which has been accompanied by an increase in fat content and decrease in plant-derived dietary fiber, is restructuring the Asian gut microbiome. In this review, we introduce the current status of obesity and diabetes in Asia and discuss the links of changes in dietary style with gut microbiota alterations which may predispose Asian people to metabolic diseases.}, } @article {pmid35849580, year = {2022}, author = {Pinto, D and Calabrese, FM and De Angelis, M and Celano, G and Giuliani, G and Rinaldi, F}, title = {Lichen Planopilaris: The first biopsy layer microbiota inspection.}, journal = {PloS one}, volume = {17}, number = {7}, pages = {e0269933}, pmid = {35849580}, issn = {1932-6203}, mesh = {Alopecia/metabolism ; Biopsy ; Humans ; Inflammation ; Interleukin-23/genetics ; *Lichen Planus/pathology ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Lichen Planopilaris (LPP) is a lymphatic disease affecting the scalp that is characterized by a chronic and destructive inflammation process, named as 'cicatricial alopecia' in which the hair follicles are targeted and may involve predominantly lymphocytes or neutrophils. Scalp and biopsy layers have never been used to investigate microbial community composition and its relative taxa abundances in LPP. We sought to examine the significant taxa of this chronic relapsing inflammatory skin disease, together with inspect the existing connections with metabolic pathways featuring this microbial community. We used a multilevel analysis based on 16S rRNA marker sequencing in order to detect OTU abundances in pathologic/healthy samples, real time PCR for measuring the levels of IL-23 interleukin expression and urinary metabolomics to find out volatile organic metabolites (VOMs). By using a linear regression model, we described peculiar taxa that significantly differentiated LPP and healthy samples. We inspected taxa abundances and interleukin mRNA levels and the Microbacteriaceae family resulted negatively correlated with the IL-23 expression. Moreover, starting from 16S taxa abundances, we predicted the metabolic pathways featuring this microbial community. By inspecting microbial composition, sample richness, metabolomics profiles and the relative metabolic pathways in a cohort of LPP and healthy samples we deepened the contribution of significant taxa that are connected to inflammation maintenance and microbiota plasticity in LPP pathology.}, } @article {pmid35832621, year = {2022}, author = {Balaji, A and Sapoval, N and Seto, C and Leo Elworth, RA and Fu, Y and Nute, MG and Savidge, T and Segarra, S and Treangen, TJ}, title = {KOMB: K-core based de novo characterization of copy number variation in microbiomes.}, journal = {Computational and structural biotechnology journal}, volume = {20}, number = {}, pages = {3208-3222}, pmid = {35832621}, issn = {2001-0370}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {Characterizing metagenomes via kmer-based, database-dependent taxonomic classification has yielded key insights into underlying microbiome dynamics. However, novel approaches are needed to track community dynamics and genomic flux within metagenomes, particularly in response to perturbations. We describe KOMB, a novel method for tracking genome level dynamics within microbiomes. KOMB utilizes K-core decomposition to identify Structural variations (SVs), specifically, population-level Copy Number Variation (CNV) within microbiomes. K-core decomposition partitions the graph into shells containing nodes of induced degree at least K, yielding reduced computational complexity compared to prior approaches. Through validation on a synthetic community, we show that KOMB recovers and profiles repetitive genomic regions in the sample. KOMB is shown to identify functionally-important regions in Human Microbiome Project datasets, and was used to analyze longitudinal data and identify keystone taxa in Fecal Microbiota Transplantation (FMT) samples. In summary, KOMB represents a novel graph-based, taxonomy-oblivious, and reference-free approach for tracking CNV within microbiomes. KOMB is open source and available for download at https://gitlab.com/treangenlab/komb.}, } @article {pmid35816586, year = {2023}, author = {Reis, DJ and Kaizer, AM and Kinney, AR and Bahraini, NH and Forster, JE and Brenner, LA}, title = {The unique association of posttraumatic stress disorder with hypertension among veterans: A replication of Kibler et al. (2009) using Bayesian estimation and data from the United States-Veteran Microbiome Project.}, journal = {Psychological trauma : theory, research, practice and policy}, volume = {15}, number = {1}, pages = {131-139}, pmid = {35816586}, issn = {1942-969X}, support = {//National Institutes of Health; National Heart, Lung, and Blood Institute/ ; //State of Colorado/ ; K01 HL151754/HL/NHLBI NIH HHS/United States ; //US Department of Defense/ ; //Rocky Mountain Mental Illness Research, Education, and Clinical Center/ ; /NH/NIH HHS/United States ; //US Department of Veterans Affairs/ ; //US Department of Veterans Affairs; Office of Academic Affiliations; Advanced Fellowship Program in Mental Illness Research and Treatment/ ; }, mesh = {Humans ; United States/epidemiology ; *Stress Disorders, Post-Traumatic/psychology ; *Veterans/psychology ; Bayes Theorem ; *Depressive Disorder, Major/epidemiology ; Comorbidity ; *Hypertension/epidemiology ; }, abstract = {OBJECTIVE: Kibler et al. (2009) reported that hypertension was related to PTSD independent of depression. These two conditions have significant diagnostic overlap. The present study sought to conceptually replicate this work with a veteran sample, using Bayesian estimation to directly update past results, as well as examine symptom severity scores in relation to hypertension.

METHOD: This was a secondary analysis of data obtained from the United States-Veteran Microbiome Project. Lifetime diagnoses of PTSD and major depressive disorder (MDD) were obtained from a structured clinical interview and hypertension diagnoses were extracted from electronic medical records. PTSD and depressive symptom severity were obtained from self-report measures. Logistic regressions with Bayesian estimation were used to estimate the associations between hypertension and (a) psychiatric diagnostic history and (b) symptom severity scores.

RESULTS: Compared with veterans without lifetime diagnoses of either disorder, the PTSD-only group was estimated to have a 29% increase in hypertension risk, and the PTSD + MDD group was estimated to have a 66% increase in hypertension risk. Additionally, higher levels of PTSD symptom severity were associated with a higher risk of hypertension.

CONCLUSION: PTSD diagnosis and symptom severity are uniquely associated with hypertension, independent of MDD or depressive symptom severity. These results support previous findings that PTSD might be a modifiable risk factor for the prevention and treatment of hypertension. (PsycInfo Database Record (c) 2023 APA, all rights reserved).}, } @article {pmid35788347, year = {2022}, author = {Nagata, N and Nishijima, S and Miyoshi-Akiyama, T and Kojima, Y and Kimura, M and Aoki, R and Ohsugi, M and Ueki, K and Miki, K and Iwata, E and Hayakawa, K and Ohmagari, N and Oka, S and Mizokami, M and Itoi, T and Kawai, T and Uemura, N and Hattori, M}, title = {Population-level Metagenomics Uncovers Distinct Effects of Multiple Medications on the Human Gut Microbiome.}, journal = {Gastroenterology}, volume = {163}, number = {4}, pages = {1038-1052}, doi = {10.1053/j.gastro.2022.06.070}, pmid = {35788347}, issn = {1528-0012}, mesh = {*Anti-Infective Agents ; Cross-Sectional Studies ; Fatty Acids, Volatile/pharmacology ; Feces/microbiology ; *Gastrointestinal Microbiome/physiology ; Humans ; Metagenomics ; *Microbiota ; }, abstract = {BACKGROUND & AIMS: Medication is a major determinant of human gut microbiome structure, and its overuse increases the risks of morbidity and mortality. However, effects of certain commonly prescribed drugs and multiple medications on the gut microbiome are still underinvestigated.

METHODS: We performed shotgun metagenomic analysis of fecal samples from 4198 individuals in the Japanese 4D (Disease, Drug, Diet, Daily life) microbiome project. A total of 759 drugs were profiled, and other metadata, such as anthropometrics, lifestyles, diets, physical activities, and diseases, were prospectively collected. Second fecal samples were collected from 243 individuals to assess the effects of drug initiation and discontinuation on the microbiome.

RESULTS: We found that numerous drugs across different treatment categories influence the microbiome; more than 70% of the drugs we profiled had not been examined before. Individuals exposed to multiple drugs, polypharmacy, showed distinct gut microbiome structures harboring significantly more abundant upper gastrointestinal species and several nosocomial pathobionts due to additive drug effects. Polypharmacy was also associated with microbial functions, including the reduction of short-chain fatty acid metabolism and increased bacterial stress responses. Even nonantibiotic drugs were significantly correlated with an increased antimicrobial resistance potential through polypharmacy. Notably, a 2-time points dataset revealed the alteration and recovery of the microbiome in response to drug initiation and cessation, corroborating the observed drug-microbe associations in the cross-sectional cohort.

CONCLUSION: Our large-scale metagenomics unravels extensive and disruptive impacts of individual and multiple drug exposures on the human gut microbiome, providing a drug-microbe catalog as a basis for a deeper understanding of the role of the microbiome in drug efficacy and toxicity.}, } @article {pmid35770164, year = {2022}, author = {Wang, J and Feng, J and Zhu, Y and Li, D and Wang, J and Chi, W}, title = {Diversity and Biogeography of Human Oral Saliva Microbial Communities Revealed by the Earth Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {931065}, pmid = {35770164}, issn = {1664-302X}, abstract = {The oral cavity is an important window for microbial communication between the environment and the human body. The oral microbiome plays an important role in human health. However, compared to the gut microbiome, the oral microbiome has been poorly explored. Here, we analyzed 404 datasets from human oral saliva samples published by the Earth Microbiome Project (EMP) and compared them with 815 samples from the human gut, nose/pharynx, and skin. The diversity of the human saliva microbiome varied significantly among individuals, and the community compositions were complex and diverse. The saliva microbiome showed the lowest species diversity among the four environment types. Human oral habitats shared a small core bacterial community containing only 14 operational taxonomic units (OTUs) under 5 phyla, which occupied over 75% of the sequence abundance. For the four habitats, the core taxa of the saliva microbiome had the greatest impact on saliva habitats than other habitats and were mostly unique. In addition, the saliva microbiome showed significant differences in the populations of different regions, which may be determined by the living environment and lifestyle/dietary habits. Finally, the correlation analysis showed high similarity between the saliva microbiome and the microbiomes of Aerosol (non-saline) and Surface (non-saline), i.e., two environment types closely related to human, suggesting that contact and shared environment being the driving factors of microbial transmission. Together, these findings expand our understanding of human oral diversity and biogeography.}, } @article {pmid35752802, year = {2022}, author = {Darcy, JL and Amend, AS and Swift, SOI and Sommers, PS and Lozupone, CA}, title = {specificity: an R package for analysis of feature specificity to environmental and higher dimensional variables, applied to microbiome species data.}, journal = {Environmental microbiome}, volume = {17}, number = {1}, pages = {34}, pmid = {35752802}, issn = {2524-6372}, support = {5 T15 LM009451-12/NH/NIH HHS/United States ; 1255972//National Science Foundation/ ; }, abstract = {BACKGROUND: Understanding the factors that influence microbes' environmental distributions is important for determining drivers of microbial community composition. These include environmental variables like temperature and pH, and higher-dimensional variables like geographic distance and host species phylogeny. In microbial ecology, "specificity" is often described in the context of symbiotic or host parasitic interactions, but specificity can be more broadly used to describe the extent to which a species occupies a narrower range of an environmental variable than expected by chance. Using a standardization we describe here, Rao's (Theor Popul Biol, 1982. https://doi.org/10.1016/0040-5809(82)90004-1, Sankhya A, 2010. https://doi.org/10.1007/s13171-010-0016-3) Quadratic Entropy can be conveniently applied to calculate specificity of a feature, such as a species, to many different environmental variables.

RESULTS: We present our R package specificity for performing the above analyses, and apply it to four real-life microbial data sets to demonstrate its application. We found that many fungi within the leaves of native Hawaiian plants had strong specificity to rainfall and elevation, even though these variables showed minimal importance in a previous analysis of fungal beta-diversity. In Antarctic cryoconite holes, our tool revealed that many bacteria have specificity to co-occurring algal community composition. Similarly, in the human gut microbiome, many bacteria showed specificity to the composition of bile acids. Finally, our analysis of the Earth Microbiome Project data set showed that most bacteria show strong ontological specificity to sample type. Our software performed as expected on synthetic data as well.

CONCLUSIONS: specificity is well-suited to analysis of microbiome data, both in synthetic test cases, and across multiple environment types and experimental designs. The analysis and software we present here can reveal patterns in microbial taxa that may not be evident from a community-level perspective. These insights can also be visualized and interactively shared among researchers using specificity's companion package, specificity.shiny.}, } @article {pmid35744617, year = {2022}, author = {García-Mato, E and Martínez-Lamas, L and Álvarez-Fernández, M and Varela-Aneiros, I and Diniz-Freitas, M and Limeres-Posse, J and Diz-Dios, P}, title = {Molecular Detection of Streptococcus downii sp. nov. from Dental Plaque Samples from Patients with Down Syndrome and Non-Syndromic Individuals.}, journal = {Microorganisms}, volume = {10}, number = {6}, pages = {}, pmid = {35744617}, issn = {2076-2607}, abstract = {A new bacterial species has recently been identified in the dental plaque of an adolescent with Down syndrome. The species is known as Streptococcus downii sp. nov. (abbreviated to S. downii), and it inhibits the growth of S. mutans and certain periodontal pathogens. The aim of this study was to determine the distribution of S. downii in the oral cavity of individuals with Down syndrome. Methods: A specific polymerase chain reaction for the operon of bacteriocin (class IIb lactobin A/cerein 7B family) was designed to detect S. downii in individuals with Down syndrome (n = 200) and in the general population (n = 100). We also compared the whole genome of S. downii and the regions related to its bacteriocins against 127 metagenomes of supragingival plaque of the "Human Microbiome Project". Results: We detected the specific gene of the S. downii bacteriocin in an individual with Down syndrome (Cq, 34.52; GE/μL, 13.0) and in an individual of the non-syndromic control group (Cq, 34.78 Cq; GE/μL, 4.93). The prevalence of S. downii was ≤1% both in Down syndrome and in the general population, which did not allow for clinical-microbiological correlations to be established. This result was confirmed by detecting only one metagenome with an ANIm with approximately 95% homology and with 100% homology with ORFs that code class IIb lactobiocin A/cerein 7B bacteriocins among the 127 metagenomes of the "Human Microbiome Project" tested. Conclusions: The detection rate of S. downii in the supragingival dental plaque was very low, both in the Down syndrome individuals and in the non-syndromic controls. A clinical-microbiological correlation could therefore not be established.}, } @article {pmid35713407, year = {2022}, author = {Shaffer, JP and Carpenter, CS and Martino, C and Salido, RA and Minich, JJ and Bryant, M and Sanders, K and Schwartz, T and Humphrey, G and Swafford, AD and Knight, R}, title = {A comparison of six DNA extraction protocols for 16S, ITS and shotgun metagenomic sequencing of microbial communities.}, journal = {BioTechniques}, volume = {73}, number = {1}, pages = {34-46}, pmid = {35713407}, issn = {1940-9818}, support = {R01 DK102932/DK/NIDDK NIH HHS/United States ; K12 GM068524/GM/NIGMS NIH HHS/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 HL134887/HL/NHLBI NIH HHS/United States ; RF1 AG058942/AG/NIA NIH HHS/United States ; }, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics/methods ; *Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.}, } @article {pmid35680554, year = {2023}, author = {Kuhl, LP and Marostica, PJC and Macedo, AJ and Kuhl, G and Siebert, M and Manica, D and Sekine, L and Schweiger, C}, title = {High microbiome variability in pediatric tracheostomy cannulas in patients with similar clinical characteristics.}, journal = {Brazilian journal of otorhinolaryngology}, volume = {89}, number = {2}, pages = {254-263}, pmid = {35680554}, issn = {1808-8686}, mesh = {RNA, Ribosomal, 16S/genetics ; *Tracheostomy ; Cannula ; *Microbiota/genetics ; Brazil ; }, abstract = {OBJECTIVES: To evaluate the bacterial microbiome found in tracheostomy cannulas of a group of children diagnosed with glossoptosis secondary to Robin Sequence (RS), and its clinical implications.

METHODS: Pediatric patients were enrolled in the study at the time of the cannula change in the hospital. During this procedure, the removed cannula was collected and stored for amplicon sequencing of 16s rRNA. DNA extraction was performed using DNeasy PowerBiofilm Kit (QIAGEN® ‒ Cat nº 24000-50) while sequencing was performed with the S5 (Ion S5™ System, Thermo Fisher Scientific), following Brazilian Microbiome Project (BMP) protocol.

RESULTS: All 12 patients included in the study were using tracheostomy uncuffed cannulas of the same brand, had tracheostomy performed for over 1-year and had used the removed cannula for approximately 3-months. Most abundant genera found were Aggregatibacter, Pseudomonas, Haemophilus, Neisseria, Staphylococcus, Fusobacterium, Moraxella, Streptococcus, Alloiococcus, and Capnocytophaga. Individual microbiome of each individual was highly variable, not correlating to any particular clinical characteristic.

CONCLUSION: The microbiome of tracheostomy cannulas is highly variable, even among patients with similar clinical characteristics, making it challenging to determine a standard for normality.}, } @article {pmid35633673, year = {2022}, author = {Maestre-Carballa, L and Navarro-López, V and Martinez-Garcia, M}, title = {A Resistome Roadmap: From the Human Body to Pristine Environments.}, journal = {Frontiers in microbiology}, volume = {13}, number = {}, pages = {858831}, pmid = {35633673}, issn = {1664-302X}, abstract = {A comprehensive characterization of the human body resistome [sets of antibiotic resistance genes (ARGs)] is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut, and oral cavity) of healthy subjects from the Human Microbiome Project (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 10[7] proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n = 271 samples; 77 Gb of sequencing data and 2.1 × 10[8] proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole.}, } @article {pmid35629064, year = {2022}, author = {Arjunan, P and Swaminathan, R}, title = {Do Oral Pathogens Inhabit the Eye and Play a Role in Ocular Diseases?.}, journal = {Journal of clinical medicine}, volume = {11}, number = {10}, pages = {}, pmid = {35629064}, issn = {2077-0383}, abstract = {Fascinatingly, the immune-privileged healthy eye has a small unique population of microbiota. The human microbiome project led to continuing interest in the ocular microbiome. Typically, ocular microflorae are commensals of low diversity that colonize the external and internal sites of the eye, without instigating any disorders. Ocular commensals modulate immunity and optimally regulate host defense against pathogenic invasion, both on the ocular surface and neuroretina. Yet, any alteration in this symbiotic relationship culminates in the perturbation of ocular homeostasis and shifts the equilibrium toward local or systemic inflammation and, in turn, impaired visual function. A compositional variation in the ocular microbiota is associated with surface disorders such as keratitis, blepharitis, and conjunctivitis. Nevertheless, innovative studies now implicate non-ocular microbial dysbiosis in glaucoma, age-related macular degeneration (AMD), uveitis, and diabetic retinopathy. Accordingly, prompt identification of the extra-ocular etiology and a methodical understanding of the mechanisms of invasion and host-microbial interaction is of paramount importance for preventative and therapeutic interventions for vision-threatening conditions. This review article aims to explore the current literature evidence to better comprehend the role of oral pathogens in the etiopathogenesis of ocular diseases, specifically AMD.}, } @article {pmid35590169, year = {2021}, author = {Song, SJ and Wang, J and Martino, C and Jiang, L and Thompson, WK and Shenhav, L and McDonald, D and Marotz, C and Harris, PR and Hernandez, CD and Henderson, N and Ackley, E and Nardella, D and Gillihan, C and Montacuti, V and Schweizer, W and Jay, M and Combellick, J and Sun, H and Garcia-Mantrana, I and Gil Raga, F and Collado, MC and Rivera-Viñas, JI and Campos-Rivera, M and Ruiz-Calderon, JF and Knight, R and Dominguez-Bello, MG}, title = {Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding.}, journal = {Med (New York, N.Y.)}, volume = {2}, number = {8}, pages = {951-964.e5}, pmid = {35590169}, issn = {2666-6340}, support = {DP1 AT010885/AT/NCCIH NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {*Cesarean Section/adverse effects ; Citizenship ; Female ; Humans ; Infant ; Infant, Newborn ; Longitudinal Studies ; *Microbiota/genetics ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.

METHODS: Using 16S rRNA gene sequencing, we followed the microbial trajectories of multiple body sites in 177 babies over the first year of life; 98 were born vaginally, and 79 were born by CS, of whom 30 were swabbed with a maternal vaginal gauze right after birth.

FINDINGS: Compositional tensor factorization analysis confirmed that microbiota trajectories of exposed CS-born babies aligned more closely with that of vaginally born babies. Interestingly, the majority of amplicon sequence variants from maternal vaginal microbiomes on the day of birth were shared with other maternal sites, in contrast to non-pregnant women from the Human Microbiome Project (HMP) study.

CONCLUSIONS: The results of this observational study prompt urgent randomized clinical trials to test whether microbial restoration reduces the increased disease risk associated with CS birth and the underlying mechanisms. It also provides evidence of the pluripotential nature of maternal vaginal fluids to provide pioneer bacterial colonizers for the newborn body sites. This is the first study showing long-term naturalization of the microbiota of CS-born infants by restoring microbial exposure at birth.

FUNDING: C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, Janssen.}, } @article {pmid35579554, year = {2022}, author = {Sim, M and Lee, J and Wy, S and Park, N and Lee, D and Kwon, D and Kim, J}, title = {Generation and application of pseudo-long reads for metagenome assembly.}, journal = {GigaScience}, volume = {11}, number = {}, pages = {}, pmid = {35579554}, issn = {2047-217X}, mesh = {High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenome ; Metagenomics/methods ; *Microbiota/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Metagenomic assembly using high-throughput sequencing data is a powerful method to construct microbial genomes in environmental samples without cultivation. However, metagenomic assembly, especially when only short reads are available, is a complex and challenging task because mixed genomes of multiple microorganisms constitute the metagenome. Although long read sequencing technologies have been developed and have begun to be used for metagenomic assembly, many metagenomic studies have been performed based on short reads because the generation of long reads requires higher sequencing cost than short reads.

RESULTS: In this study, we present a new method called PLR-GEN. It creates pseudo-long reads from metagenomic short reads based on given reference genome sequences by considering small sequence variations existing in individual genomes of the same or different species. When applied to a mock community data set in the Human Microbiome Project, PLR-GEN dramatically extended short reads in length of 101 bp to pseudo-long reads with N50 of 33 Kbp and 0.4% error rate. The use of these pseudo-long reads generated by PLR-GEN resulted in an obvious improvement of metagenomic assembly in terms of the number of sequences, assembly contiguity, and prediction of species and genes.

CONCLUSIONS: PLR-GEN can be used to generate artificial long read sequences without spending extra sequencing cost, thus aiding various studies using metagenomes.}, } @article {pmid35562600, year = {2023}, author = {Greene, LK and McKenney, EA and Gasper, W and Wrampelmeier, C and Hayer, S and Ehmke, EE and Clayton, JB}, title = {Gut Site and Gut Morphology Predict Microbiome Structure and Function in Ecologically Diverse Lemurs.}, journal = {Microbial ecology}, volume = {85}, number = {4}, pages = {1608-1619}, pmid = {35562600}, issn = {1432-184X}, support = {PRFB 1906416//Directorate for Biological Sciences/ ; }, mesh = {Animals ; *Lemur ; Retrospective Studies ; *Lemuridae ; *Microbiota ; *Strepsirhini ; }, abstract = {Most studies of wildlife gut microbiotas understandably rely on feces to approximate consortia along the gastrointestinal tract. We therefore compared microbiome structure and predicted metagenomic function in stomach, small intestinal, cecal, and colonic samples from 52 lemurs harvested during routine necropsies. The lemurs represent seven genera (Cheirogaleus, Daubentonia, Varecia, Hapalemur, Eulemur, Lemur, Propithecus) characterized by diverse feeding ecologies and gut morphologies. In particular, the hosts variably depend on fibrous foodstuffs and show correlative morphological complexity in their large intestines. Across host lineages, microbiome diversity, variability, membership, and function differed between the upper and lower gut, reflecting regional tradeoffs in available nutrients. These patterns related minimally to total gut length but were modulated by fermentation capacity (i.e., the ratio of small to large intestinal length). Irrespective of feeding strategy, host genera with limited fermentation capacity harbored more homogenized microbiome diversity along the gut, whereas those with expanded fermentation capacity harbored cecal and colonic microbiomes with greater diversity and abundant fermentative Ruminococcaceae taxa. While highlighting the value of curated sample repositories for retrospective comparisons, our results confirm that the need to survive on fibrous foods, either routinely or in hypervariable environments, can shape the morphological and microbial features of the lower gut.}, } @article {pmid35536037, year = {2022}, author = {Hu, C and Beyda, ND and Garey, KW}, title = {A Vancomycin HPLC Assay for Use in Gut Microbiome Research.}, journal = {Microbiology spectrum}, volume = {10}, number = {3}, pages = {e0168821}, pmid = {35536037}, issn = {2165-0497}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents ; Chromatography, High Pressure Liquid/methods ; *Gastrointestinal Microbiome ; Humans ; Reproducibility of Results ; *Vancomycin/pharmacokinetics ; }, abstract = {The human microbiome project has revolutionized our understanding of the interaction between commensal microbes and human health. By far, the biggest perturbation of the microbiome involves use of broad-spectrum antibiotics excreted in the gut. Thus, pharmacodynamics of microbiome changes in relation to drug exposure pharmacokinetics is an emerging field. However, reproducibility studies are necessary to develop the field. A simple and fast high-performance liquid chromatography-photodiode array detector (HPLC) method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested based on sample storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. The HPLC method enabled the complete elution of vancomycin within ~4.2 min on the reversed-phase C18 column under the isocratic elution mode, with excellent recovery (85% to 110%) over a 4-log, quantitative range (0.4-100 μg/mL). Relative standard derivations (RSD) of intra-day and inter-day results ranged from 0.4% to 5.4%. Using sample stool aliquots of various weights consistently demonstrated similar vancomycin concentrations (mean RSD: 6%; range: 2-16%). After correcting for water concentrations, vancomycin concentrations obtained after lyophilization were similar to the concentrations obtained from the original samples (RSD less than 10%). These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome. IMPORTANCE Research on antibiotic effect on the gut microbiome is an emerging field with standardization of research methods needed. In this study, a simple and fast high-performance liquid chromatography method was validated for quantitative fecal vancomycin analysis. Reproducibility of results were tested to standardize storage time, homogeneity of antibiotic within stool, and concentration consistency after lyophilization. These methodologies establish sample condition standards for a quantitative HPLC to enable vancomycin pharmacokinetic studies with the human microbiome.}, } @article {pmid35518360, year = {2022}, author = {Gan, R and Zhou, F and Si, Y and Yang, H and Chen, C and Ren, C and Wu, J and Zhang, F}, title = {DBSCAN-SWA: An Integrated Tool for Rapid Prophage Detection and Annotation.}, journal = {Frontiers in genetics}, volume = {13}, number = {}, pages = {885048}, pmid = {35518360}, issn = {1664-8021}, abstract = {As an intracellular form of a bacteriophage in the bacterial host genome, a prophage usually integrates into bacterial DNA with high specificity and contributes to horizontal gene transfer (HGT). With the exponentially increasing number of microbial sequences uncovered in genomic or metagenomics studies, there is a massive demand for a tool that is capable of fast and accurate identification of prophages. Here, we introduce DBSCAN-SWA, a command line software tool developed to predict prophage regions in bacterial genomes. DBSCAN-SWA runs faster than any previous tools. Importantly, it has great detection power based on analysis using 184 manually curated prophages, with a recall of 85% compared with Phage_Finder (63%), VirSorter (74%), and PHASTER (82%) for (Multi-) FASTA sequences. Moreover, DBSCAN-SWA outperforms the existing standalone prophage prediction tools for high-throughput sequencing data based on the analysis of 19,989 contigs of 400 bacterial genomes collected from Human Microbiome Project (HMP) project. DBSCAN-SWA also provides user-friendly result visualizations including a circular prophage viewer and interactive DataTables. DBSCAN-SWA is implemented in Python3 and is available under an open source GPLv2 license from https://github.com/HIT-ImmunologyLab/DBSCAN-SWA/.}, } @article {pmid35429105, year = {2022}, author = {Li, D and Van De Werfhorst, LC and Holden, PA}, title = {Genetic sequence data evidence that human faecal-associated HF183 sequences are on human skin and in urine.}, journal = {Journal of applied microbiology}, volume = {133}, number = {2}, pages = {232-240}, pmid = {35429105}, issn = {1365-2672}, support = {//Mr. Henry (Sam) Wheeler/ ; Proposition 84//the State of California Clean Beach Initiative/ ; }, mesh = {Environmental Monitoring/methods ; Feces ; Genetic Markers ; Humans ; Polymerase Chain Reaction/methods ; RNA, Ribosomal, 16S/genetics ; *Sewage ; *Water Microbiology ; }, abstract = {AIMS: The DNA marker HF183 is a partial 16S rRNA gene sequence highly specific to human-associated Bacteroides including Bacteroides dorei. While HF183 is used to assess human faecal contamination in aquatic environments worldwide, little is known about the existence of HF183 and B. dorei in human microbiomes outside of the human gastrointestinal tract and faeces.

METHODS AND RESULTS: Previously published human skin and urine microbiome data sets from five independent human body skin studies, the Human Microbiome Project (HMP) and three independent human urine studies were analysed. The HF183 gene sequence was detected in all skin data sets, with the ratios of positive samples ranging from 0.5% to 36.3%. Popliteal fossa (knee), volar forearm and inguinal (groin) creases were identified as hot spots. HF183 was detected in two of three urine data sets, with ratios of positive samples ranging from 0% to 37.5%. All HF183-containing sequences from these data sets were classified as associated with B. dorei.

CONCLUSIONS: HF183 is widespread on human skin and present in urine.

Skin and urine microbiomes could be sources of HF183 to environmental waters. Such non-faecal sources of HF183 might explain low concentrations of HF183 in recreational waters when swimmers are present.}, } @article {pmid35369727, year = {2022}, author = {Zhu, Q and Huang, S and Gonzalez, A and McGrath, I and McDonald, D and Haiminen, N and Armstrong, G and Vázquez-Baeza, Y and Yu, J and Kuczynski, J and Sepich-Poore, GD and Swafford, AD and Das, P and Shaffer, JP and Lejzerowicz, F and Belda-Ferre, P and Havulinna, AS and Méric, G and Niiranen, T and Lahti, L and Salomaa, V and Kim, HC and Jain, M and Inouye, M and Gilbert, JA and Knight, R}, title = {Phylogeny-Aware Analysis of Metagenome Community Ecology Based on Matched Reference Genomes while Bypassing Taxonomy.}, journal = {mSystems}, volume = {7}, number = {2}, pages = {e0016722}, pmid = {35369727}, issn = {2379-5077}, support = {RG/13/13/30194/BHF_/British Heart Foundation/United Kingdom ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; U24 CA248454/CA/NCI NIH HHS/United States ; RG/18/13/33946/BHF_/British Heart Foundation/United Kingdom ; CH/12/2/29428/BHF_/British Heart Foundation/United Kingdom ; K12 GM068524/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Phylogeny ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; *Microbiota ; Ecology ; }, abstract = {We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification, which is limited in feature resolution. To solve these challenges, we introduce operational genomic units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition and (ii) permitting use of phylogeny-aware tools. Our analysis of real-world data sets shows that it is advantageous over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGUs as an effective practice in metagenomic studies.}, } @article {pmid35314781, year = {2022}, author = {Yu, JSL and Correia-Melo, C and Zorrilla, F and Herrera-Dominguez, L and Wu, MY and Hartl, J and Campbell, K and Blasche, S and Kreidl, M and Egger, AS and Messner, CB and Demichev, V and Freiwald, A and Mülleder, M and Howell, M and Berman, J and Patil, KR and Alam, MT and Ralser, M}, title = {Microbial communities form rich extracellular metabolomes that foster metabolic interactions and promote drug tolerance.}, journal = {Nature microbiology}, volume = {7}, number = {4}, pages = {542-555}, pmid = {35314781}, issn = {2058-5276}, support = {FC001134/ARC_/Arthritis Research UK/United Kingdom ; MC_UU_00025/11/MRC_/Medical Research Council/United Kingdom ; FC001134/CRUK_/Cancer Research UK/United Kingdom ; FC001134/WT_/Wellcome Trust/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; 200829/Z/16/Z/WT_/Wellcome Trust/United Kingdom ; FC001134/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Drug Tolerance ; Metabolic Networks and Pathways ; Metabolome ; *Microbial Interactions ; *Microbiota ; }, abstract = {Microbial communities are composed of cells of varying metabolic capacity, and regularly include auxotrophs that lack essential metabolic pathways. Through analysis of auxotrophs for amino acid biosynthesis pathways in microbiome data derived from >12,000 natural microbial communities obtained as part of the Earth Microbiome Project (EMP), and study of auxotrophic-prototrophic interactions in self-establishing metabolically cooperating yeast communities (SeMeCos), we reveal a metabolically imprinted mechanism that links the presence of auxotrophs to an increase in metabolic interactions and gains in antimicrobial drug tolerance. As a consequence of the metabolic adaptations necessary to uptake specific metabolites, auxotrophs obtain altered metabolic flux distributions, export more metabolites and, in this way, enrich community environments in metabolites. Moreover, increased efflux activities reduce intracellular drug concentrations, allowing cells to grow in the presence of drug levels above minimal inhibitory concentrations. For example, we show that the antifungal action of azoles is greatly diminished in yeast cells that uptake metabolites from a metabolically enriched environment. Our results hence provide a mechanism that explains why cells are more robust to drug exposure when they interact metabolically.}, } @article {pmid35301322, year = {2022}, author = {Sharma, AK and Davison, S and Pafco, B and Clayton, JB and Rothman, JM and McLennan, MR and Cibot, M and Fuh, T and Vodicka, R and Robinson, CJ and Petrzelkova, K and Gomez, A}, title = {The primate gut mycobiome-bacteriome interface is impacted by environmental and subsistence factors.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {12}, pmid = {35301322}, issn = {2055-5008}, mesh = {Animals ; Bacteria/genetics ; *Gastrointestinal Microbiome ; *Mycobiome ; Phylogeny ; Primates ; }, abstract = {The gut microbiome of primates is known to be influenced by both host genetic background and subsistence strategy. However, these inferences have been made mainly based on adaptations in bacterial composition - the bacteriome and have commonly overlooked the fungal fraction - the mycobiome. To further understand the factors that shape the gut mycobiome of primates and mycobiome-bacteriome interactions, we sequenced 16 S rRNA and ITS2 markers in fecal samples of four different nonhuman primate species and three human groups under different subsistence patterns (n = 149). The results show that gut mycobiome composition in primates is still largely unknown but highly plastic and weakly structured by primate phylogeny, compared with the bacteriome. We find significant gut mycobiome overlap between captive apes and human populations living under industrialized subsistence contexts; this is in contrast with contemporary hunter-gatherers and agriculturalists, who share more mycobiome traits with diverse wild-ranging nonhuman primates. In addition, mycobiome-bacteriome interactions were specific to each population, revealing that individual, lifestyle and intrinsic ecological factors affect structural correspondence, number, and kind of interactions between gut bacteria and fungi in primates. Our findings indicate a dominant effect of ecological niche, environmental factors, and diet over the phylogenetic background of the host, in shaping gut mycobiome composition and mycobiome-bacteriome interactions in primates.}, } @article {pmid35273317, year = {2022}, author = {Sisti, D and Pazienza, V and Piccini, F and Citterio, B and Baffone, W and Donati Zeppa, S and Biavasco, F and Prospero, E and De Luca, A and Artico, M and Taurone, S and Minelli, A and Perri, F and Binda, E and Pracella, R and Santolini, R and Amatori, S and Sestili, P and Rocchi, MBL and Gobbi, P}, title = {A proposal for the reference intervals of the Italian microbiota "scaffold" in healthy adults.}, journal = {Scientific reports}, volume = {12}, number = {1}, pages = {3952}, pmid = {35273317}, issn = {2045-2322}, mesh = {Adult ; Feces/microbiology ; Feeding Behavior ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Numerous factors, ranging from genetics, age, lifestyle, and dietary habits to local environments, contribute to the heterogeneity of the microbiota in humans. Understanding the variability of a "healthy microbiota" is a major challenge in scientific research. The gut microbiota profiles of 148 healthy Italian volunteers were examined by 16S rRNA gene sequencing to determine the range and diversity of taxonomic compositions in the gut microbiota of healthy populations. Possible driving factors were evaluated through a detailed anamnestic questionnaire. Microbiota reference intervals were also calculated. A "scaffold" of a healthy Italian gut microbiota composition was identified. Differences in relative quantitative ratios of microbiota composition were detected in two clusters: a bigger cluster (C2), which included 124 subjects, was characterized by more people from the northern Italian regions, who habitually practised more physical activity and with fewer dietary restrictions. Species richness and diversity were significantly higher in this cluster (C2) than in the other one (C1) (C1: 146.67 ± 43.67; C2: 198.17 ± 48.47; F = 23.40; P < 0.001 and C1: 16.88 ± 8.66; C2: 35.01 ± 13.40; F = 40.50; P < 0.001, respectively). The main contribution of the present study was the identification of the existence of a primary healthy microbiological framework that is only marginally affected by variations. Taken together, our data help to contextualize studies on population-specific variations, including marginal aspects, in human microbiota composition. Such variations must be related to the primary framework of a healthy microbiota and providing this perspective could help scientists to better design experimental plans and develop strategies for precision tailored microbiota modulation.}, } @article {pmid35273169, year = {2022}, author = {Cai, YY and Huang, FQ and Lao, X and Lu, Y and Gao, X and Alolga, RN and Yin, K and Zhou, X and Wang, Y and Liu, B and Shang, J and Qi, LW and Li, J}, title = {Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis.}, journal = {NPJ biofilms and microbiomes}, volume = {8}, number = {1}, pages = {11}, pmid = {35273169}, issn = {2055-5008}, mesh = {Animals ; *Atherosclerosis ; Choline ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Methylamines ; Mice ; }, abstract = {Microbial trimethylamine (TMA)-lyase activity promotes the development of atherosclerosis by generating of TMA, the precursor of TMA N-oxide (TMAO). TMAO is well documented, but same can not be said of TMA-producing bacteria. This work aimed to identify TMA-producing genera in human intestinal microbiota. We retrieved the genomes of human-associated microorganisms from the Human Microbiome Project database comprising 1751 genomes, Unified Human Gastrointestinal Genome collection consisting 4644 gut prokaryotes, recapitulated 4930 species-level genome bins and public gut metagenomic data of 2134 individuals from 11 populations. By sequence searching, 216 TMA-lyase-containing species from 102 genera were found to contain the homologous sequences of cntA/B, yeaW/X, and/or cutC/D. We identified 13 strains from 5 genera with cntA sequences, and 30 strains from 14 genera with cutC showing detectable relative abundance in healthy individuals. Lachnoclostridium (p = 2.9e-05) and Clostridium (p = 5.8e-04), the two most abundant cutC-containing genera, were found to be much higher in atherosclerotic patients compared with healthy persons. Upon incubation with choline (substrate), L. saccharolyticum effectively transformed it to TMA at a rate higher than 98.7% while that for C. sporogenes was 63.8-67.5% as detected by liquid chromatography-triple quadrupole mass spectrometry. In vivo studies further showed that treatment of L. saccharolyticum and choline promoted a significant increase in TMAO level in the serum of ApoE[-/-] mice with obvious accumulation of aortic plaque in same. This study discloses the significance and efficiency of the gut bacterium L. saccharolyticum in transforming choline to TMA and consequently promoting the development of atherosclerosis.}, } @article {pmid35272051, year = {2022}, author = {Zhou, F and Gan, R and Zhang, F and Ren, C and Yu, L and Si, Y and Huang, Z}, title = {PHISDetector: A Tool to Detect Diverse In Silico Phage-host Interaction Signals for Virome Studies.}, journal = {Genomics, proteomics & bioinformatics}, volume = {20}, number = {3}, pages = {508-523}, pmid = {35272051}, issn = {2210-3244}, mesh = {Humans ; *Bacteriophages/genetics ; Virome ; Prophages/genetics ; Bacteria/genetics ; *Microbiota ; }, abstract = {Phage-microbe interactions are appealing systems to study coevolution, and have also been increasingly emphasized due to their roles in human health, disease, and the development of novel therapeutics. Phage-microbe interactions leave diverse signals in bacterial and phage genomic sequences, defined as phage-host interaction signals (PHISs), which include clustered regularly interspaced short palindromic repeats (CRISPR) targeting, prophage, and protein-protein interaction signals. In the present study, we developed a novel tool phage-host interaction signal detector (PHISDetector) to predict phage-host interactions by detecting and integrating diverse in silico PHISs, and scoring the probability of phage-host interactions using machine learning models based on PHIS features. We evaluated the performance of PHISDetector on multiple benchmark datasets and application cases. When tested on a dataset of 758 annotated phage-host pairs, PHISDetector yields the prediction accuracies of 0.51 and 0.73 at the species and genus levels, respectively, outperforming other phage-host prediction tools. When applied to on 125,842 metagenomic viral contigs (mVCs) derived from 3042 geographically diverse samples, a detection rate of 54.54% could be achieved. Furthermore, PHISDetector could predict infecting phages for 85.6% of 368 multidrug-resistant (MDR) bacteria and 30% of 454 human gut bacteria obtained from the National Institutes of Health (NIH) Human Microbiome Project (HMP). The PHISDetector can be run either as a web server (http://www.microbiome-bigdata.com/PHISDetector/) for general users to study individual inputs or as a stand-alone version (https://github.com/HIT-ImmunologyLab/PHISDetector) to process massive phage contigs from virome studies.}, } @article {pmid35181661, year = {2022}, author = {Johansen, J and Plichta, DR and Nissen, JN and Jespersen, ML and Shah, SA and Deng, L and Stokholm, J and Bisgaard, H and Nielsen, DS and Sørensen, SJ and Rasmussen, S}, title = {Genome binning of viral entities from bulk metagenomics data.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {965}, pmid = {35181661}, issn = {2041-1723}, mesh = {Bacteriophages/*classification/genetics ; Gastrointestinal Microbiome/*genetics/physiology ; Gastrointestinal Tract/*virology ; Genome, Viral/genetics ; Humans ; Metagenome/*genetics ; Metagenomics ; Virome/*genetics/physiology ; }, abstract = {Despite the accelerating number of uncultivated virus sequences discovered in metagenomics and their apparent importance for health and disease, the human gut virome and its interactions with bacteria in the gastrointestinal tract are not well understood. This is partly due to a paucity of whole-virome datasets and limitations in current approaches for identifying viral sequences in metagenomics data. Here, combining a deep-learning based metagenomics binning algorithm with paired metagenome and metavirome datasets, we develop Phages from Metagenomics Binning (PHAMB), an approach that allows the binning of thousands of viral genomes directly from bulk metagenomics data, while simultaneously enabling clustering of viral genomes into accurate taxonomic viral populations. When applied on the Human Microbiome Project 2 (HMP2) dataset, PHAMB recovered 6,077 high-quality genomes from 1,024 viral populations, and identified viral-microbial host interactions. PHAMB can be advantageously applied to existing and future metagenomes to illuminate viral ecological dynamics with other microbiome constituents.}, } @article {pmid35178373, year = {2021}, author = {Zhang, R and Sun, J and Wang, C and Wang, X and Zhao, P and Yuan, Y and Ai, H and Zhou, Q}, title = {The Racial Disparities in the Epidemic of Metabolic Syndrome With Increased Age: A Study From 28,049 Chinese and American Adults.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {797183}, pmid = {35178373}, issn = {2296-2565}, mesh = {Adult ; Black or African American ; Cholesterol ; Cross-Sectional Studies ; Humans ; *Metabolic Syndrome/diagnosis/epidemiology ; Middle Aged ; Nutrition Surveys ; Obesity ; Obesity, Abdominal/diagnosis/epidemiology ; Triglycerides ; United States/epidemiology ; }, abstract = {BACKGROUND: Previous studies have revealed ethnic disparities in the prevalence of metabolic syndrome (MetS); however, the literature regarding aging-related patterns of disparities in MetS and its components remains limited.

METHODS: This cross-sectional study recruited 28,049 subjects, consisting of one Chinese race and three American races, 18-85 years of age, from the National Health and Nutrition Examination Survey (NHANES, 1999-2018) of the United States, and the Guangdong Gut Microbiome Project (GGMP, 2018) of China. MetS was defined in accordance with the National Cholesterol Education Program Adult Treatment Panel III. A modified sliding-window-based algorithm was used to depict the trajectories of the prevalence of MetS with increased age. Logistic regression analysis was performed to investigate associations between MetS and its components.

RESULTS: The prevalence of MetS increased non-linearly with age, with growth speed reaching its maximum at approximately 40-50 years. Chinese subjects exhibited a lower prevalence of MetS than non-Hispanic whites, non-Hispanic blacks, and Mexican Americans in all age groups. The two most prevalent components in Chinese subjects were reduced high-density lipoprotein cholesterol levels (42.0%) and elevated blood pressure (49.5%), and elevated triglyceride levels (36.3-49.5%) and abdominal obesity (55.8-55.9%) in Americans. Before 40 years of age, the top two MetS-associated components were abdominal obesity and elevated triglyceride levels in all races, while after 40 years, the prominent associations between MetS and its components varied among the different races and age groups.

CONCLUSIONS: Although racial disparities in the epidemic of MetS varied with increased age, abdominal obesity and elevated triglyceride levels were the top two MetS-associated components in all younger adults of different races.}, } @article {pmid35176353, year = {2022}, author = {Mandal, S and Bandyopadhyay, S and Tyagi, K and Roy, A}, title = {Human microbial dysbiosis as driver of gynecological malignancies.}, journal = {Biochimie}, volume = {197}, number = {}, pages = {86-95}, doi = {10.1016/j.biochi.2022.02.005}, pmid = {35176353}, issn = {1638-6183}, mesh = {Biomarkers ; Dysbiosis/microbiology ; Female ; *Genital Neoplasms, Female ; Humans ; Lactobacillus ; *Microbiota ; }, abstract = {Gynecological cancers that affect female reproductive tract, remain at the top of the global cancer burden list with high relapse rate and mortality. Notwithstanding development of several novel therapeutic interventions including poly-ADP-ribose polymerase inhibitors, this family of malignancies remain deadly. The human microbiome project demonstrated that dysbiosis of health resident microflora is associated with several pathologies including malignancies of the female reproductive tract and detailed characterization of species variation and host-microbe interaction could provide clues for identification of early diagnostic biomarker, preventive and therapeutic interventions. Emerging evidence suggests that several microbial signatures are significantly associated with gynecological cancers. An increased population of Proteobacteria and Firmicutes followed by significantly reduced Lactobacilli are associated with lethal epithelial ovarian cancer. Similarly, a constant association of elevated level of Atopobium vaginae, Porphyromonas somerae, Micrococci and Gardnerella vaginalis are observed in endometrial and cervical cancers. Moreover, human papilloma virus infection significantly augments colonization of pathogenic microbes including Sneathia sanguinegens, Anaerococcus tetradius, and Peptostreptococcus anaerobius and drives carcinoma of the cervix. Interestingly, microbial dysbiosis in female reproductive tract modulates expression of several microbial and immune-responsive genes such as TLR-4, TLR-5, TLR-6 and NOD-1. Therefore, stringent investigation into the microbial dysbiosis and its underlying mechanism could provide valuable cues for identification of early diagnostic biomarker, preventive and therapeutic interventions against rogue gynecological malignancies.}, } @article {pmid35115690, year = {2022}, author = {Lopera-Maya, EA and Kurilshikov, A and van der Graaf, A and Hu, S and Andreu-Sánchez, S and Chen, L and Vila, AV and Gacesa, R and Sinha, T and Collij, V and Klaassen, MAY and Bolte, LA and Gois, MFB and Neerincx, PBT and Swertz, MA and , and Harmsen, HJM and Wijmenga, C and Fu, J and Weersma, RK and Zhernakova, A and Sanna, S}, title = {Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project.}, journal = {Nature genetics}, volume = {54}, number = {2}, pages = {143-151}, pmid = {35115690}, issn = {1546-1718}, mesh = {ABO Blood-Group System/*genetics ; *Bacterial Physiological Phenomena ; Bifidobacterium/physiology ; Diet ; Fucosyltransferases/genetics ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; *Genetic Variation ; Genome, Human ; Genome-Wide Association Study ; *Host Microbial Interactions ; Humans ; Lactase/*genetics ; Metabolic Networks and Pathways ; Metagenome ; Multifactorial Inheritance ; Netherlands ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Sodium Chloride, Dietary ; Triglycerides/blood ; Galactoside 2-alpha-L-fucosyltransferase ; }, abstract = {Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10[-10]) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10[-8]) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.}, } @article {pmid37938691, year = {2022}, author = {Jorge, F and Brealey, JC and Brindley, PJ and Buysse, M and Cantacessi, C and Duron, O and Fichorova, R and Fitzpatrick, CR and Hahn, M and Hunter, C and Hervé, V and Knoll, LJ and Kohl, KD and Lalle, M and Lukeš, J and Martínez, JM and Perkins, SL and Poulin, R and Rosario, K and Schneider, AC and Schriml, LM and Thompson, LR and Walls, RL and Dheilly, NM}, title = {MIxS-SA: a MIxS extension defining the minimum information standard for sequence data from symbiont-associated micro-organisms.}, journal = {ISME communications}, volume = {2}, number = {1}, pages = {9}, pmid = {37938691}, issn = {2730-6151}, support = {R01 AI144016/AI/NIAID NIH HHS/United States ; R01 CA164719/CA/NCI NIH HHS/United States ; }, abstract = {The symbiont-associated (SA) environmental package is a new extension to the minimum information about any (x) sequence (MIxS) standards, established by the Parasite Microbiome Project (PMP) consortium, in collaboration with the Genomics Standard Consortium. The SA was built upon the host-associated MIxS standard, but reflects the nestedness of symbiont-associated microbiota within and across host-symbiont-microbe interactions. This package is designed to facilitate the collection and reporting of a broad range of metadata information that apply to symbionts such as life history traits, association with one or multiple host organisms, or the nature of host-symbiont interactions along the mutualism-parasitism continuum. To better reflect the inherent nestedness of all biological systems, we present a novel feature that allows users to co-localize samples, to nest a package within another package, and to identify replicates. Adoption of the MIxS-SA and of the new terms will facilitate reports of complex sampling design from a myriad of environments.}, } @article {pmid35091681, year = {2022}, author = {Saliba, J and Coutaud, B and Makhani, K and Epstein Roth, N and Jackson, J and Park, JY and Gagnon, N and Costa, P and Jeyakumar, T and Bury, M and Beauchemin, N and Mann, KK and Blank, V}, title = {Loss of NFE2L3 protects against inflammation-induced colorectal cancer through modulation of the tumor microenvironment.}, journal = {Oncogene}, volume = {41}, number = {11}, pages = {1563-1575}, pmid = {35091681}, issn = {1476-5594}, support = {MOP-97932//CIHR/Canada ; PJT-152937//CIHR/Canada ; }, mesh = {Animals ; Basic-Leucine Zipper Transcription Factors/metabolism ; *Colorectal Neoplasms/genetics ; Forkhead Transcription Factors ; Humans ; Inflammation/genetics ; Interleukin-33 ; Mice ; T-Lymphocytes, Regulatory ; *Tumor Microenvironment/genetics ; }, abstract = {We investigated the role of the NFE2L3 transcription factor in inflammation-induced colorectal cancer. Our studies revealed that Nfe2l3[-/-] mice exhibit significantly less inflammation in the colon, reduced tumor size and numbers, and skewed localization of tumors with a more pronounced decrease of tumors in the distal colon. CIBERSORT analysis of RNA-seq data from normal and tumor tissue predicted a reduction in mast cells in Nfe2l3[-/-] animals, which was confirmed by toluidine blue staining. Concomitantly, the transcript levels of Il33 and Rab27a, both important regulators of mast cells, were reduced and increased, respectively, in the colorectal tumors of Nfe2l3[-/-] mice. Furthermore, we validated NFE2L3 binding to the regulatory sequences of the IL33 and RAB27A loci in human colorectal carcinoma cells. Using digital spatial profiling, we found that Nfe2l3[-/-] mice presented elevated FOXP3 and immune checkpoint markers CTLA4, TIM3, and LAG3, suggesting an increase in Treg counts. Staining for CD3 and FOXP3 confirmed a significant increase in immunosuppressive Tregs in the colon of Nfe2l3[-/-] animals. Also, Human Microbiome Project (HMP2) data showed that NFE2L3 transcript levels are higher in the rectum of ulcerative colitis patients. The observed changes in the tumor microenvironment provide new insights into the molecular differences regarding colon cancer sidedness. This may be exploited for the treatment of early-onset colorectal cancer as this emerging subtype primarily displays distal/left-sided tumors.}, } @article {pmid35078284, year = {2022}, author = {Su, Z and Jia, X and Fan, Y and Zhao, F and Qiao, Y}, title = {[Progress of Research on the Relationship between Lung Microbiome and Lung Cancer].}, journal = {Zhongguo fei ai za zhi = Chinese journal of lung cancer}, volume = {25}, number = {1}, pages = {40-45}, pmid = {35078284}, issn = {1999-6187}, mesh = {Humans ; Lung ; Lung Diseases ; *Lung Neoplasms ; *Microbiota ; Oncogenes ; }, abstract = {The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research. .}, } @article {pmid35058973, year = {2021}, author = {Liu, B and Huang, L and Liu, Z and Pan, X and Cui, Z and Pan, J and Xie, L}, title = {EasyMicroPlot: An Efficient and Convenient R Package in Microbiome Downstream Analysis and Visualization for Clinical Study.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {803627}, pmid = {35058973}, issn = {1664-8021}, abstract = {Advances in next-generation sequencing (NGS) have revolutionized microbial studies in many fields, especially in clinical investigation. As the second human genome, microbiota has been recognized as a new approach and perspective to understand the biological and pathologic basis of various diseases. However, massive amounts of sequencing data remain a huge challenge to researchers, especially those who are unfamiliar with microbial data analysis. The mathematic algorithm and approaches introduced from another scientific field will bring a bewildering array of computational tools and acquire higher quality of script experience. Moreover, a large cohort research together with extensive meta-data including age, body mass index (BMI), gender, medical results, and others related to subjects also aggravate this situation. Thus, it is necessary to develop an efficient and convenient software for clinical microbiome data analysis. EasyMicroPlot (EMP) package aims to provide an easy-to-use microbial analysis tool based on R platform that accomplishes the core tasks of metagenomic downstream analysis, specially designed by incorporation of popular microbial analysis and visualization used in clinical microbial studies. To illustrate how EMP works, 694 bio-samples from Guangdong Gut Microbiome Project (GGMP) were selected and analyzed with EMP package. Our analysis demonstrated the influence of dietary style on gut microbiota and proved EMP package's powerful ability and excellent convenience to address problems for this field.}, } @article {pmid35054168, year = {2021}, author = {Gouello, A and Dunyach-Remy, C and Siatka, C and Lavigne, JP}, title = {Analysis of Microbial Communities: An Emerging Tool in Forensic Sciences.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {12}, number = {1}, pages = {}, pmid = {35054168}, issn = {2075-4418}, abstract = {The objective of forensic sciences is to find clues in a crime scene in order to reconstruct the scenario. Classical samples include DNA or fingerprints, but both have inherent limitations and can be uninformative. Another type of sample has emerged recently in the form of the microbiome. Supported by the Human Microbiome Project, the characteristics of the microbial communities provide real potential in forensics. They are highly specific and can be used to differentiate and classify the originating body site of a human biological trace. Skin microbiota is also highly specific and different between individuals, leading to its possibility as an identification tool. By extension, the possibilities of the microbial communities to be deposited on everyday objects has also been explored. Other uses include the determination of the post-mortem interval or the analysis of soil communities. One challenge is that the microbiome changes over time and can be influenced by many environmental and lifestyle factors. This review offers an overview of the main methods and applications to demonstrate the benefit of the microbiome to provide forensically relevant information.}, } @article {pmid35008909, year = {2022}, author = {Popkov, VA and Zharikova, AA and Demchenko, EA and Andrianova, NV and Zorov, DB and Plotnikov, EY}, title = {Gut Microbiota as a Source of Uremic Toxins.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, pmid = {35008909}, issn = {1422-0067}, support = {21-75-30009//Russian Science Foundation/ ; }, mesh = {Animals ; Bacteria/metabolism ; Cluster Analysis ; Enzymes/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metadata ; RNA, Messenger/genetics/metabolism ; Uremic Toxins/*metabolism ; }, abstract = {Uremic retention solutes are the compounds that accumulate in the blood when kidney excretory function is impaired. Some of these compounds are toxic at high concentrations and are usually known as "uremic toxins". The cumulative detrimental effect of uremic toxins results in numerous health problems and eventually mortality during acute or chronic uremia, especially in end-stage renal disease. More than 100 different solutes increase during uremia; however, the exact origin for most of them is still debatable. There are three main sources for such compounds: exogenous ones are consumed with food, whereas endogenous ones are produced by the host metabolism or by symbiotic microbiota metabolism. In this article, we identify uremic retention solutes presumably of gut microbiota origin. We used database analysis to obtain data on the enzymatic reactions in bacteria and human organisms that potentially yield uremic retention solutes and hence to determine what toxins could be synthesized in bacteria residing in the human gut. We selected biochemical pathways resulting in uremic retention solutes synthesis related to specific bacterial strains and revealed links between toxin concentration in uremia and the proportion of different bacteria species which can synthesize the toxin. The detected bacterial species essential for the synthesis of uremic retention solutes were then verified using the Human Microbiome Project database. Moreover, we defined the relative abundance of human toxin-generating enzymes as well as the possibility of the synthesis of a particular toxin by the human metabolism. Our study presents a novel bioinformatics approach for the elucidation of the origin of both uremic retention solutes and uremic toxins and for searching for the most likely human microbiome producers of toxins that can be targeted and used for the therapy of adverse consequences of uremia.}, } @article {pmid34988495, year = {2021}, author = {Stanislawski, MA and Stamper, CE and Stearns-Yoder, KA and Hoisington, AJ and Brostow, DP and Forster, JE and Postolache, TT and Lowry, CA and Brenner, LA}, title = {Characterization of the gut microbiota among Veterans with unique military-related exposures and high prevalence of chronic health conditions: A United States-Veteran Microbiome Project (US-VMP) study.}, journal = {Brain, behavior, & immunity - health}, volume = {18}, number = {}, pages = {100346}, pmid = {34988495}, issn = {2666-3546}, abstract = {The gut microbiome is impacted by environmental exposures and has been implicated in many physical and mental health conditions, including anxiety disorders, affective disorders, and trauma- and stressor-related disorders such as posttraumatic stress disorder (PTSD). United States (US) military Veterans are a unique population in that their military-related exposures can have consequences for both physical and mental health, but the gut microbiome of this population has been understudied. In this publication, we describe exposures, health conditions, and medication use of Veterans in the US Veteran Microbiome Project (US-VMP) and examine the associations between these characteristics and the gut microbiota. This cohort included 331 US Veterans seeking healthcare with the Veterans Health Administration who were 83% male with an average (±SD) age of 47.6 ± 13.4 years. The cohort displayed a high prevalence of PTSD (49.8%) and history of traumatic brain injuries (76.1%), and high current use of prescription medications (74.9%) to treat various acute and chronic conditions. We observed significant associations between the gut microbiota composition and gastroenteritis, peripheral vascular disease (PVD), bipolar disorders, symptoms of severe depression based on the Beck Depression Inventory, stimulant and opioid use disorders, beta-blockers, serotonin and norepinephrine reuptake inhibitor antidepressants, diabetes medications, and proton pump inhibitors. Many of the Veteran characteristics examined were associated with altered relative abundances of specific taxa. We found that PVD and cardiovascular disease were associated with lower microbiota diversity in the gut (i.e., α-diversity), while supplemental vitamin use was associated with higher α-diversity. Our study contributes novel insights as to whether the unique exposures of Veterans in this cohort correlate with gut microbiota characteristics and, in line with previous findings with other population-level studies of the microbiome, confirms associations between numerous health conditions and medications with the gut microbiome.}, } @article {pmid34963427, year = {2022}, author = {Fromentin, M and Bridier-Nahmias, A and Legoff, J and Mercier-Delarue, S and Ranger, N and Vuillard, C and Do Vale, J and Zucman, N and Alberdi, A and Ricard, JD and Roux, D}, title = {The 16S rRNA lung microbiome in mechanically ventilated patients: a methodological study.}, journal = {Experimental lung research}, volume = {48}, number = {1}, pages = {23-34}, doi = {10.1080/01902148.2021.2021327}, pmid = {34963427}, issn = {1521-0499}, mesh = {Bacteria/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; *Respiration, Artificial/adverse effects ; }, abstract = {Characterization of the respiratory tract bacterial microbiome is in its infancy when compared to the gut microbiota. To limit bias mandates a robust methodology. Specific amplification of the hypervariable (V) region of the 16SrRNA gene is a crucial step. Differences in accuracy exist for one V region to another depending on the sampled environment. We aimed to assess the impact of the primer sequences targeting the V4 region currently used for gut microbiota studies in respiratory samples. Materials and methods: The original 515 F-806R primer pair targets the V4 region of the 16SrRNA gene. We compared two different 515 F-806R primer pairs before Illumina 250 paired-end sequencing for bacterial microbiome analyses of respiratory samples from critically-ill ventilated patients. "S-V4" for "Stringent V4" primer pair is used in two ongoing international projects "the Integrative Human microbiome project (iHMP)" and "the Earth microbiome project (EMP)." "R-V4" for "Relaxed V4" primer pair has been modified to reduce biases against specific environmental taxa. The optimal method was determined by concordance with conventional microbiology. Results: Twenty samples from three patients who developed a ventilator-associated pneumonia (VAP) and four who did not (control ventilated patients) were sequenced. Highly different results were obtained. "S-V4" provided the best agreement with the conventional microbiology for endotracheal aspirate: 89% as compared to 56% for "R-V4." The main difference related to poor Enterobacteriaceae detection with "R-V4" primers. Conclusions: Accuracy of the bacterial lung microbiome composition was highly dependent on the primers used for amplification of the 16 s rRNA hypervariable sequence. This work validates for future lung microbiome studies the use of the 515 F-806R "S-V4" primer pair associated to Illumina® MiSeq paired-end sequencing.}, } @article {pmid34944176, year = {2021}, author = {Eschweiler, K and Clayton, JB and Moresco, A and McKenney, EA and Minter, LJ and Suhr Van Haute, MJ and Gasper, W and Hayer, SS and Zhu, L and Cooper, K and Ange-van Heugten, K}, title = {Host Identity and Geographic Location Significantly Affect Gastrointestinal Microbial Richness and Diversity in Western Lowland Gorillas (Gorilla gorilla gorilla) under Human Care.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {12}, pages = {}, pmid = {34944176}, issn = {2076-2615}, abstract = {The last few decades have seen an outpouring of gastrointestinal (GI) microbiome studies across diverse host species. Studies have ranged from assessments of GI microbial richness and diversity to classification of novel microbial lineages. Assessments of the "normal" state of the GI microbiome composition across multiple host species has gained increasing importance for distinguishing healthy versus diseased states. This study aimed to determine baselines and trends over time to establish "typical" patterns of GI microbial richness and diversity, as well as inter-individual variation, in three populations of western lowland gorillas (Gorilla gorilla gorilla) under human care at three zoological institutions in North America. Fecal samples were collected from 19 western lowland gorillas every two weeks for seven months (n = 248). Host identity and host institution significantly affected GI microbiome community composition (p < 0.05), although host identity had the most consistent and significant effect on richness (p = 0.03) and Shannon diversity (p = 0.004) across institutions. Significant changes in microbial abundance over time were observed only at Denver Zoo (p < 0.05). Our results suggest that individuality contributes to most of the observed GI microbiome variation in the study populations. Our results also showed no significant changes in any individual's microbial richness or Shannon diversity during the 7-month study period. While some microbial taxa (Prevotella, Prevotellaceae and Ruminococcaceae) were detected in all gorillas at varying levels, determining individual baselines for microbial composition comparisons may be the most useful diagnostic tool for optimizing non-human primate health under human care.}, } @article {pmid34940122, year = {2021}, author = {Ghannoum, MA and McCormick, TS and Retuerto, M and Bebek, G and Cousineau, S and Hartman, L and Barth, C and Schrom, K}, title = {Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic.}, journal = {Current issues in molecular biology}, volume = {43}, number = {3}, pages = {2135-2146}, pmid = {34940122}, issn = {1467-3045}, support = {R01 AI145289/AI/NIAID NIH HHS/United States ; AI145289//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Candida albicans ; Dysbiosis/*microbiology ; Healthy Volunteers ; Humans ; Metagenomics/methods ; Microbial Interactions ; *Microbiota ; Mycobiome ; Probiotics/*administration & dosage ; RNA, Ribosomal, 16S ; }, abstract = {Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial-fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.}, } @article {pmid34928256, year = {2022}, author = {Verstraelen, H and Vieira-Baptista, P and De Seta, F and Ventolini, G and Lonnee-Hoffmann, R and Lev-Sagie, A}, title = {The Vaginal Microbiome: I. Research Development, Lexicon, Defining "Normal" and the Dynamics Throughout Women's Lives.}, journal = {Journal of lower genital tract disease}, volume = {26}, number = {1}, pages = {73-78}, pmid = {34928256}, issn = {1526-0976}, mesh = {Adolescent ; Bacteria ; Female ; Humans ; Infant, Newborn ; Menopause ; *Microbiota ; Research ; Vagina ; }, abstract = {OBJECTIVE: This series of articles, titled The Vaginal Microbiome, written on behalf of the International Society for the Study of Vulvovaginal Disease, aims to summarize the current findings and understanding of the vaginal bacterial microbiota, mainly regarding areas relevant to clinicians specializing in vulvovaginal disorders.

MATERIALS AND METHODS: A database search of PubMed was performed, using the search terms "vaginal microbiome" (VMB) with "research," "normal," "neonate," "puberty," "adolescent," "menopause," and "ethnicities," as well as "human microbiome project." Full article texts were reviewed. Reference lists were screened for additional articles.

RESULTS: In the last 2 decades, many studies applying molecular techniques were performed, intending to characterize the vaginal microbiota. These studies advanced our understanding of how vaginal health is defined. The first article in this series focuses on the advancement of VMB research, technical definitions, the definition of "normal" VMB, and the dynamics of VMB throughout women's lives.

CONCLUSIONS: Understanding how microorganisms inhabiting the vagina interact with each other and with the host is important for a more complete understanding of vaginal health. The clinical application of microbial community sequencing is in its beginning, and its interpretation regarding practical clinical aspects is yet to be determined.}, } @article {pmid34880965, year = {2022}, author = {Barb, JJ and Maki, KA and Kazmi, N and Meeks, BK and Krumlauf, M and Tuason, RT and Brooks, AT and Ames, NJ and Goldman, D and Wallen, GR}, title = {The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.}, journal = {Journal of oral microbiology}, volume = {14}, number = {1}, pages = {2004790}, pmid = {34880965}, issn = {2000-2297}, abstract = {BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome.

AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD.

METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing.

RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella.

CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.}, } @article {pmid34874775, year = {2021}, author = {Zhang, Z and Liu, Y and Zhang, P and Wang, J and Li, D and Li, YZ}, title = {PAAR Proteins Are Versatile Clips That Enrich the Antimicrobial Weapon Arsenals of Prokaryotes.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0095321}, pmid = {34874775}, issn = {2379-5077}, support = {2017FY100300//Special Investigation on Scientific and Technological Basic Resources/ ; 2018YFA0900400//National Key Research and Development Program/ ; 2018GSF121015//Key Research and Development Program of Shandong Province/ ; 2020GN113//Fundamental Research Funds of Shandong University/ ; 32070030//National Natural Science Foundation of China (NSFC)/ ; BK20190199//Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)/ ; }, abstract = {Protein toxins secreted by prokaryotes have been found to affect the pathogenicity of pathogens or directly mediate antagonistic interactions between prokaryotes. PAAR proteins are important carriers of toxic effectors and are located at the forefront of either the type VI secretion system (T6SS) or the extracellular contractile injection system (eCIS). This study systematically investigated PAAR homologues and related toxic effectors. We found that PAAR homologues were divided into 8 types and 16 subtypes and distributed in 23.1% of bacterial genomes and 7.8% of archaeal genomes. PAAR proteins of all types fold into a highly similar conical structure, even from relatively diverse underlying sequences. PAAR homologues associated with different secretion systems display a mixed phylogenetic relationship, indicating that PAAR proteins from such a subtype can be assembled on either a T6SS or an eCIS. More than 1,300 PAAR-related toxic effector genes were identified; one PAAR subtype can be associated with toxins of over 40 families, and toxins from one family can be associated with more than 10 PAAR subtypes. A large-scale comparison of Earth Microbiome Project data and prokaryotic genomes revealed that prokaryotes encoding PAAR genes are widely present in diverse environments worldwide, and taxa encoding multiple PAAR gene copies exhibit a wider distribution in environments than other taxa. Overall, our studies highlighted that PAAR proteins are versatile clips loaded with antimicrobial toxin bullets for secretion weapons (T6SS and eCIS), greatly enriching the weapon arsenal of prokaryotes, which, often together with VgrG, help prokaryotes fight for survival advantages in crowded environments. IMPORTANCE Infectious diseases caused by microbial pathogens are severe threats to human health and economic development. To respond to these threats, it is necessary to understand how microorganisms survive in and adapt to complex environments. Microorganic toxins, which are widely distributed in nature, are the key weapons in life domain interactions. PAAR proteins are important carriers of prokaryotic toxic effectors. We reveal the versatility of PAAR proteins between secretory systems and the massive diversity of toxic effectors carried by PAAR proteins, which helps prokaryotes enrich their arsenal and expand their ability to attack their neighbors. A large number of PAAR homologues and related toxic effectors enhance the survival competitiveness of prokaryotic populations. In conclusion, our work provides an example for large-scale analysis of the global distribution and ecological functions of prokaryotic functional genes.}, } @article {pmid34841779, year = {2021}, author = {Yin, Y and Yu, R and Chen, H}, title = {[Shotgun metagenome sequencing of Chinese gut microbiota: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3717-3733}, doi = {10.13345/j.cjb.210556}, pmid = {34841779}, issn = {1872-2075}, mesh = {China ; *Gastrointestinal Microbiome/genetics ; Humans ; Metagenome ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {The research on the relationship between gut microbiota and human health continues to be a hot topic in the field of life science. Culture independent 16S rRNA gene high-throughput sequencing is the current main research method. However, with the reduction of sequencing cost and the maturity of data analysis methods, shotgun metagenome sequencing is gradually becoming an important method for the study of gut microbiome due to its advantages of obtaining more information. With the support from the human microbiome project, 30 805 metagenome samples were sequenced in the United States. By searching NCBI PubMed and SRA databases, it was found that 72 studies collecting about 10 000 Chinese intestinal samples were used for metagenome sequencing. To date, only 56 studies were published, including 16 related to metabolic diseases, 16 related to infectious and immune diseases, and 12 related to cardiovascular and cerebrovascular diseases. The samples were mainly collected in Beijing, Guangzhou, Shanghai and other cosmopolitan cities, where great differences exist in sequencing platforms and methods. The outcome of most studies are based on correlation analysis, which has little practical value in guiding the diagnosis and treatment of clinical diseases. Standardizing sampling methods, sequencing platform and data analysis process, and carrying out multi center parallel research will contribute to data integration and comparative analysis. Moreover, insights into the functional verification and molecular mechanism by using the combination of transcriptomics, proteomics and culturomics will enable the gut microbiota research to better serve the clinical diagnosis and treatment.}, } @article {pmid34820530, year = {2021}, author = {Liang, G}, title = {Altered gut bacterial and metabolic signatures and their interaction in inflammatory bowel disease.}, journal = {Synthetic and systems biotechnology}, volume = {6}, number = {4}, pages = {377-383}, pmid = {34820530}, issn = {2405-805X}, abstract = {Dysregulation of the gut microbiome has been implicated in the progression of many diseases. This study explored the role of microbial and metabolic signatures, and their interaction between the Human inflammatory bowel disease (IBD) and healthy controls (HCs) based on the combination of machine learning and traditional statistical analysis, using data collected from the Human Microbiome Project (HMP) and the Integrative Human Microbiome Project (iHMP). It was showed that the microbial and metabolic signatures of IBD patients were significantly different from those of HCs. Compared to HCs, IBD subjects were characterized by 25 enriched species and 6 depleted species. Furthermore, a total of 17 discriminative pathways were identified between the IBD and HC groups. Those differential pathways were mainly involved in amino acid, nucleotide biosynthesis, and carbohydrate degradation. Notably, co-occurrence network analysis revealed that non-predominant bacteria Ruminococcus_obeum and predominant bacteria Faecalibacterium_prausnitzii formed the same broad and strong co-occurring relationships with pathways. Moreover, the essay identified a combinatorial marker panel that could distinguish IBD from HCs. Receiver Operating Characteristic (ROC) and Decision Curve Analysis (DCA) confirmed the high accuracy (AUC = 0.966) and effectiveness of the model. Meanwhile, an independent cohort used for external validation also showed the identical high efficacy (AUC = 0.835). These findings showed that the gut microbes may be relevant to the pathogenesis and pathophysiology, and offer universal utility as a non-invasive diagnostic test in IBD.}, } @article {pmid34718406, year = {2022}, author = {Liu, T and Xu, P and Du, Y and Lu, H and Zhao, H and Wang, T}, title = {MZINBVA: variational approximation for multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys.}, journal = {Briefings in bioinformatics}, volume = {23}, number = {1}, pages = {}, doi = {10.1093/bib/bbab443}, pmid = {34718406}, issn = {1477-4054}, mesh = {Computer Simulation ; Humans ; *Microbiota ; Models, Statistical ; Research Design ; }, abstract = {As our understanding of the microbiome has expanded, so has the recognition of its critical role in human health and disease, thereby emphasizing the importance of testing whether microbes are associated with environmental factors or clinical outcomes. However, many of the fundamental challenges that concern microbiome surveys arise from statistical and experimental design issues, such as the sparse and overdispersed nature of microbiome count data and the complex correlation structure among samples. For example, in the human microbiome project (HMP) dataset, the repeated observations across time points (level 1) are nested within body sites (level 2), which are further nested within subjects (level 3). Therefore, there is a great need for the development of specialized and sophisticated statistical tests. In this paper, we propose multilevel zero-inflated negative-binomial models for association analysis in microbiome surveys. We develop a variational approximation method for maximum likelihood estimation and inference. It uses optimization, rather than sampling, to approximate the log-likelihood and compute parameter estimates, provides a robust estimate of the covariance of parameter estimates and constructs a Wald-type test statistic for association testing. We evaluate and demonstrate the performance of our method using extensive simulation studies and an application to the HMP dataset. We have developed an R package MZINBVA to implement the proposed method, which is available from the GitHub repository https://github.com/liudoubletian/MZINBVA.}, } @article {pmid34708327, year = {2021}, author = {de Medeiros Azevedo, T and Aburjaile, FF and Ferreira-Neto, JRC and Pandolfi, V and Benko-Iseppon, AM}, title = {The endophytome (plant-associated microbiome): methodological approaches, biological aspects, and biotech applications.}, journal = {World journal of microbiology & biotechnology}, volume = {37}, number = {12}, pages = {206}, pmid = {34708327}, issn = {1573-0972}, mesh = {Agricultural Inoculants ; Agriculture ; Biotechnology/*methods ; Computational Biology ; *Endophytes ; Humans ; Metagenomics/methods ; *Microbiota ; Plant Roots/microbiology ; Plants/*microbiology ; Soil ; Soil Microbiology ; }, abstract = {Similar to other organisms, plants establish interactions with a variety of microorganisms in their natural environment. The plant microbiome occupies the host plant's tissues, either internally or on its surfaces, showing interactions that can assist in its growth, development, and adaptation to face environmental stresses. The advance of metagenomics and metatranscriptomics approaches has strongly driven the study and recognition of plant microbiome impacts. Research in this regard provides comprehensive information about the taxonomic and functional aspects of microbial plant communities, contributing to a better understanding of their dynamics. Evidence of the plant microbiome's functional potential has boosted its exploitation to develop more ecological and sustainable agricultural practices that impact human health. Although microbial inoculants' development and use are promising to revolutionize crop production, interdisciplinary studies are needed to identify new candidates and promote effective practical applications. On the other hand, there are challenges in understanding and analyzing complex data generated within a plant microbiome project's scope. This review presents aspects about the complex structuring and assembly of the microbiome in the host plant's tissues, metagenomics, and metatranscriptomics approaches for its understanding, covering descriptions of recent studies concerning metagenomics to characterize the microbiome of non-model plants under different aspects. Studies involving bio-inoculants, isolated from plant microbial communities, capable of assisting in crops' productivity, are also reviewed.}, } @article {pmid34668097, year = {2021}, author = {González-Castillo, A and Carballo, JL and Bautista-Guerrero, E}, title = {Genomics and phylogeny of the proposed phylum 'Candidatus Poribacteria' associated with the excavating sponge Thoosa mismalolli.}, journal = {Antonie van Leeuwenhoek}, volume = {114}, number = {12}, pages = {2163-2174}, pmid = {34668097}, issn = {1572-9699}, support = {254806//CONACYT-SEP/ ; }, mesh = {Animals ; *Bacteria/genetics ; Genomics ; Metagenome ; *Microbiota ; Phylogeny ; }, abstract = {Members of the proposed phylum 'Candidatus Poribacteria' are among the most abundant microorganisms in the highly diverse microbiome of the sponge mesohyl. Genomic and phylogenetic characteristics of this proposed phylum are barely known. In this study, we analyzed metagenome-assembled genomes (MAGs) obtained from the coral reef excavating sponge Thoosa mismalolli from the Mexican Pacific Ocean. Two MAGs were extracted and analyzed together with 32 MAGs and single-amplified genomes (SAGs) obtained from NCBI. The phylogenetic tree based on the sequences of 139 single-copy genes (SCG) showed two clades. Clade A (23 genomes) represented 67.7% of the total of the genomes, while clade B (11 genomes) comprised 32.3% of the genomes. The Average Nucleotide Identity (ANI) showed values between 66 and 99% for the genomes of the proposed phylum, and the pangenome of genomes revealed a total of 37,234 genes that included 1722 core gene. The number of genes used in the phylogenetic analysis increased from 28 (previous studies) to 139 (this study), which allowed a better resolution of the phylogeny of the proposed phylum. The results supported the two previously described classes, 'Candidatus Entoporibacteria' and 'Candidatus Pelagiporibacteria', and the genomes SB0101 and SB0202 obtained in this study belong to two new species of the class 'Candidatus Entoporibacteria'. This is the first comparative study that includes MAGs from a non-sponge host (Porites lutea) to elucidate the taxonomy of the poorly known Candidatus phylum in a polyphasic approach. Finally, our study also contributes to the sponge microbiome project by reporting the first MAGs of the proposed phylum 'Candidatus Poribacteria' isolated from the excavating sponge T. mismalolli.}, } @article {pmid34656848, year = {2021}, author = {Tan-Torres, AL and Brooks, JP and Singh, B and Seashols-Williams, S}, title = {Machine learning clustering and classification of human microbiome source body sites.}, journal = {Forensic science international}, volume = {328}, number = {}, pages = {111008}, doi = {10.1016/j.forsciint.2021.111008}, pmid = {34656848}, issn = {1872-6283}, mesh = {Algorithms ; Cluster Analysis ; Humans ; Machine Learning ; Metagenomics ; *Microbiota ; }, abstract = {Distinct microbial signatures associated with specific human body sites can play a role in the identification of biological materials recovered from the crime scene, but at present, methods that have capability to predict origin of biological materials based on such signatures are limited. Metagenomic sequencing and machine learning (ML) offer a promising enhancement to current identification protocols. We use ML for forensic source body site identification using shotgun metagenomic sequenced data to verify the presence of microbiomic signatures capable of discriminating between source body sites and then show that accurate prediction is possible. The consistency between cluster membership and actual source body site (purity) exceeded 99% at the genus taxonomy using off-the-shelf ML clustering algorithms. Similar results were obtained at the family level. Accurate predictions were observed for genus, family, and order taxonomies, as well as with a core set of 51 genera. The accurate outcomes from our replicable process should encourage forensic scientists to seriously consider integrating ML predictors into their source body site identification protocols.}, } @article {pmid34611047, year = {2022}, author = {Lv, S and Wang, Y and Zhang, W and Shang, H}, title = {Trimethylamine oxide: a potential target for heart failure therapy.}, journal = {Heart (British Cardiac Society)}, volume = {108}, number = {12}, pages = {917-922}, doi = {10.1136/heartjnl-2021-320054}, pmid = {34611047}, issn = {1468-201X}, mesh = {Cardiotonic Agents ; Carnitine/metabolism ; Choline/metabolism ; Diuretics ; *Gastrointestinal Microbiome/physiology ; *Heart Failure/drug therapy ; Humans ; Methylamines ; }, abstract = {Heart failure (HF) is a clinical syndrome in the late stage of cardiovascular disease and is associated with high prevalence, mortality and rehospitalisation rate. The pathophysiological mechanisms of HF have experienced the initial 'water-sodium retention' mode to 'abnormal hemodynamics' mode, and subsequent to 'abnormal activation of neuroendocrine' mode, which has extensively promoted the reform of HF treatment and updated the treatment concept. Since the Human Microbiome Project commencement, the study on intestinal microecology has swiftly developed, providing a new direction to reveal the occurrence of diseases and the mechanisms behind drug effects. Intestinal microecology comprises the gastrointestinal lumen, epithelial secretion, food entering the intestine, intestinal flora and metabolites. Choline and L-carnitine in the diet are metabolised to trimethylamine (TMA) by the intestinal micro-organisms, with TMA being absorbed into the blood. TMA then enters the liver through the portal vein circulation and is oxidised to trimethylamine oxide (TMAO) by the hepatic flavin-containing mono-oxygenase (FMO) family, especially FMO3. The circulating TMAO levels are associated with adverse outcomes in HF (mortality and readmission), and lower TMAO levels indicate better prognosis. As HF progresses, the concentration of TMAO in patients gradually increases. Whether the circulating TMAO level can be decreased by intervening with the intestinal microflora or relevant enzymes, thereby affecting the prognosis of patients with HF, has become a research hotspot. Therefore, based on the HF intestinal hypothesis, exploring the treatment strategy for HF targeting the TMAO metabolite of the intestinal flora may update the treatment concept in HF and improve its therapeutic effect.}, } @article {pmid34554215, year = {2022}, author = {Bodein, A and Scott-Boyer, MP and Perin, O and Lê Cao, KA and Droit, A}, title = {timeOmics: an R package for longitudinal multi-omics data integration.}, journal = {Bioinformatics (Oxford, England)}, volume = {38}, number = {2}, pages = {577-579}, doi = {10.1093/bioinformatics/btab664}, pmid = {34554215}, issn = {1367-4811}, support = {//Research and Innovation chair L'Oréal in Digital Biology/ ; GNT1159458//National Health and Medical Research Council (NHMRC) Career Development fellowship/ ; }, mesh = {Humans ; *Genomics/methods ; *Multiomics ; Cluster Analysis ; }, abstract = {MOTIVATION: Multi-omics data integration enables the global analysis of biological systems and discovery of new biological insights. Multi-omics experimental designs have been further extended with a longitudinal dimension to study dynamic relationships between molecules. However, methods that integrate longitudinal multi-omics data are still in their infancy.

RESULTS: We introduce the R package timeOmics, a generic analytical framework for the integration of longitudinal multi-omics data. The framework includes pre-processing, modeling and clustering to identify molecular features strongly associated with time. We illustrate this framework in a case study to detect seasonal patterns of mRNA, metabolites, gut taxa and clinical variables in patients with diabetes mellitus from the integrative Human Microbiome Project.

timeOmics is available on Bioconductor and github.com/abodein/timeOmics.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid34530857, year = {2021}, author = {Antonio Paoli, A and Mancin, L and Caprio, M and Monti, E and Narici, MV and Cenci, L and Piccini, F and Pincella, M and Grigoletto, D and Marcolin, G}, title = {Effects of 30 days of ketogenic diet on body composition, muscle strength, muscle area, metabolism, and performance in semi-professional soccer players.}, journal = {Journal of the International Society of Sports Nutrition}, volume = {18}, number = {1}, pages = {62}, pmid = {34530857}, issn = {1550-2783}, mesh = {Adult ; Athletes ; *Body Composition ; *Diet, Ketogenic ; Diet, Western ; Humans ; Male ; *Muscle Strength ; Muscle, Skeletal/*physiology ; Prospective Studies ; *Sports Nutritional Physiological Phenomena ; Young Adult ; }, abstract = {BACKGROUND: A ketogenic diet (KD) is a nutritional approach, usually adopted for weight loss, that restricts daily carbohydrates under 30 g/day. KD showed contradictory results on sport performance, whilst no data are available on team sports. We sought to investigate the influence of a KD on different parameters in semi-professional soccer players.

METHODS: Subjects were randomly assigned to a iso-protein (1.8 g/Kg body weight/day) ketogenic diet (KD) or western diet (WD) for 30 days. Body weight and body composition, resting energy expenditure (REE), respiratory exchange ratio (RER), cross sectional area (CSA) and isometric muscle strength of quadriceps, counter movement jump (CMJ) and yoyo intermittent recovery test time were measured.

RESULTS: There was a significantly higher decrease of body fat (p = 0.0359), visceral adipose tissue (VAT) (p = 0.0018), waist circumference (p = 0.0185) and extra-cellular water (p = 0.0060) in KD compared to WD group. Lean soft tissue, quadriceps muscle area, maximal strength and REE showed no changes in both groups. RER decreased significantly in KD (p = 0.0008). Yo-yo intermittent test improved significantly (p < 0.0001) in both groups without significant differences between groups. CMJ significantly improved (p = 0.0021) only in KD.

CONCLUSIONS: This is the first study investigating the effects of a KD on semi-professional soccer players. In our study KD athletes lost fat mass without any detrimental effects on strength, power and muscle mass. When the goal is a rapid weight reduction in such athletes, the use of a KD should be taken into account.

TRIAL REGISTRATION: registered retrospectively on Clinical Trial registration number NCT04078971 .}, } @article {pmid34484688, year = {2021}, author = {Mehta, S and Crane, M and Leith, E and Batut, B and Hiltemann, S and Arntzen, MØ and Kunath, BJ and Pope, PB and Delogu, F and Sajulga, R and Kumar, P and Johnson, JE and Griffin, TJ and Jagtap, PD}, title = {ASaiM-MT: a validated and optimized ASaiM workflow for metatranscriptomics analysis within Galaxy framework.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {103}, pmid = {34484688}, issn = {2046-1402}, support = {U24 CA199347/CA/NCI NIH HHS/United States ; }, mesh = {High-Throughput Nucleotide Sequencing ; Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Workflow ; }, abstract = {The Earth Microbiome Project (EMP) aided in understanding the role of microbial communities and the influence of collective genetic material (the 'microbiome') and microbial diversity patterns across the habitats of our planet. With the evolution of new sequencing technologies, researchers can now investigate the microbiome and map its influence on the environment and human health. Advances in bioinformatics methods for next-generation sequencing (NGS) data analysis have helped researchers to gain an in-depth knowledge about the taxonomic and genetic composition of microbial communities. Metagenomic-based methods have been the most commonly used approaches for microbiome analysis; however, it primarily extracts information about taxonomic composition and genetic potential of the microbiome under study, lacking quantification of the gene products (RNA and proteins). On the other hand, metatranscriptomics, the study of a microbial community's RNA expression, can reveal the dynamic gene expression of individual microbial populations and the community as a whole, ultimately providing information about the active pathways in the microbiome. In order to address the analysis of NGS data, the ASaiM analysis framework was previously developed and made available via the Galaxy platform. Although developed for both metagenomics and metatranscriptomics, the original publication demonstrated the use of ASaiM only for metagenomics, while thorough testing for metatranscriptomics data was lacking. In the current study, we have focused on validating and optimizing the tools within ASaiM for metatranscriptomics data. As a result, we deliver a robust workflow that will enable researchers to understand dynamic functional response of the microbiome in a wide variety of metatranscriptomics studies. This improved and optimized ASaiM-metatranscriptomics (ASaiM-MT) workflow is publicly available via the ASaiM framework, documented and supported with training material so that users can interrogate and characterize metatranscriptomic data, as part of larger meta-omic studies of microbiomes.}, } @article {pmid34485860, year = {2021}, author = {De Boeck, I and Wittouck, S and Martens, K and Spacova, I and Cauwenberghs, E and Allonsius, CN and Jörissen, J and Wuyts, S and Van Beeck, W and Dillen, J and Bron, PA and Steelant, B and Hellings, PW and Vanderveken, OM and Lebeer, S}, title = {The nasal mutualist Dolosigranulum pigrum AMBR11 supports homeostasis via multiple mechanisms.}, journal = {iScience}, volume = {24}, number = {9}, pages = {102978}, pmid = {34485860}, issn = {2589-0042}, abstract = {Comparing the nasal microbiome of healthy individuals and chronic rhinosinusitis (CRS) patients revealed Dolosigranulum pigrum as a species clearly associated with nasal health, although isolates obtained from healthy individuals are scarce. In this study, we explored the properties of this understudied lactic acid bacterium by integrating comparative genomics, habitat mining, cultivation, and functional characterization of interaction capacities. Mining 10.000 samples from the Earth Microbiome Project of 17 habitat types revealed that Dolosigranulum is mainly associated with the human nasal cavity. D. pigrum AMBR11 isolated from the nose of a healthy individual exerted antimicrobial activity against Staphylococcus aureus, decreased proinflammatory cytokine production in airway epithelial cells, and Galleria mellonella larvae mortality induced by this important nasal pathobiont. Furthermore, the strain protected the nasal barrier function in a mouse model using interleukin-4 as disruptive cytokine. Hence, D. pigrum AMBR11 is a mutualist with high potential as topical live biotherapeutic product.}, } @article {pmid34466295, year = {2021}, author = {Chen, YR and Jing, QL and Chen, FL and Zheng, H and Chen, LD and Yang, ZC}, title = {Desulfovibrio is not always associated with adverse health effects in the Guangdong Gut Microbiome Project.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e12033}, pmid = {34466295}, issn = {2167-8359}, abstract = {Desulfovibrio (DSV) is frequently found in the human intestine but limited knowledge is available regarding the relationship between DSV and host health. In this study, we analyzed large-scale cohort data from the Guangdong Gut Microbiome Project to study the ecology of DSV and the associations of DSV and host health parameters. Phylogenetic analysis showed that Desulfovibrio piger might be the most common and abundant DSV species in the GGMP. Predominant sub-OTUs of DSV were positively associated with bacterial community diversity. The relative abundance of DSV was positively correlated with beneficial genera, including Oscillospira, Coprococcus,Ruminococcus,Akkermansia, Roseburia,Faecalibacterium, andBacteroides, and was negatively associated with harmful genera, such as Clostridium,Escherichia,Klebsiella, and Ralstonia. Moreover, the relative abundance of DSV was negatively correlated with body mass index, waist size, triglyceride levels, and uric acid levels. This suggests that DSV is associated with healthy hosts in some human populations.}, } @article {pmid37440868, year = {2021}, author = {Shuler, K and Verbanic, S and Chen, IA and Lee, J}, title = {A Bayesian nonparametric analysis for zero-inflated multivariate count data with application to microbiome study.}, journal = {Journal of the Royal Statistical Society. Series C, Applied statistics}, volume = {70}, number = {4}, pages = {961-979}, pmid = {37440868}, issn = {0035-9254}, support = {DP2 GM123457/GM/NIGMS NIH HHS/United States ; }, abstract = {High-throughput sequencing technology has enabled researchers to profile microbial communities from a variety of environments, but analysis of multivariate taxon count data remains challenging. We develop a Bayesian nonparametric (BNP) regression model with zero inflation to analyse multivariate count data from microbiome studies. A BNP approach flexibly models microbial associations with covariates, such as environmental factors and clinical characteristics. The model produces estimates for probability distributions which relate microbial diversity and differential abundance to covariates, and facilitates community comparisons beyond those provided by simple statistical tests. We compare the model to simpler models and popular alternatives in simulation studies, showing, in addition to these additional community-level insights, it yields superior parameter estimates and model fit in various settings. The model's utility is demonstrated by applying it to a chronic wound microbiome data set and a Human Microbiome Project data set, where it is used to compare microbial communities present in different environments.}, } @article {pmid34302622, year = {2021}, author = {Hyun, DW and Lee, JY and Kim, MS and Shin, NR and Whon, TW and Kim, KH and Kim, PS and Tak, EJ and Jung, MJ and Lee, JY and Kim, HS and Kang, W and Sung, H and Jeon, CO and Bae, JW}, title = {Pathogenomics of Streptococcus ilei sp. nov., a newly identified pathogen ubiquitous in human microbiome.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {59}, number = {8}, pages = {792-806}, pmid = {34302622}, issn = {1976-3794}, mesh = {Adult ; Animals ; Gastrointestinal Microbiome ; Humans ; Ileostomy ; Male ; Mice ; Mice, Inbred C57BL ; *Microbiota ; Phylogeny ; Streptococcal Infections/*microbiology ; Streptococcus/classification/genetics/*isolation & purification/*pathogenicity ; Virulence ; }, abstract = {Viridans group streptococci are a serious health concern because most of these bacteria cause life-threatening infections, especially in immunocompromised and hospitalized individuals. We focused on two alpha-hemolytic Streptococcus strains (I-G2 and I-P16) newly isolated from an ileostomy effluent of a colorectal cancer patient. We examined their pathogenic potential by investigating their prevalence in human and assessing their pathogenicity in a mouse model. We also predicted their virulence factors and pathogenic features by using comparative genomic analysis and in vitro tests. Using polyphasic and systematic approaches, we identified the isolates as belonging to a novel Streptococcus species and designated it as Streptococcus ilei. Metagenomic survey based on taxonomic assignment of datasets from the Human Microbiome Project revealed that S. ilei is present in most human population and at various body sites but is especially abundant in the oral cavity. Intraperitoneal injection of S. ilei was lethal to otherwise healthy C57BL/6J mice. Pathogenomics and in vitro assays revealed that S. ilei possesses a unique set of virulence factors. In agreement with the in vivo and in vitro data, which indicated that S. ilei strain I-G2 is more pathogenic than strain I-P16, only the former displayed the streptococcal group A antigen. We here newly identified S. ilei sp. nov., and described its prevalence in human, virulence factors, and pathogenicity. This will help to prevent S. ilei strain misidentification in the future, and improve the understanding and management of streptococcal infections.}, } @article {pmid34259548, year = {2021}, author = {Wang, J and Wang, J and Wu, S and Zhang, Z and Li, Y}, title = {Global Geographic Diversity and Distribution of the Myxobacteria.}, journal = {Microbiology spectrum}, volume = {9}, number = {1}, pages = {e0001221}, pmid = {34259548}, issn = {2165-0497}, mesh = {*Biodiversity ; Environmental Microbiology ; Myxococcales/*classification/genetics/*isolation & purification ; Phylogeny ; Soil/chemistry ; Soil Microbiology ; }, abstract = {Bacteria are globally distributed in various environments on earth, but a global view of the geographic diversity and distribution of a single taxon is lacking. The Earth Microbiome Project (EMP) has established a global collection of microbial communities, providing the possibility for such a survey. Myxococcales is a bacterial order with a potent ability to produce diverse natural products and have wide application potential in agriculture, biomedicine, and environmental protection. In this study, through a comparative analysis of the EMP data and public information, we determined that myxobacteria account for 2.34% of the total bacterial operational taxonomic units (OTUs), and are one of the most diverse bacterial groups on Earth. Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. Myxobacteria are among the least-investigated bacterial groups. The presently cultured and genome-sequenced myxobacteria are most likely environmentally widespread and abundant taxa, and account for approximately 10% and 7% of the myxobacterial community (>97% similarity), respectively. This global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently. The diversity and distribution of myxobacteria beyond the EMP data are further discussed. IMPORTANCE The diversity and distribution of bacteria are crucial for our understanding of their ecological importance and application potential. Myxobacteria are fascinating prokaryotes with multicellular behaviors and a potent capacity for producing secondary metabolites, and have a wide range of potential applications. The ecological importance of myxobacteria in major ecosystems is becoming established, but the global geographic diversity and distribution remain unclear. From a global survey we revealed that Myxococcales OTUs are globally distributed and prefer nonsaline soil and sediments, followed by saline environments, but rarely appear in host-associated environments. The global panoramic view of the geographic distribution and diversity of myxobacteria, as well as their cultured and genome-sequenced information, will enable us to explore these important bioresources more reasonably and efficiently.}, } @article {pmid34222331, year = {2021}, author = {DiMucci, D and Kon, M and Segrè, D}, title = {BowSaw: Inferring Higher-Order Trait Interactions Associated With Complex Biological Phenotypes.}, journal = {Frontiers in molecular biosciences}, volume = {8}, number = {}, pages = {663532}, pmid = {34222331}, issn = {2296-889X}, abstract = {Machine learning is helping the interpretation of biological complexity by enabling the inference and classification of cellular, organismal and ecological phenotypes based on large datasets, e.g., from genomic, transcriptomic and metagenomic analyses. A number of available algorithms can help search these datasets to uncover patterns associated with specific traits, including disease-related attributes. While, in many instances, treating an algorithm as a black box is sufficient, it is interesting to pursue an enhanced understanding of how system variables end up contributing to a specific output, as an avenue toward new mechanistic insight. Here we address this challenge through a suite of algorithms, named BowSaw, which takes advantage of the structure of a trained random forest algorithm to identify combinations of variables ("rules") frequently used for classification. We first apply BowSaw to a simulated dataset and show that the algorithm can accurately recover the sets of variables used to generate the phenotypes through complex Boolean rules, even under challenging noise levels. We next apply our method to data from the integrative Human Microbiome Project and find previously unreported high-order combinations of microbial taxa putatively associated with Crohn's disease. By leveraging the structure of trees within a random forest, BowSaw provides a new way of using decision trees to generate testable biological hypotheses.}, } @article {pmid32742640, year = {2020}, author = {Wagner, J and Kancherla, J and Braccia, D and Matsumara, J and Felix, V and Crabtree, J and Mahurkar, A and Corrada Bravo, H}, title = {Interactive exploratory data analysis of Integrative Human Microbiome Project data using Metaviz.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {601}, pmid = {32742640}, issn = {2046-1402}, support = {R01 GM114267/GM/NIGMS NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {*Data Analysis ; Data Interpretation, Statistical ; Humans ; *Microbiota ; Research Design ; }, abstract = {The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In this work we describe infrastructure that integrates Metaviz, an interactive microbiome data analysis and visualization tool, with the iHMP Data Coordination Center web portal and the HMP2Data R/Bioconductor package. We describe integrative statistical and visual analyses of two datasets from iHMP using Metaviz along with the metagenomeSeq R/Bioconductor package for statistical analysis of differential abundance analysis. These use cases demonstrate the utility of a combined approach to access and analyze data from this resource.}, } @article {pmid34108237, year = {2022}, author = {Le Roy, T and Moens de Hase, E and Van Hul, M and Paquot, A and Pelicaen, R and Régnier, M and Depommier, C and Druart, C and Everard, A and Maiter, D and Delzenne, NM and Bindels, LB and de Barsy, M and Loumaye, A and Hermans, MP and Thissen, JP and Vieira-Silva, S and Falony, G and Raes, J and Muccioli, GG and Cani, PD}, title = {Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice.}, journal = {Gut}, volume = {71}, number = {3}, pages = {534-543}, pmid = {34108237}, issn = {1468-3288}, mesh = {Animals ; Case-Control Studies ; Clostridiales/*isolation & purification ; Cohort Studies ; Humans ; Insulin Resistance ; Metabolic Diseases/*microbiology/*prevention & control ; Mice ; Mice, Obese ; Obesity/*microbiology/*prevention & control ; }, abstract = {OBJECTIVE: To investigate the abundance and the prevalence of Dysosmobacter welbionis J115[T], a novel butyrate-producing bacterium isolated from the human gut both in the general population and in subjects with metabolic syndrome. To study the impact of this bacterium on host metabolism using diet-induced obese and diabetic mice.

DESIGN: We analysed the presence and abundance of the bacterium in 11 984 subjects using four human cohorts (ie, Human Microbiome Project, American Gut Project, Flemish Gut Flora Project and Microbes4U). Then, we tested the effects of daily oral gavages with live D. welbionis J115[T] on metabolism and several hallmarks of obesity, diabetes, inflammation and lipid metabolism in obese/diabetic mice.

RESULTS: This newly identified bacterium was detected in 62.7%-69.8% of the healthy population. Strikingly, in obese humans with a metabolic syndrome, the abundance of Dysosmobacter genus correlates negatively with body mass index, fasting glucose and glycated haemoglobin. In mice, supplementation with live D. welbionis J115[T], but not with the pasteurised bacteria, partially counteracted diet-induced obesity development, fat mass gain, insulin resistance and white adipose tissue hypertrophy and inflammation. In addition, live D. welbionis J115[T] administration protected the mice from brown adipose tissue inflammation in association with increased mitochondria number and non-shivering thermogenesis. These effects occurred with minor impact on the mouse intestinal microbiota composition.

CONCLUSIONS: These results suggest that D. welbionis J115[T] directly and beneficially influences host metabolism and is a strong candidate for the development of next-generation beneficial bacteria targeting obesity and associated metabolic diseases.}, } @article {pmid34084131, year = {2021}, author = {Hollingsworth, BA and Cassatt, DR and DiCarlo, AL and Rios, CI and Satyamitra, MM and Winters, TA and Taliaferro, LP}, title = {Acute Radiation Syndrome and the Microbiome: Impact and Review.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {643283}, pmid = {34084131}, issn = {1663-9812}, abstract = {Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.}, } @article {pmid34040632, year = {2021}, author = {Andreu-Sánchez, S and Chen, L and Wang, D and Augustijn, HE and Zhernakova, A and Fu, J}, title = {A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing.}, journal = {Frontiers in genetics}, volume = {12}, number = {}, pages = {648229}, pmid = {34040632}, issn = {1664-8021}, abstract = {Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK's tools as reliable variant callers for metagenomic samples.}, } @article {pmid34040404, year = {2021}, author = {Zhou, Q and Pang, G and Zhang, Z and Yuan, H and Chen, C and Zhang, N and Yang, Z and Sun, L}, title = {Association Between Gut Akkermansia and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study.}, journal = {Diabetes, metabolic syndrome and obesity : targets and therapy}, volume = {14}, number = {}, pages = {2177-2188}, pmid = {34040404}, issn = {1178-7007}, abstract = {OBJECTIVE: Akkermansia muciniphila is among the most abundant bacterial species in the human intestine; however, its relationship to metabolic syndrome (MetS)-which is linked to gut dysbiosis-is not known. In this study, we investigated the association between Akkermansia abundance and risk of MetS and its components, as well as dose-response effects and the influence of microbial interactions on the association.

METHODS: This cross-sectional study included 6896 Chinese participants aged 18 to 97 years from the Guangdong Gut Microbiome Project. MetS was defined according to Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults criteria. The abundance of Akkermansia was assessed by 16S rRNA sequencing. Logistic regression analysis with adjustment for common confounders was performed to evaluate the association between Akkermansia and MetS and its components. Models with restricted cubic splines and interaction terms were used to examine the dose-response association and microbial interactions, respectively.

RESULTS: The prevalence of MetS was 20.4%, and the median abundance of Akkermansia was 0.08% (interquartile range: 0.04-0.93%). Increased Akkermansia abundance was associated with decreased risk of MetS (P nonlinear<0.05), but this effect was not observed until the Akkermansia level was 0.2% of the total gut microbiota abundance (odds ratio=0.96, 95% confidence interval: 0.94-0.98). Of the 5 MetS components, obesity and hypertriglyceridemia showed the strongest association with Akkermansia, followed by reduced high-density lipoprotein cholesterol, hypertension, and hyperglycemia. Microbial interaction analyses showed that Ruminococcaceae and Lachnospiraceae were the predominant bacterial families and were not only correlated with Akkermansia abundance but also influenced the Akkermansia-MetS association.

CONCLUSION: There is a dose-response association between reduced risk of MetS and increased abundance of Akkermansia. The association between Akkermansia and 5 MetS components is variable and affected by microbial interactions.}, } @article {pmid34026361, year = {2021}, author = {Rogers, AE and Hu, YJ and Yue, Y and Wissel, EF and Petit Iii, RA and Jarrett, S and Christie, J and Read, TD}, title = {Shiftwork, functional bowel symptoms, and the microbiome.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e11406}, pmid = {34026361}, issn = {2167-8359}, support = {R01 GM116065/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms.

METHODS: Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS.

RESULTS: There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.}, } @article {pmid34020714, year = {2021}, author = {Liu, C and Du, MX and Abuduaini, R and Yu, HY and Li, DH and Wang, YJ and Zhou, N and Jiang, MZ and Niu, PX and Han, SS and Chen, HH and Shi, WY and Wu, L and Xin, YH and Ma, J and Zhou, Y and Jiang, CY and Liu, HW and Liu, SJ}, title = {Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {119}, pmid = {34020714}, issn = {2049-2618}, mesh = {Bacteria/genetics ; Biological Specimen Banks ; Darkness ; *Gastrointestinal Microbiome/genetics ; Humans ; *Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: In gut microbiome studies, the cultured gut microbial resource plays essential roles, such as helping to unravel gut microbial functions and host-microbe interactions. Although several major studies have been performed to elucidate the cultured human gut microbiota, up to 70% of the Unified Human Gastrointestinal Genome species have not been cultured to date. Large-scale gut microbial isolation and identification as well as availability to the public are imperative for gut microbial studies and further characterizing human gut microbial functions.

RESULTS: In this study, we constructed a human Gut Microbial Biobank (hGMB; homepage: hgmb.nmdc.cn) through the cultivation of 10,558 isolates from 31 sample mixtures of 239 fresh fecal samples from healthy Chinese volunteers, and deposited 1170 strains representing 400 different species in culture collections of the International Depository Authority for long-term preservation and public access worldwide. Following the rules of the International Code of Nomenclature of Prokaryotes, 102 new species were characterized and denominated, while 28 new genera and 3 new families were proposed. hGMB represented over 80% of the common and dominant human gut microbial genera and species characterized from global human gut 16S rRNA gene amplicon data (n = 11,647) and cultured 24 "most-wanted" and "medium priority" taxa proposed by the Human Microbiome Project. We in total sequenced 115 genomes representing 102 novel taxa and 13 previously known species. Further in silico analysis revealed that the newly sequenced hGMB genomes represented 22 previously uncultured species in the Unified Human Gastrointestinal Genome (UHGG) and contributed 24 representatives of potentially "dark taxa" that had not been discovered by UHGG. The nonredundant gene catalogs generated from the hGMB genomes covered over 50% of the functionally known genes (KEGG orthologs) in the largest global human gut gene catalogs and approximately 10% of the "most wanted" functionally unknown proteins in the FUnkFams database.

CONCLUSIONS: A publicly accessible human Gut Microbial Biobank (hGMB) was established that contained 1170 strains and represents 400 human gut microbial species. hGMB expands the gut microbial resources and genomic repository by adding 102 novel species, 28 new genera, 3 new families, and 115 new genomes of human gut microbes. Video abstract.}, } @article {pmid33998042, year = {2021}, author = {Herzig, AF and Velo-Suárez, L and Le Folgoc, G and Boland, A and Blanché, H and Olaso, R and Le Roux, L and Delmas, C and Goldberg, M and Zins, M and Lethimonnier, F and Deleuze, JF and Génin, E}, title = {Evaluation of saliva as a source of accurate whole-genome and microbiome sequencing data.}, journal = {Genetic epidemiology}, volume = {45}, number = {5}, pages = {537-548}, doi = {10.1002/gepi.22386}, pmid = {33998042}, issn = {1098-2272}, mesh = {Genome, Human ; Genotype ; Humans ; *Microbiota/genetics ; *Saliva ; Whole Genome Sequencing ; }, abstract = {This study sets out to establish the suitability of saliva-based whole-genome sequencing (WGS) through a comparison against blood-based WGS. To fully appraise the observed differences, we developed a novel technique of pseudo-replication. We also investigated the potential of characterizing individual salivary microbiomes from non-human DNA fragments found in saliva. We observed that the majority of discordant genotype calls between blood and saliva fell into known regions of the human genome that are typically sequenced with low confidence; and could be identified by quality control measures. Pseudo-replication demonstrated that the levels of discordance between blood- and saliva-derived WGS data were entirely similar to what one would expect between technical replicates if an individual's blood or saliva had been sequenced twice. Finally, we successfully sequenced salivary microbiomes in parallel to human genomes as demonstrated by a comparison against the Human Microbiome Project.}, } @article {pmid33888782, year = {2021}, author = {Pinto, D and Ciardiello, T and Franzoni, M and Pasini, F and Giuliani, G and Rinaldi, F}, title = {Effect of commonly used cosmetic preservatives on skin resident microflora dynamics.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {8695}, pmid = {33888782}, issn = {2045-2322}, mesh = {Cosmetics/*chemistry ; Histone Deacetylases/metabolism ; Humans ; Microbiota/*drug effects ; Preservatives, Pharmaceutical/*pharmacology ; Propionibacterium acnes/drug effects ; Skin/enzymology/*microbiology ; Staphylococcus aureus/drug effects ; Staphylococcus epidermidis/drug effects ; }, abstract = {Human skin is populated by various microorganisms, the so-called microbiota, such as bacteria, viruses, yeasts, fungi, and archaea. The skin microbiota is in constant contact with the surrounding environment which can alter its eubiotic state. Recently it has been also observed that the application of cosmetic products can alter the balance of the skin microbiota. This effect may be attributed to many factors including the residual activity of the preservatives on the skin. In the present work, we studied the effect of eleven preservatives commonly found in cosmetic products on Propionibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus in vitro using 3D skin models and culture-dependent methods. Also, the effect on Histone deacetylase 3 (HDAC3) has been investigated. Among tested combinations, three resulted as the best suitable for restoring a pre-existing dysbiosis since they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis. The other four combinations resulted as the best suitable for use in topical products for skin and scalp in which it is necessary to preserve the eubiosis of the microbiota. Some of the tested were also able to increase HDAC3 expression. Taking together these data highlight the role of preservatives of skin resident microflora dynamics and could provide a reference for correctly choice preservatives and dosage in cosmetic formulations to preserve or restore homeostasis of skin microbiota.}, } @article {pmid33796485, year = {2021}, author = {Ceprnja, M and Oros, D and Melvan, E and Svetlicic, E and Skrlin, J and Barisic, K and Starcevic, L and Zucko, J and Starcevic, A}, title = {Modeling of Urinary Microbiota Associated With Cystitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {643638}, pmid = {33796485}, issn = {2235-2988}, mesh = {*Cystitis ; Dysbiosis ; Female ; Humans ; *Microbiota ; *Urinary Tract Infections ; }, abstract = {A decade ago, when the Human Microbiome Project was starting, urinary tract (UT) was not included because the bladder and urine were considered to be sterile. Today, we are presented with evidence that healthy UT possesses native microbiota and any major event disrupting its "equilibrium" can impact the host also. This dysbiosis often leads to cystitis symptoms, which is the most frequent lower UT complaint, especially among women. Cystitis is one of the most common causes of antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of majority of cystitis cases is a single pathogen overgrowth, or a systemic disorder affecting entire UT microbiota. There are relatively few studies monitoring changes and dynamics of UT microbiota in cystitis patients, making this field of research still an unknown. In this study variations to the UT microbiota of cystitis patients were identified and microbial dynamics has been modeled. The microbial genetic profile of urine samples from 28 patients was analyzed by 16S rDNA Illumina sequencing and bioinformatics analysis. One patient with bacterial cystitis symptoms was prescribed therapy based on national guideline recommendations on antibacterial treatment of urinary tract infections (UTI) and UT microbiota change was monitored by 16S rDNA sequencing on 24 h basis during the entire therapy duration. The results of sequencing implied that a particular class of bacteria is associated with majority of cystitis cases in this study. The contributing role of this class of bacteria - Gammaproteobacteria, was further predicted by generalized Lotka-Volterra modeling (gLVM). Longitudinal microbiota insight obtained from a single patient under prescribed antimicrobial therapy revealed rapid and extensive changes in microbial composition and emphasized the need for current guidelines revision in regards to therapy duration. Models based on gLVM indicated protective role of two taxonomic classes of bacteria, Actinobacteria and Bacteroidia class, which appear to actively suppress pathogen overgrowth.}, } @article {pmid33738265, year = {2021}, author = {Ma, Y and Zhang, Y and Xiang, J and Xiang, S and Zhao, Y and Xiao, M and Du, F and Ji, H and Kaboli, PJ and Wu, X and Li, M and Wen, Q and Shen, J and Yang, Z and Li, J and Xiao, Z}, title = {Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {599734}, pmid = {33738265}, issn = {2235-2988}, mesh = {Bacteria/genetics ; *Colorectal Neoplasms ; Humans ; *Inflammatory Bowel Diseases ; Metagenome ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVES: Several reports suggesting that the intestinal microbiome plays a key role in the development of inflammatory bowel disease (IBD) or colorectal cancer (CRC), but the changes of intestinal bacteria in healthy people, patients with IBD and CRC are not fully explained. The study aimed to investigate changes of intestinal bacteria in healthy subjects, patients with IBD, and patients with CRC.

MATERIALS: We collected data from the European Nucleotide Archive on healthy people and patients with colorectal cancer with the study accession number PRJEB6070, PRJEB7774, PRJEB27928, PRJEB12449, and PRJEB10878, collected IBD patient data from the Integrated Human Microbiome Project from the Human Microbiome Project Data Portal. We performed metagenome-wide association studies on the fecal samples from 290 healthy subjects, 512 IBD patients, and 285 CRC patients. We used the metagenomics dataset to study bacterial community structure, relative abundance, functional prediction, differentially abundant bacteria, and co-occurrence networks.

RESULTS: The bacterial community structure in both IBD and CRC was significantly different from healthy subjects. Our results showed that IBD patients had low intestinal bacterial diversity and CRC patients had high intestinal bacterial diversity compared to healthy subjects. At the phylum level, the relative abundance of Firmicutes in IBD decreased significantly, while the relative abundance of Bacteroidetes increased significantly. At the genus level, the relative abundance of Bacteroides in IBD was higher than in healthy people and CRC. Compared with healthy people and CRC, the main difference of intestinal bacteria in IBD patients was Bacteroidetes, and compared with healthy people and IBD, the main difference of intestinal bacteria in CRC patients was in Fusobacteria, Verrucomicrobia, and Proteobacteria. The main differences in the functional composition of intestinal bacteria in healthy people, IBD and CRC patients were L-homoserine and L-methionine biosynthesis, 5-aminoimidazole ribonucleotide biosynthesis II, L-methionine biosynthesis I, and superpathway of L-lysine, L-threonine, and L-methionine biosynthesis I. The results of stratified showed that the abundance of Firmicutes, Bacteroidetes, and Actinobacteria involved in metabolic pathways has significantly changed. Besides, the association network of intestinal bacteria in healthy people, IBD, and CRC patients has also changed.

CONCLUSIONS: In conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in IBD and CRC patients was significantly changed.}, } @article {pmid33718417, year = {2021}, author = {Zhou, Y and He, Y and Liu, L and Zhou, W and Wang, P and Hu, H and Nie, Y and Chen, Y}, title = {Alterations in Gut Microbial Communities Across Anatomical Locations in Inflammatory Bowel Diseases.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {615064}, pmid = {33718417}, issn = {2296-861X}, abstract = {We previously discovered that gut microbiota can serve as universal microbial biomarkers for diagnosis, disease activity assessment, and predicting the response to infliximab treatment for inflammatory bowel diseases (IBD). Much still remains unknown about the relationship between alterations in gut microbiota and IBD affected bowel region, in particular in the case of ulcerative colitis (UC) and colonic Crohn's disease (cCD) without endoscopic and biopsy data. In the current study gut microbiota from a population in China was found to be distinct from that of the Western world [Human Microbiome Project (HMP) data]. Furthermore, both gut microbiota greatly differed from microbiota of other anatomical locations (oral, skin, airway, and vagina), with higher alpha-diversity (Chinese gut > HMP gut > oral microbiome > airway microbiome > skin microbiome > vaginal microbiome), and marked differences in microbiome composition. In patients with IBD in China, UC was characterized by the presence of Gardnerella, while cCD was characterized by the presence of Fusobacterium. Moreover, gut microbiota, such as Gardnerella and Fusobacterium, may be potential biomarkers for identifying UC from cCD. Together, this study revealed crucial differences in microbial communities across anatomical locations, and demonstrated that there was an important association between IBD affected bowel region and gut microbiota.}, } @article {pmid33682945, year = {2021}, author = {Bar, J and Sarig, O and Lotan-Pompan, M and Dassa, B and Miodovnik, M and Weinberger, A and Sprecher, E and Segal, E and Samuelov, L}, title = {Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.}, journal = {Clinical and experimental dermatology}, volume = {46}, number = {7}, pages = {1223-1229}, doi = {10.1111/ced.14592}, pmid = {33682945}, issn = {1365-2230}, support = {//EB Research Partnership foundation/ ; }, mesh = {Adolescent ; Adult ; Bacteria/*isolation & purification ; Case-Control Studies ; Child, Preschool ; Dysbiosis/*complications ; Epidermolysis Bullosa Dystrophica/complications/genetics/*microbiology ; Genotype ; Humans ; *Microbiota ; Skin/*microbiology ; Staphylococcus/isolation & purification ; Young Adult ; }, abstract = {BACKGROUND: The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome.

AIM: To characterize the skin microbiome in a series of patients with DEB.

METHODS: This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools.

RESULTS: The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin.

CONCLUSIONS: These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.}, } @article {pmid33674782, year = {2021}, author = {Nuzzo, A and Saha, S and Berg, E and Jayawickreme, C and Tocker, J and Brown, JR}, title = {Expanding the drug discovery space with predicted metabolite-target interactions.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {288}, pmid = {33674782}, issn = {2399-3642}, mesh = {Anti-Inflammatory Agents/*pharmacology ; Bacteria/immunology/*metabolism ; Cells, Cultured ; Data Mining ; Databases, Factual ; *Drug Discovery ; Gastrointestinal Agents/*pharmacology ; *Gastrointestinal Microbiome ; Gene Expression Profiling ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*drug therapy/immunology/metabolism/microbiology ; Ligands ; *Machine Learning ; Metabolome ; Metabolomics ; Molecular Targeted Therapy ; *Protein Interaction Maps ; Signal Transduction ; Transcriptome ; }, abstract = {Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite-host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite-target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2). Using a consensus of multiple machine learning methods, we ranked metabolites based on importance to IBD, followed by virtual ligand-based screening to identify possible human targets and adding evidence from compound assay, differential gene expression, pathway enrichment, and genome-wide association studies. We confirmed known metabolite-target pairs such as nicotinic acid-GPR109a or linoleoyl ethanolamide-GPR119 and inferred interactions of interest including oleanolic acid-GABRG2 and alpha-CEHC-THRB. Eleven metabolites were tested for bioactivity in vitro using human primary cell-types. By expanding the universe of possible microbial metabolite-host protein interactions, we provide multiple drug targets for potential immune-therapies.}, } @article {pmid33671853, year = {2021}, author = {Huang, E and Kim, S and Ahn, T}, title = {Deep Learning for Integrated Analysis of Insulin Resistance with Multi-Omics Data.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, pmid = {33671853}, issn = {2075-4426}, support = {P0009477, 2020//This research is supported through the Ministry of Trade, Industry and Energy(MOTIE)/ ; }, abstract = {Technological advances in next-generation sequencing (NGS) have made it possible to uncover extensive and dynamic alterations in diverse molecular components and biological pathways across healthy and diseased conditions. Large amounts of multi-omics data originating from emerging NGS experiments require feature engineering, which is a crucial step in the process of predictive modeling. The underlying relationship among multi-omics features in terms of insulin resistance is not well understood. In this study, using the multi-omics data of type II diabetes from the Integrative Human Microbiome Project, from 10,783 features, we conducted a data analytic approach to elucidate the relationship between insulin resistance and multi-omics features, including microbiome data. To better explain the impact of microbiome features on insulin classification, we used a developed deep neural network interpretation algorithm for each microbiome feature's contribution to the discriminative model output in the samples.}, } @article {pmid33517907, year = {2021}, author = {Blaustein, RA and Michelitsch, LM and Glawe, AJ and Lee, H and Huttelmaier, S and Hellgeth, N and Ben Maamar, S and Hartmann, EM}, title = {Toothbrush microbiomes feature a meeting ground for human oral and environmental microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {32}, pmid = {33517907}, issn = {2049-2618}, support = {TL1 TR001423/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; *Built Environment ; Drug Resistance, Microbial/drug effects/genetics ; Humans ; Metagenome/drug effects/genetics ; *Microbiota/drug effects/genetics ; Middle Aged ; Mouth/drug effects/*microbiology ; *Toothbrushing ; Triclosan/pharmacology ; Young Adult ; }, abstract = {BACKGROUND: While indoor microbiomes impact our health and well-being, much remains unknown about taxonomic and functional transitions that occur in human-derived microbial communities once they are transferred away from human hosts. Toothbrushes are a model to investigate the potential response of oral-derived microbiota to conditions of the built environment. Here, we characterize metagenomes of toothbrushes from 34 subjects to define the toothbrush microbiome and resistome and possible influential factors.

RESULTS: Toothbrush microbiomes often comprised a dominant subset of human oral taxa and less abundant or site-specific environmental strains. Although toothbrushes contained lower taxonomic diversity than oral-associated counterparts (determined by comparison with the Human Microbiome Project), they had relatively broader antimicrobial resistance gene (ARG) profiles. Toothbrush resistomes were enriched with a variety of ARGs, notably those conferring multidrug efflux and putative resistance to triclosan, which were primarily attributable to versatile environmental taxa. Toothbrush microbial communities and resistomes correlated with a variety of factors linked to personal health, dental hygiene, and bathroom features.

CONCLUSIONS: Selective pressures in the built environment may shape the dynamic mixture of human (primarily oral-associated) and environmental microbiota that encounter each other on toothbrushes. Harboring a microbial diversity and resistome distinct from human-associated counterparts suggests toothbrushes could potentially serve as a reservoir that may enable the transfer of ARGs. Video abstract.}, } @article {pmid33499991, year = {2020}, author = {Sidiropoulos, DN and Al-Ghalith, GA and Shields-Cutler, RR and Ward, TL and Johnson, AJ and Vangay, P and Knights, D and Kashyap, PC and Xian, Y and Ramer-Tait, AE and Clayton, JB}, title = {Wild primate microbiomes prevent weight gain in germ-free mice.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {16}, pmid = {33499991}, issn = {2524-4671}, support = {R01 DK114007/DK/NIDDK NIH HHS/United States ; DK114007//Foundation for the National Institutes of Health/ ; T32 DA007097-32/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.

RESULTS: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.

CONCLUSIONS: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.}, } @article {pmid33498226, year = {2021}, author = {Garcia, EM and Serrano, MG and Edupuganti, L and Edwards, DJ and Buck, GA and Jefferson, KK}, title = {Sequence Comparison of Vaginolysin from Different Gardnerella Species.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {2}, pages = {}, pmid = {33498226}, issn = {2076-0817}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/NH/NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, abstract = {Gardnerella vaginalis has recently been split into 13 distinct species. In this study, we tested the hypotheses that species-specific variations in the vaginolysin (VLY) amino acid sequence could influence the interaction between the toxin and vaginal epithelial cells and that VLY variation may be one factor that distinguishes less virulent or commensal strains from more virulent strains. This was assessed by bioinformatic analyses of publicly available Gardnerella spp. sequences and quantification of cytotoxicity and cytokine production from purified, recombinantly produced versions of VLY. After identifying conserved differences that could distinguish distinct VLY types, we analyzed metagenomic data from a cohort of female subjects from the Vaginal Human Microbiome Project to investigate whether these different VLY types exhibited any significant associations with symptoms or Gardnerella spp.-relative abundance in vaginal swab samples. While Type 1 VLY was most prevalent among the subjects and may be associated with increased reports of symptoms, subjects with Type 2 VLY dominant profiles exhibited increased relative Gardnerella spp. abundance. Our findings suggest that amino acid differences alter the interaction of VLY with vaginal keratinocytes, which may potentiate differences in bacterial vaginosis (BV) immunopathology in vivo.}, } @article {pmid33398950, year = {2020}, author = {Duan, Y and Wang, S and Chen, Y and Yang, R and Li, H and Zhu, H and Tong, Y and Wu, W and Fu, Y and Hu, S and Wang, J and Xin, Y and Zhao, F and Bao, Y and Zhang, W and Li, J and Zeng, M and Niu, H and Zhou, X and Li, Y and Cui, S and Yuan, J and Li, J and Wang, J and Liu, D and Ni, M and Sun, Q and Deng, Y and Zhu, B}, title = {[Expert consensus on microbiome sequencing and analysis].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {36}, number = {12}, pages = {2516-2524}, doi = {10.13345/j.cjb.200386}, pmid = {33398950}, issn = {1872-2075}, mesh = {China ; Consensus ; Humans ; Industry ; *Microbiota ; }, abstract = {In the past ten years, the research and application of microbiome has continued to increase. The microbiome has gradually become the research focus in the fields of life science, environmental science, and medicine. Meanwhile, many countries and organizations around the world are launching their own microbiome projects and conducting a multi-faceted layout, striving to gain a strategic position in this promising field. In addition, whether it is scientific research or industrial applications, there has been a climax of research and a wave of investment and financing, accordingly, products and services related to the microbiome are constantly emerging. However, due to the rapid development of microbiome sequencing and analysis related technologies and methods, the research and application from various countries have not yet unified on the standards of technology, programs, and data. Domestic industry participants also have insufficient understanding of the microbiome. New methods, technologies, and theories have not yet been fully accepted and used. In addition, some of the existing standards and guidelines are too general with poor practicality. This not only causes obstacles in the integration of scientific research data and waste of resources, but also gives related companies unfair competition opportunity. More importantly, China still lacks national standards related to the microbiome, and the national microbiome project is still in the process of preparation. In this context, the experts and practitioners of the microbiome worked together and developed the consensus of experts. It can not only guide domestic scientific research and industrial institutions to regulate the production, learning and research of the microbiome, the application can also provide reference technical basis for the relevant national functional departments, protect the scale and standardized corporate company's interests, strengthen industry self-discipline, avoid unregulated enterprises from disrupting the market, and ultimately promote the benign development of microbiome-related industries.}, } @article {pmid33323705, year = {2020}, author = {Gomes, JÁP and Frizon, L and Demeda, VF}, title = {Ocular Surface Microbiome in Health and Disease.}, journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)}, volume = {9}, number = {6}, pages = {505-511}, pmid = {33323705}, issn = {2162-0989}, mesh = {Bacteria/*isolation & purification ; Eye/*microbiology ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics/metabolism ; }, abstract = {The ocular surface is exposed continuously to the environment and, as a consequence, to a variety of different microbes. After the results of the Human Microbiome Project became publicly available, international research groups started to focus interest on exploring the ocular surface microbiome and its physiopathological relationship to the eye. For example, numerous research studies the existence of the ocular surface's bacterial flora, typically gathering cultures from healthy patients and finding few variations in the bacterial species. More recently, culture-independent methods, including 16S ribosomal ribonucleic acid (rRNA) gene sequencing, are being used to define the ocular microbiome. These newer methods suggest that the microbial communities have a greater diversity than previously reported. These communities seem to serve an immune-modulating function and maintain relationships with other microbes and organs, even distant ones. This review summarizes the literature exploring the ocular microbiome, both in health and in different diseases.}, } @article {pmid33323129, year = {2020}, author = {Utter, DR and Borisy, GG and Eren, AM and Cavanaugh, CM and Mark Welch, JL}, title = {Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {293}, pmid = {33323129}, issn = {1474-760X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Chromosome Mapping ; Haemophilus parainfluenzae/genetics ; Humans ; *Metagenome ; Microbiota/*genetics ; Micrococcaceae/genetics ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.

RESULTS: Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa, Haemophilus parainfluenzae and the genus Rothia, metapangenomes reveal distinct genomic groups based on shared genome content. H. parainfluenzae genomes separate into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identify an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genus Rothia, grouping by shared genome content recapitulates species-level taxonomy and habitat preferences. However, while most R. mucilaginosa are restricted to the tongue as expected, two genomes represent a cryptic population of R. mucilaginosa in many buccal mucosa samples. For both H. parainfluenzae and the genus Rothia, we identify not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences are absent or ubiquitous.

CONCLUSIONS: Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.}, } @article {pmid33322780, year = {2020}, author = {Oliveira, BFR and Lopes, IR and Canellas, ALB and Muricy, G and Dobson, ADW and Laport, MS}, title = {Not That Close to Mommy: Horizontal Transmission Seeds the Microbiome Associated with the Marine Sponge Plakina cyanorosea.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33322780}, issn = {2076-2607}, abstract = {Marine sponges are excellent examples of invertebrate-microbe symbioses. In this holobiont, the partnership has elegantly evolved by either transmitting key microbial associates through the host germline and/or capturing microorganisms from the surrounding seawater. We report here on the prokaryotic microbiota during different developmental stages of Plakina cyanorosea and their surrounding environmental samples by a 16S rRNA metabarcoding approach. In comparison with their source adults, larvae housed slightly richer and more diverse microbial communities, which are structurally more related to the environmental microbiota. In addition to the thaumarchaeal Nitrosopumilus, parental sponges were broadly dominated by Alpha- and Gamma-proteobacteria, while the offspring were particularly enriched in the Vibrionales, Alteromonodales, Enterobacterales orders and the Clostridia and Bacteroidia classes. An enterobacterial operational taxonomic unit (OTU) was the dominant member of the strict core microbiota. The most abundant and unique OTUs were not significantly enriched amongst the microbiomes from host specimens included in the sponge microbiome project. In a wider context, Oscarella and Plakina are the sponge genera with higher divergence in their associated microbiota compared to their Homoscleromorpha counterparts. Our results indicate that P. cyanorosea is a low microbial abundance sponge (LMA), which appears to heavily depend on the horizontal transmission of its microbial partners that likely help the sponge host in the adaptation to its habitat.}, } @article {pmid33307384, year = {2021}, author = {Ghemrawi, M and Torres, AR and Duncan, G and Colwell, R and Dadlani, M and McCord, B}, title = {The genital microbiome and its potential for detecting sexual assault.}, journal = {Forensic science international. Genetics}, volume = {51}, number = {}, pages = {102432}, doi = {10.1016/j.fsigen.2020.102432}, pmid = {33307384}, issn = {1878-0326}, mesh = {Adult ; Aged ; DNA, Bacterial/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Metagenomics ; *Microbiota ; Middle Aged ; Penis/*microbiology ; Pilot Projects ; Sequence Analysis, DNA ; *Sex Offenses ; Skin/microbiology ; Vagina/*microbiology ; Young Adult ; }, abstract = {Since its inception, the Human Microbiome Project (HMP) has provided key discoveries that can be applied to forensics, in addition to those of obvious medical value. Whether for postmortem interval estimation, geolocation, or human identification, there are many applications of the microbiome as an investigative lead for forensic casework. The human skin microbiome has shown great potential for use in studies of transfer and human identification, however there has been little focus on the genital microbiome, in particular penile skin which differs from other body sites. Our preliminary data on both the penile and vaginal microbiome demonstrates potential value in cases of sexual assault. In this study we describe genital microbial signatures based on the analysis of five male and five female genital samples and compare these results to those from longitudinal studies. Selected taxa, e.g., Gardnerella, Lactobacilli, Finegoldia, Peptoniphilus, and Anaerococci, are shown to be candidate constituents of the genital microbiome that merit investigation for use in sexual assault casework.}, } @article {pmid33305317, year = {2021}, author = {Creasy, HH and Felix, V and Aluvathingal, J and Crabtree, J and Ifeonu, O and Matsumura, J and McCracken, C and Nickel, L and Orvis, J and Schor, M and Giglio, M and Mahurkar, A and White, O}, title = {HMPDACC: a Human Microbiome Project Multi-omic data resource.}, journal = {Nucleic acids research}, volume = {49}, number = {D1}, pages = {D734-D742}, pmid = {33305317}, issn = {1362-4962}, support = {OT3 OD025459/OD/NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Humans ; Internet ; *Microbiota ; Search Engine ; }, abstract = {The Human Microbiome Project (HMP) explored microbial communities of the human body in both healthy and disease states. Two phases of the HMP (HMP and iHMP) together generated >48TB of data (public and controlled access) from multiple, varied omics studies of both the microbiome and associated hosts. The Human Microbiome Project Data Coordination Center (HMPDACC) was established to provide a portal to access data and resources produced by the HMP. The HMPDACC provides a unified data repository, multi-faceted search functionality, analysis pipelines and standardized protocols to facilitate community use of HMP data. Recent efforts have been put toward making HMP data more findable, accessible, interoperable and reusable. HMPDACC resources are freely available at www.hmpdacc.org.}, } @article {pmid33290720, year = {2021}, author = {Durrant, MG and Bhatt, AS}, title = {Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes.}, journal = {Cell host & microbe}, volume = {29}, number = {1}, pages = {121-131.e4}, pmid = {33290720}, issn = {1934-6069}, support = {P30 CA124435/CA/NCI NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Bacterial Proteins/genetics ; Computational Biology ; Deep Learning ; *Genome, Bacterial ; Humans ; Markov Chains ; Microbiota ; Models, Theoretical ; *Molecular Sequence Annotation ; *Open Reading Frames ; }, abstract = {Small open reading frames (smORFs) and their encoded microproteins play central roles in microbes. However, there is a vast unexplored space of smORFs within human-associated microbes. A recent bioinformatic analysis used evolutionary conservation signals to enhance prediction of small protein families. To facilitate the annotation of specific smORFs, we introduce SmORFinder. This tool combines profile hidden Markov models of each smORF family and deep learning models that better generalize to smORF families not seen in the training set, resulting in predictions enriched for Ribo-seq translation signals. Feature importance analysis reveals that the deep learning models learn to identify Shine-Dalgarno sequences, deprioritize the wobble position in each codon, and group codon synonyms found in the codon table. A core-genome analysis of 26 bacterial species identifies several core smORFs of unknown function. We pre-compute smORF annotations for thousands of RefSeq isolate genomes and Human Microbiome Project metagenomes and provide these data through a public web portal.}, } @article {pmid33281440, year = {2020}, author = {Joseph, N and Clayton, JB and Hoops, SL and Linhardt, CA and Mohd Hashim, A and Mohd Yusof, BN and Kumar, S and Amin Nordin, S}, title = {Alteration of the Gut Microbiome in Normal and Overweight School Children from Selangor with Lactobacillus Fermented Milk Administration.}, journal = {Evolutionary bioinformatics online}, volume = {16}, number = {}, pages = {1176934320965943}, pmid = {33281440}, issn = {1176-9343}, abstract = {Childhood obesity is a serious public health problem worldwide. Perturbations in the gut microbiota composition have been associated with the development of obesity in both children and adults. Probiotics, on the other hand, are proven to restore the composition of the gut microbiome which helps reduce the development of obesity. However, data on the effect of probiotics on gut microbiota and its association with childhood obesity is limited. This study aims to determine the effect of probiotics supplement intervention on gut microbiota profiles in obese and normal-weight children. A total of 37 children, 17 normal weight, and 20 overweight school children from a government school in Selangor were selected to participate in this study. Participants were further divided into intervention and control groups. The intervention groups received daily probiotic drinks while the control groups continued eating their typical diet. Fecal samples were collected from the participants for DNA extraction. The hypervariable V3 and V4 regions of 16S rRNA gene were amplified and sequenced using the Illumina MiSeq platform. No significant differences in alpha diversity were observed between normal weight and obese children in terms of the Shannon Index for evenness or species richness. However, a higher intervention effect on alpha diversity was observed among normal-weight participants compared to obese. The participants' microbiome was found to fluctuate throughout the study. Analysis of the taxa at species level showed an increase in Bacteroides ovatus among the normal weight cohort. Genus-level comparison revealed a rise in genus Lachnospira and Ruminococcus in the overweight participants after intervention, compared to the normal-weight participants. The probiotics intervention causes an alteration in gut microbiota composition in both normal and overweight children. Though the association could not be defined statistically, this study has provided an improved understanding of the intervention effect of probiotics on gut microbiome dysbiosis in an underrepresented population.}, } @article {pmid33215610, year = {2020}, author = {Madi, N and Vos, M and Murall, CL and Legendre, P and Shapiro, BJ}, title = {Does diversity beget diversity in microbiomes?.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {33215610}, issn = {2050-084X}, mesh = {*Biodiversity ; Biota/genetics ; Ecosystem ; High-Throughput Nucleotide Sequencing ; *Microbiota/genetics ; }, abstract = {Microbes are embedded in complex communities where they engage in a wide array of intra- and inter-specific interactions. The extent to which these interactions drive or impede microbiome diversity is not well understood. Historically, two contrasting hypotheses have been suggested to explain how species interactions could influence diversity. 'Ecological Controls' (EC) predicts a negative relationship, where the evolution or migration of novel types is constrained as niches become filled. In contrast, 'Diversity Begets Diversity' (DBD) predicts a positive relationship, with existing diversity promoting the accumulation of further diversity via niche construction and other interactions. Using high-throughput amplicon sequencing data from the Earth Microbiome Project, we provide evidence that DBD is strongest in low-diversity biomes, but weaker in more diverse biomes, consistent with biotic interactions initially favouring the accumulation of diversity (as predicted by DBD). However, as niches become increasingly filled, diversity hits a plateau (as predicted by EC).}, } @article {pmid33117966, year = {2020}, author = {Mise, K and Iwasaki, W}, title = {Environmental Atlas of Prokaryotes Enables Powerful and Intuitive Habitat-Based Analysis of Community Structures.}, journal = {iScience}, volume = {23}, number = {10}, pages = {101624}, pmid = {33117966}, issn = {2589-0042}, abstract = {The recent prevalence of high-throughput sequencing has been producing numerous prokaryotic community structure datasets. Although the trait-based approach is useful to interpret those datasets from ecological perspectives, available trait information is biased toward culturable prokaryotes, especially those of clinical and public health relevance, and thus may not represent the breadth of microbiota found across many of Earth's environments. To facilitate habitat-based analysis free of such bias, here we report a ready-to-use prokaryotic habitat database, ProkAtlas. ProkAtlas comprehensively links 16S rRNA gene sequences to prokaryotic habitats, using public shotgun metagenome datasets. We also developed a computational pipeline for habitat-based analysis of given prokaryotic community structures. After confirmation of the method effectiveness using 16S rRNA gene sequence datasets from individual genomes and the Earth Microbiome Project, we showed its validness and effectiveness in drawing ecological insights by applying it to six empirical prokaryotic community datasets from soil, aquatic, and human gut samples.}, } @article {pmid33077849, year = {2020}, author = {Sternes, PR and Martin, TM and Paley, M and Diamond, S and Asquith, MJ and Brown, MA and Rosenbaum, JT}, title = {HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17636}, pmid = {33077849}, issn = {2045-2322}, support = {R01 EY029266/EY/NEI NIH HHS/United States ; EY029266/NH/NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Alleles ; Birdshot Chorioretinopathy/*genetics/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; HLA-A Antigens/*genetics ; Humans ; Male ; *Metagenome ; Middle Aged ; Whole Genome Sequencing ; }, abstract = {Birdshot retinochoroidopathy occurs exclusively in individuals who are HLA-A29 positive. The mechanism to account for this association is unknown. The gut microbiome has been causally implicated in many immune-mediated diseases. We hypothesized that HLA-A29 would affect the composition of the gut microbiome, leading to a dysbiosis and immune-mediated eye disease. Fecal and intestinal biopsy samples were obtained from 107 healthy individuals from Portland, Oregon environs, 10 of whom were HLA-A29 positive, undergoing routine colonoscopy. Bacterial profiling was achieved via 16S rRNA metabarcoding. Publicly available whole meta-genome sequencing data from the Human Microbiome Project (HMP), consisting of 298 healthy controls mostly of US origin, were also interrogated. PERMANOVA and sparse partial least squares discriminant analysis (sPLSDA) demonstrated that subjects who were HLA-A29 positive differed in bacterial species composition (beta diversity) compared to HLA-A29 negative subjects in both the Portland (p = 0.019) and HMP cohorts (p = 0.0002). The Portland and HMP cohorts evidenced different subsets of bacterial species associated with HLA-A29 status, likely due to differences in the metagenomic techniques employed. The functional composition of the HMP cohort did not differ overall (p = 0.14) between HLA-A29 positive and negative subjects, although some distinct pathways such as heparan sulfate biosynthesis showed differences. As we and others have shown for various HLA alleles, the HLA allotype impacts the composition of the microbiome. We hypothesize that HLA-A29 may predispose chorioretinitis via an altered gut microbiome.}, } @article {pmid33044333, year = {2021}, author = {Mancin, L and Rollo, I and Mota, JF and Piccini, F and Carletti, M and Susto, GA and Valle, G and Paoli, A}, title = {Optimizing Microbiota Profiles for Athletes.}, journal = {Exercise and sport sciences reviews}, volume = {49}, number = {1}, pages = {42-49}, doi = {10.1249/JES.0000000000000236}, pmid = {33044333}, issn = {1538-3008}, mesh = {Athletes ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Sports ; }, abstract = {Gut microbiome influences athletes' physiology, but because of the complexity of sport performance and the great intervariability of microbiome features, it is not reasonable to define a single healthy microbiota profile for athletes. We suggest the use of specific meta-omics analysis coupled with innovative computational systems to uncover the hidden association between microbes and athlete's physiology and predict personalized recommendation.}, } @article {pmid33042093, year = {2020}, author = {Zelaya, AJ and Gerardo, NM and Blumer, LS and Beck, CW}, title = {The Bean Beetle Microbiome Project: A Course-Based Undergraduate Research Experience in Microbiology.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {577621}, pmid = {33042093}, issn = {1664-302X}, abstract = {Course-based undergraduate research experiences (CUREs) are an effective means of transforming the learning and teaching of science by involving students in the scientific process. The potential importance of the microbiome in shaping both environmental health and disease makes investigations of microbiomes an excellent teaching tool for undergraduate microbiology. Here, we present a CURE based on the microbiome of the bean beetle (Callosobruchus maculatus), a model system for undergraduate laboratory education. Despite the extensive research literature on bean beetles, little is known about their microbiome, making them an ideal system for a discovery-based CURE. In the CURE, students acquire microbiological technical skills by characterizing both culturable and unculturable members of the beetle gut-microbial community. Students plate beetle gut homogenates on different media, describe the colonies that are formed to estimate taxonomic diversity, extract DNA from colonies of interest, PCR amplify the16S rRNA gene for Sanger sequencing, and use the NCBI-nBLAST database to taxonomically classify sequences. Additionally, students extract total DNA from beetle gut homogenates for high-throughput paired-end sequencing and perform bioinformatic and statistical analyses of bacterial communities using a combination of open-access data processing software. Each activity allows students to engage with studies of microbiomes in a real-world context, to apply concepts and laboratory techniques to investigate either student or faculty-driven research questions, and to gain valuable experiences working with large high-throughput datasets. The CURE is designed such that it can be implemented over either 6-weeks (half semester) or 12-weeks (full semester), allowing for flexibility within the curriculum. Furthermore, student-generated data from the CURE (including bacterial colony phenotypic data, full-length 16S rRNA gene sequences from cultured isolates, and bacterial community sequences from gut homogenates) has been compiled in a continuously curated open-access database on the Bean Beetle Microbiome Project website, facilitating the generation of broader research questions across laboratory classrooms.}, } @article {pmid32993284, year = {2020}, author = {Ervin, SM and Simpson, JB and Gibbs, ME and Creekmore, BC and Lim, L and Walton, WG and Gharaibeh, RZ and Redinbo, MR}, title = {Structural Insights into Endobiotic Reactivation by Human Gut Microbiome-Encoded Sulfatases.}, journal = {Biochemistry}, volume = {59}, number = {40}, pages = {3939-3950}, doi = {10.1021/acs.biochem.0c00711}, pmid = {32993284}, issn = {1520-4995}, mesh = {Bacteria/chemistry/*enzymology/genetics/metabolism ; Catalytic Domain ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genes, Bacterial ; Humans ; *Microbiota ; Models, Molecular ; Protein Conformation ; Sulfatases/chemistry/genetics/*metabolism ; }, abstract = {Phase II drug metabolism inactivates xenobiotics and endobiotics through the addition of either a glucuronic acid or sulfate moiety prior to excretion, often via the gastrointestinal tract. While the human gut microbial β-glucuronidase enzymes that reactivate glucuronide conjugates in the intestines are becoming well characterized and even controlled by targeted inhibitors, the sulfatases encoded by the human gut microbiome have not been comprehensively examined. Gut microbial sulfatases are poised to reactivate xenobiotics and endobiotics, which are then capable of undergoing enterohepatic recirculation or exerting local effects on the gut epithelium. Here, using protein structure-guided methods, we identify 728 distinct microbiome-encoded sulfatase proteins from the 4.8 million unique proteins present in the Human Microbiome Project Stool Sample database and 1766 gut microbial sulfatases from the 9.9 million sequences in the Integrated Gene Catalogue. We purify a representative set of these sulfatases, elucidate crystal structures, and pinpoint unique structural motifs essential to endobiotic sulfate processing. Gut microbial sulfatases differentially process sulfated forms of the neurotransmitters serotonin and dopamine, and the hormones melatonin, estrone, dehydroepiandrosterone, and thyroxine in a manner dependent both on variabilities in active site architecture and on markedly distinct oligomeric states. Taken together, these data provide initial insights into the structural and functional diversity of gut microbial sulfatases, providing a path toward defining the roles these enzymes play in health and disease.}, } @article {pmid32976571, year = {2021}, author = {Gail, MH and Wan, Y and Shi, J}, title = {Power of Microbiome Beta-Diversity Analyses Based on Standard Reference Samples.}, journal = {American journal of epidemiology}, volume = {190}, number = {3}, pages = {439-447}, pmid = {32976571}, issn = {1476-6256}, mesh = {*Body Mass Index ; Feces/microbiology ; Humans ; Microbiota/*physiology ; Nose/microbiology ; Reference Standards ; Saliva/microbiology ; Skin/microbiology ; }, abstract = {A simple method to analyze microbiome beta-diversity computes mean beta-diversity distances from a test sample to standard reference samples. We used reference stool and nasal samples from the Human Microbiome Project and regressed an outcome on mean distances (2 degrees-of-freedom (df) test) or additionally on squares and cross-product of mean distances (5-df test). We compared the power of 2-df and 5-df tests with the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2-df test for discriminating skin versus saliva and skin versus nasal samples, but differences were negligible for skin versus stool and stool versus nasal samples. The 2-df test had slightly greater power than MiRKAT for Dirichlet multinomial samples. In associating body mass index with beta-diversity in stool samples from the American Gut Project, the 5-df test yielded smaller P values than MiRKAT for most taxonomic levels and beta-diversity measures. Unlike procedures like MiRKAT that are based on the beta-diversity matrix, mean distances to reference samples can be analyzed with standard statistical tools and shared or meta-analyzed without sharing primary DNA data. Our data indicate that standard reference tests have power comparable to MiRKAT's (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.}, } @article {pmid32966309, year = {2020}, author = {Walters, KE and Martiny, JBH}, title = {Alpha-, beta-, and gamma-diversity of bacteria varies across habitats.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0233872}, pmid = {32966309}, issn = {1932-6203}, mesh = {Bacteria/*classification ; Databases, Genetic ; *Ecosystem ; Microbiota ; RNA, Ribosomal, 16S/genetics ; *Soil Microbiology ; }, abstract = {Bacteria are essential parts of ecosystems and are the most diverse organisms on the planet. Yet, we still do not know which habitats support the highest diversity of bacteria across multiple scales. We analyzed alpha-, beta-, and gamma-diversity of bacterial assemblages using 11,680 samples compiled by the Earth Microbiome Project. We found that soils contained the highest bacterial richness within a single sample (alpha-diversity), but sediment assemblages displayed the highest gamma-diversity. Sediment, biofilms/mats, and inland water exhibited the most variation in community composition among geographic locations (beta-diversity). Within soils, agricultural lands, hot deserts, grasslands, and shrublands contained the highest richness, while forests, cold deserts, and tundra biomes consistently harbored fewer bacterial species. Surprisingly, agricultural soils encompassed similar levels of beta-diversity as other soil biomes. These patterns were robust to the alpha- and beta- diversity metrics used and the taxonomic binning approach. Overall, the results support the idea that spatial environmental heterogeneity is an important driver of bacterial diversity.}, } @article {pmid32938501, year = {2020}, author = {Zhang, Z and Wang, J and Wang, J and Wang, J and Li, Y}, title = {Estimate of the sequenced proportion of the global prokaryotic genome.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {134}, pmid = {32938501}, issn = {2049-2618}, mesh = {Archaea/classification/genetics/isolation & purification ; Bacteria/classification/genetics/isolation & purification ; Databases, Genetic ; *Earth, Planet ; Genome/*genetics ; Genomics/*statistics & numerical data ; Microbiota/*genetics ; Prokaryotic Cells/*classification/*metabolism ; Sequence Alignment ; Sequence Analysis/*statistics & numerical data ; }, abstract = {BACKGROUND: Sequencing prokaryotic genomes has revolutionized our understanding of the many roles played by microorganisms. However, the cell and taxon proportions of genome-sequenced bacteria or archaea on earth remain unknown. This study aimed to explore this basic question using large-scale alignment between the sequences released by the Earth Microbiome Project and 155,810 prokaryotic genomes from public databases.

RESULTS: Our results showed that the median proportions of the genome-sequenced cells and taxa (at 100% identities in the 16S-V4 region) in different biomes reached 38.1% (16.4-86.3%) and 18.8% (9.1-52.6%), respectively. The sequenced proportions of the prokaryotic genomes in biomes were significantly negatively correlated with the alpha diversity indices, and the proportions sequenced in host-associated biomes were significantly higher than those in free-living biomes. Due to a set of cosmopolitan OTUs that are found in multiple samples and preferentially sequenced, only 2.1% of the global prokaryotic taxa are represented by sequenced genomes. Most of the biomes were occupied by a few predominant taxa with a high relative abundance and much higher genome-sequenced proportions than numerous rare taxa.

CONCLUSIONS: These results reveal the current situation of prokaryotic genome sequencing for earth biomes, provide a more reasonable and efficient exploration of prokaryotic genomes, and promote our understanding of microbial ecological functions. Video Abstract.}, } @article {pmid32938362, year = {2020}, author = {Guerrini, V and Louza, FA and Rosone, G}, title = {Metagenomic analysis through the extended Burrows-Wheeler transform.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 8}, pages = {299}, pmid = {32938362}, issn = {1471-2105}, mesh = {*Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Reproducibility of Results ; }, abstract = {BACKGROUND: The development of Next Generation Sequencing (NGS) has had a major impact on the study of genetic sequences. Among problems that researchers in the field have to face, one of the most challenging is the taxonomic classification of metagenomic reads, i.e., identifying the microorganisms that are present in a sample collected directly from the environment. The analysis of environmental samples (metagenomes) are particularly important to figure out the microbial composition of different ecosystems and it is used in a wide variety of fields: for instance, metagenomic studies in agriculture can help understanding the interactions between plants and microbes, or in ecology, they can provide valuable insights into the functions of environmental communities.

RESULTS: In this paper, we describe a new lightweight alignment-free and assembly-free framework for metagenomic classification that compares each unknown sequence in the sample to a collection of known genomes. We take advantage of the combinatorial properties of an extension of the Burrows-Wheeler transform, and we sequentially scan the required data structures, so that we can analyze unknown sequences of large collections using little internal memory. The tool LiME (Lightweight Metagenomics via eBWT) is available at https://github.com/veronicaguerrini/LiME .

CONCLUSIONS: In order to assess the reliability of our approach, we run several experiments on NGS data from two simulated metagenomes among those provided in benchmarking analysis and on a real metagenome from the Human Microbiome Project. The experiment results on the simulated data show that LiME is competitive with the widely used taxonomic classifiers. It achieves high levels of precision and specificity - e.g. 99.9% of the positive control reads are correctly assigned and the percentage of classified reads of the negative control is less than 0.01% - while keeping a high sensitivity. On the real metagenome, we show that LiME is able to deliver classification results comparable to that of MagicBlast. Overall, the experiments confirm the effectiveness of our method and its high accuracy even in negative control samples.}, } @article {pmid32917276, year = {2020}, author = {Golovko, G and Kamil, K and Albayrak, L and Nia, AM and Duarte, RSA and Chumakov, S and Fofanov, Y}, title = {Identification of multidimensional Boolean patterns in microbial communities.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {131}, pmid = {32917276}, issn = {2049-2618}, support = {R03 DE028596/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/isolation & purification ; Humans ; *Microbial Interactions ; *Microbiota/physiology ; }, abstract = {BACKGROUND: Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches.

RESULTS: We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data.

CONCLUSIONS: The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract.}, } @article {pmid32888342, year = {2020}, author = {Reyes-Gibby, CC and Wang, J and Zhang, L and Peterson, CB and Do, KA and Jenq, RR and Shelburne, S and Shah, DP and Chambers, MS and Hanna, EY and Yeung, SJ and Shete, S}, title = {Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.}, journal = {Cancer}, volume = {126}, number = {23}, pages = {5124-5136}, pmid = {32888342}, issn = {1097-0142}, support = {RP160693//Cancer Prevention and Research Institute of Texas/ ; R01 CA131324/CA/NCI NIH HHS/United States ; P50 CA140388/CA/NCI NIH HHS/United States ; P50CA140388/CA/NCI NIH HHS/United States ; RP170259//Cancer Prevention and Research Institute of Texas/ ; UL1 TR003167/TR/NCATS NIH HHS/United States ; 1R01CA131324/CA/NCI NIH HHS/United States ; R01DE022891/DE/NIDCR NIH HHS/United States ; R21DE026837/DE/NIDCR NIH HHS/United States ; CA016672/CA/NCI NIH HHS/United States ; //Betty B. Marcus Chair in Cancer Prevention/ ; R21 DE026837/DE/NIDCR NIH HHS/United States ; R01 DE022891/DE/NIDCR NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Female ; Head and Neck Neoplasms/microbiology/*therapy ; Humans ; Male ; *Microbiota/drug effects/radiation effects ; Middle Aged ; RNA, Ribosomal, 16S ; Squamous Cell Carcinoma of Head and Neck/microbiology/*therapy ; Stomatitis/*etiology/microbiology ; Time Factors ; }, abstract = {BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC.

METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM.

RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data.

CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.}, } @article {pmid32884579, year = {2020}, author = {Katongole, P and Sande, OJ and Joloba, M and Reynolds, SJ and Niyonzima, N}, title = {The human microbiome and its link in prostate cancer risk and pathogenesis.}, journal = {Infectious agents and cancer}, volume = {15}, number = {}, pages = {53}, pmid = {32884579}, issn = {1750-9378}, support = {D43 TW010132/TW/FIC NIH HHS/United States ; }, abstract = {There is growing evidence of the microbiome's role in human health and disease since the human microbiome project. The microbiome plays a vital role in influencing cancer risk and pathogenesis. Several studies indicate microbial pathogens to account for over 15-20% of all cancers. Furthermore, the interaction of the microbiota, especially the gut microbiota in influencing response to chemotherapy, immunotherapy, and radiotherapy remains an area of active research. Certain microbial species have been linked to the improved clinical outcome when on different cancer therapies. The recent discovery of the urinary microbiome has enabled the study to understand its connection to genitourinary malignancies, especially prostate cancer. Prostate cancer is the second most common cancer in males worldwide. Therefore research into understanding the factors and mechanisms associated with prostate cancer etiology, pathogenesis, and disease progression is of utmost importance. In this review, we explore the current literature concerning the link between the gut and urinary microbiome and prostate cancer risk and pathogenesis.}, } @article {pmid32881767, year = {2020}, author = {Brenner, LA and Stamper, CE and Hoisington, AJ and Stearns-Yoder, KA and Stanislawksi, MA and Brostow, DP and Hoffmire, CA and Forster, JE and Schneider, AL and Postolache, TT and Lowry, CA}, title = {Microbial Diversity and Community Structures Among Those With Moderate to Severe TBI: A United States-Veteran Microbiome Project Study.}, journal = {The Journal of head trauma rehabilitation}, volume = {35}, number = {5}, pages = {332-341}, doi = {10.1097/HTR.0000000000000615}, pmid = {32881767}, issn = {1550-509X}, mesh = {*Brain Concussion/microbiology ; *Brain Injuries, Traumatic/microbiology ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S/genetics ; United States/epidemiology ; *Veterans ; }, abstract = {OBJECTIVE: To evaluate the association between distal moderate/severe traumatic brain injury (TBI) history and the human gut microbiome.

SETTING: Veterans Affairs Medical Center.

PARTICIPANTS: Veterans from the United States-Veteran Microbiome Project (US-VMP). Veterans with moderate/severe TBI (n = 34) were compared with (1) Veterans with a history of no TBI (n = 79) and (2) Veterans with a history of no TBI or mild TBI only (n = 297).

DESIGN: Microbiome analyses from 16S rRNA gene sequencing with gut microbiota function inferred using PICRUSt2.

MAIN MEASURES: α-Diversity and β-diversity of the gut microbiome, as well as taxonomic and functional signatures associated with moderate/severe TBI.

RESULTS: There were no significant differences in gut bacterial α- and β-diversity associated with moderate/severe TBI status. No differentially abundant taxa were identified when comparing samples from moderate/severe TBI to those with no TBI or no TBI/mild TBI.

CONCLUSION: Results suggest that moderate/severe TBI-related changes to the gut microbiome do not persist for years postinjury.}, } @article {pmid32879794, year = {2020}, author = {Odogwu, NM and Olayemi, OO and Omigbodun, AO}, title = {The vaginal microbiome of sub-Saharan African women: revealing important gaps in the era of next-generation sequencing.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9684}, pmid = {32879794}, issn = {2167-8359}, abstract = {Accurate characterization of the vaginal microbiome remains a fundamental goal of the Human Microbiome project (HMP). For over a decade, this goal has been made possible deploying high-throughput next generation sequencing technologies (NGS), which indeed has revolutionized medical research and enabled large-scale genomic studies. The 16S rRNA marker-gene survey is the most commonly explored approach for vaginal microbial community studies. With this approach, prior studies have elucidated substantial variations in the vaginal microbiome of women from different ethnicities. This review provides a comprehensive account of studies that have deployed this approach to describe the vaginal microbiota of African women in health and disease. On the basis of published data, the few studies reported from the African population are mainly in non-pregnant post pubertal women and calls for more detailed studies in pregnant and postnatal cohorts. We provide insight on the use of more sophisticated cutting-edge technologies in characterizing the vaginal microbiome. These technologies offer high-resolution detection of vaginal microbiome variations and community functional capabilities, which can shed light into several discrepancies observed in the vaginal microbiota of African women in an African population versus women of African descent in the diaspora.}, } @article {pmid32815317, year = {2020}, author = {Nascimento Lemos, L and Manoharan, L and William Mendes, L and Monteiro Venturini, A and Satler Pylro, V and Tsai, SM}, title = {Metagenome assembled-genomes reveal similar functional profiles of CPR/Patescibacteria phyla in soils.}, journal = {Environmental microbiology reports}, volume = {12}, number = {6}, pages = {651-655}, doi = {10.1111/1758-2229.12880}, pmid = {32815317}, issn = {1758-2229}, support = {//Brazilian Microbiome Project/International ; 140032/2015-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; 161931/2015-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; Finance Code 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/International ; 2014/50320-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2015/13546-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2016/18215-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2017/09643-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2017/24037-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; //Coordination for the Improvement of Higher Education Personnel/International ; //National Council for Scientific and Technological Development/International ; //São Paulo Research Foundation/International ; }, mesh = {Bacteria/classification/*genetics/isolation & purification ; Databases, Genetic ; Genome Size ; *Genome, Bacterial ; Metagenome ; Microbiota ; Phylogeny ; *Soil Microbiology ; }, abstract = {Soil microbiome is one of the most heterogeneous biological systems. State-of-the-art molecular approaches such as those based on single-amplified genomes (SAGs) and metagenome assembled-genomes (MAGs) are now improving our capacity for disentailing soil microbial-mediated processes. Here, we analysed publicly available datasets of soil microbial genomes and MAG's reconstructed from the Amazon's tropical soil (primary forest and pasture) and active layer of permafrost, aiming to evaluate their genome size. Our results suggest that the Candidate Phyla Radiation (CPR)/Patescibacteria phyla have genomes with an average size fourfold smaller than the mean identified in the RefSoil database, which lacks any representative of this phylum. Also, by analysing the potential metabolism of 888 soil microbial genomes, we show that CPR/Patescibacteria representatives share similar functional profiles, but different from other microbial phyla and are frequently neglected in the soil microbial surveys. Finally, we argue that the use of MAGs may be a better choice over SAGs to expand the soil microbial databases, like RefSoil.}, } @article {pmid32717337, year = {2021}, author = {Chadha, J and Nandi, D and Atri, Y and Nag, A}, title = {Significance of human microbiome in breast cancer: Tale of an invisible and an invincible.}, journal = {Seminars in cancer biology}, volume = {70}, number = {}, pages = {112-127}, doi = {10.1016/j.semcancer.2020.07.010}, pmid = {32717337}, issn = {1096-3650}, mesh = {Animals ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/*drug therapy/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Prebiotics/*administration & dosage ; *Precision Medicine ; }, abstract = {The human microbiome is a mysterious treasure of the body playing endless important roles in the well-being of the host metabolism, digestion, and immunity. On the other hand, it actively participates in the development of a variety of pathological conditions including cancer. With the Human Microbiome Project initiative, metagenomics, and next-generation sequencing technologies in place, the last decade has witnessed immense explorations and investigations on the enigmatic association of breast cancer with the human microbiome. However, the connection between the human microbiome and breast cancer remains to be explored in greater detail. In fact, there are several emerging questions such as whether the host microbiota contributes to disease initiation, or is it a consequence of the disease is an irrevocably important question that demands a valid answer. Since the microbiome is an extremely complex community, gaps still remain on how this vital microbial organ plays a role in orchestrating breast cancer development. Nevertheless, undeniable evidence from studies has pinpointed the presence of specific microbial elements of the breast and gut to play a role in governing breast cancer. It is still unclear if an alteration in microbiome/dysbiosis leads to breast cancer or is it vice versa. Though specific microbial signatures have been detected to be associated with various breast cancer subtypes, the structure and composition of a core "healthy" microbiome is yet to be established. Probiotics seem to be a promising antidote for targeted prevention and treatment of breast cancer. Interestingly, these microbial communities can serve as potential biomarkers for prognosis, diagnosis, and treatment of breast cancer, thereby leading to the rise of a completely new era of personalized medicine. This review is a humble attempt to summarize the research findings on the human microbiome and its relation to breast cancer.}, } @article {pmid32684275, year = {2020}, author = {Joseph, TA and Pasarkar, AP and Pe'er, I}, title = {Efficient and Accurate Inference of Mixed Microbial Population Trajectories from Longitudinal Count Data.}, journal = {Cell systems}, volume = {10}, number = {6}, pages = {463-469.e6}, doi = {10.1016/j.cels.2020.05.006}, pmid = {32684275}, issn = {2405-4720}, support = {R01 LM013327/LM/NLM NIH HHS/United States ; }, mesh = {Data Analysis ; Humans ; Longitudinal Studies ; Microbiota/*physiology ; Research Design ; }, abstract = {The recently completed second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease, motivating new microbiome study designs based on longitudinal sampling. Yet, analysis of such data is hindered by presence of technical noise, high dimensionality, and data sparsity. Here, we introduce LUMINATE (longitudinal microbiome inference and zero detection), a fast and accurate method for inferring relative abundances from noisy read count data. We demonstrate that LUMINATE is orders of magnitude faster than current approaches, with better or similar accuracy. We further show that LUMINATE can accurately distinguish biological zeros, when a taxon is absent from the community, from technical zeros, when a taxon is below the detection threshold. We conclude by demonstrating the utility of LUMINATE on a real dataset, showing that LUMINATE smooths trajectories observed from noisy data. LUMINATE is freely available from https://github.com/tyjo/luminate.}, } @article {pmid32660414, year = {2020}, author = {Huh, JW and Roh, TY}, title = {Opportunistic detection of Fusobacterium nucleatum as a marker for the early gut microbial dysbiosis.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {208}, pmid = {32660414}, issn = {1471-2180}, support = {NRF-2014M3C9A3064548, NRF-2017M3C9A6047625//National Research Foundation of Korea/International ; 10Z20130012243//Ministry of Education/International ; S2632274//Technology Development Program of MSS, Republic of Korea/International ; }, mesh = {Bacteria/*classification/isolation & purification ; Discriminant Analysis ; Dysbiosis/*diagnosis ; Feces/microbiology ; Female ; Fusobacterium nucleatum/*isolation & purification ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Logistic Models ; Longitudinal Studies ; Male ; Phylogeny ; }, abstract = {BACKGROUND: The essential roles of gut microbiome have been emphasized in modulating human health and disease. Fusobacterium nucleatum (F. nucleatum), an obligate Gram-negative microorganism residing in oral cavity, gastrointestinal tract and elsewhere, has been recently considered as a potential oncobacterium associated with human cancers. However, the consequence of its enrichment was not extensively explored in terms of microbial homeostasis and stability at the early stage of disease development.

RESULT: Our analysis on longitudinal metagenomic data generated by the Integrative Human Microbiome Project (iHMP) showed that F. nucleatum was frequently found in inflammatory bowel diseases (IBD) subjects with reduced microbial diversity. Using non-parametric logarithmic linear discriminant analysis (LDA) effect size (LEfSe) algorithm, 12 IBD- and 14 non-IBD-specific bacterial species were identified in the fecal metagenome and the IBD-specific ones were over-represented in the F. nucleatum-experienced subjects during long-term surveillance. In addition, F. nucleatum experience severely abrogated intra-personal stability of microbiome in IBD patients and induced highly variable gut microbiome between subjects. From the longitudinal comparison between microbial distributions prior and posterior to F. nucleatum detection, 41 species could be proposed as indicative "classifiers" for dysbiotic gut state. By multiple logistic regression models established on these classifiers, the high probability of experiencing F. nucleatum was significantly correlated with decreased alpha-diversity and increased number of biomarker species for IBD and colorectal cancer (CRC). Finally, microbial clustering confirmed that biomarker species for IBD and non-IBD conditions as well as CRC signature markers were well distinguishable and could be utilized for explaining gut symbiosis and dysbiosis.

CONCLUSION: F. nucleatum opportunistically appeared under early dysbiotic condition in gut, and discriminative classifier species associated with F. nucleatum were successfully applied to predict microbial alterations in both IBD and non-IBD conditions. Our prediction model and microbial classifier biomarkers for estimating gut dysbiosis should provide a novel aspect of microbial homeostasis/dynamics and useful information on non-invasive biomarker screening.}, } @article {pmid32615913, year = {2020}, author = {Ames, NJ and Barb, JJ and Schuebel, K and Mudra, S and Meeks, BK and Tuason, RTS and Brooks, AT and Kazmi, N and Yang, S and Ratteree, K and Diazgranados, N and Krumlauf, M and Wallen, GR and Goldman, D}, title = {Longitudinal gut microbiome changes in alcohol use disorder are influenced by abstinence and drinking quantity.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1608-1631}, pmid = {32615913}, issn = {1949-0984}, support = {Z01 AA000280/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Adult ; Alcohol Abstinence/psychology ; Alcohol Drinking/*metabolism/*psychology ; Ethanol/adverse effects/analysis/*metabolism ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Longitudinal Studies ; Male ; Microbiota/drug effects ; Middle Aged ; }, abstract = {Many patients with alcohol use disorder (AUD) consume alcohol chronically and in large amounts that alter intestinal microbiota, damage the gastrointestinal tract, and thereby injure other organs via malabsorption and intestinal inflammation. We hypothesized that alcohol consumption and subsequent abstinence would change the gut microbiome in adults admitted to a treatment program. Stool and oral specimens, diet data, gastrointestinal assessment scores, anxiety, depression measures and drinking amounts were collected longitudinally for up to 4 weeks in 22 newly abstinent inpatients with AUD who were dichotomized as less heavy drinkers (LHD, <10 drinks/d) and very heavy drinkers (VHD, 10 or more drinks/d). Next-generation 16 S rRNA gene sequencing was performed to measure the gut and oral microbiome at up to ten time points/subject and LHD and VHD were compared for change in principal components, Shannon diversity index and specific genera. The first three principal components explained 46.7% of the variance in gut microbiome diversity across time and all study subjects, indicating the change in gut microbiome following abstinence. The first time point was an outlier in three-dimensional principal component space versus all other time points. The gut microbiota in LHD and VHD were significantly dissimilar in change from day 1 to day 5 (p = .03) and from day 1 to week 3 (p = .02). The VHD drinking group displayed greater change from baseline. The Shannon diversity index of the gut microbiome changed significantly during abstinence in five participants. In both groups, the Shannon diversity was lower in the oral microbiome than gut. Ten total genera were shared between oral and stool in the AUD participants. These data were compared with healthy controls from the Human Microbiome Project to investigate the concept of a core microbiome. Rapid changes in gut microbiome following abstinence from alcohol suggest resilience of the gut microbiome in AUD and reflects the benefits of refraining from the highest levels of alcohol and potential benefits of abstinence.}, } @article {pmid32563152, year = {2020}, author = {Hu, Y and Fang, L and Nicholson, C and Wang, K}, title = {Implications of Error-Prone Long-Read Whole-Genome Shotgun Sequencing on Characterizing Reference Microbiomes.}, journal = {iScience}, volume = {23}, number = {6}, pages = {101223}, pmid = {32563152}, issn = {2589-0042}, abstract = {Long-read sequencing techniques, such as the Oxford Nanopore Technology, can generate reads that are tens of kilobases in length and are therefore particularly relevant for microbiome studies. However, owing to the higher per-base error rates than typical short-read sequencing, the application of long-read sequencing on microbiomes remains largely unexplored. Here we deeply sequenced two human microbiota mock community samples (HM-276D and HM-277D) from the Human Microbiome Project. We showed that assembly programs consistently achieved high accuracy (∼99%) and completeness (∼99%) for bacterial strains with adequate coverage. We also found that long-read sequencing provides accurate estimates of species-level abundance (R = 0.94 for 20 bacteria with abundance ranging from 0.005% to 64%). Our results not only demonstrate the feasibility of characterizing complete microbial genomes and populations from error-prone Nanopore sequencing data but also highlight necessary bioinformatics improvements for future metagenomics tool development.}, } @article {pmid32528054, year = {2020}, author = {Fukui, S and Morimoto, S and Ichinose, K and Nakashima, S and Ishimoto, H and Hara, A and Kakugawa, T and Sakamoto, N and Tsuji, Y and Aramaki, T and Koga, T and Kawashiri, SY and Iwamoto, N and Tamai, M and Nakamura, H and Origuchi, T and Ueki, Y and Suzuki, S and Mukae, H and Kawakami, A}, title = {Comparison of lung microbiota between antineutrophil cytoplasmic antibody-associated vasculitis and sarcoidosis.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9466}, pmid = {32528054}, issn = {2045-2322}, mesh = {Aged ; Aged, 80 and over ; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/immunology/*microbiology ; Antibodies, Antineutrophil Cytoplasmic/*immunology ; Bacteria/genetics/*immunology ; Bronchoalveolar Lavage Fluid/immunology/microbiology ; Female ; Humans ; Lung/*immunology/*microbiology ; Male ; Microbiota/genetics/*immunology ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sarcoidosis/immunology/*microbiology ; }, abstract = {Microbial involvement in the pathogenesis have been suggested in both antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and sarcoidosis, both of which have lung involvement. However, exhaustive research to assess the bacteria in the lung in AAV and in sarcoidosis have not been performed. We sought to elucidate the distinct dysbiotic lung microbiota between AAV and sarcoidosis. We used 16S rRNA gene high-throughput sequencing to obtain the bacterial community composition of bronchoalveolar lavage fluid (BALF) in patients with AAV (n = 16) compared to patients with sarcoidosis (n = 21). The patients had not undergone therapy with immunosuppressive medication when their BALF was acquired. No difference was observed in α-diversity between patients with AAV and patients with sarcoidosis when using all the detected taxa. We defined the taxa of the oral cavity by using the data of oral microbiota of healthy individuals from the Human Microbiome Project (HMP). The analysis using only oral taxa made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. Besides, the analysis using detected taxa except for oral taxa also made the difference in α-diversity between AAV and sarcoidosis clearer compared with those using all the detected taxa. A linear negative relationship between the α-diversity and Birmingham vasculitis activity score (BVAS) was detected in the AAV group. The observed p-value for the effect of the disease groups on the ß-diversity was small while the effect of other factors including sex and smoking status did not have small p-values. By excluding oral taxa from all the detected taxa, we found a cluster mainly consisted of sarcoidosis patients which was characterized with microbial community monopolized by Erythrobacteraceae family. Our results suggested the importance of considering the influence of oral microbiota in evaluating lung microbiota.}, } @article {pmid32518316, year = {2020}, author = {Chen, YR and Zheng, HM and Zhang, GX and Chen, FL and Chen, LD and Yang, ZC}, title = {High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9364}, pmid = {32518316}, issn = {2045-2322}, mesh = {*Body Mass Index ; China ; Clostridiales/*isolation & purification/physiology ; Constipation/*microbiology ; Female ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Male ; Middle Aged ; }, abstract = {Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.}, } @article {pmid32515629, year = {2020}, author = {Voth, E and Khanna, S}, title = {The Integrative Human microbiome project: a mile stone in the understanding of the gut microbiome.}, journal = {Expert review of gastroenterology & hepatology}, volume = {14}, number = {8}, pages = {639-642}, doi = {10.1080/17474124.2020.1780912}, pmid = {32515629}, issn = {1747-4132}, mesh = {Diabetes Mellitus/*microbiology ; Dysbiosis/complications ; Female ; Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Metabolomics ; Microbiota/*physiology ; National Institutes of Health (U.S.) ; Pregnancy ; Pregnancy Complications/microbiology ; United States ; }, } @article {pmid32498714, year = {2020}, author = {Ma, B and Wang, Y and Ye, S and Liu, S and Stirling, E and Gilbert, JA and Faust, K and Knight, R and Jansson, JK and Cardona, C and Röttjers, L and Xu, J}, title = {Earth microbial co-occurrence network reveals interconnection pattern across microbiomes.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {82}, pmid = {32498714}, issn = {2049-2618}, mesh = {Animals ; *Bacteria/genetics ; Microbial Consortia ; *Microbiota ; Soil ; *Soil Microbiology ; }, abstract = {BACKGROUND: Microbial interactions shape the structure and function of microbial communities; microbial co-occurrence networks in specific environments have been widely developed to explore these complex systems, but their interconnection pattern across microbiomes in various environments at the global scale remains unexplored. Here, we have inferred an Earth microbial co-occurrence network from a communal catalog with 23,595 samples and 12,646 exact sequence variants from 14 environments in the Earth Microbiome Project dataset.

RESULTS: This non-random scale-free Earth microbial co-occurrence network consisted of 8 taxonomy distinct modules linked with different environments, which featured environment specific microbial co-occurrence relationships. Different topological features of subnetworks inferred from datasets trimmed into uniform size indicate distinct co-occurrence patterns in the microbiomes of various environments. The high number of specialist edges highlights that environmental specific co-occurrence relationships are essential features across microbiomes. The microbiomes of various environments were clustered into two groups, which were mainly bridged by the microbiomes of plant and animal surface. Acidobacteria Gp2 and Nisaea were identified as hubs in most of subnetworks. Negative edges proportions ranged from 1.9% in the soil subnetwork to 48.9% the non-saline surface subnetwork, suggesting various environments experience distinct intensities of competition or niche differentiation. Video abstract CONCLUSION: This investigation highlights the interconnection patterns across microbiomes in various environments and emphasizes the importance of understanding co-occurrence feature of microbiomes from a network perspective.}, } @article {pmid32467266, year = {2020}, author = {Zhang, XL and Yang, X and Wang, SJ and Jiang, ZW and Xie, ZX and Zhang, L and Dai, J and Fan, CQ and Tian, XQ and Yang, Q}, title = {Draft Genome Sequences of Nine Cultivable Heterotrophic Proteobacteria Isolated from Phycosphere Microbiota of Toxic Alexandrium catenella LZT09.}, journal = {Microbiology resource announcements}, volume = {9}, number = {22}, pages = {}, pmid = {32467266}, issn = {2576-098X}, abstract = {Microscopic interactions between phycosphere microbiota and host algae play crucial roles in aquatic ecosystems. Despite their significance, there is a scarcity of available genome sequences derived from the phycosphere microbiome. Here, we report the draft genome sequences of nine heterotrophic proteobacterial strains isolated from the toxic dinoflagellate Alexandrium catenella LZT09 during execution of our Phycosphere Microbiome Project. Further exploration of the genomic features of the alga-associated bacterial community will profoundly help in deeply deciphering the processes and mechanisms governing the host-microbe interactome within algal holobionts in the ocean.}, } @article {pmid32372951, year = {2020}, author = {Abdelsalam, NA and Ramadan, AT and ElRakaiby, MT and Aziz, RK}, title = {Toxicomicrobiomics: The Human Microbiome vs. Pharmaceutical, Dietary, and Environmental Xenobiotics.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {390}, pmid = {32372951}, issn = {1663-9812}, abstract = {The harmful impact of xenobiotics on the environment and human health is being more widely recognized; yet, inter- and intraindividual genetic variations among humans modulate the extent of harm, mostly through modulating the outcome of xenobiotic metabolism and detoxification. As the Human Genome Project revealed that host genetic, epigenetic, and regulatory variations could not sufficiently explain the complexity of interindividual variability in xenobiotics metabolism, its sequel, the Human Microbiome Project, is investigating how this variability may be influenced by human-associated microbial communities. Xenobiotic-microbiome relationships are mutual and dynamic. Not only does the human microbiome have a direct metabolizing potential on xenobiotics, but it can also influence the expression of the host metabolizing genes and the activity of host enzymes. On the other hand, xenobiotics may alter the microbiome composition, leading to a state of dysbiosis, which is linked to multiple diseases and adverse health outcomes, including increased toxicity of some xenobiotics. Toxicomicrobiomics studies these mutual influences between the ever-changing microbiome cloud and xenobiotics of various origins, with emphasis on their fate and toxicity, as well the various classes of microbial xenobiotic-modifying enzymes. This review article discusses classic and recent findings in toxicomicrobiomics, with examples of interactions between gut, skin, urogenital, and oral microbiomes with pharmaceutical, food-derived, and environmental xenobiotics. The current state and future prospects of toxicomicrobiomic research are discussed, and the tools and strategies for performing such studies are thoroughly and critically compared.}, } @article {pmid32369899, year = {2020}, author = {Lee-Sarwar, KA and Lasky-Su, J and Kelly, RS and Litonjua, AA and Weiss, ST}, title = {Metabolome-Microbiome Crosstalk and Human Disease.}, journal = {Metabolites}, volume = {10}, number = {5}, pages = {}, pmid = {32369899}, issn = {2218-1989}, support = {R01HL141826/NH/NIH HHS/United States ; R01 DK125273/DK/NIDDK NIH HHS/United States ; K08 HL148178/NH/NIH HHS/United States ; R01 HL123915/HL/NHLBI NIH HHS/United States ; R01 HL155742/HL/NHLBI NIH HHS/United States ; R01 HL141826/HL/NHLBI NIH HHS/United States ; UH3OD023268/NH/NIH HHS/United States ; K08 HL148178/HL/NHLBI NIH HHS/United States ; R01HL123915/NH/NIH HHS/United States ; K01 HL146980/NH/NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; K01 HL146980/HL/NHLBI NIH HHS/United States ; }, abstract = {In this review, we discuss the growing literature demonstrating robust and pervasive associations between the microbiome and metabolome. We focus on the gut microbiome, which harbors the taxonomically most diverse and the largest collection of microorganisms in the human body. Methods for integrative analysis of these "omics" are under active investigation and we discuss the advances and challenges in the combined use of metabolomics and microbiome data. Findings from large consortia, including the Human Microbiome Project and Metagenomics of the Human Intestinal Tract (MetaHIT) and others demonstrate the impact of microbiome-metabolome interactions on human health. Mechanisms whereby the microbes residing in the human body interact with metabolites to impact disease risk are beginning to be elucidated, and discoveries in this area will likely be harnessed to develop preventive and treatment strategies for complex diseases.}, } @article {pmid32366680, year = {2020}, author = {Zhou, X and Johnson, JS and Spakowicz, D and Zhou, W and Zhou, Y and Sodergren, E and Snyder, M and Weinstock, GM}, title = {Longitudinal Analysis of Serum Cytokine Levels and Gut Microbial Abundance Links IL-17/IL-22 With Clostridia and Insulin Sensitivity in Humans.}, journal = {Diabetes}, volume = {69}, number = {8}, pages = {1833-1842}, pmid = {32366680}, issn = {1939-327X}, support = {P30 CA034196/CA/NCI NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; }, mesh = {Bayes Theorem ; Firmicutes/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Interleukin-17/*blood ; Interleukins/*blood ; Longitudinal Studies ; Microbiota/physiology ; Prediabetic State/immunology/microbiology ; Interleukin-22 ; }, abstract = {Recent studies using mouse models suggest that interaction between the gut microbiome and IL-17/IL-22-producing cells plays a role in the development of metabolic diseases. We investigated this relationship in humans using data from the prediabetes study of the Integrated Human Microbiome Project (iHMP). Specifically, we addressed the hypothesis that early in the onset of metabolic diseases there is a decline in serum levels of IL-17/IL-22, with concomitant changes in the gut microbiome. Clustering iHMP study participants on the basis of longitudinal IL-17/IL-22 profiles identified discrete groups. Individuals distinguished by low levels of IL-17/IL-22 were linked to established markers of metabolic disease, including insulin sensitivity. These individuals also displayed gut microbiome dysbiosis, characterized by decreased diversity, and IL-17/IL-22-related declines in the phylum Firmicutes, class Clostridia, and order Clostridiales This ancillary analysis of the iHMP data therefore supports a link between the gut microbiome, IL-17/IL-22, and the onset of metabolic diseases. This raises the possibility for novel, microbiome-related therapeutic targets that may effectively alleviate metabolic diseases in humans as they do in animal models.}, } @article {pmid32332073, year = {2020}, author = {Manasson, J and Blank, RB and Scher, JU}, title = {The microbiome in rheumatology: Where are we and where should we go?.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {6}, pages = {727-733}, doi = {10.1136/annrheumdis-2019-216631}, pmid = {32332073}, issn = {1468-2060}, support = {R01 AR074500/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/drug therapy/*microbiology ; Biomedical Research ; Humans ; *Microbiota ; Rheumatic Diseases/drug therapy/*microbiology ; }, abstract = {From birth, humans coexist and coevolve with trillions of micro-organisms inhabiting most body surfaces and cavities, referred to as the human microbiome. Advances in sequencing technologies and computational methods have propelled the exploration of the microbiome's contribution to human health and disease, spearheaded by massive efforts such as the Human Microbiome Project and the Europe-based MetaHit Consortium. Yet, despite the accumulated body of literature and a growing awareness among patients, microbiome research in rheumatology has not had a key impact on clinical practice. Herein, we describe some of the landmark microbiome studies in autoimmunity and rheumatology, the challenges and opportunities of microbiome research and how to navigate them, advances in related fields that have overcome these pitfalls, and future directions of harnessing the microbiome for diagnostic and therapeutic purposes.}, } @article {pmid32299880, year = {2020}, author = {Yang, X and Jiang, ZW and Chen, Z and Dai, J and Wang, L and Zhang, XL and Yang, Q}, title = {Complete Genome Sequence of a Toxic and Bioactive Exopolysaccharide-Bearing Bacterium, Sulfitobacter sp. Strain AM1-D1.}, journal = {Microbiology resource announcements}, volume = {9}, number = {16}, pages = {}, pmid = {32299880}, issn = {2576-098X}, abstract = {Sulfitobacter sp. strain AM1-D1, a toxic bacterium of the family Rhodobacteraceae, was isolated from the cultivable phycosphere microbiota of marine toxigenic dinoflagellate Alexandrium minutum amtk4. The complete 4.69-Mb genome comprises one single circular chromosome and five circular plasmids. It has 4,559 coding genes, including those for biosynthesis or degradation of saxitoxin and bioactive exopolysaccharides.}, } @article {pmid32279227, year = {2020}, author = {Rinaldi, F and Trink, A and Pinto, D}, title = {Efficacy of Postbiotics in a PRP-Like Cosmetic Product for the Treatment of Alopecia Area Celsi: A Randomized Double-Blinded Parallel-Group Study.}, journal = {Dermatology and therapy}, volume = {10}, number = {3}, pages = {483-493}, pmid = {32279227}, issn = {2193-8210}, abstract = {INTRODUCTION: Alopecia areata (AA), also known as 'area Celsi', is the second most common form of hair loss affecting the scalp. Newly proposed treatments for AA include low-level light therapy, biologics such as Janus kinase inhibitors and autologous platelet-rich plasma (PRP), which is a well-known "elixir" for hair growth. Bioactive peptides developed through biotechnological applications have been used to overcome the limitations of PRP. More recently, the involvement of microbiota in hair growth disorders, in AA in particular, has been reported, and the usefulness of microbial metabolites, i.e. postbiotics, has been suggested.

METHODS: This study was a randomized double-blinded parallel-group study in which 160 persons of both sexes affected by AA and aged between 18 and 60 years were enrolled. The subjects were randomly assigned to a treatment group (group 1), receiving the TR-PRP plus-Celsi cosmetic product, and a placebo group (group 2). The SALT (Severity of Alopecia Tool) score was determined in both groups at baseline and after 2 and 3 months of treatment, and the results compared between groups.

RESULTS: The subjects in group 1 showed a significant change from baseline in SALT score at 2 months of treatment (61.04% ± 3.45%; p < 0.0001), with a further improvement at the end of treatment (3 months) (69.56% ± 4.32%; p < 0.0001). No significant changes from baseline were reported for the subjects in group 2 (T1: 26.45% ± 3.64%; T3: 27.63% ± 7.61%).

CONCLUSIONS: The results of this study provide further proof of the efficacy of bioactive peptides that mimick the growth factors present in PRP in subjects affected by AA. They also add to our knowledge of the link between microbiota and hair growth disorders, emphasizing the importance of studies on the microbial community and microbial metabolites as a novel therapeutic approach.}, } @article {pmid32247371, year = {2020}, author = {Keshavarzian, A and Engen, P and Bonvegna, S and Cilia, R}, title = {The gut microbiome in Parkinson's disease: A culprit or a bystander?.}, journal = {Progress in brain research}, volume = {252}, number = {}, pages = {357-450}, doi = {10.1016/bs.pbr.2020.01.004}, pmid = {32247371}, issn = {1875-7855}, mesh = {Animals ; Dopamine Agents/*pharmacology ; *Dysbiosis/immunology/metabolism/microbiology ; *Gastrointestinal Microbiome/immunology ; Humans ; *Inflammation/immunology/metabolism/microbiology ; *Life Style ; *Parkinson Disease/drug therapy/immunology/metabolism/microbiology ; *alpha-Synuclein/metabolism ; }, abstract = {In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest. In the present review, we first provide the basis to the understanding of the role of gut microbiota in healthy subjects and the molecular basis of the gut-brain interaction, focusing on metabolic and neuroinflammatory factors that could trigger the alpha-synuclein conformational changes and aggregation. Then, we critically explored preclinical and clinical studies reporting on the changes in gut microbiota in PD, as compared to healthy subjects. Furthermore, we examined the relationship between the gut microbiota and PD clinical features, discussing data consistently reported across studies, as well as the potential sources of inconsistencies. As a further step toward understanding the effects of gut microbiota on PD, we discussed the relationship between dysbiosis and response to dopamine replacement therapy, focusing on Levodopa metabolism. We conclude that further studies are needed to determine whether the gut microbiota changes observed so far in PD patients is the cause or, instead, it is merely a consequence of lifestyle changes associated with the disease. Regardless, studies so far strongly suggest that changes in microbiota appears to be impactful in pathogenesis of neuroinflammation. Thus, dysbiotic microbiota in PD could influence the disease course and response to medication, especially Levodopa. Future research will assess the impact of microbiota-directed therapeutic intervention in PD patients.}, } @article {pmid32239603, year = {2020}, author = {Bruessow, F and Brüssow, H}, title = {Our extended genotype-An argument for the study of domesticated microbes.}, journal = {Environmental microbiology}, volume = {22}, number = {5}, pages = {1669-1674}, doi = {10.1111/1462-2920.15001}, pmid = {32239603}, issn = {1462-2920}, mesh = {Animals ; Bacteria/*classification/*genetics ; Fermentation ; Fermented Foods/*microbiology ; Food Microbiology/*methods ; Genotype ; Humans ; Microbiota/genetics ; }, abstract = {We interpret the domesticated organisms-plants, animals, and the domesticated microbes used for food fermentation-as an extended genotype of humans due to their close relationship with our species. We propose to analyse the role of microbes in traditionally fermented food with the approaches used in the human microbiome project, and we expect to find associations with ethnic groups, explaining part of human (culinary) culture.}, } @article {pmid32238913, year = {2020}, author = {Greene, LK and Williams, CV and Junge, RE and Mahefarisoa, KL and Rajaonarivelo, T and Rakotondrainibe, H and O'Connell, TM and Drea, CM}, title = {A role for gut microbiota in host niche differentiation.}, journal = {The ISME journal}, volume = {14}, number = {7}, pages = {1675-1687}, pmid = {32238913}, issn = {1751-7370}, mesh = {Feces ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Metagenome ; *Microbiota ; }, abstract = {If gut microbes influence host behavioral ecology in the short term, over evolutionary time, they could drive host niche differentiation. We explored this possibility by comparing the gut microbiota of Madagascar's folivorous lemurs from Indriidae and Lepilemuridae. Occurring sympatrically in the eastern rainforest, our four, target species have different dietary specializations, including frugo-folivory (sifakas), young-leaf folivory (indri and woolly lemurs), and mature-leaf folivory (sportive lemurs). We collected fecal samples, from 2013 to 2017, and used amplicon sequencing, metagenomic sequencing, and nuclear magnetic resonance spectroscopy, respectively, to integrate analyses of gut microbiome structure and function with analysis of the colonic metabolome. The lemurs harbored species-specific microbiomes, metagenomes, and metabolomes that were tuned to their dietary specializations: Frugo-folivores had greater microbial and metagenomic diversity, and harbored generalist taxa. Mature-leaf folivores had greater individual microbiome variation, and taxa and metabolites putatively involved in cellulolysis. The consortia even differed between related, young-leaf specialists, with indri prioritizing metabolism of fiber and plant secondary compounds, and woolly lemurs prioritizing amino-acid cycling. Specialized gut microbiota and associated gastrointestinal morphologies enable folivores to variably tolerate resource fluctuation and support nutrient extraction from challenging resources (e.g., by metabolizing plant secondary compounds or recalcitrant fibers), perhaps ultimately facilitating host species' diversity and specialized feeding ecologies.}, } @article {pmid32231664, year = {2020}, author = {Al-Nasiry, S and Ambrosino, E and Schlaepfer, M and Morré, SA and Wieten, L and Voncken, JW and Spinelli, M and Mueller, M and Kramer, BW}, title = {The Interplay Between Reproductive Tract Microbiota and Immunological System in Human Reproduction.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {378}, pmid = {32231664}, issn = {1664-3224}, mesh = {Dysbiosis/immunology ; Female ; Genitalia, Female/*immunology/*microbiology ; Host Microbial Interactions/*immunology ; Humans ; *Microbiota ; Pregnancy/*immunology ; Pregnancy Complications/immunology/microbiology ; }, abstract = {In the last decade, the microbiota, i.e., combined populations of microorganisms living inside and on the surface of the human body, has increasingly attracted attention of researchers in the medical field. Indeed, since the completion of the Human Microbiome Project, insight and interest in the role of microbiota in health and disease, also through study of its combined genomes, the microbiome, has been steadily expanding. One less explored field of microbiome research has been the female reproductive tract. Research mainly from the past decade suggests that microbial communities residing in the reproductive tract represent a large proportion of the female microbial network and appear to be involved in reproductive failure and pregnancy complications. Microbiome research is facing technological and methodological challenges, as detection techniques and analysis methods are far from being standardized. A further hurdle is understanding the complex host-microbiota interaction and the confounding effect of a multitude of constitutional and environmental factors. A key regulator of this interaction is the maternal immune system that, during the peri-conceptional stage and even more so during pregnancy, undergoes considerable modulation. This review aims to summarize the current literature on reproductive tract microbiota describing the composition of microbiota in different anatomical locations (vagina, cervix, endometrium, and placenta). We also discuss putative mechanisms of interaction between such microbial communities and various aspects of the immune system, with a focus on the characteristic immunological changes during normal pregnancy. Furthermore, we discuss how abnormal microbiota composition, "dysbiosis," is linked to a spectrum of clinical disorders related to the female reproductive system and how the maternal immune system is involved. Finally, based on the data presented in this review, the future perspectives in diagnostic approaches, research directions and therapeutic opportunities are explored.}, } @article {pmid32214244, year = {2020}, author = {Poore, GD and Kopylova, E and Zhu, Q and Carpenter, C and Fraraccio, S and Wandro, S and Kosciolek, T and Janssen, S and Metcalf, J and Song, SJ and Kanbar, J and Miller-Montgomery, S and Heaton, R and Mckay, R and Patel, SP and Swafford, AD and Knight, R}, title = {Microbiome analyses of blood and tissues suggest cancer diagnostic approach.}, journal = {Nature}, volume = {579}, number = {7800}, pages = {567-574}, pmid = {32214244}, issn = {1476-4687}, support = {P50 DA026306/DA/NIDA NIH HHS/United States ; HHSN261201400008C/CA/NCI NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; HHSN261201500003I/CA/NCI NIH HHS/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; F30 CA243480/CA/NCI NIH HHS/United States ; R01 DA026334/DA/NIDA NIH HHS/United States ; P01 DA012065/DA/NIDA NIH HHS/United States ; R00 AA020235/AA/NIAAA NIH HHS/United States ; P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Case-Control Studies ; Cohort Studies ; DNA, Bacterial/blood ; DNA, Viral/blood ; Datasets as Topic ; Female ; Humans ; Liquid Biopsy ; Lung Neoplasms/blood/diagnosis/microbiology ; Male ; Melanoma/blood/diagnosis/microbiology ; Microbiota/*genetics ; Neoplasms/blood/*diagnosis/*microbiology ; Plasma/*microbiology ; Prostatic Neoplasms/blood/diagnosis/microbiology ; Reproducibility of Results ; }, abstract = {Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. Following recent demonstrations that some types of cancer show substantial microbial contributions[1-10], we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas[11] (TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.}, } @article {pmid32191789, year = {2020}, author = {Falcon, T and Foletto, KC and Siebert, M and Pinto, DE and Andrades, M and Bertoluci, MC}, title = {Metabarcoding reveals that a non-nutritive sweetener and sucrose yield similar gut microbiota patterns in Wistar rats.}, journal = {Genetics and molecular biology}, volume = {43}, number = {1}, pages = {e20190028}, pmid = {32191789}, issn = {1415-4757}, abstract = {The effects of non-nutritive sweeteners (NNS) on the gut microbiota are an area of increasing research interest due to their potential influence on weight gain, insulin resistance, and inflammation. Studies have shown that mice and rats fed saccharin develop weight gain and metabolic alterations, possibly related to changes in gut microbiota. Here, we hypothesized that chronic exposure to a commercial NNS would change the gut microbiota composition in Wistar rats when compared to sucrose exposure. To test this hypothesis, Wistar rats were fed either NNS- or sucrose-supplemented yogurt for 17 weeks alongside standard chow (ad libitum). The gut microbiome was assessed by 16S rDNA deep sequencing. Assembly and quantification were conducted using the Brazilian Microbiome Project pipeline for Ion Torrent data with modifications. Statistical analyses were performed in the R software environment. We found that chronic feeding of a commercial NNS-sweetened yogurt to Wistar rats, within the recommended dose range, did not significantly modify gut microbiota composition in comparison to sucrose-sweetened yogurt. Our findings do not support the hypothesis that moderate exposure to NNS is associated with changes in gut microbiota pattern compared to sucrose, at least in this experimental model.}, } @article {pmid32156071, year = {2020}, author = {Pan, S and Hullar, MAJ and Lai, LA and Peng, H and May, DH and Noble, WS and Raftery, D and Navarro, SL and Neuhouser, ML and Lampe, PD and Lampe, JW and Chen, R}, title = {Gut Microbial Protein Expression in Response to Dietary Patterns in a Controlled Feeding Study: A Metaproteomic Approach.}, journal = {Microorganisms}, volume = {8}, number = {3}, pages = {}, pmid = {32156071}, issn = {2076-2607}, support = {R01 CA192222/NH/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; U54 CA116847/NH/NIH HHS/United States ; R01 CA211892/CA/NCI NIH HHS/United States ; R01 CA192222/CA/NCI NIH HHS/United States ; R01 CA211892/NH/NIH HHS/United States ; P30 CA015704/NH/NIH HHS/United States ; }, abstract = {Although the gut microbiome has been associated with dietary patterns linked to health, microbial metabolism is not well characterized. This ancillary study was a proof of principle analysis for a novel application of metaproteomics to study microbial protein expression in a controlled dietary intervention. We measured the response of the microbiome to diet in a randomized crossover dietary intervention of a whole-grain, low glycemic load diet (WG) and a refined-grain, high glycemic load diet (RG). Total proteins in stools from 9 participants at the end of each diet period (n = 18) were analyzed by LC MS/MS and proteins were identified using the Human Microbiome Project (HMP) human gut microbiome database and UniProt human protein databases. T-tests, controlling for false discovery rate (FDR) <10%, were used to compare the Gene Ontology (GO) biological processes and bacterial enzymes between the two interventions. Using shotgun proteomics, more than 53,000 unique peptides were identified including microbial (89%) and human peptides (11%). Forty-eight bacterial enzymes were statistically different between the diets, including those implicated in SCFA production and degradation of fatty acids. Enzymes associated with degradation of human mucin were significantly enriched in the RG diet. These results illustrate that the metaproteomic approach is a valuable tool to study the microbial metabolism of diets that may influence host health.}, } @article {pmid32129192, year = {2020}, author = {Vairakkani, R and Fernando, ME and Raj, TY}, title = {Metabolome and microbiome in kidney diseases.}, journal = {Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia}, volume = {31}, number = {1}, pages = {1-9}, doi = {10.4103/1319-2442.279927}, pmid = {32129192}, issn = {1319-2442}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Kidney Diseases/metabolism/microbiology/physiopathology/therapy ; *Metabolome ; }, abstract = {Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.}, } @article {pmid32098835, year = {2020}, author = {Rosa, BA and Mihindukulasuriya, K and Hallsworth-Pepin, K and Wollam, A and Martin, J and Snowden, C and Dunne, WM and Weinstock, GM and Burnham, CA and Mitreva, M}, title = {Improving Characterization of Understudied Human Microbiomes Using Targeted Phylogenetics.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32098835}, issn = {2379-5077}, abstract = {Whole-genome bacterial sequences are required to better understand microbial functions, niche-specific bacterial metabolism, and disease states. Although genomic sequences are available for many of the human-associated bacteria from commonly tested body habitats (e.g., feces), as few as 13% of bacterium-derived reads from other sites such as the skin map to known bacterial genomes. To facilitate a better characterization of metagenomic shotgun reads from underrepresented body sites, we collected over 10,000 bacterial isolates originating from 14 human body habitats, identified novel taxonomic groups based on full-length 16S rRNA gene sequences, clustered the sequences to ensure that no individual taxonomic group was overselected for sequencing, prioritized bacteria from underrepresented body sites (such as skin and respiratory and urinary tracts), and sequenced and assembled genomes for 665 new bacterial strains. Here, we show that addition of these genomes improved read mapping rates of Human Microbiome Project (HMP) metagenomic samples by nearly 30% for the previously underrepresented phylum Fusobacteria, and 27.5% of the novel genomes generated here had high representation in at least one of the tested HMP samples, compared to 12.5% of the sequences in the public databases, indicating an enrichment of useful novel genomic sequences resulting from the prioritization procedure. As our understanding of the human microbiome continues to improve and to enter the realm of therapy developments, targeted approaches such as this to improve genomic databases will increase in importance from both an academic and a clinical perspective.IMPORTANCE The human microbiome plays a critically important role in health and disease, but current understanding of the mechanisms underlying the interactions between the varying microbiome and the different host environments is lacking. Having access to a database of fully sequenced bacterial genomes provides invaluable insights into microbial functions, but currently sequenced genomes for the human microbiome have largely come from a limited number of body sites (primarily feces), while other sites such as the skin, respiratory tract, and urinary tract are underrepresented, resulting in as little as 13% of bacterium-derived reads mapping to known bacterial genomes. Here, we sequenced and assembled 665 new bacterial genomes, prioritized from a larger database to select underrepresented body sites and bacterial taxa in the existing databases. As a result, we substantially improve mapping rates for samples from the Human Microbiome Project and provide an important contribution to human bacterial genomic databases for future studies.}, } @article {pmid32094388, year = {2020}, author = {Marsland, R and Cui, W and Mehta, P}, title = {A minimal model for microbial biodiversity can reproduce experimentally observed ecological patterns.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {3308}, pmid = {32094388}, issn = {2045-2322}, support = {R35 GM119461/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/classification/metabolism ; *Biodiversity ; Humans ; Microbiota ; *Models, Biological ; Principal Component Analysis ; }, abstract = {Surveys of microbial biodiversity such as the Earth Microbiome Project (EMP) and the Human Microbiome Project (HMP) have revealed robust ecological patterns across different environments. A major goal in ecology is to leverage these patterns to identify the ecological processes shaping microbial ecosystems. One promising approach is to use minimal models that can relate mechanistic assumptions at the microbe scale to community-level patterns. Here, we demonstrate the utility of this approach by showing that the Microbial Consumer Resource Model (MiCRM) - a minimal model for microbial communities with resource competition, metabolic crossfeeding and stochastic colonization - can qualitatively reproduce patterns found in survey data including compositional gradients, dissimilarity/overlap correlations, richness/harshness correlations, and nestedness of community composition. By using the MiCRM to generate synthetic data with different environmental and taxonomical structure, we show that large scale patterns in the EMP can be reproduced by considering the energetic cost of surviving in harsh environments and HMP patterns may reflect the importance of environmental filtering in shaping competition. We also show that recently discovered dissimilarity-overlap correlations in the HMP likely arise from communities that share similar environments rather than reflecting universal dynamics. We identify ecologically meaningful changes in parameters that alter or destroy each one of these patterns, suggesting new mechanistic hypotheses for further investigation. These findings highlight the promise of minimal models for microbial ecology.}, } @article {pmid32047925, year = {2020}, author = {Ordiz, MI and Janssen, S and Humphrey, G and Ackermann, G and Stephenson, K and Agapova, S and Divala, O and Kaimila, Y and Maleta, K and Zhong, C and Knight, R and Trehan, I and Tarr, PI and Rusconi, B and Manary, MJ}, title = {The effect of legume supplementation on the gut microbiota in rural Malawian infants aged 6 to 12 months.}, journal = {The American journal of clinical nutrition}, volume = {111}, number = {4}, pages = {884-892}, pmid = {32047925}, issn = {1938-3207}, mesh = {Bacteria/classification/genetics/isolation & purification ; Breast Feeding ; Double-Blind Method ; Fabaceae/*metabolism ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant ; Infant Nutritional Physiological Phenomena ; Intestines/growth & development/microbiology ; Malawi ; Male ; Rural Population/statistics & numerical data ; }, abstract = {BACKGROUND: Common bean and cowpea contain about 25% protein and 25% fiber, and are recommended as complementary foods in sub-Saharan Africa.

OBJECTIVE: The objective of this study was to determine if a daily legume supplement given to Malawian infants aged 6 to 12 mo alters the 16S configuration of the fecal microbiota as read out by amplicon sequence variants (ASVs).

METHODS: This study was conducted within the context of a randomized, double-blind, controlled clinical trial to assess whether cowpea or common bean supplementation reduced intestinal permeability or increased linear growth. There were 2 village clusters in which the study was conducted. Fresh stool collections were flash frozen from 236 infants at ≤6 time points. The stools were sequenced using Earth Microbiome project protocols and data were processed using Qiime and Qiita, open-source, validated software packages. α-diversity was measured using the Faith's test. The 16S configuration was characterized by determining the weighted UniFrac distances of the ASVs and comparing them using permutational multivariate ANOVA.

RESULTS: Among the 1249 samples analyzed, the α-diversity of the fecal microbiome was unchanged among subjects after initiation of legume supplementation. Neither cowpea nor common bean altered the overall 16S configuration at any age. The 16S configuration differed between children with adequate and poor linear growth aged from 6 to 9 mo, but no specific ASVs differed in relative abundance. The 16S configuration differed between children with normal and abnormal intestinal permeability at 9 mo, but no specific ASVs differed in relative abundance. Among categorical characteristics of the population associated with different 16S configurations, village cluster was most pronounced.

CONCLUSION: Legume supplementation in breastfed, rural African infants did not affect the structure of the gut microbial communities until the children were aged 9 mo. This trial was registered at clinicaltrials.gov as NCT02472262.}, } @article {pmid32023941, year = {2020}, author = {Chowdhury, S and Fong, SS}, title = {Computational Modeling of the Human Microbiome.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {32023941}, issn = {2076-2607}, support = {U54HD080784//Office of Extramural Research, National Institutes of Health/ ; }, abstract = {The impact of microorganisms on human health has long been acknowledged and studied, but recent advances in research methodologies have enabled a new systems-level perspective on the collections of microorganisms associated with humans, the human microbiome. Large-scale collaborative efforts such as the NIH Human Microbiome Project have sought to kick-start research on the human microbiome by providing foundational information on microbial composition based upon specific sites across the human body. Here, we focus on the four main anatomical sites of the human microbiome: gut, oral, skin, and vaginal, and provide information on site-specific background, experimental data, and computational modeling. Each of the site-specific microbiomes has unique organisms and phenomena associated with them; there are also high-level commonalities. By providing an overview of different human microbiome sites, we hope to provide a perspective where detailed, site-specific research is needed to understand causal phenomena that impact human health, but there is equally a need for more generalized methodology improvements that would benefit all human microbiome research.}, } @article {pmid32014020, year = {2020}, author = {Woodhams, DC and Bletz, MC and Becker, CG and Bender, HA and Buitrago-Rosas, D and Diebboll, H and Huynh, R and Kearns, PJ and Kueneman, J and Kurosawa, E and LaBumbard, BC and Lyons, C and McNally, K and Schliep, K and Shankar, N and Tokash-Peters, AG and Vences, M and Whetstone, R}, title = {Host-associated microbiomes are predicted by immune system complexity and climate.}, journal = {Genome biology}, volume = {21}, number = {1}, pages = {23}, pmid = {32014020}, issn = {1474-760X}, mesh = {Adaptation, Physiological ; Animals ; *Climate ; Host-Pathogen Interactions/*immunology ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: Host-associated microbiomes, the microorganisms occurring inside and on host surfaces, influence evolutionary, immunological, and ecological processes. Interactions between host and microbiome affect metabolism and contribute to host adaptation to changing environments. Meta-analyses of host-associated bacterial communities have the potential to elucidate global-scale patterns of microbial community structure and function. It is possible that host surface-associated (external) microbiomes respond more strongly to variations in environmental factors, whereas internal microbiomes are more tightly linked to host factors.

RESULTS: Here, we use the dataset from the Earth Microbiome Project and accumulate data from 50 additional studies totaling 654 host species and over 15,000 samples to examine global-scale patterns of bacterial diversity and function. We analyze microbiomes from non-captive hosts sampled from natural habitats and find patterns with bioclimate and geophysical factors, as well as land use, host phylogeny, and trophic level/diet. Specifically, external microbiomes are best explained by variations in mean daily temperature range and precipitation seasonality. In contrast, internal microbiomes are best explained by host factors such as phylogeny/immune complexity and trophic level/diet, plus climate.

CONCLUSIONS: Internal microbiomes are predominantly associated with top-down effects, while climatic factors are stronger determinants of microbiomes on host external surfaces. Host immunity may act on microbiome diversity through top-down regulation analogous to predators in non-microbial ecosystems. Noting gaps in geographic and host sampling, this combined dataset represents a global baseline available for interrogation by future microbial ecology studies.}, } @article {pmid31987701, year = {2020}, author = {Yadav, A and Vilcáez, J and Farag, IF and Johnson, B and Mueller, K and Youssef, NH and Elshahed, MS}, title = {Candidatus Mcinerneyibacterium aminivorans gen. nov., sp. nov., the first representative of the candidate phylum Mcinerneyibacteriota phyl. nov. recovered from a high temperature, high salinity tertiary oil reservoir in north central Oklahoma, USA.}, journal = {Systematic and applied microbiology}, volume = {43}, number = {2}, pages = {126057}, doi = {10.1016/j.syapm.2020.126057}, pmid = {31987701}, issn = {1618-0984}, mesh = {Bacterial Proteins/genetics ; Culture Media ; DNA, Bacterial/genetics ; Ecosystem ; Genome, Bacterial/genetics ; Gram-Negative Anaerobic Straight, Curved, and Helical Rods/*classification/*genetics/isolation & purification/metabolism ; Oil and Gas Fields/chemistry/*microbiology ; Oklahoma ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; Soybean Proteins/metabolism ; Temperature ; }, abstract = {We report on the characterization of a novel genomic assembly (ARYD3) recovered from formation water (17.6% salinity) and crude oil enrichment amended by isolated soy proteins (0.2%), and incubated for 100 days under anaerobic conditions at 50°C. Phylogenetic and phylogenomic analysis demonstrated that the ARYD3 is unaffiliated with all currently described bacterial phyla and candidate phyla, as evident by the low AAI (34.7%), shared gene content (19.4%), and 78.9% 16S rRNA gene sequence similarity to Halothiobacillus neapolitanus, its closest cultured relative. Genomic characterization predicts a slow-growing, non-spore forming, and non-motile Gram-negative rod. Adaptation to high salinity is potentially mediated by the production of the compatible solutes cyclic 2,3-diphosphoglycerate (cDPG), α-glucosylglycerate, as well as the uptake of glycine betaine. Metabolically, the genome encodes primarily aminolytic capabilities for a wide range of amino acids and peptides. Interestingly, evidence of propionate degradation to succinate via methyl-malonyl CoA was identified, suggesting possible capability for syntrophic propionate degradation. Analysis of ARYD3 global distribution patterns identified its occurrence in a very small fraction of Earth Microbiome Project datasets examined (318/27,068), where it consistently represented an extremely rare fraction (maximum 0.28%, average 0.004%) of the overall community. We propose the Candidatus name Mcinerneyibacterium aminivorans gen. nov, sp. nov. for ARYD3[T], with the genome serving as the type material for the novel family Mcinerneyibacteriaceae fam. nov., order Mcinerneyibacteriales ord. nov., class Mcinerneyibacteria class nov., and phylum Mcinerneyibacteriota phyl. nov. The type material genome assembly is deposited in GenBank under accession number VSIX00000000.}, } @article {pmid33814114, year = {2020}, author = {Hopson, LM and Singleton, SS and David, JA and Basuchoudhary, A and Prast-Nielsen, S and Klein, P and Sen, S and Mazumder, R}, title = {Bioinformatics and machine learning in gastrointestinal microbiome research and clinical application.}, journal = {Progress in molecular biology and translational science}, volume = {176}, number = {}, pages = {141-178}, doi = {10.1016/bs.pmbts.2020.08.011}, pmid = {33814114}, issn = {1878-0814}, mesh = {Computational Biology ; *Gastrointestinal Microbiome ; Humans ; Machine Learning ; Metagenomics ; }, abstract = {The scientific community currently defines the human microbiome as all the bacteria, viruses, fungi, archaea, and eukaryotes that occupy the human body. When considering the variable locations, composition, diversity, and abundance of our microbial symbionts, the sheer volume of microorganisms reaches hundreds of trillions. With the onset of next generation sequencing (NGS), also known as high-throughput sequencing (HTS) technologies, the barriers to studying the human microbiome lowered significantly, making in-depth microbiome research accessible. Certain locations on the human body, such as the gastrointestinal, oral, nasal, and skin microbiomes have been heavily studied through community-focused projects like the Human Microbiome Project (HMP). In particular, the gastrointestinal microbiome (GM) has received significant attention due to links to neurological, immunological, and metabolic diseases, as well as cancer. Though HTS technologies allow deeper exploration of the GM, data informing the functional characteristics of microbiota and resulting effects on human function or disease are still sparse. This void is compounded by microbiome variability observed among humans through factors like genetics, environment, diet, metabolic activity, and even exercise; making GM research inherently difficult to study. This chapter describes an interdisciplinary approach to GM research with the goal of mitigating the hindrances of translating findings into a clinical setting. By applying tools and knowledge from microbiology, metagenomics, bioinformatics, machine learning, predictive modeling, and clinical study data from children with treatment-resistant epilepsy, we describe a proof-of-concept approach to clinical translation and precision application of GM research.}, } @article {pmid31886477, year = {2021}, author = {Tomassi, D and Forzani, L and Duarte, S and Pfeiffer, RM}, title = {Sufficient dimension reduction for compositional data.}, journal = {Biostatistics (Oxford, England)}, volume = {22}, number = {4}, pages = {687-705}, pmid = {31886477}, issn = {1468-4357}, mesh = {Humans ; Likelihood Functions ; *Microbiota ; }, abstract = {Recent efforts to characterize the human microbiome and its relation to chronic diseases have led to a surge in statistical development for compositional data. We develop likelihood-based sufficient dimension reduction methods (SDR) to find linear combinations that contain all the information in the compositional data on an outcome variable, i.e., are sufficient for modeling and prediction of the outcome. We consider several models for the inverse regression of the compositional vector or transformations of it, as a function of outcome. They include normal, multinomial, and Poisson graphical models that allow for complex dependencies among observed counts. These methods yield efficient estimators of the reduction and can be applied to continuous or categorical outcomes. We incorporate variable selection into the estimation via penalties and address important invariance issues arising from the compositional nature of the data. We illustrate and compare our methods and some established methods for analyzing microbiome data in simulations and using data from the Human Microbiome Project. Displaying the data in the coordinate system of the SDR linear combinations allows visual inspection and facilitates comparisons across studies.}, } @article {pmid31857734, year = {2020}, author = {Martiny, JBH and Whiteson, KL and Bohannan, BJM and David, LA and Hynson, NA and McFall-Ngai, M and Rawls, JF and Schmidt, TM and Abdo, Z and Blaser, MJ and Bordenstein, S and Bréchot, C and Bull, CT and Dorrestein, P and Eisen, JA and Garcia-Pichel, F and Gilbert, J and Hofmockel, KS and Holtz, ML and Knight, R and Mark Welch, DB and McDonald, D and Methé, B and Mouncey, NJ and Mueller, NT and Pfister, CA and Proctor, L and Sachs, JL}, title = {The emergence of microbiome centres.}, journal = {Nature microbiology}, volume = {5}, number = {1}, pages = {2-3}, pmid = {31857734}, issn = {2058-5276}, support = {K01 HL141589/HL/NHLBI NIH HHS/United States ; R21 AI149354/AI/NIAID NIH HHS/United States ; N00014-19-1-2313//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/International ; DEB-1925761//NSF | BIO | Division of Environmental Biology (DEB)/International ; }, mesh = {Animals ; Capital Financing ; Communication ; Humans ; Interdisciplinary Research/economics/*organization & administration/*trends ; *Microbiota ; }, } @article {pmid31832327, year = {2019}, author = {Ma, ZS and Li, W}, title = {How and Why Men and Women Differ in Their Microbiomes: Medical Ecology and Network Analyses of the Microgenderome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {23}, pages = {1902054}, pmid = {31832327}, issn = {2198-3844}, abstract = {Microgenderome or sexual dimorphism in microbiome refers to the bidirectional interactions between microbiotas, sex hormones, and immune systems, and it is highly relevant to disease susceptibility. A critical step in exploring microgenderome is to dissect the sex differences in key community ecology properties, which has not been systematically analyzed. This study aims at filling the gap by reanalyzing the Human Microbiome Project datasets with two objectives: (i) dissecting the sex differences in community diversity and their intersubject scaling, species composition, core/periphery species, and high-salience skeletons (species interactions); (ii) offering mechanistic interpretations for (i). Conceptually, the Vellend-Hanson synthesis of community ecology that stipulates selection, drift, speciation, and dispersal as the four processes driving community dynamics is followed. Methodologically, seven approaches reflecting the state-of-the-art research in medical ecology of human microbiomes are harnessed to achieve the objectives. It is postulated that the revealed microgenderome characteristics (categorized as seven aspects of differences/similarities) exert far reaching influences on disease susceptibility, and are primarily due to the sex difference in selection effects (deterministic fitness differences in microbial species and/or species interactions with each other or with their hosts), which are, in turn, shaped/modulated by host physiology (immunity, hormones, gut-brain communications, etc.).}, } @article {pmid31822687, year = {2019}, author = {Eguíluz, VM and Salazar, G and Fernández-Gracia, J and Pearman, JK and Gasol, JM and Acinas, SG and Sunagawa, S and Irigoien, X and Duarte, CM}, title = {Scaling of species distribution explains the vast potential marine prokaryote diversity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {18710}, pmid = {31822687}, issn = {2045-2322}, mesh = {Aquatic Organisms/*classification ; *Biodiversity ; Demography ; Ecosystem ; Indian Ocean ; Microbiota ; Models, Theoretical ; Population Density ; Prokaryotic Cells/*classification ; Seawater ; }, abstract = {Global ocean expeditions have provided minimum estimates of ocean's prokaryote diversity, supported by apparent asymptotes in the number of prokaryotes with sampling effort, of about 40,000 species, representing <1% of the species cataloged in the Earth Microbiome Project, despite being the largest habitat in the biosphere. Here we demonstrate that the abundance of prokaryote OTUs follows a scaling that can be represented by a power-law distribution, and as a consequence, we demonstrate, mathematically and through simulations, that the asymptote of rarefaction curves is an apparent one, which is only reached with sample sizes approaching the entire ecosystem. We experimentally confirm these findings using exhaustive repeated sampling of a prokaryote community in the Red Sea and the exploration of global assessments of prokaryote diversity in the ocean. Our findings indicate that, far from having achieved a thorough sampling of prokaryote species abundance in the ocean, global expeditions provide just a start for this quest as the richness in the global ocean is much larger than estimated.}, } @article {pmid31683170, year = {2019}, author = {Orlandi, E and Iacovelli, NA and Tombolini, V and Rancati, T and Polimeni, A and De Cecco, L and Valdagni, R and De Felice, F}, title = {Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer.}, journal = {Oral oncology}, volume = {99}, number = {}, pages = {104453}, doi = {10.1016/j.oraloncology.2019.104453}, pmid = {31683170}, issn = {1879-0593}, mesh = {Carcinogenesis/*genetics ; Head and Neck Neoplasms/*genetics/*therapy ; Humans ; Immunotherapy/*methods ; Microbiota/*genetics ; Prognosis ; Treatment Outcome ; }, abstract = {In the last decade, human microbiome research is rapidly growing involving several fields of clinical medicine and population health. Although the microbiome seems to be linked to all sorts of diseases, cancer has the biggest potential to be investigated. Following the publication of the National Institute of Health - Human Microbiome Project (NIH-HMP), the link between Head and Neck Cancer (HNC) and microbiome seems to be a fast-moving field in research area. However, robust evidence-based literature is still quite scarce. Nevertheless the relationship between oral microbiome and HNC could have important consequences for prevention and early detection of this type of tumors. The aims of the present review are: (i) to discuss current pre-clinical evidence of a role of oral microbiome in HNC; (ii) to report recent developments in understanding the human microbiome's relationship with HNC oncogenesis; (iii) to explore the issue of treatment response and treatment toxicity; (iv) to describe the role of microbiota as potentially modifiable factor suitable for targeting by therapeutics. Further studies are needed to better establish the causal relationship between oral microbiome and HNC oncogenesis. Future trials should continue to explore oral microbiome in order to build the scientific and clinical rationale of HNC preventative and ameliorate treatment outcome.}, } @article {pmid31649646, year = {2019}, author = {Engevik, MA and Morra, CN and Röth, D and Engevik, K and Spinler, JK and Devaraj, S and Crawford, SE and Estes, MK and Kalkum, M and Versalovic, J}, title = {Microbial Metabolic Capacity for Intestinal Folate Production and Modulation of Host Folate Receptors.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2305}, pmid = {31649646}, issn = {1664-302X}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; }, abstract = {Microbial metabolites, including B complex vitamins contribute to diverse aspects of human health. Folate, or vitamin B9, refers to a broad category of biomolecules that include pterin, para-aminobenzoic acid (pABA), and glutamate subunits. Folates are required for DNA synthesis and epigenetic regulation. In addition to dietary nutrients, the gut microbiota has been recognized as a source of B complex vitamins, including folate. This study evaluated the predicted folate synthesis capabilities in the genomes of human commensal microbes identified in the Human Microbiome Project and folate production by representative strains of six human intestinal bacterial phyla. Bacterial folate synthesis genes were ubiquitous across 512 gastrointestinal reference genomes with 13% of the genomes containing all genes required for complete de novo folate synthesis. An additional 39% of the genomes had the genetic capacity to synthesize folates in the presence of pABA, an upstream intermediate that can be obtained through diet or from other intestinal microbes. Bacterial folate synthesis was assessed during exponential and stationary phase growth through the evaluation of expression of select folate synthesis genes, quantification of total folate production, and analysis of folate polyglutamylation. Increased expression of key folate synthesis genes was apparent in exponential phase, and increased folate polyglutamylation occurred during late stationary phase. Of the folate producers, we focused on the commensal Lactobacillus reuteri to examine host-microbe interactions in relation to folate and examined folate receptors in the physiologically relevant human enteroid model. RNAseq data revealed segment-specific folate receptor distribution. Treatment of human colonoid monolayers with conditioned media (CM) from wild-type L. reuteri did not influence the expression of key folate transporters proton-coupled folate transporter (PCFT) or reduced folate carrier (RFC). However, CM from L. reuteri containing a site-specific inactivation of the folC gene, which prevents the bacteria from synthesizing a polyglutamate tail on folate, significantly upregulated RFC expression. No effects were observed using L. reuteri with a site inactivation of folC2, which results in no folate production. This work sheds light on the contributions of microbial folate to overall folate status and mammalian host metabolism.}, } @article {pmid31617360, year = {2019}, author = {Lam, KL and Cheung, PC}, title = {Carbohydrate-Based Prebiotics in Targeted Modulation of Gut Microbiome.}, journal = {Journal of agricultural and food chemistry}, volume = {67}, number = {45}, pages = {12335-12340}, doi = {10.1021/acs.jafc.9b04811}, pmid = {31617360}, issn = {1520-5118}, mesh = {Animals ; Bacteria/classification/genetics/isolation & purification/metabolism ; Carbohydrates/chemistry/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/microbiology ; Prebiotics/*analysis ; }, abstract = {The Human Microbiome Project has prompted unprecedented advancement in microbiome science. Personalized microbiome modulation with precision (PMMP) is one of the emerging yet challenging fields in microbiome research. Carbohydrate-based prebiotics (CBPs) have been shown to modulate the gut microbiome to various extents according to different structural characteristics, such as degree of polymerization, branching, glycosidic linkage, monosaccharide profile, and chemical modification. Subsequently, a targeted modulation of the microbiome might be achieved by using CBPs with a specific structure. A multidimensional database can be established based on the structure-microbiome and structure-microbial-marker relationships. Such relationships could facilitate the development of synbiotics and PMMP.}, } @article {pmid31600339, year = {2019}, author = {Dheilly, NM and Martínez Martínez, J and Rosario, K and Brindley, PJ and Fichorova, RN and Kaye, JZ and Kohl, KD and Knoll, LJ and Lukeš, J and Perkins, SL and Poulin, R and Schriml, L and Thompson, LR}, title = {Parasite microbiome project: Grand challenges.}, journal = {PLoS pathogens}, volume = {15}, number = {10}, pages = {e1008028}, pmid = {31600339}, issn = {1553-7374}, support = {U01 AI065871/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification ; *Evolution, Molecular ; *Host-Pathogen Interactions ; Humans ; *Microbiota ; Parasites/*microbiology ; }, } @article {pmid31588499, year = {2020}, author = {Bradley, PH and Pollard, KS}, title = {phylogenize: correcting for phylogeny reveals genes associated with microbial distributions.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {4}, pages = {1289-1290}, pmid = {31588499}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {SUMMARY: Phylogenetic comparative methods are powerful but presently under-utilized ways to identify microbial genes underlying differences in community composition. These methods help to identify functionally important genes because they test for associations beyond those expected when related microbes occupy similar environments. We present phylogenize, a pipeline with web, QIIME 2 and R interfaces that allows researchers to perform phylogenetic regression on 16S amplicon and shotgun sequencing data and to visualize results. phylogenize applies broadly to both host-associated and environmental microbiomes. Using Human Microbiome Project and Earth Microbiome Project data, we show that phylogenize draws similar conclusions from 16S versus shotgun sequencing and reveals both known and candidate pathways associated with host colonization.

phylogenize is available at https://phylogenize.org and https://bitbucket.org/pbradz/phylogenize.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid31506265, year = {2019}, author = {Zhang, CJ and Pan, J and Duan, CH and Wang, YM and Liu, Y and Sun, J and Zhou, HC and Song, X and Li, M}, title = {Prokaryotic Diversity in Mangrove Sediments across Southeastern China Fundamentally Differs from That in Other Biomes.}, journal = {mSystems}, volume = {4}, number = {5}, pages = {}, pmid = {31506265}, issn = {2379-5077}, abstract = {Mangroves, as a blue carbon reservoir, provide an environment for a variety of microorganisms. Mangroves lie in special locations connecting coastal and estuarine areas and experience fluctuating conditions, which are expected to intensify with climate change, creating a need to better understand the relative roles of stochastic and deterministic processes in shaping microbial community assembly. Here, a study of microbial communities inhabiting mangrove sediments across southeastern China, spanning mangroves in six nature reserves, was conducted. We performed high-throughput DNA sequencing of these samples and compared them with data of 1,370 sediment samples collected from the Earth Microbiome Project (EMP) to compare the microbial diversity of mangroves with that of other biomes. Our results showed that prokaryotic alpha diversity in mangroves was significantly higher than that in other biomes and that microbial beta diversity generally clustered according to biome types. The core operational taxonomic units (OTUs) in mangroves were mostly assigned to Gammaproteobacteria, Deltaproteobacteria, Chloroflexi, and Euryarchaeota The majority of beta nearest-taxon index values were higher than 2, indicating that community assembly in mangroves was better explained through a deterministic process than through a stochastic process. Mean annual precipitation (MAP) and total organic carbon (TOC) were main deterministic factors explaining variation in the microbial community. This study fills a gap in addressing the unique microbial diversity of mangrove ecosystems and their microbial community assembly mechanisms.IMPORTANCE Understanding the underlying mechanisms of microbial community assembly patterns is a vital issue in microbial ecology. Mangroves, as an important and special ecosystem, provide a unique environment for examining the relative importance of stochastic and deterministic processes. We made the first global-scale comparison and found that microbial diversity was significantly different in mangrove sediments compared to that of other biomes. Furthermore, our results suggest that a deterministic process is more important in shaping microbial community assembly in mangroves.}, } @article {pmid31502171, year = {2020}, author = {Kumar, M and Singh, P and Murugesan, S and Vetizou, M and McCulloch, J and Badger, JH and Trinchieri, G and Al Khodor, S}, title = {Microbiome as an Immunological Modifier.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2055}, number = {}, pages = {595-638}, pmid = {31502171}, issn = {1940-6029}, support = {ZIA BC011153/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Age Factors ; Aged ; Bacteria/*classification/genetics/isolation & purification ; Bacterial Proteins/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota ; Middle Aged ; Sequence Analysis, DNA ; }, abstract = {Humans are living ecosystems composed of human cells and microbes. The microbiome is the collection of microbes (microbiota) and their genes. Recent breakthroughs in the high-throughput sequencing technologies have made it possible for us to understand the composition of the human microbiome. Launched by the National Institutes of Health in USA, the human microbiome project indicated that our bodies harbor a wide array of microbes, specific to each body site with interpersonal and intrapersonal variabilities. Numerous studies have indicated that several factors influence the development of the microbiome including genetics, diet, use of antibiotics, and lifestyle, among others. The microbiome and its mediators are in a continuous cross talk with the host immune system; hence, any imbalance on one side is reflected on the other. Dysbiosis (microbiota imbalance) was shown in many diseases and pathological conditions such as inflammatory bowel disease, celiac disease, multiple sclerosis, rheumatoid arthritis, asthma, diabetes, and cancer. The microbial composition mirrors inflammation variations in certain disease conditions, within various stages of the same disease; hence, it has the potential to be used as a biomarker.}, } @article {pmid31455640, year = {2019}, author = {Creekmore, BC and Gray, JH and Walton, WG and Biernat, KA and Little, MS and Xu, Y and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {Mouse Gut Microbiome-Encoded β-Glucuronidases Identified Using Metagenome Analysis Guided by Protein Structure.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31455640}, issn = {2379-5077}, support = {R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; }, abstract = {Gut microbial β-glucuronidase (GUS) enzymes play important roles in drug efficacy and toxicity, intestinal carcinogenesis, and mammalian-microbial symbiosis. Recently, the first catalog of human gut GUS proteins was provided for the Human Microbiome Project stool sample database and revealed 279 unique GUS enzymes organized into six categories based on active-site structural features. Because mice represent a model biomedical research organism, here we provide an analogous catalog of mouse intestinal microbial GUS proteins-a mouse gut GUSome. Using metagenome analysis guided by protein structure, we examined 2.5 million unique proteins from a comprehensive mouse gut metagenome created from several mouse strains, providers, housing conditions, and diets. We identified 444 unique GUS proteins and organized them into six categories based on active-site features, similarly to the human GUSome analysis. GUS enzymes were encoded by the major gut microbial phyla, including Firmicutes (60%) and Bacteroidetes (21%), and there were nearly 20% for which taxonomy could not be assigned. No differences in gut microbial gus gene composition were observed for mice based on sex. However, mice exhibited gus differences based on active-site features associated with provider, location, strain, and diet. Furthermore, diet yielded the largest differences in gus composition. Biochemical analysis of two low-fat-associated GUS enzymes revealed that they are variable with respect to their efficacy of processing both sulfated and nonsulfated heparan nonasaccharides containing terminal glucuronides.IMPORTANCE Mice are commonly employed as model organisms of mammalian disease; as such, our understanding of the compositions of their gut microbiomes is critical to appreciating how the mouse and human gastrointestinal tracts mirror one another. GUS enzymes, with importance in normal physiology and disease, are an attractive set of proteins to use for such analyses. Here we show that while the specific GUS enzymes differ at the sequence level, a core GUSome functionality appears conserved between mouse and human gastrointestinal bacteria. Mouse strain, provider, housing location, and diet exhibit distinct GUSomes and gus gene compositions, but sex seems not to affect the GUSome. These data provide a basis for understanding the gut microbial GUS enzymes present in commonly used laboratory mice. Further, they demonstrate the utility of metagenome analysis guided by protein structure to provide specific sets of functionally related proteins from whole-genome metagenome sequencing data.}, } @article {pmid31425594, year = {2019}, author = {Mougeot, JC and Stevens, CB and Morton, DS and Brennan, MT and Mougeot, FB}, title = {Oral Microbiome and Cancer Therapy-Induced Oral Mucositis.}, journal = {Journal of the National Cancer Institute. Monographs}, volume = {2019}, number = {53}, pages = {}, doi = {10.1093/jncimonographs/lgz002}, pmid = {31425594}, issn = {1745-6614}, mesh = {Disease Susceptibility ; Humans ; Intestinal Mucosa/metabolism/microbiology/pathology ; Metagenome ; Metagenomics/methods ; *Microbiota ; Mouth Mucosa/microbiology/pathology ; Neoplasms/*complications/therapy ; Stomatitis/diagnosis/drug therapy/*etiology/prevention & control ; Systems Biology/methods ; }, abstract = {Characterization of the role of oral microbiome in cancer therapy-induced oral mucositis (CTOM) is critical in preventing the clinically deleterious effects on patients' health that are associated with CTOM. Funding initiatives related to the National Institutes of Health human microbiome project have resulted in groundbreaking advancements in biology and medicine during the last decade. These advancements have shown that a human being is in fact a superorganism made of human cells and associated symbiotic or commensal microbiota. In this review, we describe the state of science as it relates to fundamental knowledge on oral microbiome and its role in CTOM. We also discuss how state-of-the-art technologies and systems biology tools may be used to help tackle the difficult challenges ahead to develop effective treatments or preventive therapies for oral mucositis. We make a clear distinction between disease processes pertaining to the oral microbiome, which includes opportunistic pathogens that may be defined as pathobionts, and those infectious disease processes initiated by exogenous pathogens. We also explored the extent to which knowledge from the gastrointestinal tract in disease and intestinal mucositis could help us better understand CTOM pathobiology. Finally, we propose a model in which the oral microbiome participates in the current five-step CTOM pathobiology model. With the advent of more sophisticated metagenomics technologies and methods of analysis, much hope lies ahead to implement an effective holistic approach to treat cancer patients affected by CTOM.}, } @article {pmid31409660, year = {2019}, author = {Zhang, S and Song, W and Wemheuer, B and Reveillaud, J and Webster, N and Thomas, T}, title = {Comparative Genomics Reveals Ecological and Evolutionary Insights into Sponge-Associated Thaumarchaeota.}, journal = {mSystems}, volume = {4}, number = {4}, pages = {}, pmid = {31409660}, issn = {2379-5077}, abstract = {Thaumarchaeota are frequently reported to associate with marine sponges (phylum Porifera); however, little is known about the features that distinguish them from their free-living thaumarchaeal counterparts. In this study, thaumarchaeal metagenome-assembled genomes (MAGs) were reconstructed from metagenomic data sets derived from the marine sponges Hexadella detritifera, Hexadella cf. detritifera, and Stylissa flabelliformis Phylogenetic and taxonomic analyses revealed that the three thaumarchaeal MAGs represent two new species within the genus Nitrosopumilus and one novel genus, for which we propose the names "Candidatus [U]Nitrosopumilus hexadellus," "Candidatus [U]Nitrosopumilus detritiferus," and "Candidatus [U]Cenporiarchaeum stylissum" (the U superscript indicates that the taxon is uncultured). Comparison of these genomes to data from the Sponge Earth Microbiome Project revealed that "Ca [U]Cenporiarchaeum stylissum" has been exclusively detected in sponges and can hence be classified as a specialist, while "Ca [U]Nitrosopumilus detritiferus" and "Ca [U]Nitrosopumilus hexadellus" are also detected outside the sponge holobiont and likely lead a generalist lifestyle. Comparison of the sponge-associated MAGs to genomes of free-living Thaumarchaeota revealed signatures that indicate functional features of a sponge-associated lifestyle, and these features were related to nutrient transport and metabolism, restriction-modification, defense mechanisms, and host interactions. Each species exhibited distinct functional traits, suggesting that they have reached different stages of evolutionary adaptation and/or occupy distinct ecological niches within their sponge hosts. Our study therefore offers new evolutionary and ecological insights into the symbiosis between sponges and their thaumarchaeal symbionts.IMPORTANCE Sponges represent ecologically important models to understand the evolution of symbiotic interactions of metazoans with microbial symbionts. Thaumarchaeota are commonly found in sponges, but their potential adaptations to a host-associated lifestyle are largely unknown. Here, we present three novel sponge-associated thaumarchaeal species and compare their genomic and predicted functional features with those of closely related free-living counterparts. We found different degrees of specialization of these thaumarchaeal species to the sponge environment that is reflected in their host distribution and their predicted molecular and metabolic properties. Our results indicate that Thaumarchaeota may have reached different stages of evolutionary adaptation in their symbiosis with sponges.}, } @article {pmid31399723, year = {2019}, author = {Bolyen, E and Rideout, JR and Dillon, MR and Bokulich, NA and Abnet, CC and Al-Ghalith, GA and Alexander, H and Alm, EJ and Arumugam, M and Asnicar, F and Bai, Y and Bisanz, JE and Bittinger, K and Brejnrod, A and Brislawn, CJ and Brown, CT and Callahan, BJ and Caraballo-Rodríguez, AM and Chase, J and Cope, EK and Da Silva, R and Diener, C and Dorrestein, PC and Douglas, GM and Durall, DM and Duvallet, C and Edwardson, CF and Ernst, M and Estaki, M and Fouquier, J and Gauglitz, JM and Gibbons, SM and Gibson, DL and Gonzalez, A and Gorlick, K and Guo, J and Hillmann, B and Holmes, S and Holste, H and Huttenhower, C and Huttley, GA and Janssen, S and Jarmusch, AK and Jiang, L and Kaehler, BD and Kang, KB and Keefe, CR and Keim, P and Kelley, ST and Knights, D and Koester, I and Kosciolek, T and Kreps, J and Langille, MGI and Lee, J and Ley, R and Liu, YX and Loftfield, E and Lozupone, C and Maher, M and Marotz, C and Martin, BD and McDonald, D and McIver, LJ and Melnik, AV and Metcalf, JL and Morgan, SC and Morton, JT and Naimey, AT and Navas-Molina, JA and Nothias, LF and Orchanian, SB and Pearson, T and Peoples, SL and Petras, D and Preuss, ML and Pruesse, E and Rasmussen, LB and Rivers, A and Robeson, MS and Rosenthal, P and Segata, N and Shaffer, M and Shiffer, A and Sinha, R and Song, SJ and Spear, JR and Swafford, AD and Thompson, LR and Torres, PJ and Trinh, P and Tripathi, A and Turnbaugh, PJ and Ul-Hasan, S and van der Hooft, JJJ and Vargas, F and Vázquez-Baeza, Y and Vogtmann, E and von Hippel, M and Walters, W and Wan, Y and Wang, M and Warren, J and Weber, KC and Williamson, CHD and Willis, AD and Xu, ZZ and Zaneveld, JR and Zhang, Y and Zhu, Q and Knight, R and Caporaso, JG}, title = {Author Correction: Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.}, journal = {Nature biotechnology}, volume = {37}, number = {9}, pages = {1091}, doi = {10.1038/s41587-019-0252-6}, pmid = {31399723}, issn = {1546-1696}, abstract = {An amendment to this paper has been published and can be accessed via a link at the top of the paper.}, } @article {pmid31384012, year = {2019}, author = {Klinges, JG and Rosales, SM and McMinds, R and Shaver, EC and Shantz, AA and Peters, EC and Eitel, M and Wörheide, G and Sharp, KH and Burkepile, DE and Silliman, BR and Vega Thurber, RL}, title = {Phylogenetic, genomic, and biogeographic characterization of a novel and ubiquitous marine invertebrate-associated Rickettsiales parasite, Candidatus Aquarickettsia rohweri, gen. nov., sp. nov.}, journal = {The ISME journal}, volume = {13}, number = {12}, pages = {2938-2953}, pmid = {31384012}, issn = {1751-7370}, mesh = {Animals ; Aquatic Organisms/*microbiology ; Genome, Bacterial ; Genomics ; Gram-Negative Bacterial Infections/microbiology/*veterinary ; Invertebrates/*microbiology ; Parasites/classification/genetics/isolation & purification ; *Phylogeny ; Rickettsiales/classification/genetics/*isolation & purification ; }, abstract = {Bacterial symbionts are integral to the health and homeostasis of invertebrate hosts. Notably, members of the Rickettsiales genus Wolbachia influence several aspects of the fitness and evolution of their terrestrial hosts, but few analogous partnerships have been found in marine systems. We report here the genome, phylogenetics, and biogeography of a ubiquitous and novel Rickettsiales species that primarily associates with marine organisms. We previously showed that this bacterium was found in scleractinian corals, responds to nutrient exposure, and is associated with reduced host growth and increased mortality. This bacterium, like other Rickettsiales, has a reduced genome indicative of a parasitic lifestyle. Phylogenetic analysis places this Rickettsiales within a new genus we define as "Candidatus Aquarickettsia." Using data from the Earth Microbiome Project and SRA databases, we also demonstrate that members of "Ca. Aquarickettsia" are found globally in dozens of invertebrate lineages. The coral-associated "Candidatus A. rohweri" is the first finished genome in this new clade. "Ca. A. rohweri" lacks genes to synthesize most sugars and amino acids but possesses several genes linked to pathogenicity including Tlc, an antiporter that exchanges host ATP for ADP, and a complete Type IV secretion system. Despite its inability to metabolize nitrogen, "Ca. A. rohweri" possesses the NtrY-NtrX two-component system involved in sensing and responding to extracellular nitrogen. Given these data, along with visualization of the parasite in host tissues, we hypothesize that "Ca. A. rohweri" reduces coral health by consuming host nutrients and energy, thus weakening and eventually killing host cells. Last, we hypothesize that nutrient enrichment, which is increasingly common on coral reefs, encourages unrestricted growth of "Ca. A. rohweri" in its host by providing abundant N-rich metabolites to be scavenged.}, } @article {pmid31341288, year = {2019}, author = {Bolyen, E and Rideout, JR and Dillon, MR and Bokulich, NA and Abnet, CC and Al-Ghalith, GA and Alexander, H and Alm, EJ and Arumugam, M and Asnicar, F and Bai, Y and Bisanz, JE and Bittinger, K and Brejnrod, A and Brislawn, CJ and Brown, CT and Callahan, BJ and Caraballo-Rodríguez, AM and Chase, J and Cope, EK and Da Silva, R and Diener, C and Dorrestein, PC and Douglas, GM and Durall, DM and Duvallet, C and Edwardson, CF and Ernst, M and Estaki, M and Fouquier, J and Gauglitz, JM and Gibbons, SM and Gibson, DL and Gonzalez, A and Gorlick, K and Guo, J and Hillmann, B and Holmes, S and Holste, H and Huttenhower, C and Huttley, GA and Janssen, S and Jarmusch, AK and Jiang, L and Kaehler, BD and Kang, KB and Keefe, CR and Keim, P and Kelley, ST and Knights, D and Koester, I and Kosciolek, T and Kreps, J and Langille, MGI and Lee, J and Ley, R and Liu, YX and Loftfield, E and Lozupone, C and Maher, M and Marotz, C and Martin, BD and McDonald, D and McIver, LJ and Melnik, AV and Metcalf, JL and Morgan, SC and Morton, JT and Naimey, AT and Navas-Molina, JA and Nothias, LF and Orchanian, SB and Pearson, T and Peoples, SL and Petras, D and Preuss, ML and Pruesse, E and Rasmussen, LB and Rivers, A and Robeson, MS and Rosenthal, P and Segata, N and Shaffer, M and Shiffer, A and Sinha, R and Song, SJ and Spear, JR and Swafford, AD and Thompson, LR and Torres, PJ and Trinh, P and Tripathi, A and Turnbaugh, PJ and Ul-Hasan, S and van der Hooft, JJJ and Vargas, F and Vázquez-Baeza, Y and Vogtmann, E and von Hippel, M and Walters, W and Wan, Y and Wang, M and Warren, J and Weber, KC and Williamson, CHD and Willis, AD and Xu, ZZ and Zaneveld, JR and Zhang, Y and Zhu, Q and Knight, R and Caporaso, JG}, title = {Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2.}, journal = {Nature biotechnology}, volume = {37}, number = {8}, pages = {852-857}, pmid = {31341288}, issn = {1546-1696}, support = {R35 GM133420/GM/NIGMS NIH HHS/United States ; U54 MD012388/MD/NIMHD NIH HHS/United States ; U54 CA143925/CA/NCI NIH HHS/United States ; T32 ES015459/ES/NIEHS NIH HHS/United States ; Z99 CA999999/ImNIH/Intramural NIH HHS/United States ; }, mesh = {*Computational Biology ; *Data Science ; Databases, Factual ; Humans ; *Microbiota ; *Software ; }, } @article {pmid31312608, year = {2019}, author = {Gallon, P and Parekh, M and Ferrari, S and Fasolo, A and Ponzin, D and Borroni, D}, title = {Metagenomics in ophthalmology: Hypothesis or real prospective?.}, journal = {Biotechnology reports (Amsterdam, Netherlands)}, volume = {23}, number = {}, pages = {e00355}, pmid = {31312608}, issn = {2215-017X}, abstract = {Metagenomic analysis was originally associated with the studies of genetic material from environmental samples. But, with the advent of the Human Microbiome Project, it has now been applied in clinical practices. The ocular surface (OS) is the most exposed part of the eye, colonized by several microbial communities (both, OS and environmental) that contribute to the maintenance of the physiological state. Limited knowledge has been acquired on these microbes due to the limitations of conventional diagnostic methods. Emerging fields of research are focusing on Next Generation Sequencing (NGS) technologies to obtain reliable information on the OS microbiome. Currently only pre-specified pathogens can be detected by conventional culture-based techniques or Polymerase Chain Reaction (PCR), but there are conditions to state whether metagenomics could revolutionize the diagnosis of ocular diseases. The aim of this review is to provide an updated overview of the studies involving NGS technology for OS microbiome.}, } @article {pmid31311141, year = {2019}, author = {Paoli, A and Mancin, L and Bianco, A and Thomas, E and Mota, JF and Piccini, F}, title = {Ketogenic Diet and Microbiota: Friends or Enemies?.}, journal = {Genes}, volume = {10}, number = {7}, pages = {}, pmid = {31311141}, issn = {2073-4425}, mesh = {Animals ; Biological Variation, Individual ; Carbohydrate Metabolism ; *Diet, Ketogenic ; Gastrointestinal Microbiome ; Humans ; Ketosis ; *Microbiota ; }, abstract = {Over the last years, a growing body of evidence suggests that gut microbial communities play a fundamental role in many aspects of human health and diseases. The gut microbiota is a very dynamic entity influenced by environment and nutritional behaviors. Considering the influence of such a microbial community on human health and its multiple mechanisms of action as the production of bioactive compounds, pathogens protection, energy homeostasis, nutrients metabolism and regulation of immunity, establishing the influences of different nutritional approach is of pivotal importance. The very low carbohydrate ketogenic diet is a very popular dietary approach used for different aims: from weight loss to neurological diseases. The aim of this review is to dissect the complex interactions between ketogenic diet and gut microbiota and how this large network may influence human health.}, } @article {pmid31301004, year = {2019}, author = {Li, JKM and Chiu, PKF and Ng, CF}, title = {The impact of microbiome in urological diseases: a systematic review.}, journal = {International urology and nephrology}, volume = {51}, number = {10}, pages = {1677-1697}, pmid = {31301004}, issn = {1573-2584}, mesh = {Humans ; *Microbiota ; Urologic Diseases/*microbiology ; }, abstract = {OBJECTIVE: The term microbiome is used to signify the ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space, in which there were increasing evidences to suggest that they might have potential roles in various medical conditions. While the study of microbiome in the urinary system is not as robust as the systems included in the Human Microbiome Project, there are still evidences in the literature showing that microbiome may have a role in urological diseases. Therefore, we would like to perform a systematic review on the topic and summarize the available evidence on the impact of microbiome on urological diseases.

METHODOLOGY: This review was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. After screening 589 abstracts and including additional studies (such as references from review papers), 76 studies were included for review and discussion.

RESULTS: Studies had suggested that there were correlations of microbiome of different body cavities (e.g., fecal, urinary and seminal fluid) with urological diseases. Also, different diseases would have different microbiome profile in different body cavities. Unfortunately, the studies on the association of microbiome and urological diseases were still either weak or inconsistent.

CONCLUSION: Studies suggested that there might be some relationship between microbiome and various urological diseases. However, further large-scale studies with control of confounding factors should be performed under a standardized methodology in order to have better understanding of the relationship. Also, more standardized reporting protocol for microbiome studies should be considered for better communications in future studies.}, } @article {pmid31279340, year = {2019}, author = {Velsko, IM and Fellows Yates, JA and Aron, F and Hagan, RW and Frantz, LAF and Loe, L and Martinez, JBR and Chaves, E and Gosden, C and Larson, G and Warinner, C}, title = {Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {102}, pmid = {31279340}, issn = {2049-2618}, mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics ; Biofilms/*growth & development ; Bone and Bones/microbiology ; DNA, Ancient/analysis ; DNA, Bacterial/genetics ; Dental Calculus/history/*microbiology ; Dental Plaque/*microbiology ; Female ; History, Ancient ; Humans ; Male ; Metagenomics ; Microbiota/*physiology ; Periodontal Diseases/microbiology ; Proteomics ; Tooth/*microbiology ; }, abstract = {BACKGROUND: Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.

RESULTS: Metagenomic data was generated from modern and historic calculus samples, and dental plaque metagenomic data was downloaded from the Human Microbiome Project. Microbial composition and functional profile were assessed. Metaproteomic data was obtained from a subset of historic calculus samples. Comparisons between microbial, protein, and metabolomic profiles revealed distinct taxonomic and metabolic functional profiles between plaque, modern calculus, and historic calculus, but not between calculus collected from healthy teeth and periodontal disease-affected teeth. Species co-exclusion was related to biofilm environment. Proteomic profiling revealed that healthy tooth samples contain low levels of bacterial virulence proteins and a robust innate immune response. Correlations between proteomic and metabolomic profiles suggest co-preservation of bacterial lipid membranes and membrane-associated proteins.

CONCLUSIONS: Overall, we find that there are systematic microbial differences between plaque and calculus related to biofilm physiology, and recognizing these differences is important for accurate data interpretation in studies comparing dental plaque and calculus.}, } @article {pmid31202028, year = {2019}, author = {Liu, T and Chen, X and Xu, Y and Wu, W and Tang, W and Chen, Z and Ji, G and Peng, J and Jiang, Q and Xiao, J and Li, X and Zeng, W and Xu, X and Hu, J and Guo, Y and Zou, F and Du, Q and Zhou, H and He, Y and Ma, W}, title = {Gut microbiota partially mediates the effects of fine particulate matter on type 2 diabetes: Evidence from a population-based epidemiological study.}, journal = {Environment international}, volume = {130}, number = {}, pages = {104882}, doi = {10.1016/j.envint.2019.05.076}, pmid = {31202028}, issn = {1873-6750}, mesh = {Adult ; Aged ; Air Pollutants/*adverse effects ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/blood/*epidemiology/microbiology ; Environmental Exposure/adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Particulate Matter/*adverse effects ; }, abstract = {BACKGROUND: Experimental studies have indicated that alterations in the gut microbiota might play a role in the pathway of diabetes induction resulting from particulate matter pollution with aerodynamic diameters < 2.5 μm (PM2.5). However, few human studies have examined such experimental findings. Here, we examine the mediating effects of gut microbial dysbiosis on the associations between PM2.5 and particulate matter pollution with aerodynamic diameters < 1 μm (PM1) on diabetes using the Guangdong Gut Microbiome Project (GGMP) dataset.

METHODS: A multistage cluster sampling method was employed to recruit adult participants from communities in Guangdong. Each participant was interviewed using a questionnaire, fasting blood and stool samples were collected, and the exposure to air pollutants was assessed using a spatiotemporal land-use regression model. The mediation analysis was conducted to estimate the associations among air pollutants, gut microbiota diversity and diabetes.

RESULTS: Both PM2.5 and PM1 were positively associated with the risks of impaired fasting glucose (IFG) or type 2 diabetes and negatively associated with alpha diversity indices of the gut microbiota. The mediation analyses indicated that the associations of PM2.5 and PM1 with the risk of type 2 diabetes were partially mediated by the decrease in gut microbiota diversity. Moreover, we found that 79 (PM2.5 on IFG), 84 (PM2.5 on type 2 diabetes), 83 (PM1 on IFG) and 89 (PM1 on type 2 diabetes) bacterial taxa could partially mediate the associations of PM2.5 and PM1 with IFG and type 2 diabetes, respectively. The relative abundance of most Firmicutes, Proteobacteria and Verrucomicrobia bacteria were negatively associated with particulate matter (PM) concentrations and the risks of diabetes.

CONCLUSIONS: Long-term exposure to PM may increase the risk of diabetes, and alterations in the gut microbiota partially explained these associations.}, } @article {pmid31185820, year = {2019}, author = {Greene, LK and Clayton, JB and Rothman, RS and Semel, BP and Semel, MA and Gillespie, TR and Wright, PC and Drea, CM}, title = {Local habitat, not phylogenetic relatedness, predicts gut microbiota better within folivorous than frugivorous lemur lineages.}, journal = {Biology letters}, volume = {15}, number = {6}, pages = {20190028}, pmid = {31185820}, issn = {1744-957X}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Lemur ; *Lemuridae ; Madagascar ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {Both host phylogenetic placement and feeding strategy influence the structure of the gut microbiome (GMB); however, parsing their relative contributions presents a challenge. To meet this challenge, we compared GMB structure in two genera of lemurs characterized by different dietary specializations, the frugivorous brown lemurs (Eulemur spp.) and the folivorous sifakas (Propithecus spp.). These genera sympatrically occupy similar habitats (dry forests and rainforests) and diverged over similar evolutionary timescales. We collected fresh faeces from 12 species (six per host genus), at seven sites across Madagascar, and sequenced the 16S rRNA gene to determine GMB membership, diversity and variability. The lemurs' GMBs clustered predominantly by host genus; nevertheless, within genera, host relatedness did not predict GMB distance between species. The GMBs of brown lemurs had greater evenness and diversity, but were more homogeneous across species, whereas the GMBs of sifakas were differentiated between habitats. Thus, over relatively shallow timescales, environmental factors can override the influence of host phylogenetic placement on GMB phylogenetic composition. Moreover, feeding strategy can underlie the relative strength of host-microbiome coadaptation, with Madagascar's folivores perhaps requiring locally adapted GMBs to facilitate their highly specialized diets.}, } @article {pmid31169073, year = {2019}, author = {Hsu, T and Gemmell, MR and Franzosa, EA and Berry, S and Mukhopadhya, I and Hansen, R and Michaud, M and Nielsen, H and Miller, WG and Nielsen, H and Bajaj-Elliott, M and Huttenhower, C and Garrett, WS and Hold, GL}, title = {Comparative genomics and genome biology of Campylobacter showae.}, journal = {Emerging microbes & infections}, volume = {8}, number = {1}, pages = {827-840}, pmid = {31169073}, issn = {2222-1751}, support = {R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics ; Campylobacter/classification/*genetics/isolation & purification/pathogenicity ; Campylobacter Infections/*microbiology ; Crohn Disease/microbiology ; Gastroenteritis/microbiology ; *Genome, Bacterial ; Genomics ; Humans ; Phenotype ; Phylogeny ; Virulence ; Virulence Factors/genetics ; }, abstract = {Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn's disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.}, } @article {pmid31167634, year = {2019}, author = {LaPierre, N and Mangul, S and Alser, M and Mandric, I and Wu, NC and Koslicki, D and Eskin, E}, title = {MiCoP: microbial community profiling method for detecting viral and fungal organisms in metagenomic samples.}, journal = {BMC genomics}, volume = {20}, number = {Suppl 5}, pages = {423}, pmid = {31167634}, issn = {1471-2164}, support = {R01 ES021801/ES/NIEHS NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; K25 HL080079/HL/NHLBI NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DA024417/DA/NIDA NIH HHS/United States ; T32 EB016640/EB/NIBIB NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 GM083198/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology/*methods ; Fungi/classification/*genetics ; *Genetic Markers ; Genome, Fungal ; Genome, Viral ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Sequence Analysis, DNA/*methods ; Viruses/classification/*genetics ; }, abstract = {BACKGROUND: High throughput sequencing has spurred the development of metagenomics, which involves the direct analysis of microbial communities in various environments such as soil, ocean water, and the human body. Many existing methods based on marker genes or k-mers have limited sensitivity or are too computationally demanding for many users. Additionally, most work in metagenomics has focused on bacteria and archaea, neglecting to study other key microbes such as viruses and eukaryotes.

RESULTS: Here we present a method, MiCoP (Microbiome Community Profiling), that uses fast-mapping of reads to build a comprehensive reference database of full genomes from viruses and eukaryotes to achieve maximum read usage and enable the analysis of the virome and eukaryome in each sample. We demonstrate that mapping of metagenomic reads is feasible for the smaller viral and eukaryotic reference databases. We show that our method is accurate on simulated and mock community data and identifies many more viral and fungal species than previously-reported results on real data from the Human Microbiome Project.

CONCLUSIONS: MiCoP is a mapping-based method that proves more effective than existing methods at abundance profiling of viruses and eukaryotes in metagenomic samples. MiCoP can be used to detect the full diversity of these communities. The code, data, and documentation are publicly available on GitHub at: https://github.com/smangul1/MiCoP .}, } @article {pmid31164869, year = {2019}, author = {Belforte, FS and Fernandez, N and Tonín Monzón, F and Rosso, AD and Quesada, S and Cimolai, MC and Millán, A and Cerrone, GE and Frechtel, GD and Burcelin, R and Coluccio Leskow, F and Penas-Steinhardt, A}, title = {Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {965}, pmid = {31164869}, issn = {1664-302X}, support = {T37 MD001452/MD/NIMHD NIH HHS/United States ; }, abstract = {In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m[2]), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.}, } @article {pmid31142868, year = {2019}, author = {}, title = {After the Integrative Human Microbiome Project, what's next for the microbiome community?.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {599}, doi = {10.1038/d41586-019-01674-w}, pmid = {31142868}, issn = {1476-4687}, mesh = {Female ; Humans ; Infant, Newborn ; *Microbiota ; Pregnancy ; *Premature Birth ; Vagina ; }, } @article {pmid31142855, year = {2019}, author = {Lloyd-Price, J and Arze, C and Ananthakrishnan, AN and Schirmer, M and Avila-Pacheco, J and Poon, TW and Andrews, E and Ajami, NJ and Bonham, KS and Brislawn, CJ and Casero, D and Courtney, H and Gonzalez, A and Graeber, TG and Hall, AB and Lake, K and Landers, CJ and Mallick, H and Plichta, DR and Prasad, M and Rahnavard, G and Sauk, J and Shungin, D and Vázquez-Baeza, Y and White, RA and , and Braun, J and Denson, LA and Jansson, JK and Knight, R and Kugathasan, S and McGovern, DPB and Petrosino, JF and Stappenbeck, TS and Winter, HS and Clish, CB and Franzosa, EA and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {655-662}, pmid = {31142855}, issn = {1476-4687}, support = {U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK040561/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fungi/pathogenicity ; Gastrointestinal Microbiome/*genetics/immunology ; Health ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology/therapy/virology ; Phylogeny ; Species Specificity ; Transcriptome ; Viruses/pathogenicity ; }, abstract = {Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.}, } @article {pmid31142853, year = {2019}, author = {, }, title = {The Integrative Human Microbiome Project.}, journal = {Nature}, volume = {569}, number = {7758}, pages = {641-648}, pmid = {31142853}, issn = {1476-4687}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Diet ; Female ; Gastrointestinal Microbiome/physiology ; Host Microbial Interactions/physiology ; Humans ; Infant, Newborn ; *Infant, Premature ; Infections/complications/microbiology ; Inflammatory Bowel Diseases/*microbiology ; *Microbiota/physiology ; National Institutes of Health (U.S.)/*organization & administration ; Prediabetic State/complications/*microbiology ; Pregnancy ; Research/*organization & administration ; Time Factors ; United States ; Vagina/microbiology ; }, abstract = {The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host-microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome.}, } @article {pmid31142849, year = {2019}, author = {Fettweis, JM and Serrano, MG and Brooks, JP and Edwards, DJ and Girerd, PH and Parikh, HI and Huang, B and Arodz, TJ and Edupuganti, L and Glascock, AL and Xu, J and Jimenez, NR and Vivadelli, SC and Fong, SS and Sheth, NU and Jean, S and Lee, V and Bokhari, YA and Lara, AM and Mistry, SD and Duckworth, RA and Bradley, SP and Koparde, VN and Orenda, XV and Milton, SH and Rozycki, SK and Matveyev, AV and Wright, ML and Huzurbazar, SV and Jackson, EM and Smirnova, E and Korlach, J and Tsai, YC and Dickinson, MR and Brooks, JL and Drake, JI and Chaffin, DO and Sexton, AL and Gravett, MG and Rubens, CE and Wijesooriya, NR and Hendricks-Muñoz, KD and Jefferson, KK and Strauss, JF and Buck, GA}, title = {The vaginal microbiome and preterm birth.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {1012-1021}, pmid = {31142849}, issn = {1546-170X}, support = {UH2 AI083263/AI/NIAID NIH HHS/United States ; R21 HD092965/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R25 GM090084/GM/NIGMS NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Black or African American ; Biodiversity ; Cohort Studies ; Cytokines/metabolism ; Female ; Host Microbial Interactions/immunology ; Humans ; Infant, Newborn ; Inflammation Mediators/metabolism ; Longitudinal Studies ; Metagenomics ; *Microbiota/genetics/immunology ; Premature Birth/etiology/immunology/*microbiology ; Risk Factors ; United States ; Vagina/immunology/*microbiology ; Young Adult ; }, abstract = {The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.}, } @article {pmid31106872, year = {2019}, author = {Hale, VL and Tan, CL and Niu, K and Yang, Y and Zhang, Q and Knight, R and Amato, KR}, title = {Gut microbiota in wild and captive Guizhou snub-nosed monkeys, Rhinopithecus brelichi.}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22989}, doi = {10.1002/ajp.22989}, pmid = {31106872}, issn = {1098-2345}, support = {//Purdue University Andrews Fellowship/International ; //Offield Family Foundation/International ; //Earth Microbiome Project/International ; //Purdue Research Foundation Research Grant/International ; //Fanjingshan National Nature Reserve/International ; //Margot Marsh Biodiversity Foundation/International ; //San Diego Zoo Global/International ; }, mesh = {Animals ; Bacteria/classification/genetics/metabolism ; Bacterial Physiological Phenomena ; Biodiversity ; Carbohydrate Metabolism ; Colobinae/*microbiology ; Diet/*veterinary ; *Gastrointestinal Microbiome ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Many colobine species-including the endangered Guizhou snub-nosed monkey (Rhinopithecus brelichi) are difficult to maintain in captivity and frequently exhibit gastrointestinal (GI) problems. GI problems are commonly linked to alterations in the gut microbiota, which lead us to examine the gut microbial communities of wild and captive R. brelichi. We used high-throughput sequencing of the 16S rRNA gene to compare the gut microbiota of wild (N = 7) and captive (N = 8) R. brelichi. Wild monkeys exhibited increased gut microbial diversity based on the Chao1 but not Shannon diversity metric and greater relative abundances of bacteria in the Lachnospiraceae and Ruminococcaceae families. Microbes in these families digest complex plant materials and produce butyrate, a short chain fatty acid critical to colonocyte health. Captive monkeys had greater relative abundances of Prevotella and Bacteroides species, which degrade simple sugars and carbohydrates, like those present in fruits and cornmeal, two staples of the captive R. brelichi diet. Captive monkeys also had a greater abundance of Akkermansia species, a microbe that can thrive in the face of host malnutrition. Taken together, these findings suggest that poor health in captive R. brelichi may be linked to diet and an altered gut microbiota.}, } @article {pmid31031092, year = {2019}, author = {Hull, NM and Ling, F and Pinto, AJ and Albertsen, M and Jang, HG and Hong, PY and Konstantinidis, KT and LeChevallier, M and Colwell, RR and Liu, WT}, title = {Drinking Water Microbiome Project: Is it Time?.}, journal = {Trends in microbiology}, volume = {27}, number = {8}, pages = {670-677}, doi = {10.1016/j.tim.2019.03.011}, pmid = {31031092}, issn = {1878-4380}, mesh = {Drinking Water/*microbiology ; Humans ; *Microbiota ; Water Microbiology ; }, abstract = {Now is an opportune time to foster collaborations across sectors and geographical boundaries to enable development of best practices for drinking water (DW) microbiome research, focusing on accuracy and reproducibility of meta-omic techniques (while learning from past microbiome projects). A large-scale coordinated effort that builds on this foundation will enable the urgently needed comprehensive spatiotemporal understanding and control of DW microbiomes by engineering interventions to protect public health. This opinion paper highlights the need to initiate and conduct a large-scale coordinated DW microbiome project by addressing key knowledge gaps and recommends a roadmap for this effort.}, } @article {pmid31003081, year = {2019}, author = {Díez López, C and Vidaki, A and Ralf, A and Montiel González, D and Radjabzadeh, D and Kraaij, R and Uitterlinden, AG and Haas, C and Lao, O and Kayser, M}, title = {Novel taxonomy-independent deep learning microbiome approach allows for accurate classification of different forensically relevant human epithelial materials.}, journal = {Forensic science international. Genetics}, volume = {41}, number = {}, pages = {72-82}, doi = {10.1016/j.fsigen.2019.03.015}, pmid = {31003081}, issn = {1878-0326}, mesh = {*Deep Learning ; Female ; Forensic Genetics/methods ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Microbiota ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; *Sequence Analysis, RNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Correct identification of different human epithelial materials such as from skin, saliva and vaginal origin is relevant in forensic casework as it provides crucial information for crime reconstruction. However, the overlap in human cell type composition between these three epithelial materials provides challenges for their differentiation and identification when using previously proposed human cell biomarkers, while their microbiota composition largely differs. By using validated 16S rRNA gene massively parallel sequencing data from the Human Microbiome Project of 1636 skin, oral and vaginal samples, 50 taxonomy-independent deep learning networks were trained to classify these three tissues. Validation testing was performed in de-novo generated high-throughput 16S rRNA gene sequencing data using the Ion Torrent[™] Personal Genome Machine from 110 test samples: 56 hand skin, 31 saliva and 23 vaginal secretion specimens. Body-site classification accuracy of these test samples was very high as indicated by AUC values of 0.99 for skin, 0.99 for oral, and 1 for vaginal secretion. Misclassifications were limited to 3 (5%) skin samples. Additional forensic validation testing was performed in mock casework samples by de-novo high-throughput sequencing of 19 freshly-prepared samples and 22 samples aged for 1 up to 7.6 years. All of the 19 fresh and 20 (91%) of the 22 aged mock casework samples were correctly tissue-type classified. Moreover, comparing the microbiome results with outcomes from previous human mRNA-based tissue identification testing in the same 16 aged mock casework samples reveals that our microbiome approach performs better in 12 (75%), similarly in 2 (12.5%), and less good in 2 (12.5%) of the samples. Our results demonstrate that this new microbiome approach allows for accurate tissue-type classification of three human epithelial materials of skin, oral and vaginal origin, which is highly relevant for future forensic investigations.}, } @article {pmid30997937, year = {2019}, author = {Clayton, JB and Shields-Cutler, RR and Hoops, SL and Al-Ghalith, GA and Sha, JCM and Johnson, TJ and Knights, D}, title = {Bacterial community structure and function distinguish gut sites in captive red-shanked doucs (Pygathrix nemaeus).}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22977}, pmid = {30997937}, issn = {1098-2345}, support = {T32 DA007097/DA/NIDA NIH HHS/United States ; //Margot Marsh Biodiversity Foundation/International ; }, mesh = {Animals ; Bacteria/*classification/genetics ; Biodiversity ; Colobinae/*microbiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genome, Bacterial ; Intestines/microbiology/physiology ; Sequence Analysis, DNA ; Stomach/microbiology/physiology ; }, abstract = {The mammalian order primates contains wide species diversity. Members of the subfamily Colobinae are unique amongst extant primates in that their gastrointestinal systems more closely resemble those of ruminants than other members of the primate order. In the growing literature surrounding nonhuman primate microbiomes, analysis of microbial communities has been limited to the hindgut, since few studies have captured data on other gut sites, including the foregut of colobine primates. In this study, we used the red-shanked douc (Pygathrix nemaeus) as a model for colobine primates to study the relationship between gastrointestinal bacterial community structure and gut site within and between subjects. We analyzed fecal and pregastric stomach content samples, representative of the hindgut and foregut respectively, using 16S recombinant DNA (rDNA) sequencing and identified microbiota using closed-reference operational taxonomic unit (OTU) picking against the GreenGenes database. Our results show divergent bacterial communities clearly distinguish the foregut and hindgut microbiomes. We found higher bacterial biodiversity and a higher Firmicutes:Bacteroides ratio in the hindgut as opposed to the foregut. These gut sites showed strong associations with bacterial function. Specifically, energy metabolism was upregulated in the hindgut, whereas detoxification was increased in the foregut. Our results suggest a red-shanked douc's foregut microbiome is no more concordant with its own hindgut than it is with any other red-shanked douc's hindgut microbiome, thus reinforcing the notion that the bacterial communities of the foregut and hindgut are distinctly unique. OPEN PRACTICES: This article has been awarded Open Materials and Open Data badges. All materials and data are publicly accessible via the IRIS Repository at https://www.iris-database.org/iris/app/home/detail?id=york:934328. Learn more about the Open Practices badges from the Center for Open Science: https://osf.io/tvyxz/wiki.}, } @article {pmid30981803, year = {2019}, author = {Parida, S and Sharma, D}, title = {The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer.}, journal = {Biochimica et biophysica acta. Reviews on cancer}, volume = {1871}, number = {2}, pages = {392-405}, pmid = {30981803}, issn = {1879-2561}, support = {R01 CA204555/CA/NCI NIH HHS/United States ; R01 CA204555/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast Neoplasms/*microbiology ; *Dysbiosis ; Female ; Humans ; }, abstract = {Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the "forgotten organ" contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [1,2]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia, Actinobacteria, Proteobacteria, Tenericutes and Cyanobacteria [2-7]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [1,7-14] and now it has been established that microbiome significantly contributes to many organ specific cancers [1,15,16].}, } @article {pmid30976019, year = {2019}, author = {Jeong, H and Arif, B and Caetano-Anollés, G and Kim, KM and Nasir, A}, title = {Horizontal gene transfer in human-associated microorganisms inferred by phylogenetic reconstruction and reconciliation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5953}, pmid = {30976019}, issn = {2045-2322}, mesh = {Bacteria/classification/*genetics/isolation & purification ; Computational Biology/*methods ; Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Models, Genetic ; *Phylogeny ; }, abstract = {Horizontal gene transfer (HGT) is widespread in the evolution of prokaryotes, especially those associated with the human body. Here, we implemented large-scale gene-species phylogenetic tree reconstructions and reconciliations to identify putative HGT-derived genes in the reference genomes of microbiota isolated from six major human body sites by the NIH Human Microbiome Project. Comparisons with a control group representing microbial genomes from diverse natural environments indicated that HGT activity increased significantly in the genomes of human microbiota, which is confirmatory of previous findings. Roughly, more than half of total genes in the genomes of human-associated microbiota were transferred (donated or received) by HGT. Up to 60% of the detected HGTs occurred either prior to the colonization of the human body or involved bacteria residing in different body sites. The latter could suggest 'genetic crosstalk' and movement of bacterial genes within the human body via hitherto poorly understood mechanisms. We also observed that HGT activity increased significantly among closely-related microorganisms and especially when they were united by physical proximity, suggesting that the 'phylogenetic effect' can significantly boost HGT activity. Finally, we identified several core and widespread genes least influenced by HGT that could become useful markers for building robust 'trees of life' and address several outstanding technical challenges to improve the phylogeny-based genome-wide HGT detection method for future applications.}, } @article {pmid30973913, year = {2019}, author = {Pinto, D and Sorbellini, E and Marzani, B and Rucco, M and Giuliani, G and Rinaldi, F}, title = {Scalp bacterial shift in Alopecia areata.}, journal = {PloS one}, volume = {14}, number = {4}, pages = {e0215206}, pmid = {30973913}, issn = {1932-6203}, mesh = {Adult ; Alopecia Areata/complications/*microbiology ; Case-Control Studies ; DNA, Bacterial/genetics/isolation & purification ; Dysbiosis/complications/*microbiology ; Female ; Humans ; Male ; Microbiota/genetics ; Middle Aged ; Propionibacterium/isolation & purification ; Scalp/*microbiology ; Staphylococcus aureus/isolation & purification ; Staphylococcus epidermidis/isolation & purification ; Young Adult ; }, abstract = {The role of microbial dysbiosis in scalp disease has been recently hypothesized. However, little information is available with regards to the association between microbial population on the scalp and hair diseases related to hair growth. Here we investigated bacterial communities in healthy and Alopecia areata (AA) subjects. The analysis of bacterial distribution at the genus level highlighted an increase of Propionibacterium in AA subjects alongside a general decrease of Staphylococcus. Analysis of log Relative abundance of main bacterial species inhabiting the scalp showed a significant increase of Propionibacterium acnes in AA subjects compared to control ones. AA scalp condition is also associated with a significant decrease of Staphylococcus epidermidis relative abundance. No significant changes were found for Staphylococcus aureus. Therefore, data from sequencing profiling of the bacterial population strongly support a different microbial composition of the different area surrounded hair follicle from the epidermis to hypodermis, highlighting differences between normal and AA affected the scalp. Our results highlight, for the first time, the presence of a microbial shift on the scalp of patients suffering from AA and gives the basis for a larger and more complete study of microbial population involvement in hair disorders.}, } @article {pmid30942867, year = {2019}, author = {Brown, SM and Chen, H and Hao, Y and Laungani, BP and Ali, TA and Dong, C and Lijeron, C and Kim, B and Wultsch, C and Pei, Z and Krampis, K}, title = {MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.}, journal = {GigaScience}, volume = {8}, number = {4}, pages = {}, pmid = {30942867}, issn = {2047-217X}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; G12 MD007599/MD/NIMHD NIH HHS/United States ; R01 AI110372/AI/NIAID NIH HHS/United States ; U54 CA221705/CA/NCI NIH HHS/United States ; UL1 TR002384/TR/NCATS NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; R21 DE025352/DE/NIDCR NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenome ; Metagenomics/*methods ; Microbiology ; Microbiota ; Molecular Sequence Annotation ; Reproducibility of Results ; *Software ; Workflow ; }, abstract = {BACKGROUND: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.

RESULTS: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.

CONCLUSIONS: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.}, } @article {pmid30937887, year = {2019}, author = {Sharma, A and Buschmann, MM and Gilbert, JA}, title = {Pharmacomicrobiomics: The Holy Grail to Variability in Drug Response?.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {2}, pages = {317-328}, doi = {10.1002/cpt.1437}, pmid = {30937887}, issn = {1532-6535}, mesh = {*Host Microbial Interactions/drug effects/physiology ; Humans ; *Microbiota/drug effects/physiology ; Pharmaceutical Preparations/*metabolism ; *Pharmacogenetics ; Systems Biology ; }, abstract = {The human body, with 3.0 × 10[13] cells and more than 3.8 × 10[13] microorganisms, has nearly a one-to-one ratio of resident microbes to human cells. Initiatives like the Human Microbiome Project, American Gut, and Flemish Gut have identified associations between microbial taxa and human health. The study of interactions between microbiome and pharmaceutical agents, i.e., pharmacomicrobiomics, has revealed an instrumental role of the microbiome in modulating drug response that alters the therapeutic outcomes. In this review, we present our current comprehension of the relationship of the microbiome, host biology, and pharmaceutical agents such as cardiovascular drugs, analgesics, and chemotherapeutic agents to human disease and treatment outcomes. We also discuss the significance of studying diet-gene-drug interactions and further address the key challenges associated with pharmacomicrobiomics. Finally, we examine proposed models employing systems biology for the application of pharmacomicrobiomics and other -omics data, and provide approaches to elucidate microbiome-drug interactions to improve future translation to personalized medicine.}, } @article {pmid30932230, year = {2019}, author = {Greene, LK and Bornbusch, SL and McKenney, EA and Harris, RL and Gorvetzian, SR and Yoder, AD and Drea, CM}, title = {The importance of scale in comparative microbiome research: New insights from the gut and glands of captive and wild lemurs.}, journal = {American journal of primatology}, volume = {81}, number = {10-11}, pages = {e22974}, doi = {10.1002/ajp.22974}, pmid = {30932230}, issn = {1098-2345}, support = {//Duke University/International ; //Margot Marsh Biodiversity Foundation/International ; //Duke Lemur Center/International ; S10 OD018164/OD/NIH HHS/United States ; 1749465//Division of Behavioral and Cognitive Sciences/International ; 1749898//Division of Behavioral and Cognitive Sciences/International ; }, mesh = {Animal Husbandry ; Animals ; Diet/veterinary ; *Feeding Behavior ; Female ; Gastrointestinal Microbiome ; Host Microbial Interactions ; Lemuridae/*microbiology ; Madagascar ; Male ; *Microbiota ; Phylogeny ; Scent Glands/*microbiology ; }, abstract = {Research on animal microbiomes is increasingly aimed at determining the evolutionary and ecological factors that govern host-microbiome dynamics, which are invariably intertwined and potentially synergistic. We present three empirical studies related to this topic, each of which relies on the diversity of Malagasy lemurs (representing a total of 19 species) and the comparative approach applied across scales of analysis. In Study 1, we compare gut microbial membership across 14 species in the wild to test the relative importance of host phylogeny and feeding strategy in mediating microbiome structure. Whereas host phylogeny strongly predicted community composition, the same feeding strategies shared by distant relatives did not produce convergent microbial consortia, but rather shaped microbiomes in host lineage-specific ways, particularly in folivores. In Study 2, we compare 14 species of wild and captive folivores, frugivores, and omnivores, to highlight the importance of captive populations for advancing gut microbiome research. We show that the perturbational effect of captivity is mediated by host feeding strategy and can be mitigated, in part, by modified animal management. In Study 3, we examine various scent-gland microbiomes across three species in the wild or captivity and show them to vary by host species, sex, body site, and a proxy of social status. These rare data provide support for the bacterial fermentation hypothesis in olfactory signal production and implicate steroid hormones as mediators of microbial community structure. We conclude by discussing the role of scale in comparative microbial studies, the links between feeding strategy and host-microbiome coadaptation, the underappreciated benefits of captive populations for advancing conservation research, and the need to consider the entirety of an animal's microbiota. Ultimately, these studies will help move the field from exploratory to hypothesis-driven research.}, } @article {pmid30919073, year = {2019}, author = {Ames, NJ and Barb, JJ and Ranucci, A and Kim, H and Mudra, SE and Cashion, AK and Townsley, DM and Childs, R and Paster, BJ and Faller, LL and Wallen, GR}, title = {The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study.}, journal = {Annals of hematology}, volume = {98}, number = {6}, pages = {1351-1365}, doi = {10.1007/s00277-019-03599-w}, pmid = {30919073}, issn = {1432-0584}, mesh = {Adult ; Aged ; Anemia, Aplastic/drug therapy/*microbiology/therapy ; Anti-Bacterial Agents/pharmacology ; Antilymphocyte Serum/therapeutic use ; Benzoates/pharmacology/therapeutic use ; Biodiversity ; Cyclosporine/therapeutic use ; DNA, Bacterial/analysis ; Dental Health Surveys ; Female ; Graft vs Host Disease/etiology/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Hydrazines/pharmacology/therapeutic use ; Immunocompromised Host ; Immunosuppressive Agents/therapeutic use ; Male ; *Microbiota/drug effects ; Middle Aged ; Mouth/*microbiology ; Pilot Projects ; Pyrazoles/pharmacology/therapeutic use ; Ribotyping ; Sequence Analysis, DNA ; Smoking/epidemiology ; T-Lymphocytes/immunology ; Tongue/microbiology ; Young Adult ; }, abstract = {The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.}, } @article {pmid30858577, year = {2019}, author = {Cabana, F and Clayton, JB and Nekaris, KAI and Wirdateti, W and Knights, D and Seedorf, H}, title = {Nutrient-based diet modifications impact on the gut microbiome of the Javan slow loris (Nycticebus javanicus).}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4078}, pmid = {30858577}, issn = {2045-2322}, mesh = {Animals ; Animals, Wild ; Animals, Zoo ; Bacteroides/classification/drug effects/isolation & purification ; Bifidobacterium/classification/drug effects/isolation & purification ; *Diet ; Gastrointestinal Microbiome/drug effects/*genetics ; Lorisidae/microbiology/*physiology ; Nutrients/*pharmacology ; Prevotella/classification/drug effects/isolation & purification ; Primates/genetics ; }, abstract = {Environment and diet are key factors which shape the microbiome of organisms. There is also a disparity between captive and wild animals of the same species, presumably because of the change in diet. Being able to reverse the microbiome to the wild type is thus particularly important for the reintroduction efforts of Critically Endangered animals. The Javan slow loris (Nycticebus javanicus) is a suitable model, being kept in the thousands within rescue centres throughout Southeast Asia. With next-generation sequencing, we show how a naturalistic diet impacts the gut microbiome of captive slow lorises (Primates: Nycticebus). A comparison of the microbiome of wild animals with captive animals that had been fed a standard captive or improved diet reveals strong microbiome differences between wild and captive animals; however, diet changes failed to alter the microbiome of captive populations significantly. Bifidobacterium was the most abundant genus in wild animals (46.7%) while Bacteroides (11.6%) and Prevotella (18.9%) were the most abundant in captive animals fed the captive and improved diets, respectively. Correlation analyses of nutrients with microbial taxa suggest important implications in using nutrition to suppress potential pathogens, with soluble fibre and water-soluble carbohydrates both being associated with opposing microbiome profiles. The improved diet significantly increased microbe diversity, which exemplifies the importance of high fibre diets; however, wild individuals had lower diversity, which contradicts recent studies. Detection of methanogens appeared to be dependent on diet and whether the animals were living in captivity or in the wild. This study highlights the potential of nutrition in modulating the microbiome of animals prior to release. Unexpectedly, the results were not as significant as has been suggested in recent studies.}, } @article {pmid30832730, year = {2019}, author = {Meyer, F and Bremges, A and Belmann, P and Janssen, S and McHardy, AC and Koslicki, D}, title = {Assessing taxonomic metagenome profilers with OPAL.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {51}, pmid = {30832730}, issn = {1474-760X}, mesh = {Classification/methods ; Humans ; Metagenomics/methods/*standards ; *Software ; }, abstract = {The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiative for the Critical Assessment of Metagenome Interpretation (CAMI), together with convenient visualizations. In addition, we perform in-depth performance comparisons with seven profilers on datasets of CAMI and the Human Microbiome Project. OPAL is freely available at https://github.com/CAMI-challenge/OPAL .}, } @article {pmid30814984, year = {2019}, author = {Song, Z and Wang, X and Zhou, X and Jiang, S and Li, Y and Ahmad, O and Qi, L and Li, P and Li, J}, title = {Taxonomic Distribution of FosB in Human-Microbiota and Activity Comparison of Fosfomycin Resistance.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {200}, pmid = {30814984}, issn = {1664-302X}, abstract = {FosB, a Mg[2+] dependent thioltransferase, confers antibiotic resistance to fosfomycin through enzymatic drug inactivation. Among all antibiotic resistant proteins in the Antibiotic Resistance Genes Database and the Comprehensive Antibiotic Resistance Database, FosB is within 5% of the most number of ARPs identified in Human Microbiome Project reference database but mainly distributed in limited genera, i.e., 122 of total 133 FosB homologues are found from Bacillus and Staphylococcus. Furthermore, these FosB sequences could be divided into three clusters based on their phylogenetic relationship, i.e., two groups of FosB were mainly from Bacillus, and another was mainly from Staphylococcus. Finally, we confirmed that FosB from the group of Staphylococcus presented the highest resistance ability to fosfomycin by in silico and in vitro comparisons. In summary, this study elaborates the specific taxonomic characteristics and resistant abilities of FosB in human microbiota, which might help in developing more promising fosfomycin-like antibiotics.}, } @article {pmid30808411, year = {2019}, author = {, }, title = {A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Years 2007-2016.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {31}, pmid = {30808411}, issn = {2049-2618}, mesh = {Biomedical Research/*economics/*organization & administration ; Humans ; Metagenomics/economics/organization & administration ; Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) is the primary federal government agency for biomedical research in the USA. NIH provides extensive support for human microbiome research with 21 of 27 NIH Institutes and Centers (ICs) currently funding this area through their extramural research programs. This analysis of the NIH extramural portfolio in human microbiome research briefly reviews the early history of this field at NIH, summarizes the program objectives and the resources developed in the recently completed 10-year (fiscal years 2007-2016) $215 M Human Microbiome Project (HMP) program, evaluates the scope and range of the $728 M NIH investment in extramural human microbiome research activities outside of the HMP over fiscal years 2012-2016, and highlights some specific areas of research which emerged from this investment. This analysis closes with a few comments on the technical needs and knowledge gaps which remain for this field to be able to advance over the next decade and for the outcomes of this research to be able to progress to microbiome-based interventions for treating disease and supporting health.}, } @article {pmid30808401, year = {2019}, author = {, }, title = {2017 NIH-wide workshop report on "The Human Microbiome: Emerging Themes at the Horizon of the 21st Century".}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {32}, pmid = {30808401}, issn = {2049-2618}, support = {U54 DE023789/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA014236/CA/NCI NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; Internet ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {The National Institutes of Health (NIH) organized a three-day human microbiome research workshop, August 16-18, 2017, to highlight the accomplishments of the 10-year Human Microbiome Project program, the outcomes of the investments made by the 21 NIH Institutes and Centers which now fund this area, and the technical challenges and knowledge gaps which will need to be addressed in order for this field to advance over the next 10 years. This report summarizes the key points in the talks, round table discussions, and Joint Agency Panel from this workshop.}, } @article {pmid30718869, year = {2019}, author = {Forster, SC and Kumar, N and Anonye, BO and Almeida, A and Viciani, E and Stares, MD and Dunn, M and Mkandawire, TT and Zhu, A and Shao, Y and Pike, LJ and Louie, T and Browne, HP and Mitchell, AL and Neville, BA and Finn, RD and Lawley, TD}, title = {A human gut bacterial genome and culture collection for improved metagenomic analyses.}, journal = {Nature biotechnology}, volume = {37}, number = {2}, pages = {186-192}, pmid = {30718869}, issn = {1546-1696}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification ; Computational Biology/methods ; Contig Mapping ; Gastrointestinal Microbiome ; *Genome, Bacterial ; Genome, Human ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; RNA, Ribosomal, 16S/metabolism ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial genomes derived from human gastrointestinal microbiota by 37%. The resulting global Human Gastrointestinal Bacteria Genome Collection (HGG) classifies 83% of genera by abundance across 13,490 shotgun-sequenced metagenomic samples, improves taxonomic classification by 61% compared to the Human Microbiome Project (HMP) genome collection and achieves subspecies-level classification for almost 50% of sequences. The improved resource of gastrointestinal bacterial reference sequences circumvents dependence on de novo assembly of metagenomes and enables accurate and cost-effective shotgun metagenomic analyses of human gastrointestinal microbiota.}, } @article {pmid30705670, year = {2018}, author = {Whittle, E and Leonard, MO and Harrison, R and Gant, TW and Tonge, DP}, title = {Multi-Method Characterization of the Human Circulating Microbiome.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3266}, pmid = {30705670}, issn = {1664-302X}, abstract = {The term microbiome describes the genetic material encoding the various microbial populations that inhabit our body. Whilst colonization of various body niches (e.g., the gut) by dynamic communities of microorganisms is now universally accepted, the existence of microbial populations in other "classically sterile" locations, including the blood, is a relatively new concept. The presence of bacteria-specific DNA in the blood has been reported in the literature for some time, yet the true origin of this is still the subject of much deliberation. The aim of this study was to investigate the phenomenon of a "blood microbiome" by providing a comprehensive description of bacterially derived nucleic acids using a range of complementary molecular and classical microbiological techniques. For this purpose we utilized a set of plasma samples from healthy subjects (n = 5) and asthmatic subjects (n = 5). DNA-level analyses involved the amplification and sequencing of the 16S rRNA gene. RNA-level analyses were based upon the de novo assembly of unmapped mRNA reads and subsequent taxonomic identification. Molecular studies were complemented by viability data from classical aerobic and anaerobic microbial culture experiments. At the phylum level, the blood microbiome was predominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes. The key phyla detected were consistent irrespective of molecular method (DNA vs. RNA), and consistent with the results of other published studies. In silico comparison of our data with that of the Human Microbiome Project revealed that members of the blood microbiome were most likely to have originated from the oral or skin communities. To our surprise, aerobic and anaerobic cultures were positive in eight of out the ten donor samples investigated, and we reflect upon their source. Our data provide further evidence of a core blood microbiome, and provide insight into the potential source of the bacterial DNA/RNA detected in the blood. Further, data reveal the importance of robust experimental procedures, and identify areas for future consideration.}, } @article {pmid30658055, year = {2019}, author = {Pellock, SJ and Walton, WG and Ervin, SM and Torres-Rivera, D and Creekmore, BC and Bergan, G and Dunn, ZD and Li, B and Tripathy, A and Redinbo, MR}, title = {Discovery and Characterization of FMN-Binding β-Glucuronidases in the Human Gut Microbiome.}, journal = {Journal of molecular biology}, volume = {431}, number = {5}, pages = {970-980}, pmid = {30658055}, issn = {1089-8638}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Catalytic Domain/physiology ; Clostridiales/metabolism ; Flavin Mononucleotide/*metabolism ; Gastrointestinal Microbiome/*physiology ; Glucuronidase/*metabolism ; Humans ; Kinetics ; Metagenome/physiology ; Microbiota/physiology ; Ruminococcus/metabolism ; }, abstract = {The human gut microbiota encodes β-glucuronidases (GUSs) that play key roles in health and disease via the metabolism of glucuronate-containing carbohydrates and drugs. Hundreds of putative bacterial GUS enzymes have been identified by metagenomic analysis of the human gut microbiome, but less than 10% have characterized structures and functions. Here we describe a set of unique gut microbial GUS enzymes that bind flavin mononucleotide (FMN). First, we show using mass spectrometry, isothermal titration calorimetry, and x-ray crystallography that a purified GUS from the gut commensal microbe Faecalibacterium prausnitzii binds to FMN on a surface groove located 30 Å away from the active site. Second, utilizing structural and functional data from this FMN-binding GUS, we analyzed the 279 unique GUS sequences from the Human Microbiome Project database and identified 14 putative FMN-binding GUSs. We characterized four of these hits and solved the structure of two, the GUSs from Ruminococcus gnavus and Roseburia hominis, which confirmed that these are FMN binders. Third, binding and kinetic analysis of the FMN-binding site mutants of these five GUSs show that they utilize a conserved site to bind FMN that is not essential for GUS activity, but can affect KM. Lastly, a comprehensive structural review of the PDB reveals that the FMN-binding site employed by these enzymes is unlike any structurally characterized FMN binders to date. These findings reveal the first instance of an FMN-binding glycoside hydrolase and suggest a potential link between FMN and carbohydrate metabolism in the human gut microbiota.}, } @article {pmid30649168, year = {2019}, author = {Griffith, JC and Morgan, XC}, title = {Invited Commentary: Improving the Accessibility of Human Microbiome Project Data Through Integration With R/Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1027-1030}, doi = {10.1093/aje/kwz007}, pmid = {30649168}, issn = {1476-6256}, mesh = {Computational Biology ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S ; }, abstract = {Alterations in the composition of the microbiota have been implicated in many diseases. The Human Microbiome Project (HMP) provides a comprehensive reference data set of the "normal" human microbiome of 242 healthy adults at 5 major body sites. The HMP used both 16S ribosomal RNA gene sequencing and whole-genome metagenomic sequencing to profile the subjects' microbial communities. However, accessing and analyzing the HMP data set still presents technical and bioinformatic challenges, given that researchers must import the microbiome data, integrate phylogenetic trees, and access and merge public and restricted metadata. The HMP16SData R/Bioconductor package developed by Schiffer et al. (Am J Epidemiol. 2019;188(6):1023-1026) greatly simplifies access to the HMP data by combining 16S taxonomic abundance data, public patient metadata, and phylogenetic trees as a single data object. The authors also provide an interface for users with approved Database of Genotypes and Phenotypes (dbGaP) projects to easily retrieve and merge the controlled-access HMP metadata. This package has a broad range of appeal to researchers across disciplines and with various levels of expertise in using R and/or other statistical tools, which translates to improved data accessibility for public health research, with data from healthy individuals serving as a reference for disease-associated studies.}, } @article {pmid30649166, year = {2019}, author = {Schiffer, L and Azhar, R and Shepherd, L and Ramos, M and Geistlinger, L and Huttenhower, C and Dowd, JB and Segata, N and Waldron, L}, title = {HMP16SData: Efficient Access to the Human Microbiome Project Through Bioconductor.}, journal = {American journal of epidemiology}, volume = {188}, number = {6}, pages = {1023-1026}, pmid = {30649166}, issn = {1476-6256}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; R21 AI121784/AI/NIAID NIH HHS/United States ; U24 CA180996/CA/NCI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Computational Biology ; Databases, Genetic/*statistics & numerical data ; Female ; Humans ; Male ; Microbiota/*physiology ; RNA, Ribosomal, 16S/*metabolism ; Young Adult ; }, abstract = {Phase 1 of the Human Microbiome Project (HMP) investigated 18 body subsites of 242 healthy American adults to produce the first comprehensive reference for the composition and variation of the "healthy" human microbiome. Publicly available data sets from amplicon sequencing of two 16S ribosomal RNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S ribosomal RNA variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.}, } @article {pmid30637337, year = {2018}, author = {Bayer, K and Jahn, MT and Slaby, BM and Moitinho-Silva, L and Hentschel, U}, title = {Marine Sponges as Chloroflexi Hot Spots: Genomic Insights and High-Resolution Visualization of an Abundant and Diverse Symbiotic Clade.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30637337}, issn = {2379-5077}, abstract = {Members of the widespread bacterial phylum Chloroflexi can dominate high-microbial-abundance (HMA) sponge microbiomes. In the Sponge Microbiome Project, Chloroflexi sequences amounted to 20 to 30% of the total microbiome of certain HMA sponge genera with the classes/clades SAR202, Caldilineae, and Anaerolineae being the most prominent. We performed metagenomic and single-cell genomic analyses to elucidate the functional gene repertoire of Chloroflexi symbionts of Aplysina aerophoba. Eighteen draft genomes were reconstructed and placed into phylogenetic context of which six were investigated in detail. Common genomic features of Chloroflexi sponge symbionts were related to central energy and carbon converting pathways, amino acid and fatty acid metabolism, and respiration. Clade-specific metabolic features included a massively expanded genomic repertoire for carbohydrate degradation in Anaerolineae and Caldilineae genomes, but only amino acid utilization by SAR202. While Anaerolineae and Caldilineae import cofactors and vitamins, SAR202 genomes harbor genes encoding components involved in cofactor biosynthesis. A number of features relevant to symbiosis were further identified, including CRISPR-Cas systems, eukaryote-like repeat proteins, and secondary metabolite gene clusters. Chloroflexi symbionts were visualized in the sponge extracellular matrix at ultrastructural resolution by the fluorescence in situ hybridization-correlative light and electron microscopy (FISH-CLEM) method. Carbohydrate degradation potential was reported previously for "Candidatus Poribacteria" and SAUL, typical symbionts of HMA sponges, and we propose here that HMA sponge symbionts collectively engage in degradation of dissolved organic matter, both labile and recalcitrant. Thus, sponge microbes may not only provide nutrients to the sponge host, but they may also contribute to dissolved organic matter (DOM) recycling and primary productivity in reef ecosystems via a pathway termed the sponge loop. IMPORTANCE Chloroflexi represent a widespread, yet enigmatic bacterial phylum with few cultivated members. We used metagenomic and single-cell genomic approaches to characterize the functional gene repertoire of Chloroflexi symbionts in marine sponges. The results of this study suggest clade-specific metabolic specialization and that Chloroflexi symbionts have the genomic potential for dissolved organic matter (DOM) degradation from seawater. Considering the abundance and dominance of sponges in many benthic environments, we predict that the role of sponge symbionts in biogeochemical cycles is larger than previously thought.}, } @article {pmid30623484, year = {2019}, author = {Zhai, J and Knox, K and Twigg, HL and Zhou, H and Zhou, JJ}, title = {Exact variance component tests for longitudinal microbiome studies.}, journal = {Genetic epidemiology}, volume = {43}, number = {3}, pages = {250-262}, pmid = {30623484}, issn = {1098-2272}, support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; R01 HG006139/HG/NHGRI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; HG006139/HG/NHGRI NIH HHS/United States ; K01DK106116/DK/NIDDK NIH HHS/United States ; GM053275/GM/NIGMS NIH HHS/United States ; GM105785/GM/NIGMS NIH HHS/United States ; K01 DK106116/DK/NIDDK NIH HHS/United States ; R01 GM053275/GM/NIGMS NIH HHS/United States ; U01 HL121831/HL/NHLBI NIH HHS/United States ; }, mesh = {Computer Simulation ; Humans ; Longitudinal Studies ; Lung/microbiology ; *Microbiota ; *Models, Genetic ; }, abstract = {In metagenomic studies, testing the association between microbiome composition and clinical outcomes translates to testing the nullity of variance components. Motivated by a lung human immunodeficiency virus (HIV) microbiome project, we study longitudinal microbiome data by using variance component models with more than two variance components. Current testing strategies only apply to models with exactly two variance components and when sample sizes are large. Therefore, they are not applicable to longitudinal microbiome studies. In this paper, we propose exact tests (score test, likelihood ratio test, and restricted likelihood ratio test) to (a) test the association of the overall microbiome composition in a longitudinal design and (b) detect the association of one specific microbiome cluster while adjusting for the effects from related clusters. Our approach combines the exact tests for null hypothesis with a single variance component with a strategy of reducing multiple variance components to a single one. Simulation studies demonstrate that our method has a correct type I error rate and superior power compared to existing methods at small sample sizes and weak signals. Finally, we apply our method to a longitudinal pulmonary microbiome study of HIV-infected patients and reveal two interesting genera Prevotella and Veillonella associated with forced vital capacity. Our findings shed light on the impact of the lung microbiome on HIV complexities. The method is implemented in the open-source, high-performance computing language Julia and is freely available at https://github.com/JingZhai63/VCmicrobiome.}, } @article {pmid32422014, year = {2019}, author = {Lambring, CB and Siraj, S and Patel, K and Sankpal, UT and Mathew, S and Basha, R}, title = {Impact of the Microbiome on the Immune System.}, journal = {Critical reviews in immunology}, volume = {39}, number = {5}, pages = {313-328}, pmid = {32422014}, issn = {1040-8401}, support = {P20 CA233355/CA/NCI NIH HHS/United States ; R25 HL125447/HL/NHLBI NIH HHS/United States ; S21 MD012472/MD/NIMHD NIH HHS/United States ; U54 MD006882/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/*immunology/microbiology ; Host-Pathogen Interactions ; Humans ; Immune System/immunology/*microbiology ; Immunity ; Infections/*immunology/microbiology ; Metabolic Diseases/*immunology/microbiology ; Microbiota/immunology ; Neoplasms/*immunology/microbiology ; }, abstract = {Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.}, } @article {pmid30578265, year = {2019}, author = {Stubbendieck, RM and May, DS and Chevrette, MG and Temkin, MI and Wendt-Pienkowski, E and Cagnazzo, J and Carlson, CM and Gern, JE and Currie, CR}, title = {Competition among Nasal Bacteria Suggests a Role for Siderophore-Mediated Interactions in Shaping the Human Nasal Microbiota.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {10}, pages = {}, pmid = {30578265}, issn = {1098-5336}, support = {P01 HL070831/HL/NHLBI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; U19 AI109673/AI/NIAID NIH HHS/United States ; }, mesh = {Actinobacteria/*physiology ; Humans ; Microbiota/*physiology ; Nasal Cavity/*microbiology ; Siderophores/*metabolism ; Staphylococcus/*physiology ; }, abstract = {Resources available in the human nasal cavity are limited. Therefore, to successfully colonize the nasal cavity, bacteria must compete for scarce nutrients. Competition may occur directly through interference (e.g., antibiotics) or indirectly by nutrient sequestration. To investigate the nature of nasal bacterial competition, we performed coculture inhibition assays between nasal Actinobacteria and Staphylococcus spp. We found that isolates of coagulase-negative staphylococci (CoNS) were sensitive to growth inhibition by Actinobacteria but that Staphylococcus aureus isolates were resistant to inhibition. Among Actinobacteria, we observed that Corynebacterium spp. were variable in their ability to inhibit CoNS. We sequenced the genomes of 10 Corynebacterium species isolates, including 3 Corynebacterium propinquum isolates that strongly inhibited CoNS and 7 other Corynebacterium species isolates that only weakly inhibited CoNS. Using a comparative genomics approach, we found that the C. propinquum genomes were enriched in genes for iron acquisition and harbored a biosynthetic gene cluster (BGC) for siderophore production, absent in the noninhibitory Corynebacterium species genomes. Using a chrome azurol S assay, we confirmed that C. propinquum produced siderophores. We demonstrated that iron supplementation rescued CoNS from inhibition by C. propinquum, suggesting that inhibition was due to iron restriction through siderophore production. Through comparative metabolomics and molecular networking, we identified the siderophore produced by C. propinquum as dehydroxynocardamine. Finally, we confirmed that the dehydroxynocardamine BGC is expressed in vivo by analyzing human nasal metatranscriptomes from the NIH Human Microbiome Project. Together, our results suggest that bacteria produce siderophores to compete for limited available iron in the nasal cavity and improve their fitness.IMPORTANCE Within the nasal cavity, interference competition through antimicrobial production is prevalent. For instance, nasal Staphylococcus species strains can inhibit the growth of other bacteria through the production of nonribosomal peptides and ribosomally synthesized and posttranslationally modified peptides. In contrast, bacteria engaging in exploitation competition modify the external environment to prevent competitors from growing, usually by hindering access to or depleting essential nutrients. As the nasal cavity is a nutrient-limited environment, we hypothesized that exploitation competition occurs in this system. We determined that Corynebacterium propinquum produces an iron-chelating siderophore, and this iron-sequestering molecule correlates with the ability to inhibit the growth of coagulase-negative staphylococci. Furthermore, we found that the genes required for siderophore production are expressed in vivo Thus, although siderophore production by bacteria is often considered a virulence trait, our work indicates that bacteria may produce siderophores to compete for limited iron in the human nasal cavity.}, } @article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11988-E11995}, pmid = {30559213}, issn = {1091-6490}, support = {R01 AI132606/AI/NIAID NIH HHS/United States ; U01 CK000538/CK/NCEZID CDC HHS/United States ; U01CK000538//ACL HHS/United States ; U54 GM088558/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/immunology/*pharmacology ; Bacteria/classification/*drug effects/immunology ; Child ; Child, Preschool ; Drug Resistance, Bacterial/*drug effects/immunology ; Escherichia coli/drug effects ; Humans ; Infant ; Infant, Newborn ; Microbial Sensitivity Tests/methods ; Microbiota/*drug effects/immunology ; Pneumococcal Infections ; Pneumococcal Vaccines/immunology ; Species Specificity ; Staphylococcus aureus/drug effects ; Streptococcus pneumoniae/drug effects ; United States ; Vaccination ; Vaccines, Conjugate/immunology ; Young Adult ; }, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("proportion of bystander exposures"). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.}, } @article {pmid30536921, year = {2019}, author = {Clayton, JB and Danzeisen, JL and Johnson, TJ and Trent, AM and Hayer, SS and Murphy, T and Wuenschmann, A and Elder, M and Shen, Z and Mannion, A and Bryant, E and Knights, D and Fox, JG}, title = {Characterization of Campylobacter jejuni, Campylobacter upsaliensis, and a novel Campylobacter sp. in a captive non-human primate zoological collection.}, journal = {Journal of medical primatology}, volume = {48}, number = {2}, pages = {114-122}, pmid = {30536921}, issn = {1600-0684}, support = {R01 OD011141/OD/NIH HHS/United States ; T32 DA007097/DA/NIDA NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Zoo ; Ape Diseases/*epidemiology/microbiology ; Campylobacter/*isolation & purification ; Campylobacter Infections/epidemiology/microbiology/*veterinary ; Campylobacter jejuni/isolation & purification ; Campylobacter upsaliensis/isolation & purification ; Female ; Haplorhini ; Hominidae ; Male ; Minnesota/epidemiology ; Monkey Diseases/*epidemiology/microbiology ; Phylogeny ; Prevalence ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Species Specificity ; }, abstract = {BACKGROUND: The aim of this study was to longitudinally investigate the prevalence and characterization of Campylobacter spp. from non-human primates primate (NHP) with a history of endemic diarrhea housed at Como Park Zoo.

METHODS: Fecal samples from 33 symptom-free NHP belonging to eight different species were collected weekly for 9 weeks. Species-level characterization and phylogenetic analysis of isolates included biochemical testing and 16S rRNA sequencing.

RESULTS: Campylobacter spp. were isolated from the feces of 42% (14/33) of the primates. Three Campylobacter spp. (C upsaliensis, C jejuni, and novel Campylobacter sp.) were identified from three NHP species. A possible positive host Campylobacter species-specificity was observed. However, no statistical association was observed between the isolation of Campylobacter spp. and age and sex of the animal.

CONCLUSIONS: The study revealed the value of conducting repeated fecal sampling to establish the overall prevalence of Campylobacter in zoo-maintained NHP; it also importantly identifies a novel Campylobacter sp. isolated from white-faced saki monkeys.}, } @article {pmid30534599, year = {2018}, author = {Escapa, IF and Chen, T and Huang, Y and Gajare, P and Dewhirst, FE and Lemon, KP}, title = {New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract.}, journal = {mSystems}, volume = {3}, number = {6}, pages = {}, pmid = {30534599}, issn = {2379-5077}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; R01 DE016937/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; R01 GM117174/GM/NIGMS NIH HHS/United States ; }, abstract = {The expanded Human Oral Microbiome Database (eHOMD) is a comprehensive microbiome database for sites along the human aerodigestive tract that revealed new insights into the nostril microbiome. The eHOMD provides well-curated 16S rRNA gene reference sequences linked to available genomes and enables assignment of species-level taxonomy to most next-generation sequences derived from diverse aerodigestive tract sites, including the nasal passages, sinuses, throat, esophagus, and mouth. Using minimum entropy decomposition coupled with the RDP Classifier and our eHOMD V1-V3 training set, we reanalyzed 16S rRNA V1-V3 sequences from the nostrils of 210 Human Microbiome Project participants at the species level, revealing four key insights. First, we discovered that Lawsonella clevelandensis, a recently named bacterium, and Neisseriaceae [G-1] HMT-174, a previously unrecognized bacterium, are common in adult nostrils. Second, just 19 species accounted for 90% of the total sequences from all participants. Third, 1 of these 19 species belonged to a currently uncultivated genus. Fourth, for 94% of the participants, 2 to 10 species constituted 90% of their sequences, indicating that the nostril microbiome may be represented by limited consortia. These insights highlight the strengths of the nostril microbiome as a model system for studying interspecies interactions and microbiome function. Also, in this cohort, three common nasal species (Dolosigranulum pigrum and two Corynebacterium species) showed positive differential abundance when the pathobiont Staphylococcus aureus was absent, generating hypotheses regarding colonization resistance. By facilitating species-level taxonomic assignment to microbes from the human aerodigestive tract, the eHOMD is a vital resource enhancing clinical relevance of microbiome studies. IMPORTANCE The eHOMD (http://www.ehomd.org) is a valuable resource for researchers, from basic to clinical, who study the microbiomes and the individual microbes in body sites in the human aerodigestive tract, which includes the nasal passages, sinuses, throat, esophagus, and mouth, and the lower respiratory tract, in health and disease. The eHOMD is an actively curated, web-based, open-access resource. eHOMD provides the following: (i) species-level taxonomy based on grouping 16S rRNA gene sequences at 98.5% identity, (ii) a systematic naming scheme for unnamed and/or uncultivated microbial taxa, (iii) reference genomes to facilitate metagenomic, metatranscriptomic, and proteomic studies and (iv) convenient cross-links to other databases (e.g., PubMed and Entrez). By facilitating the assignment of species names to sequences, the eHOMD is a vital resource for enhancing the clinical relevance of 16S rRNA gene-based microbiome studies, as well as metagenomic studies.}, } @article {pmid30521034, year = {2018}, author = {Moitinho-Silva, L and Nielsen, S and Amir, A and Gonzalez, A and Ackermann, GL and Cerrano, C and Astudillo-Garcia, C and Easson, C and Sipkema, D and Liu, F and Steinert, G and Kotoulas, G and McCormack, GP and Feng, G and Bell, JJ and Vicente, J and Björk, JR and Montoya, JM and Olson, JB and Reveillaud, J and Steindler, L and Pineda, MC and Marra, MV and Ilan, M and Taylor, MW and Polymenakou, P and Erwin, PM and Schupp, PJ and Simister, RL and Knight, R and Thacker, RW and Costa, R and Hill, RT and Lopez-Legentil, S and Dailianis, T and Ravasi, T and Hentschel, U and Li, Z and Webster, NS and Thomas, T}, title = {Erratum to: The sponge microbiome project.}, journal = {GigaScience}, volume = {7}, number = {12}, pages = {}, doi = {10.1093/gigascience/giy145}, pmid = {30521034}, issn = {2047-217X}, } @article {pmid30510919, year = {2018}, author = {Brenner, LA and Hoisington, AJ and Stearns-Yoder, KA and Stamper, CE and Heinze, JD and Postolache, TT and Hadidi, DA and Hoffmire, CA and Stanislawski, MA and Lowry, CA}, title = {Military-Related Exposures, Social Determinants of Health, and Dysbiosis: The United States-Veteran Microbiome Project (US-VMP).}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {400}, pmid = {30510919}, issn = {2235-2988}, mesh = {Adult ; Aged ; Cohort Studies ; *Dysbiosis ; Female ; Humans ; Male ; Mental Health ; *Microbiota ; Middle Aged ; Military Personnel/*psychology ; *Social Determinants of Health ; United States ; United States Department of Veterans Affairs ; Veterans ; *Veterans Health ; Young Adult ; }, abstract = {Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) measures regarding their past and current medical history. Participants also provide skin, oral, and gut microbiome samples, and permission to track their health status via the VHA electronic medical record. To date, data collection efforts have been cross-diagnostic. Within this manuscript, we describe current data collection practices and procedures, as well as highlight demographic, military, and psychiatric characteristics of the first 188 Veterans enrolled in the study. Based on these findings, we assert that this cohort is unique as compared to those enrolled in recent large-scale studies of the microbiome. To increase understanding regarding disease and health among diverse cohorts, efforts such as the US-VMP are vital. Ongoing barriers and facilitators to data collection are discussed, as well as future research directions, with an emphasis on the importance of shifting current thinking regarding the microbiome from a focus on normalcy and dysbiosis to health promotion and disease prevention.}, } @article {pmid30481125, year = {2018}, author = {Kim, JW and Lee, JS and Kim, JH and Jeong, JW and Lee, DH and Nam, S}, title = {Comparison of Microbiota Variation in Korean Healthy Adolescents with Adults Suggests Notable Maturity Differences.}, journal = {Omics : a journal of integrative biology}, volume = {22}, number = {12}, pages = {770-778}, pmid = {30481125}, issn = {1557-8100}, mesh = {Adolescent ; Gastrointestinal Microbiome/*genetics ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; }, abstract = {Comparative studies of microbiome variation in world populations and different developmental stages of organisms are essential to decipher the linkages among microbiome, health, and disease. Notably, the gut microbiota are believed to mature in early life. In this context, we compared the gut microbiota diversity in Korean adolescent healthy samples (KAHSs) to healthy Korean adults (HKAs) as well as the Human Microbiome Project healthy samples (HMPHSs), the latter being one of the largest adult cohorts, based on organismal composition, alpha- and beta-diversities, function/pathway prediction analysis, and co-occurrence networks. We found that the gut microbiota compositions, including the ratios of firmicutes to bacteroidetes, between KAHSs and HMPHSs were different, and the diversities of KAHSs were less than those of HMPHSs. The predicted functions, for example, secondary bile acid synthesis and insulin signaling of KAHSs and HMPHSs, were also significantly different. Genus-level networks showed that co-occurrences among different taxa more frequently happened in HMPHSs than in KAHSs. Even though both KAHSs and HMPHSs represent healthy microbiomes, comparisons showed substantial differences, likely implicating different diets, environments, and demographics. Interestingly, we observed lower microbial diversities and less frequent co-occurrences among different taxa in KAHSs than adult HMPHSs and HKAs. These new findings collectively suggest that the adolescent gut microbiota in the present Korean sample did not reach the extent of maturity of adult microbiota diversity. In all, further population studies of microbiome variation across geographies and developmental stages are warranted, and should usefully inform future diagnostics and therapeutics innovation targeting the microbiome.}, } @article {pmid30465353, year = {2018}, author = {Wang, H and Kang, D and Zhou, XD and Li, YQ}, title = {[Prevention of infectious diseases through microecology modulation techniques].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {5}, pages = {564-567}, pmid = {30465353}, issn = {2618-0456}, mesh = {Humans ; *Microbiota ; Mouth/microbiology ; Skin/microbiology ; }, abstract = {The microbe is small in volume, but large in quantity and species. The symbiotic microbe, which is far more than human cells, code millions times of genes than human being. Somatic cells and these symbiotic microbe distributing in human body skin, respiratory tract, oral cavity and gastrointestinal tract, urinary tract and other parts form a complex ecosystem whose dynamic balance is highly related to body health. With the successful implementation of Human Microbiome Project, more attentions have been paid to the next generation microbiome technologies. New tools and methods for ecological regulation of human microbiome are emerging. The way we improve the world of human microbiology will be more convenient. This paper will make a review on the modulation techniques of human microbiome.}, } @article {pmid30452039, year = {2019}, author = {Rajakovich, LJ and Balskus, EP}, title = {Metabolic functions of the human gut microbiota: the role of metalloenzymes.}, journal = {Natural product reports}, volume = {36}, number = {4}, pages = {593-625}, pmid = {30452039}, issn = {1460-4752}, mesh = {Ammonia/metabolism ; Cresols/metabolism ; Enzymes/chemistry/*metabolism ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/immunology/*physiology ; Humans ; Hydrogen Sulfide/metabolism ; Metals/chemistry/metabolism ; Methylamines/metabolism ; Nucleoside Q/biosynthesis ; Polysaccharides/metabolism ; Vitamins/biosynthesis ; Xenobiotics/pharmacokinetics ; }, abstract = {Covering: up to the end of 2017 The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.}, } @article {pmid30425147, year = {2018}, author = {Su, X and Jing, G and McDonald, D and Wang, H and Wang, Z and Gonzalez, A and Sun, Z and Huang, S and Navas, J and Knight, R and Xu, J}, title = {Identifying and Predicting Novelty in Microbiome Studies.}, journal = {mBio}, volume = {9}, number = {6}, pages = {}, pmid = {30425147}, issn = {2150-7511}, mesh = {*Computational Biology ; *Databases, Factual ; Humans ; Microbiota/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {With the expansion of microbiome sequencing globally, a key challenge is to relate new microbiome samples to the existing space of microbiome samples. Here, we present Microbiome Search Engine (MSE), which enables the rapid search of query microbiome samples against a large, well-curated reference microbiome database organized by taxonomic similarity at the whole-microbiome level. Tracking the microbiome novelty score (MNS) over 8 years of microbiome depositions based on searching in more than 100,000 global 16S rRNA gene amplicon samples, we detected that the structural novelty of human microbiomes is approaching saturation and likely bounded, whereas that in environmental habitats remains 5 times higher. Via the microbiome focus index (MFI), which is derived from the MNS and microbiome attention score (MAS), we objectively track and compare the structural-novelty and attracted-attention scores of individual microbiome samples and projects, and we predict future trends in the field. For example, marine and indoor environments and mother-baby interactions are likely to receive disproportionate additional attention based on recent trends. Therefore, MNS, MAS, and MFI are proposed "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.IMPORTANCE We introduce two concepts to quantify the novelty of a microbiome. The first, the microbiome novelty score (MNS), allows identification of microbiomes that are especially different from what is already sequenced. The second, the microbiome attention score (MAS), allows identification of microbiomes that have many close neighbors, implying that considerable scientific attention is devoted to their study. By computing a microbiome focus index based on the MNS and MAS, we objectively track and compare the novelty and attention scores of individual microbiome samples and projects over time and predict future trends in the field; i.e., we work toward yielding fundamentally new microbiomes rather than filling in the details. Therefore, MNS, MAS, and MFI can serve as "alt-metrics" for evaluating a microbiome project or prospective developments in the microbiome field, both of which are done in the context of existing microbiome big data.}, } @article {pmid30423063, year = {2018}, author = {Frioux, C and Fremy, E and Trottier, C and Siegel, A}, title = {Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {17}, pages = {i934-i943}, pmid = {30423063}, issn = {1367-4811}, mesh = {Humans ; *Microbial Consortia ; Microbiota ; Software ; }, abstract = {MOTIVATION: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.

RESULTS: We present the Miscoto tool to facilitate the selection of a community optimizing a desired function in a microbiome by reporting several possibilities which can be then sorted according to biological criteria. Communities are exhaustively identified using logical programming and by combining the non-compartmentalized and the compartmentalized frameworks. The benchmarking of 4.9 million metabolic functions associated with the Human Microbiome Project, shows that Miscoto is suited to screen and classify metabolic producibility in terms of feasibility, functional redundancy and cooperation processes involved. As an illustration of a host-microbial system, screening the Recon 2.2 human metabolism highlights the role of different consortia within a family of 773 intestinal bacteria.

Miscoto source code, instructions for use and examples are available at: https://github.com/cfrioux/miscoto.}, } @article {pmid30419494, year = {2019}, author = {Ventura Spagnolo, E and Stassi, C and Mondello, C and Zerbo, S and Milone, L and Argo, A}, title = {Forensic microbiology applications: A systematic review.}, journal = {Legal medicine (Tokyo, Japan)}, volume = {36}, number = {}, pages = {73-80}, doi = {10.1016/j.legalmed.2018.11.002}, pmid = {30419494}, issn = {1873-4162}, mesh = {Adult ; Aged ; Body Fluids/*microbiology ; Brain/*microbiology ; Cause of Death ; Databases, Bibliographic ; Digestive System/*microbiology ; Female ; *Forensic Medicine ; Heart/*microbiology ; Humans ; Male ; *Microbiota ; Middle Aged ; *Postmortem Changes ; Skin/*microbiology ; Time Factors ; }, abstract = {According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.}, } @article {pmid30400268, year = {2018}, author = {Ojo-Okunola, A and Nicol, M and du Toit, E}, title = {Human Breast Milk Bacteriome in Health and Disease.}, journal = {Nutrients}, volume = {10}, number = {11}, pages = {}, pmid = {30400268}, issn = {2072-6643}, support = {U01 AI110466/AI/NIAID NIH HHS/United States ; 1U01AI110466-01A1//H3Africa U01 AWARD FROM THE NATIONAL INSTITUTES OF HEALTH OF THE USA/ ; U54HG009824//NIH Office of the Director/ ; OPP1017641; OPP1017579//Bill and Melinda Gates Foundation/ ; U54 HG009824/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/isolation & purification ; Feces/microbiology ; Female ; HIV Infections/microbiology/therapy ; Humans ; Infant ; Mastitis/microbiology/therapy ; *Microbiota ; Milk, Human/*microbiology ; Neoplasms/microbiology/therapy ; }, abstract = {It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.}, } @article {pmid30397444, year = {2018}, author = {Ma, ZS}, title = {DAR (diversity-area relationship): Extending classic SAR (species-area relationship) for biodiversity and biogeography analyses.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10023-10038}, pmid = {30397444}, issn = {2045-7758}, abstract = {I extend the classic SAR, which has achieved status of ecological law and plays a critical role in global biodiversity and biogeography analyses, to general DAR (diversity-area relationship). The extension was aimed to remedy a serious application limitation of the traditional SAR that only addressed one aspect of biodiversity scaling-species richness scaling over space, but ignoring species abundance information. The extension was further inspired by a recent consensus that Hill numbers offer the most appropriate measures for alpha-diversity and multiplicative beta-diversity. In particular, Hill numbers are essentially a series of Renyi's entropy values weighted differently along the rare-common-dominant spectrum of species abundance distribution and are in the units of effective number of species (or species equivalents such as OTUs). I therefore postulate that Hill numbers should follow the same or similar law of the traditional SAR. I test the postulation with the American gut microbiome project (AGP) dataset of 1,473 healthy North American individuals. I further propose three new concepts and develop their statistical estimation formulae based on the new DAR extension, including: (i) DAR profile-z-q relationship (DAR scaling parameter z at different diversity order q), (ii) PDO (pair-wise diversity overlap) profile-g-q relationship (PDO parameter g at order q, and (iii) MAD (maximal accrual diversity: D max) profile-D max-q. While the classic SAR is a special case of our new DAR profile, the PDO and MAD profiles offer novel tools for analyzing biodiversity (including alpha-diversity and beta-diversity) and biogeography over space.}, } @article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, pmid = {30367598}, issn = {1471-2105}, support = {R03 AA016008/AA/NIAAA NIH HHS/United States ; }, mesh = {*Algorithms ; *Bacteria ; Bacterial Physiological Phenomena ; Computational Biology/*methods ; *Disease ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Risk Factors ; }, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.

RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC = 0.906, AUPR =0.526) and demonstrates its superiority by ~ 7% and ~ 5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.

CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, } @article {pmid30349509, year = {2018}, author = {Chaudhari, NM and Gautam, A and Gupta, VK and Kaur, G and Dutta, C and Paul, S}, title = {PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2322}, pmid = {30349509}, issn = {1664-302X}, abstract = {The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM (http://www.bioinfo.iicb.res.in/pangfr-hm/) - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.}, } @article {pmid30349024, year = {2018}, author = {Chen, Z and Yeoh, YK and Hui, M and Wong, PY and Chan, MCW and Ip, M and Yu, J and Burk, RD and Chan, FKL and Chan, PKS}, title = {Diversity of macaque microbiota compared to the human counterparts.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15573}, pmid = {30349024}, issn = {2045-2322}, mesh = {Anal Canal/*microbiology ; Animals ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Healthy Volunteers ; Humans ; Macaca mulatta ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; }, abstract = {Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.}, } @article {pmid30332487, year = {2018}, author = {Wyman, SK and Avila-Herrera, A and Nayfach, S and Pollard, KS}, title = {A most wanted list of conserved microbial protein families with no known domains.}, journal = {PloS one}, volume = {13}, number = {10}, pages = {e0205749}, pmid = {30332487}, issn = {1932-6203}, mesh = {Bacterial Proteins/*chemistry/genetics ; Computational Biology ; *Databases, Nucleic Acid ; Humans ; Metagenome/*genetics ; Metagenomics ; Microbiota/*genetics ; Phylogeny ; Protein Domains/*genetics ; Sequence Homology, Nucleic Acid ; }, abstract = {The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a "most wanted" list of genes to prioritize for further characterization.}, } @article {pmid30275573, year = {2018}, author = {Gonzalez, A and Navas-Molina, JA and Kosciolek, T and McDonald, D and Vázquez-Baeza, Y and Ackermann, G and DeReus, J and Janssen, S and Swafford, AD and Orchanian, SB and Sanders, JG and Shorenstein, J and Holste, H and Petrus, S and Robbins-Pianka, A and Brislawn, CJ and Wang, M and Rideout, JR and Bolyen, E and Dillon, M and Caporaso, JG and Dorrestein, PC and Knight, R}, title = {Qiita: rapid, web-enabled microbiome meta-analysis.}, journal = {Nature methods}, volume = {15}, number = {10}, pages = {796-798}, pmid = {30275573}, issn = {1548-7105}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; P30 MH062512/MH/NIMH NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Humans ; *Internet ; *Metagenomics ; *Microbiota ; *Software ; User-Computer Interface ; }, abstract = {Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.}, } @article {pmid30269615, year = {2018}, author = {Aziz, RK and Hegazy, SM and Yasser, R and Rizkallah, MR and ElRakaiby, MT}, title = {Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.}, journal = {Expert opinion on drug metabolism & toxicology}, volume = {14}, number = {10}, pages = {1043-1055}, doi = {10.1080/17425255.2018.1530216}, pmid = {30269615}, issn = {1744-7607}, mesh = {Animals ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; Pharmaceutical Preparations/administration & dosage/*metabolism ; Pharmacogenetics/methods ; Precision Medicine/methods ; Toxicogenetics/methods ; }, abstract = {Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloging to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multiomic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.}, } @article {pmid30249275, year = {2018}, author = {He, Y and Wu, W and Wu, S and Zheng, HM and Li, P and Sheng, HF and Chen, MX and Chen, ZH and Ji, GY and Zheng, ZD and Mujagond, P and Chen, XJ and Rong, ZH and Chen, P and Lyu, LY and Wang, X and Xu, JB and Wu, CB and Yu, N and Xu, YJ and Yin, J and Raes, J and Ma, WJ and Zhou, HW}, title = {Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {172}, pmid = {30249275}, issn = {2049-2618}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation & purification ; Economic Status ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metabolic Syndrome/*economics/metabolism/*microbiology ; Middle Aged ; Phylogeny ; }, abstract = {BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status.

RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population.

CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.}, } @article {pmid30230652, year = {2018}, author = {Little, MS and Ervin, SM and Walton, WG and Tripathy, A and Xu, Y and Liu, J and Redinbo, MR}, title = {Active site flexibility revealed in crystal structures of Parabacteroides merdae β-glucuronidase from the human gut microbiome.}, journal = {Protein science : a publication of the Protein Society}, volume = {27}, number = {12}, pages = {2010-2022}, pmid = {30230652}, issn = {1469-896X}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; DGS-1650116//National Science Foundation/International ; }, mesh = {Bacteroidaceae/*enzymology ; Catalytic Domain ; Crystallography, X-Ray ; *Gastrointestinal Microbiome ; Glucuronidase/*metabolism ; Humans ; Models, Molecular ; Protein Conformation ; }, abstract = {β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.}, } @article {pmid30197908, year = {2017}, author = {Xia, Y and Sun, J}, title = {Hypothesis Testing and Statistical Analysis of Microbiome.}, journal = {Genes & diseases}, volume = {4}, number = {3}, pages = {138-148}, pmid = {30197908}, issn = {2352-4820}, support = {R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; }, abstract = {After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.}, } @article {pmid30172254, year = {2018}, author = {Lager, S and de Goffau, MC and Sovio, U and Peacock, SJ and Parkhill, J and Charnock-Jones, DS and Smith, GCS}, title = {Detecting eukaryotic microbiota with single-cell sensitivity in human tissue.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {151}, pmid = {30172254}, issn = {2049-2618}, support = {MR/K021133/1/MRC_/Medical Research Council/United Kingdom ; G1100221//Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Adult ; Eukaryota/classification/genetics/*isolation & purification ; Female ; Humans ; Placenta/*microbiology/*parasitology ; Plasmodium falciparum/genetics/isolation & purification ; Pregnancy ; Pregnancy Complications/*microbiology/*parasitology/physiopathology ; Pregnancy Outcome ; Saccharomyces cerevisiae/genetics/isolation & purification ; Toxoplasma/genetics/isolation & purification ; Young Adult ; }, abstract = {BACKGROUND: Fetal growth restriction, pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes. These complications are considerable contributors to fetal/maternal morbidity and mortality worldwide. A significant proportion of these cases are thought to be due to dysfunction of the placenta. However, the underlying mechanisms of placental dysfunction are unclear. The aim of the present study was to investigate whether adverse pregnancy outcomes are associated with evidence of placental eukaryotic infection.

RESULTS: We modified the 18S Illumina Amplicon Protocol of the Earth Microbiome Project and made it capable of detecting just a single spiked-in genome copy of Plasmodium falciparum, Saccharomyces cerevisiae, or Toxoplasma gondii among more than 70,000 human cells. Using this method, we were unable to detect eukaryotic pathogens in placental biopsies in instances of adverse pregnancy outcome (n = 199) or in healthy controls (n = 99).

CONCLUSIONS: Eukaryotic infection of the placenta is not an underlying cause of the aforementioned pregnancy complications. Possible clinical applications for this non-targeted, yet extremely sensitive, eukaryotic screening method are manifest.}, } @article {pmid30155556, year = {2019}, author = {Ma, ZS}, title = {Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.}, journal = {Microbial ecology}, volume = {77}, number = {3}, pages = {821-838}, pmid = {30155556}, issn = {1432-184X}, mesh = {Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; Humans ; Metagenomics ; *Microbiota ; Models, Biological ; }, abstract = {SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography "maps" for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.}, } @article {pmid30131772, year = {2018}, author = {Ma, ZS and Li, L and Li, W}, title = {Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1619}, pmid = {30131772}, issn = {1664-302X}, abstract = {A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (D max-q) for the within-body biogeography of the human microbiome. These profiles constitute the "maps" of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an "average Joe" that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the "long tail" of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.}, } @article {pmid30129002, year = {2018}, author = {Lin, J and Kimura, BY and Oikarinen, S and Nykter, M}, title = {Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1838}, number = {}, pages = {261-272}, doi = {10.1007/978-1-4939-8682-8_18}, pmid = {30129002}, issn = {1940-6029}, mesh = {*Computational Biology/methods ; Enterovirus B, Human/*genetics ; *Genome, Viral ; *Genomics/methods ; Humans ; Metagenome ; Metagenomics/methods/standards ; Quality Control ; }, abstract = {The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.}, } @article {pmid30098679, year = {2018}, author = {Kroon, SJ and Ravel, J and Huston, WM}, title = {Cervicovaginal microbiota, women's health, and reproductive outcomes.}, journal = {Fertility and sterility}, volume = {110}, number = {3}, pages = {327-336}, doi = {10.1016/j.fertnstert.2018.06.036}, pmid = {30098679}, issn = {1556-5653}, support = {R01 NR014826/NR/NINR NIH HHS/United States ; R01 NR014784/NR/NINR NIH HHS/United States ; R01 AI116799/AI/NIAID NIH HHS/United States ; }, mesh = {Cervix Uteri/microbiology/*physiology ; Dysbiosis/complications/diagnosis/microbiology ; Female ; Humans ; Infertility, Female/diagnosis/etiology/microbiology ; Lactobacillus/isolation & purification/physiology ; Microbiota/*physiology ; Pregnancy ; Reproduction/*physiology ; Vagina/microbiology/*physiology ; *Women's Health/trends ; }, abstract = {The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.}, } @article {pmid30071492, year = {2018}, author = {Hanssen, EN and Liland, KH and Gill, P and Snipen, L}, title = {Optimizing body fluid recognition from microbial taxonomic profiles.}, journal = {Forensic science international. Genetics}, volume = {37}, number = {}, pages = {13-20}, doi = {10.1016/j.fsigen.2018.07.012}, pmid = {30071492}, issn = {1878-0326}, mesh = {Bacteria/*genetics ; Discriminant Analysis ; Feces/*microbiology ; Female ; Forensic Genetics/methods ; High-Throughput Nucleotide Sequencing ; Humans ; Least-Squares Analysis ; Microbiota ; Mouth/*microbiology ; Nasal Cavity/*microbiology ; *RNA, Ribosomal, 16S ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Skin/*microbiology ; Vagina/*microbiology ; }, abstract = {In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.}, } @article {pmid30059804, year = {2018}, author = {Tripathi, A and Marotz, C and Gonzalez, A and Vázquez-Baeza, Y and Song, SJ and Bouslimani, A and McDonald, D and Zhu, Q and Sanders, JG and Smarr, L and Dorrestein, PC and Knight, R}, title = {Are microbiome studies ready for hypothesis-driven research?.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {61-69}, pmid = {30059804}, issn = {1879-0364}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Biomedical Research/methods/*standards ; Humans ; *Microbiota ; }, abstract = {Hypothesis-driven research has led to many scientific advances, but hypotheses cannot be tested in isolation: rather, they require a framework of aggregated scientific knowledge to allow questions to be posed meaningfully. This framework is largely still lacking in microbiome studies, and the only way to create it is by discovery-driven, tool-driven, and standards-driven research projects. Here we illustrate these issues using several such non-hypothesis-driven projects from our own laboratories, including spatial mapping, the American Gut Project, the Earth Microbiome Project (which is an umbrella project integrating many smaller hypothesis-driven projects), and the knowledgebase-driven tools GNPS and Qiita. We argue that an investment of community resources in infrastructure tasks, and in the controls and standards that underpin them, will greatly enhance the investment in hypothesis-driven research programs.}, } @article {pmid30057577, year = {2018}, author = {Riiser, ES and Haverkamp, THA and Borgan, Ø and Jakobsen, KS and Jentoft, S and Star, B}, title = {A Single Vibrionales 16S rRNA Oligotype Dominates the Intestinal Microbiome in Two Geographically Separated Atlantic cod Populations.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1561}, pmid = {30057577}, issn = {1664-302X}, abstract = {Atlantic cod (Gadus morhua) provides an interesting species for the study of host-microbe interactions because it lacks the MHC II complex that is involved in the presentation of extracellular pathogens. Nonetheless, little is known about the diversity of its microbiome in natural populations. Here, we use high-throughput sequencing of the 16S rRNA V4 region, amplified with the primer design of the Earth Microbiome Project (EMP), to investigate the microbial composition in gut content and mucosa of 22 adult individuals from two coastal populations in Norway, located 470 km apart. We identify a core microbiome of 23 OTUs (97% sequence similarity) in all individuals that comprises 93% of the total number of reads. The most abundant orders are classified as Vibrionales, Fusobacteriales, Clostridiales, and Bacteroidales. While mucosal samples show significantly lower diversity than gut content samples, no differences in OTU community composition are observed between the two geographically separated populations. All specimens share a limited number of abundant OTUs. Moreover, the most abundant OTU consists of a single oligotype (order Vibrionales, genus Photobacterium) that represents nearly 50% of the reads in both locations. Our results suggest that these microbiomes comprise a limited number of species or that the EMP V4 primers do not yield sufficient resolution to confidently separate these communities. Our study contributes to a growing body of literature that shows limited spatial differentiation of the intestinal microbiomes in marine fish based on 16S rRNA sequencing, highlighting the need for multi-gene approaches to provide more insight into the diversity of these communities.}, } @article {pmid30042392, year = {2018}, author = {Clayton, JB and Al-Ghalith, GA and Long, HT and Tuan, BV and Cabana, F and Huang, H and Vangay, P and Ward, T and Minh, VV and Tam, NA and Dat, NT and Travis, DA and Murtaugh, MP and Covert, H and Glander, KE and Nadler, T and Toddes, B and Sha, JCM and Singer, R and Knights, D and Johnson, TJ}, title = {Associations Between Nutrition, Gut Microbiome, and Health in A Novel Nonhuman Primate Model.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {11159}, pmid = {30042392}, issn = {2045-2322}, support = {T32 DA007097/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Bacteroidetes/classification/genetics ; Biodiversity ; Cercopithecidae/*physiology ; Chloroplasts/genetics ; Diet, Vegan ; Dysbiosis ; Endangered Species ; Feces/microbiology ; Firmicutes/classification/genetics ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/microbiology ; *Health Status ; Life Style ; Metagenome ; Models, Animal ; Nutritional Status/*physiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA ; Statistics, Nonparametric ; }, abstract = {Red-shanked doucs (Pygathrix nemaeus) are endangered, foregut-fermenting colobine primates which are difficult to maintain in captivity. There are critical gaps in our understanding of their natural lifestyle, including dietary habits such as consumption of leaves, unripe fruit, flowers, seeds, and other plant parts. There is also a lack of understanding of enteric adaptations, including their unique microflora. To address these knowledge gaps, we used the douc as a model to study relationships between gastrointestinal microbial community structure and lifestyle. We analyzed published fecal samples as well as detailed dietary history from doucs with four distinct lifestyles (wild, semi-wild, semi-captive, and captive) and determined gastrointestinal bacterial microbiome composition using 16S rRNA sequencing. A clear gradient of microbiome composition was revealed along an axis of natural lifestyle disruption, including significant associations with diet, biodiversity, and microbial function. We also identified potential microbial biomarkers of douc dysbiosis, including Bacteroides and Prevotella, which may be related to health. Our results suggest a gradient-like shift in captivity causes an attendant shift to severe gut dysbiosis, thereby resulting in gastrointestinal issues.}, } @article {pmid30010718, year = {2019}, author = {Zheng, W and Mao, Q and Genco, RJ and Wactawski-Wende, J and Buck, M and Cai, Y and Sun, Y}, title = {A parallel computational framework for ultra-large-scale sequence clustering analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {35}, number = {3}, pages = {380-388}, pmid = {30010718}, issn = {1367-4811}, support = {R01 AI125982/AI/NIAID NIH HHS/United States ; R01 DE024523/DE/NIDCR NIH HHS/United States ; }, mesh = {*Algorithms ; *Cluster Analysis ; Computational Biology ; *Microbiota ; *Software ; }, abstract = {MOTIVATION: The rapid development of sequencing technology has led to an explosive accumulation of genomic data. Clustering is often the first step to be performed in sequence analysis. However, existing methods scale poorly with respect to the unprecedented growth of input data size. As high-performance computing systems are becoming widely accessible, it is highly desired that a clustering method can easily scale to handle large-scale sequence datasets by leveraging the power of parallel computing.

RESULTS: In this paper, we introduce SLAD (Separation via Landmark-based Active Divisive clustering), a generic computational framework that can be used to parallelize various de novo operational taxonomic unit (OTU) picking methods and comes with theoretical guarantees on both accuracy and efficiency. The proposed framework was implemented on Apache Spark, which allows for easy and efficient utilization of parallel computing resources. Experiments performed on various datasets demonstrated that SLAD can significantly speed up a number of popular de novo OTU picking methods and meanwhile maintains the same level of accuracy. In particular, the experiment on the Earth Microbiome Project dataset (∼2.2B reads, 437 GB) demonstrated the excellent scalability of the proposed method.

Open-source software for the proposed method is freely available at https://www.acsu.buffalo.edu/~yijunsun/lab/SLAD.html.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid30006754, year = {2018}, author = {Sorbellini, E and Rucco, M and Rinaldi, F}, title = {Photodynamic and photobiological effects of light-emitting diode (LED) therapy in dermatological disease: an update.}, journal = {Lasers in medical science}, volume = {33}, number = {7}, pages = {1431-1439}, pmid = {30006754}, issn = {1435-604X}, mesh = {Aging/radiation effects ; Alopecia/drug therapy/radiotherapy ; Humans ; *Light ; *Photochemotherapy ; Photosensitizing Agents/therapeutic use ; Skin Diseases/*drug therapy ; }, abstract = {Benefit deriving from the use of light is known since ancient time, but, only in the last decades of twentieth century, we witnessed the rapid expansion of knowledge and techniques. Light-emitted diode (LED)-based devices represent the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The present work reviews the current knowledge about LED-based therapeutic approaches in different skin and hair disorders. LED therapy represents the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The use of LED in the treatment of such conditions has now entered common practice among dermatologists. Additional controlled studies are still needed to corroborate the efficacy of such kind of treatment.}, } @article {pmid29984938, year = {2018}, author = {Li, BL and Cheng, L and Zhou, XD and Peng, X}, title = {[Research progress on the relationship between oral microbes and digestive system diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {36}, number = {3}, pages = {331-335}, pmid = {29984938}, issn = {2618-0456}, mesh = {*Dental Caries/microbiology ; *Digestive System Diseases/microbiology ; Humans ; *Microbiota ; *Mouth Diseases/microbiology ; *Periodontal Diseases ; }, abstract = {The human microbiome project promoted further understanding on human oral microbes. Besides oral diseases such as dental caries, periodontal disease, and oral cancer, oral microbes are closely associated with systematic diseases. They have a close connection with digestive system diseases and even contribute to the origination and progression of colorectal cancer. By reviewing recent studies involving oral microbe-related digestive systemic diseases, we aim to propose the considerable role of oral microbes in relation to digestive systemic diseases and the way of oral microbes to multiple organs of digestive system.}, } @article {pmid29974051, year = {2018}, author = {Fankhauser, M and Moser, C and Nyfeler, T}, title = {Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {6}, number = {}, pages = {84}, pmid = {29974051}, issn = {2296-4185}, abstract = {The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets.}, } @article {pmid29900563, year = {2018}, author = {Coleman, M and Elkins, C and Gutting, B and Mongodin, E and Solano-Aguilar, G and Walls, I}, title = {Microbiota and Dose Response: Evolving Paradigm of Health Triangle.}, journal = {Risk analysis : an official publication of the Society for Risk Analysis}, volume = {38}, number = {10}, pages = {2013-2028}, doi = {10.1111/risa.13121}, pmid = {29900563}, issn = {1539-6924}, mesh = {Animals ; *Bacteria ; *Dysbiosis ; *Gastrointestinal Microbiome ; Genomics ; Humans ; Immunity, Innate ; Immunity, Mucosal ; Intestines/immunology/microbiology ; Mice ; Models, Biological ; Prebiotics ; Probiotics/*analysis ; Risk Assessment/*methods ; }, abstract = {SRA Dose-Response and Microbial Risk Analysis Specialty Groups jointly sponsored symposia that addressed the intersections between the "microbiome revolution" and dose response. Invited speakers presented on innovations and advances in gut and nasal microbiota (normal microbial communities) in the first decade after the Human Microbiome Project began. The microbiota and their metabolites are now known to influence health and disease directly and indirectly, through modulation of innate and adaptive immune systems and barrier function. Disruption of healthy microbiota is often associated with changes in abundance and diversity of core microbial species (dysbiosis), caused by stressors including antibiotics, chemotherapy, and disease. Nucleic-acid-based metagenomic methods demonstrated that the dysbiotic host microbiota no longer provide normal colonization resistance to pathogens, a critical component of innate immunity of the superorganism. Diverse pathogens, probiotics, and prebiotics were considered in human and animal models (in vivo and in vitro). Discussion included approaches for design of future microbial dose-response studies to account for the presence of the indigenous microbiota that provide normal colonization resistance, and the absence of the protective microbiota in dysbiosis. As NextGen risk analysis methodology advances with the "microbiome revolution," a proposed new framework, the Health Triangle, may replace the old paradigm based on the Disease Triangle (focused on host, pathogen, and environment) and germophobia. Collaborative experimental designs are needed for testing hypotheses about causality in dose-response relationships for pathogens present in our environments that clearly compete in complex ecosystems with thousands of bacterial species dominating the healthy superorganism.}, } @article {pmid29878050, year = {2018}, author = {Albayrak, L and Khanipov, K and Golovko, G and Fofanov, Y}, title = {Detection of multi-dimensional co-exclusion patterns in microbial communities.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {21}, pages = {3695-3701}, doi = {10.1093/bioinformatics/bty414}, pmid = {29878050}, issn = {1367-4811}, mesh = {Humans ; *Microbiota ; Software ; }, abstract = {MOTIVATION: Identification of complex relationships among members of microbial communities is key to understand and control the microbiota. Co-exclusion is arguably one of the most important patterns reflecting micro-organisms' intolerance to each other's presence. Knowing these relations opens an opportunity to manipulate microbiotas, personalize anti-microbial and probiotic treatments as well as guide microbiota transplantation. The co-exclusion pattern however, cannot be appropriately described by a linear function nor its strength be estimated using covariance or (negative) Pearson and Spearman correlation coefficients. This manuscript proposes a way to quantify the strength and evaluate the statistical significance of co-exclusion patterns between two, three or more variables describing a microbiota and allows one to extend analysis beyond micro-organism abundance by including other microbiome associated measurements such as, pH, temperature etc., as well as estimate the expected numbers of false positive co-exclusion patterns in a co-exclusion network.

RESULTS: The implemented computational pipeline (CoEx) tested against 2380 microbial profiles (samples) from The Human Microbiome Project resulted in body-site specific pairwise co-exclusion patterns.

C++ source code for calculation of the score and P-value for two, three and four dimensional co-exclusion patterns as well as source code and executable files for the CoEx pipeline are available at https://scsb.utmb.edu/labgroups/fofanov/co-exclusion_in_microbial_communities.asp.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid29862519, year = {2018}, author = {Clayton, JB and Gomez, A and Amato, K and Knights, D and Travis, DA and Blekhman, R and Knight, R and Leigh, S and Stumpf, R and Wolf, T and Glander, KE and Cabana, F and Johnson, TJ}, title = {The gut microbiome of nonhuman primates: Lessons in ecology and evolution.}, journal = {American journal of primatology}, volume = {80}, number = {6}, pages = {e22867}, doi = {10.1002/ajp.22867}, pmid = {29862519}, issn = {1098-2345}, mesh = {Animals ; Bacteria/classification ; *Biological Evolution ; Diet/veterinary ; Ecology ; *Gastrointestinal Microbiome ; Phylogeny ; Primates/classification/immunology/*microbiology/physiology ; }, abstract = {The mammalian gastrointestinal (GI) tract is home to trillions of bacteria that play a substantial role in host metabolism and immunity. While progress has been made in understanding the role that microbial communities play in human health and disease, much less attention has been given to host-associated microbiomes in nonhuman primates (NHPs). Here we review past and current research exploring the gut microbiome of NHPs. First, we summarize methods for characterization of the NHP gut microbiome. Then we discuss variation in gut microbiome composition and function across different NHP taxa. Finally, we highlight how studying the gut microbiome offers new insights into primate nutrition, physiology, and immune system function, as well as enhances our understanding of primate ecology and evolution. Microbiome approaches are useful tools for studying relevant issues in primate ecology. Further study of the gut microbiome of NHPs will offer new insight into primate ecology and evolution as well as human health.}, } @article {pmid29854953, year = {2018}, author = {Cardona, C and Lax, S and Larsen, P and Stephens, B and Hampton-Marcell, J and Edwardson, CF and Henry, C and Van Bonn, B and Gilbert, JA}, title = {Environmental Sources of Bacteria Differentially Influence Host-Associated Microbial Dynamics.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29854953}, issn = {2379-5077}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, abstract = {Host-associated microbial dynamics are influenced by dietary and immune factors, but how exogenous microbial exposure shapes host-microbe dynamics remains poorly characterized. To investigate this phenomenon, we characterized the skin, rectum, and respiratory tract-associated microbiota in four aquarium-housed dolphins daily over a period of 6 weeks, including administration of a probiotic during weeks 4 to 6. The environmental bacterial sources were also characterized, including the animals' human handlers, the aquarium air and water, and the dolphins' food supply. Continuous microbial exposure occurred between all sites, yet each environment maintained a characteristic microbiota, suggesting that the majority of exposure events do not result in colonization. Small changes in water physicochemistry had a significant but weak correlation with change in dolphin-associated bacterial richness but had no influence on phylogenetic diversity. Food and air microbiota were the richest and had the largest conditional influence on other microbiota in the absence of probiotics, but during probiotic administration, food alone had the largest influence on the stability of the dolphin microbiota. Our results suggest that respiratory tract and gastrointestinal epithelium interactions with air- and food-associated microbes had the biggest influence on host-microbiota dynamics, while other interactions, such as skin transmission, played only a minor role. Finally, direct oral stimulation with a foreign exogenous microbial source can have a profound effect on microbial stability. IMPORTANCE These results provide valuable insights into the ecological influence of exogenous microbial exposure, as well as laying the foundation for improving aquarium management practices. By comparing data for dolphins from aquaria that use natural versus artificial seawater, we demonstrate the potential influence of aquarium water disinfection procedures on dolphin microbial dynamics.}, } @article {pmid29795809, year = {2018}, author = {McDonald, D and Hyde, E and Debelius, JW and Morton, JT and Gonzalez, A and Ackermann, G and Aksenov, AA and Behsaz, B and Brennan, C and Chen, Y and DeRight Goldasich, L and Dorrestein, PC and Dunn, RR and Fahimipour, AK and Gaffney, J and Gilbert, JA and Gogul, G and Green, JL and Hugenholtz, P and Humphrey, G and Huttenhower, C and Jackson, MA and Janssen, S and Jeste, DV and Jiang, L and Kelley, ST and Knights, D and Kosciolek, T and Ladau, J and Leach, J and Marotz, C and Meleshko, D and Melnik, AV and Metcalf, JL and Mohimani, H and Montassier, E and Navas-Molina, J and Nguyen, TT and Peddada, S and Pevzner, P and Pollard, KS and Rahnavard, G and Robbins-Pianka, A and Sangwan, N and Shorenstein, J and Smarr, L and Song, SJ and Spector, T and Swafford, AD and Thackray, VG and Thompson, LR and Tripathi, A and Vázquez-Baeza, Y and Vrbanac, A and Wischmeyer, P and Wolfe, E and Zhu, Q and , and Knight, R}, title = {American Gut: an Open Platform for Citizen Science Microbiome Research.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29795809}, issn = {2379-5077}, support = {MR/N01183X/1/MRC_/Medical Research Council/United Kingdom ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; MR/N030125/1/MRC_/Medical Research Council/United Kingdom ; T32 GM007752/GM/NIGMS NIH HHS/United States ; /WT_/Wellcome Trust/United Kingdom ; }, abstract = {Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the United States, United Kingdom, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes compared to environmental samples; demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations; uncover new molecules and kinds of molecular communities in the human stool metabolome; and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education. IMPORTANCE We show that a citizen science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n = 1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet, which we confirm with untargeted metabolomics on hundreds of samples.}, } @article {pmid29760467, year = {2018}, author = {Xian, P and Xuedong, Z and Xin, X and Yuqing, L and Yan, L and Jiyao, L and Xiaoquan, S and Shi, H and Jian, X and Ga, L}, title = {The Oral Microbiome Bank of China.}, journal = {International journal of oral science}, volume = {10}, number = {2}, pages = {16}, pmid = {29760467}, issn = {2049-3169}, mesh = {China ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome project (HMP) promoted further understanding of human oral microbes. However, research on the human oral microbiota has not made as much progress as research on the gut microbiota. Currently, the causal relationship between the oral microbiota and oral diseases remains unclear, and little is known about the link between the oral microbiota and human systemic diseases. To further understand the contribution of the oral microbiota in oral diseases and systemic diseases, a Human Oral Microbiome Database (HOMD) was established in the US. The HOMD includes 619 taxa in 13 phyla, and most of the microorganisms are from American populations. Due to individual differences in the microbiome, the HOMD does not reflect the Chinese oral microbial status. Herein, we established a new oral microbiome database-the Oral Microbiome Bank of China (OMBC, http://www.sklod.org/ombc). Currently, the OMBC includes information on 289 bacterial strains and 720 clinical samples from the Chinese population, along with lab and clinical information. The OMBC is the first curated description of a Chinese-associated microbiome; it provides tools for use in investigating the role of the oral microbiome in health and diseases, and will give the community abundant data and strain information for future oral microbial studies.}, } @article {pmid29724017, year = {2018}, author = {Avershina, E and Angell, IL and Simpson, M and Storrø, O and Øien, T and Johnsen, R and Rudi, K}, title = {Low Maternal Microbiota Sharing across Gut, Breast Milk and Vagina, as Revealed by 16S rRNA Gene and Reduced Metagenomic Sequencing.}, journal = {Genes}, volume = {9}, number = {5}, pages = {}, pmid = {29724017}, issn = {2073-4425}, abstract = {The maternal microbiota plays an important role in infant gut colonization. In this work we have investigated which bacterial species are shared across the breast milk, vaginal and stool microbiotas of 109 women shortly before and after giving birth using 16S rRNA gene sequencing and a novel reduced metagenomic sequencing (RMS) approach in a subgroup of 16 women. All the species predicted by the 16S rRNA gene sequencing were also detected by RMS analysis and there was good correspondence between their relative abundances estimated by both approaches. Both approaches also demonstrate a low level of maternal microbiota sharing across the population and RMS analysis identified only two species common to most women and in all sample types (Bifidobacterium longum and Enterococcus faecalis). Breast milk was the only sample type that had significantly higher intra- than inter- individual similarity towards both vaginal and stool samples. We also searched our RMS dataset against an in silico generated reference database derived from bacterial isolates in the Human Microbiome Project. The use of this reference-based search enabled further separation of Bifidobacterium longum into Bifidobacterium longum ssp. longum and Bifidobacterium longum ssp. infantis. We also detected the Lactobacillus rhamnosus GG strain, which was used as a probiotic supplement by some women, demonstrating the potential of RMS approach for deeper taxonomic delineation and estimation.}, } @article {pmid29721973, year = {2018}, author = {Rowan, S and Taylor, A}, title = {The Role of Microbiota in Retinal Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1074}, number = {}, pages = {429-435}, doi = {10.1007/978-3-319-75402-4_53}, pmid = {29721973}, issn = {0065-2598}, mesh = {Animals ; Conjunctiva/microbiology ; Cornea/microbiology ; Diabetic Retinopathy/microbiology/prevention & control ; Disease Models, Animal ; Gastrointestinal Microbiome/drug effects/physiology ; Germ-Free Life ; Glaucoma/microbiology ; Humans ; Macular Degeneration/microbiology ; Metformin/pharmacology ; Mice ; Microbiota/*physiology ; Mouth/microbiology ; Retinal Diseases/*microbiology ; Uveitis/microbiology ; }, abstract = {The ten years since the first publications on the human microbiome project have brought enormous attention and insight into the role of the human microbiome in health and disease. Connections between populations of microbiota and ocular disease are now being established, and increased accessibility to microbiome research and insights into other diseases is expected to yield enormous information in the coming years. With the characterization of the ocular microbiome, important insights have already been made regarding corneal and conjunctival tissues. Roles for non-ocular microbiomes in complex retinal diseases are now being evaluated. For example, the gut microbiome has been implicated in the pathogenesis of uveitis. This short review will summarize the few studies linking gut or oral microbiota to diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD). We will also conjecture where the most significant findings still remain to be elucidated. Finally, we will propose the gut-retina axis, related but distinct from the gut-brain axis.}, } @article {pmid29692798, year = {2018}, author = {Roche-Lima, A and Carrasquillo-Carrión, K and Gómez-Moreno, R and Cruz, JM and Velázquez-Morales, DM and Rogozin, IB and Baerga-Ortiz, A}, title = {The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases.}, journal = {Frontiers in genetics}, volume = {9}, number = {}, pages = {116}, pmid = {29692798}, issn = {1664-8021}, support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; G12 RR003051/RR/NCRR NIH HHS/United States ; G12 MD007600/MD/NIMHD NIH HHS/United States ; R21 CA198963/CA/NCI NIH HHS/United States ; }, abstract = {Background: The human gut microbiota is a dynamic community of microorganisms that mediate important biochemical processes. Differences in the gut microbial composition have been associated with inflammatory bowel diseases (IBD) and other intestinal disorders. In this study, we quantified and compared the frequencies of eight genotoxic and/or pro-inflammatory bacterial genes found in metagenomic Whole Genome Sequences (mWGSs) of samples from individuals with IBD vs. a cohort of healthy human subjects. Methods: The eight selected gene sequences were clbN, clbB, cif, cnf-1, usp, tcpC from Escherichia coli, gelE from Enterococcus faecalis and murB from Akkermansia muciniphila. We also included the sequences for the conserved murB genes from E. coli and E. faecalis as markers for the presence of Enterobacteriaceae or Enterococci in the samples. The gene sequences were chosen based on their previously reported ability to disrupt normal cellular processes to either promote inflammation or to cause DNA damage in cultured cells or animal models, which could be linked to a role in IBD. The selected sequences were searched in three different mWGS datasets accessed through the Human Microbiome Project (HMP): a healthy cohort (N = 251), a Crohn's disease cohort (N = 60) and an ulcerative colitis cohort (N = 17). Results: Firstly, the sequences for the murB housekeeping genes from Enterobacteriaceae and Enterococci were more frequently found in the IBD cohorts (32% E. coli in IBD vs. 12% in healthy; 13% E. faecalis in IBD vs. 3% in healthy) than in the healthy cohort, confirming earlier reports of a higher presence of both of these taxa in IBD. For some of the sequences in our study, especially usp and gelE, their frequency was even more sharply increased in the IBD cohorts than in the healthy cohort, suggesting an association with IBD that is not easily explained by the increased presence of E. coli or E. faecalis in those samples. Conclusion: Our results suggest a significant association between the presence of some of these genotoxic or pro-inflammatory gene sequences and IBDs. In addition, these results illustrate the power and limitations of the HMP database in the detection of possible clinical correlations for individual bacterial genes.}, } @article {pmid29668831, year = {2018}, author = {Maziarz, M and Pfeiffer, RM and Wan, Y and Gail, MH}, title = {Using standard microbiome reference groups to simplify beta-diversity analyses and facilitate independent validation.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {19}, pages = {3249-3257}, pmid = {29668831}, issn = {1367-4811}, mesh = {*Computational Biology ; Feces/microbiology ; Humans ; *Microbiota ; Nose/microbiology ; }, abstract = {MOTIVATION: Comparisons of microbiome communities across populations are often based on pairwise distance measures (beta-diversity). Standard analyses (principal coordinate plots, permutation tests, kernel methods) require access to primary data if another investigator wants to add or compare independent data. We propose using standard reference measurements to simplify microbiome beta-diversity analyses, to make them more transparent, and to facilitate independent validation and comparisons across studies.

RESULTS: Using stool and nasal reference sets from the Human Microbiome Project (HMP), we computed mean distances (actually Bray-Curtis or Pearson correlation dissimilarities) to each reference set for each new sample. Thus, each new sample has two mean distances that can be plotted and analyzed with classical statistical methods. To test the approach, we studied independent (not reference) HMP subjects. Simple Hotelling tests demonstrated statistically significant differences in mean distances to reference sets between all pairs of body sites (stool, skin, nasal, saliva and vagina) at the phylum, class, order, family and genus levels. Using the distance to a single reference set was usually sufficient, but using both reference sets always worked well. The use of reference sets simplifies standard analyses of beta-diversity and facilitates the independent validation and combining of such data because others can compute distances to the same reference sets. Moreover, standard statistical methods for survival analysis, logistic regression and other procedures can be applied to vectors of mean distances to reference sets, thereby greatly expanding the potential uses of beta-diversity information. More work is needed to identify the best reference sets for particular applications.

https://github.com/NCI-biostats/microbiome-fixed-reference.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid29658784, year = {2018}, author = {Popic, V and Kuleshov, V and Snyder, M and Batzoglou, S}, title = {Fast Metagenomic Binning via Hashing and Bayesian Clustering.}, journal = {Journal of computational biology : a journal of computational molecular cell biology}, volume = {25}, number = {7}, pages = {677-688}, doi = {10.1089/cmb.2017.0250}, pmid = {29658784}, issn = {1557-8666}, mesh = {*Bayes Theorem ; Cluster Analysis ; Computational Biology/*statistics & numerical data ; Humans ; Metagenome/genetics ; Metagenomics/*statistics & numerical data ; Microbiota/*genetics ; }, abstract = {We introduce GATTACA, a framework for fast unsupervised binning of metagenomic contigs. Similar to recent approaches, GATTACA clusters contigs based on their coverage profiles across a large cohort of metagenomic samples; however, unlike previous methods that rely on read mapping, GATTACA quickly estimates these profiles from kmer counts stored in a compact index. This approach can result in over an order of magnitude speedup, while matching the accuracy of earlier methods on synthetic and real data benchmarks. It also provides a way to index metagenomic samples (e.g., from public repositories such as the Human Microbiome Project) offline once and reuse them across experiments; furthermore, the small size of the sample indices allows them to be easily transferred and stored. Leveraging the MinHash technique, GATTACA also provides an efficient way to identify publicly available metagenomic data that can be incorporated into the set of reference metagenomes to further improve binning accuracy. Thus, enabling easy indexing and reuse of publicly available metagenomic data sets, GATTACA makes accurate metagenomic analyses accessible to a much wider range of researchers.}, } @article {pmid29657969, year = {2018}, author = {Gilbert, JA and Jansson, JK and Knight, R}, title = {Earth Microbiome Project and Global Systems Biology.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, pmid = {29657969}, issn = {2379-5077}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, } @article {pmid29608646, year = {2018}, author = {Sinha, R and Goedert, JJ and Vogtmann, E and Hua, X and Porras, C and Hayes, R and Safaeian, M and Yu, G and Sampson, J and Ahn, J and Shi, J}, title = {Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.}, journal = {American journal of epidemiology}, volume = {187}, number = {6}, pages = {1282-1290}, pmid = {29608646}, issn = {1476-6256}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R03 CA159414/CA/NCI NIH HHS/United States ; }, mesh = {Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Time Factors ; }, abstract = {Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.}, } @article {pmid29568289, year = {2018}, author = {Flores Saiffe Farías, A and Mendizabal, AP and Morales, JA}, title = {An Ontology Systems Approach on Human Brain Expression and Metaproteomics.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {406}, pmid = {29568289}, issn = {1664-302X}, abstract = {Research in the last decade has shown growing evidence of the gut microbiota influence on brain physiology. While many mechanisms of this influence have been proposed in animal models, most studies in humans are the result of a pathology-dysbiosis association and very few have related the presence of certain taxa with brain substructures or molecular pathways. In this paper, we associated the functional ontologies in the differential expression of brain substructures from the Allen Brain Atlas database, with those of the metaproteome from the Human Microbiome Project. Our results showed several coherent clustered ontologies where many taxa could influence brain expression and physiology. A detailed analysis of psychobiotics showed specific slim ontologies functionally associated with substructures in the basal ganglia and cerebellar cortex. Some of the most relevant slim ontology groups are related to Ion transport, Membrane potential, Synapse, DNA and RNA metabolism, and Antigen processing, while the most relevant neuropathology found was Parkinson disease. In some of these cases, new hypothetical gut microbiota-brain interaction pathways are proposed.}, } @article {pmid29492330, year = {2017}, author = {Lang, JM and Coil, DA and Neches, RY and Brown, WE and Cavalier, D and Severance, M and Hampton-Marcell, JT and Gilbert, JA and Eisen, JA}, title = {A microbial survey of the International Space Station (ISS).}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e4029}, pmid = {29492330}, issn = {2167-8359}, abstract = {BACKGROUND: Modern advances in sequencing technology have enabled the census of microbial members of many natural ecosystems. Recently, attention is increasingly being paid to the microbial residents of human-made, built ecosystems, both private (homes) and public (subways, office buildings, and hospitals). Here, we report results of the characterization of the microbial ecology of a singular built environment, the International Space Station (ISS). This ISS sampling involved the collection and microbial analysis (via 16S rDNA PCR) of 15 surfaces sampled by swabs onboard the ISS. This sampling was a component of Project MERCCURI (Microbial Ecology Research Combining Citizen and University Researchers on ISS). Learning more about the microbial inhabitants of the "buildings" in which we travel through space will take on increasing importance, as plans for human exploration continue, with the possibility of colonization of other planets and moons.

RESULTS: Sterile swabs were used to sample 15 surfaces onboard the ISS. The sites sampled were designed to be analogous to samples collected for (1) the Wildlife of Our Homes project and (2) a study of cell phones and shoes that were concurrently being collected for another component of Project MERCCURI. Sequencing of the 16S rDNA genes amplified from DNA extracted from each swab was used to produce a census of the microbes present on each surface sampled. We compared the microbes found on the ISS swabs to those from both homes on Earth and data from the Human Microbiome Project.

CONCLUSIONS: While significantly different from homes on Earth and the Human Microbiome Project samples analyzed here, the microbial community composition on the ISS was more similar to home surfaces than to the human microbiome samples. The ISS surfaces are species-rich with 1,036-4,294 operational taxonomic units (OTUs per sample). There was no discernible biogeography of microbes on the 15 ISS surfaces, although this may be a reflection of the small sample size we were able to obtain.}, } @article {pmid29490879, year = {2019}, author = {Wu, WK and Chen, CC and Panyod, S and Chen, RA and Wu, MS and Sheen, LY and Chang, SC}, title = {Optimization of fecal sample processing for microbiome study - The journey from bathroom to bench.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {2}, pages = {545-555}, doi = {10.1016/j.jfma.2018.02.005}, pmid = {29490879}, issn = {0929-6646}, mesh = {DNA/*isolation & purification ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Reagent Kits, Diagnostic ; Sequence Analysis, DNA ; Specimen Handling/*methods/*standards ; }, abstract = {Although great interest has been displayed by researchers in the contribution of gut microbiota to human health, there is still no standard protocol with consensus to guarantee the sample quality of metagenomic analysis. Here we reviewed existing methodology studies and present suggestions for optimizing research pipeline from fecal sample collection to DNA extraction. First, we discuss strategies of clinical metadata collection as common confounders for microbiome research. Second, we propose general principles for freshly collected fecal sample and its storage and share a DIY stool collection kit protocol based on the manual procedure of Human Microbiome Project (HMP). Third, we provide a useful information of collection kit with DNA stabilization buffers and compare their pros and cons for multi-omic study. Fourth, we offer technical strategies as well as information of novel tools for sample aliquoting before long-term storage. Fifth, we discuss the substantial impact of different DNA extraction protocols on technical variations of metagenomic analysis. And lastly, we point out the limitation of current methods and the unmet needs for better quality control of metagenomic analysis. We hope the information provided here will help investigators in this exciting field to advance their studies while avoiding experimental artifacts.}, } @article {pmid29378630, year = {2018}, author = {Kolde, R and Franzosa, EA and Rahnavard, G and Hall, AB and Vlamakis, H and Stevens, C and Daly, MJ and Xavier, RJ and Huttenhower, C}, title = {Host genetic variation and its microbiome interactions within the Human Microbiome Project.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {6}, pmid = {29378630}, issn = {1756-994X}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; 5U54HG003067-13/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {*Genetic Variation ; Genotype ; Humans ; Metagenome ; Microbiota/*genetics ; Principal Component Analysis ; Sequence Analysis, DNA ; Tissue Donors ; }, abstract = {BACKGROUND: Despite the increasing recognition that microbial communities within the human body are linked to health, we have an incomplete understanding of the environmental and molecular interactions that shape the composition of these communities. Although host genetic factors play a role in these interactions, these factors have remained relatively unexplored given the requirement for large population-based cohorts in which both genotyping and microbiome characterization have been performed.

METHODS: We performed whole-genome sequencing of 298 donors from the Human Microbiome Project (HMP) healthy cohort study to accompany existing deep characterization of their microbiomes at various body sites. This analysis yielded an average sequencing depth of 32x, with which we identified 27 million (M) single nucleotide variants and 2.3 M insertions-deletions.

RESULTS: Taxonomic composition and functional potential of the microbiome covaried significantly with genetic principal components in the gastrointestinal tract and oral communities, but not in the nares or vaginal microbiota. Example associations included validation of known associations between FUT2 secretor status, as well as a variant conferring hypolactasia near the LCT gene, with Bifidobacterium longum abundance in stool. The associations of microbial features with both high-level genetic attributes and single variants were specific to particular body sites, highlighting the opportunity to find unique genetic mechanisms controlling microbiome properties in the microbial communities from multiple body sites.

CONCLUSIONS: This study adds deep sequencing of host genomes to the body-wide microbiome sequences already extant from the HMP healthy cohort, creating a unique, versatile, and well-controlled reference for future studies seeking to identify host genetic modulators of the microbiome.}, } @article {pmid29373999, year = {2018}, author = {Fuks, G and Elgart, M and Amir, A and Zeisel, A and Turnbaugh, PJ and Soen, Y and Shental, N}, title = {Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {17}, pmid = {29373999}, issn = {2049-2618}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; 3-11174//Ministry of Science and Technology, Israel/International ; }, mesh = {Algorithms ; Animals ; Bacteria/classification ; Computer Simulation ; DNA Probes/genetics ; DNA, Bacterial/genetics ; Drosophila melanogaster/*microbiology ; Microbiota ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing the 16S rRNA gene. The use of next-generation sequencing methods has increased sample number and sequencing depth, but the read length of the most widely used sequencing platforms today is quite short, requiring the researcher to choose a subset of the gene to sequence (typically 16-33% of the total length). Thus, many bacteria may share the same amplified region, and the resolution of profiling is inherently limited. Platforms that offer ultra-long read lengths, whole genome shotgun sequencing approaches, and computational frameworks formerly suggested by us and by others all allow different ways to circumvent this problem yet suffer various shortcomings. There is a need for a simple and low-cost 16S rRNA gene-based profiling approach that harnesses the short read length to provide a much larger coverage of the gene to allow for high resolution, even in harsh conditions of low bacterial biomass and fragmented DNA.

RESULTS: This manuscript suggests Short MUltiple Regions Framework (SMURF), a method to combine sequencing results from different PCR-amplified regions to provide one coherent profiling. The de facto amplicon length is the total length of all amplified regions, thus providing much higher resolution compared to current techniques. Computationally, the method solves a convex optimization problem that allows extremely fast reconstruction and requires only moderate memory. We demonstrate the increase in resolution by in silico simulations and by profiling two mock mixtures and real-world biological samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved about twofold improvement in resolution when combing two independent regions. Using a custom set of six primer pairs spanning about 1200 bp (80%) of the 16S rRNA gene, we were able to achieve ~ 100-fold improvement in resolution compared to a single region, over a mock mixture of common human gut bacterial isolates. Finally, the profiling of a Drosophila melanogaster microbiome using the set of six primer pairs provided a ~ 100-fold increase in resolution and thus enabling efficient downstream analysis.

CONCLUSIONS: SMURF enables the identification of near full-length 16S rRNA gene sequences in microbial communities, having resolution superior compared to current techniques. It may be applied to standard sample preparation protocols with very little modifications. SMURF also paves the way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA exposed to other degrading conditions. The approach is not restricted to combining amplicons of the 16S rRNA gene and may be applied to any set of amplicons, e.g., in multilocus sequence typing (MLST).}, } @article {pmid29340028, year = {2017}, author = {Guerrero-Preston, R and White, JR and Godoy-Vitorino, F and Rodríguez-Hilario, A and Navarro, K and González, H and Michailidi, C and Jedlicka, A and Canapp, S and Bondy, J and Dziedzic, A and Mora-Lagos, B and Rivera-Alvarez, G and Ili-Gangas, C and Brebi-Mieville, P and Westra, W and Koch, W and Kang, H and Marchionni, L and Kim, Y and Sidransky, D}, title = {High-resolution microbiome profiling uncovers Fusobacterium nucleatum, Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral and oropharyngeal cancer in saliva from HPV positive and HPV negative patients treated with surgery and chemo-radiation.}, journal = {Oncotarget}, volume = {8}, number = {67}, pages = {110931-110948}, pmid = {29340028}, issn = {1949-2553}, support = {RC2 DE020957/DE/NIDCR NIH HHS/United States ; P50 DE019032/DE/NIDCR NIH HHS/United States ; R01 CA121113/CA/NCI NIH HHS/United States ; K01 CA164092/CA/NCI NIH HHS/United States ; U01 CA084986/CA/NCI NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {Microbiome studies show altered microbiota in head and neck squamous cell carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity. These studies utilized a traditional bioinformatics methodology, which allows for accurate taxonomic assignment down to the genus level, but cannot accurately resolve species level membership. We applied Resphera Insight, a high-resolution methodology for 16S rRNA taxonomic assignment that is able to provide species-level context in its assignments of 16S rRNA next generation sequencing (NGS) data. Resphera Insight applied to saliva samples from HNSCC patients and healthy controls led to the discovery that a subset of HNSCC saliva samples is significantly enriched with commensal species from the vaginal flora, including Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus vaginalis (52x higher in saliva). These species were not observed in normal saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the Human Microbiome Project (HMP). Interestingly, both species were only observed in saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal cancer patients. We confirmed the representation of both species in HMP data obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity flora commensal bacterium linked to colon cancer, is enriched (600x higher) in saliva from a subset of HNSCC patients with advanced tumors stages. Together, these high-resolution analyses on 583 samples suggest a possible role for bacterial species in the therapeutic outcome of HPV positive and HPV negative HNSCC patients.}, } @article {pmid29311644, year = {2018}, author = {Schirmer, M and Franzosa, EA and Lloyd-Price, J and McIver, LJ and Schwager, R and Poon, TW and Ananthakrishnan, AN and Andrews, E and Barron, G and Lake, K and Prasad, M and Sauk, J and Stevens, B and Wilson, RG and Braun, J and Denson, LA and Kugathasan, S and McGovern, DPB and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {337-346}, pmid = {29311644}, issn = {2058-5276}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Colitis, Ulcerative/microbiology ; Crohn Disease/microbiology ; Dysbiosis ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Profiling ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Longitudinal Studies ; Male ; *Metagenomics ; Phenotype ; *Transcription, Genetic ; Young Adult ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.}, } @article {pmid29281638, year = {2017}, author = {Lo, C and Marculescu, R}, title = {MPLasso: Inferring microbial association networks using prior microbial knowledge.}, journal = {PLoS computational biology}, volume = {13}, number = {12}, pages = {e1005915}, pmid = {29281638}, issn = {1553-7358}, mesh = {Algorithms ; Computational Biology ; Data Mining ; Databases, Genetic ; Humans ; Machine Learning ; Microbial Consortia/genetics/*physiology ; Microbial Interactions/*physiology ; Microbiota/genetics/*physiology ; Models, Biological ; }, abstract = {Due to the recent advances in high-throughput sequencing technologies, it becomes possible to directly analyze microbial communities in human body and environment. To understand how microbial communities adapt, develop, and interact with the human body and the surrounding environment, one of the fundamental challenges is to infer the interactions among different microbes. However, due to the compositional and high-dimensional nature of microbial data, statistical inference cannot offer reliable results. Consequently, new approaches that can accurately and robustly estimate the associations (putative interactions) among microbes are needed to analyze such compositional and high-dimensional data. We propose a novel framework called Microbial Prior Lasso (MPLasso) which integrates graph learning algorithm with microbial co-occurrences and associations obtained from scientific literature by using automated text mining. We show that MPLasso outperforms existing models in terms of accuracy, microbial network recovery rate, and reproducibility. Furthermore, the association networks we obtain from the Human Microbiome Project datasets show credible results when compared against laboratory data.}, } @article {pmid29277868, year = {2018}, author = {Maltez Thomas, A and Prata Lima, F and Maria Silva Moura, L and Maria da Silva, A and Dias-Neto, E and Setubal, JC}, title = {Comparative Metagenomics.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1704}, number = {}, pages = {243-260}, doi = {10.1007/978-1-4939-7463-4_8}, pmid = {29277868}, issn = {1940-6029}, mesh = {Computational Biology ; Humans ; Metagenomics/*methods ; *Microbiota ; Mouth Mucosa/*microbiology ; Sequence Analysis, DNA/methods ; Software ; Tongue/*microbiology ; }, abstract = {Thanks in large part to newer, better, and cheaper DNA sequencing technologies, an enormous number of metagenomic sequence datasets have been and continue to be generated, covering a huge variety of environmental niches, including several different human body sites. Comparing these metagenomes and identifying their commonalities and differences is a challenging task, due not only to the large amounts of data, but also because there are several methodological considerations that need to be taken into account to ensure an appropriate and sound comparison between datasets. In this chapter, we describe current techniques aimed at comparing metagenomes generated by 16S ribosomal RNA and shotgun DNA sequencing, emphasizing methodological issues that arise in these comparative studies. We provide a detailed case study to illustrate some of these techniques using data from the Human Microbiome Project comparing the microbial communities from ten buccal mucosa samples with ten tongue dorsum samples in terms of alpha diversity, beta diversity, and their taxonomic and functional profiles.}, } @article {pmid29253074, year = {2018}, author = {Huang, L and Krüger, J and Sczyrba, A}, title = {Analyzing large scale genomic data on the cloud with Sparkhit.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {9}, pages = {1457-1465}, pmid = {29253074}, issn = {1367-4811}, mesh = {Algorithms ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; Sequence Analysis, DNA/methods ; *Software ; }, abstract = {MOTIVATION: The increasing amount of next-generation sequencing data poses a fundamental challenge on large scale genomic analytics. Existing tools use different distributed computational platforms to scale-out bioinformatics workloads. However, the scalability of these tools is not efficient. Moreover, they have heavy run time overheads when pre-processing large amounts of data. To address these limitations, we have developed Sparkhit: a distributed bioinformatics framework built on top of the Apache Spark platform.

RESULTS: Sparkhit integrates a variety of analytical methods. It is implemented in the Spark extended MapReduce model. It runs 92-157 times faster than MetaSpark on metagenomic fragment recruitment and 18-32 times faster than Crossbow on data pre-processing. We analyzed 100 terabytes of data across four genomic projects in the cloud in 21 h, which includes the run times of cluster deployment and data downloading. Furthermore, our application on the entire Human Microbiome Project shotgun sequencing data was completed in 2 h, presenting an approach to easily associate large amounts of public datasets with reference data.

Sparkhit is freely available at: https://rhinempi.github.io/sparkhit/.

CONTACT: asczyrba@cebitec.uni-bielefeld.de.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid29232932, year = {2017}, author = {Vitetta, L and Saltzman, ET and Thomsen, M and Nikov, T and Hall, S}, title = {Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes.}, journal = {Vaccines}, volume = {5}, number = {4}, pages = {}, pmid = {29232932}, issn = {2076-393X}, abstract = {Immune defence against pathogenic agents comprises the basic premise for the administration of vaccines. Vaccinations have hence prevented millions of infectious illnesses, hospitalizations and mortality. Acquired immunity comprises antibody and cell mediated responses and is characterized by its specificity and memory. Along a similar congruent yet diverse mode of disease prevention, the human host has negotiated from in utero and at birth with the intestinal commensal bacterial cohort to maintain local homeostasis in order to achieve immunological tolerance in the new born. The advent of the Human Microbiome Project has redefined an appreciation of the interactions between the host and bacteria in the intestines from one of a collection of toxic waste to one of a symbiotic existence. Probiotics comprise bacterial genera thought to provide a health benefit to the host. The intestinal microbiota has profound effects on local and extra-intestinal end organ physiology. As such, we further posit that the adjuvant administration of dedicated probiotic formulations can encourage the intestinal commensal cohort to beneficially participate in the intestinal microbiome-intestinal epithelia-innate-cell mediated immunity axes and cell mediated cellular immunity with vaccines aimed at preventing infectious diseases whilst conserving immunological tolerance. The strength of evidence for the positive effect of probiotic administration on acquired immune responses has come from various studies with viral and bacterial vaccines. We posit that the introduction early of probiotics may provide significant beneficial immune outcomes in neonates prior to commencing a vaccination schedule or in elderly adults prior to the administration of vaccinations against influenza viruses.}, } @article {pmid29196353, year = {2017}, author = {Moffatt, MF and Cookson, WO}, title = {The lung microbiome in health and disease.}, journal = {Clinical medicine (London, England)}, volume = {17}, number = {6}, pages = {525-529}, pmid = {29196353}, issn = {1473-4893}, mesh = {Asthma/microbiology ; Bronchiectasis/microbiology ; Cystic Fibrosis/microbiology ; Humans ; Lung/*microbiology ; Lung Diseases/*microbiology ; Metagenomics ; *Microbiota/genetics ; Pulmonary Disease, Chronic Obstructive/microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics.}, } @article {pmid29178920, year = {2017}, author = {Nash, AK and Auchtung, TA and Wong, MC and Smith, DP and Gesell, JR and Ross, MC and Stewart, CJ and Metcalf, GA and Muzny, DM and Gibbs, RA and Ajami, NJ and Petrosino, JF}, title = {The gut mycobiome of the Human Microbiome Project healthy cohort.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {153}, pmid = {29178920}, issn = {2049-2618}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; 2 U54 HG003273//National Human Genome Research Institute/ ; }, mesh = {Candida/classification/genetics/isolation & purification ; Cohort Studies ; DNA, Ribosomal Spacer/genetics ; Feces/microbiology ; Fungi/classification/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Genetic Variation ; *Healthy Volunteers ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Malassezia/classification/genetics/isolation & purification ; Metagenomics/methods ; *Microbiota ; *Mycobiome ; RNA, Ribosomal, 18S/genetics ; Saccharomyces/classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene.

RESULTS: Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents.

CONCLUSIONS: Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.}, } @article {pmid29177026, year = {2017}, author = {Jackson, WJ and Agarwal, I and Pe'er, I}, title = {2-Way k-Means as a Model for Microbiome Samples.}, journal = {Journal of healthcare engineering}, volume = {2017}, number = {}, pages = {5284145}, pmid = {29177026}, issn = {2040-2295}, mesh = {Algorithms ; Female ; Humans ; *Microbiota ; *Normal Distribution ; Sequence Analysis, DNA ; Vagina/microbiology ; }, abstract = {Motivation. Microbiome sequencing allows defining clusters of samples with shared composition. However, this paradigm poorly accounts for samples whose composition is a mixture of cluster-characterizing ones and which therefore lie in between them in the cluster space. This paper addresses unsupervised learning of 2-way clusters. It defines a mixture model that allows 2-way cluster assignment and describes a variant of generalized k-means for learning such a model. We demonstrate applicability to microbial 16S rDNA sequencing data from the Human Vaginal Microbiome Project.}, } @article {pmid29152585, year = {2017}, author = {d'Hennezel, E and Abubucker, S and Murphy, LO and Cullen, TW}, title = {Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.}, journal = {mSystems}, volume = {2}, number = {6}, pages = {}, pmid = {29152585}, issn = {2379-5077}, abstract = {Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact, actively repressed by the bacteria of the gut microbiome, supporting the idea that beneficial microbes themselves contribute to the immune tolerance in support of homeostasis. These findings are important for two reasons. First, many currently assume that proinflammatory signaling by lipopolysaccharide is a fundamental feature of the gut flora. This assumption influences greatly how host-microbiome interactions are theoretically modeled but also how they are experimentally studied, by using robust TLR signaling conditions to simulate commensals. Second, elucidation of the mechanisms that support host-microbe tolerance is key to the development of therapeutics for both intestinal and systemic inflammatory disorders.}, } @article {pmid29140991, year = {2017}, author = {Schwager, E and Mallick, H and Ventz, S and Huttenhower, C}, title = {A Bayesian method for detecting pairwise associations in compositional data.}, journal = {PLoS computational biology}, volume = {13}, number = {11}, pages = {e1005852}, pmid = {29140991}, issn = {1553-7358}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; T32 GM074897/GM/NIGMS NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; *Bayes Theorem ; Computational Biology/*methods ; *Computer Simulation ; Ecology ; Humans ; Markov Chains ; Microbiota ; *Models, Biological ; Proteobacteria ; }, abstract = {Compositional data consist of vectors of proportions normalized to a constant sum from a basis of unobserved counts. The sum constraint makes inference on correlations between unconstrained features challenging due to the information loss from normalization. However, such correlations are of long-standing interest in fields including ecology. We propose a novel Bayesian framework (BAnOCC: Bayesian Analysis of Compositional Covariance) to estimate a sparse precision matrix through a LASSO prior. The resulting posterior, generated by MCMC sampling, allows uncertainty quantification of any function of the precision matrix, including the correlation matrix. We also use a first-order Taylor expansion to approximate the transformation from the unobserved counts to the composition in order to investigate what characteristics of the unobserved counts can make the correlations more or less difficult to infer. On simulated datasets, we show that BAnOCC infers the true network as well as previous methods while offering the advantage of posterior inference. Larger and more realistic simulated datasets further showed that BAnOCC performs well as measured by type I and type II error rates. Finally, we apply BAnOCC to a microbial ecology dataset from the Human Microbiome Project, which in addition to reproducing established ecological results revealed unique, competition-based roles for Proteobacteria in multiple distinct habitats.}, } @article {pmid29136663, year = {2017}, author = {Zhang, Y and Alekseyenko, AV}, title = {Phylogenic inference using alignment-free methods for applications in microbial community surveys using 16s rRNA gene.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187940}, pmid = {29136663}, issn = {1932-6203}, support = {R01 CA164964/CA/NCI NIH HHS/United States ; R21 AR067459/AR/NIAMS NIH HHS/United States ; }, mesh = {Microbiota/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The diversity of microbiota is best explored by understanding the phylogenetic structure of the microbial communities. Traditionally, sequence alignment has been used for phylogenetic inference. However, alignment-based approaches come with significant challenges and limitations when massive amounts of data are analyzed. In the recent decade, alignment-free approaches have enabled genome-scale phylogenetic inference. Here we evaluate three alignment-free methods: ACS, CVTree, and Kr for phylogenetic inference with 16s rRNA gene data. We use a taxonomic gold standard to compare the accuracy of alignment-free phylogenetic inference with that of common microbiome-wide phylogenetic inference pipelines based on PyNAST and MUSCLE alignments with FastTree and RAxML. We re-simulate fecal communities from Human Microbiome Project data to evaluate the performance of the methods on datasets with properties of real data. Our comparisons show that alignment-free methods are not inferior to alignment-based methods in giving accurate and robust phylogenic trees. Moreover, consensus ensembles of alignment-free phylogenies are superior to those built from alignment-based methods in their ability to highlight community differences in low power settings. In addition, the overall running times of alignment-based and alignment-free phylogenetic inference are comparable. Taken together our empirical results suggest that alignment-free methods provide a viable approach for microbiome-wide phylogenetic inference.}, } @article {pmid29129355, year = {2018}, author = {Li, J and Fu, R and Yang, Y and Horz, HP and Guan, Y and Lu, Y and Lou, H and Tian, L and Zheng, S and Liu, H and Shi, M and Tang, K and Wang, S and Xu, S}, title = {A metagenomic approach to dissect the genetic composition of enterotypes in Han Chinese and two Muslim groups.}, journal = {Systematic and applied microbiology}, volume = {41}, number = {1}, pages = {1-12}, doi = {10.1016/j.syapm.2017.09.006}, pmid = {29129355}, issn = {1618-0984}, mesh = {Asian People ; Bacteria/*classification/*genetics ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Ethnicity ; *Gastrointestinal Microbiome ; Genetic Association Studies ; Healthy Volunteers ; Humans ; Islam ; Lysophospholipase/genetics ; *Metagenomics ; *Microbiota ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Distinct enterotypes have been observed in the human gut but little is known about the genetic basis of the microbiome. Moreover, it is not clear how many genetic differences exist between enterotypes within or between populations. In this study, both the 16S rRNA gene and the metagenomes of the gut microbiota were sequenced from 48 Han Chinese, 48 Kazaks, and 96 Uyghurs, and taxonomies were assigned after de novo assembly. Single nucleotide polymorphisms were also identified by referring to data from the Human Microbiome Project. Systematic analysis of the gut communities in terms of their abundance and genetic composition was also performed, together with a genome-wide association study of the host genomes. The gut microbiota of 192 subjects was clearly classified into two enterotypes (Bacteroides and Prevotella). Interestingly, both enterotypes showed a clear genetic differentiation in terms of their functional catalogue of genes, especially for genes involved in amino acid and carbohydrate metabolism. In addition, several differentiated genera and genes were found among the three populations. Notably, one human variant (rs878394) was identified that showed significant association with the abundance of Prevotella, which is linked to LYPLAL1, a gene associated with body fat distribution, the waist-hip ratio and insulin sensitivity. Taken together, considerable differentiation was observed in gut microbes between enterotypes and among populations that was reflected in both the taxonomic composition and the genetic makeup of their functional genes, which could have been influenced by a variety of factors, such as diet and host genetic variation.}, } @article {pmid29122007, year = {2017}, author = {Li, S and Fuhler, GM and Bn, N and Jose, T and Bruno, MJ and Peppelenbosch, MP and Konstantinov, SR}, title = {Pancreatic cyst fluid harbors a unique microbiome.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {147}, pmid = {29122007}, issn = {2049-2618}, mesh = {Aged ; Bacteria/classification/genetics/*isolation & purification ; Bacterial Translocation ; Bacteroides/genetics/isolation & purification ; DNA, Bacterial/genetics/*isolation & purification ; Female ; Fusobacterium/genetics/isolation & purification ; Gastrointestinal Tract/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Neoplastic Processes ; Pancreas/microbiology/physiopathology ; Pancreatic Cyst/*microbiology ; Phylogeny ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Staphylococcus/genetics/isolation & purification ; }, abstract = {BACKGROUND: It is clear that specific intestinal bacteria are involved in the development of different premalignant conditions along the gastrointestinal tract. An analysis of the microbial constituents in the context of pancreatic cystic lesions has, however, as yet not been performed. This consideration prompted us to explore whether endoscopically obtained pancreatic cyst fluids (PCF) contain bacterial DNA and to determine the genera of bacteria present in such material.

METHODS: Total DNA was isolated from 69 PCF samples. Bacterial 16S rRNA gene-specific PCR was performed followed by Sanger sequencing and de novo deep sequencing for the V3-V4 variable region of 16S rRNA gene.

RESULTS: We observed that 98.2% of the samples were positive in conventional PCR, and that 100% of selected PCF samples (n = 33) were positive for bacterial microbiota as determined by next generation sequencing (NGS). Comprehensive NGS data analysis of PCF showed the presence of 408 genera of bacteria, of which 17 bacterial genera were uniquely abundant to PCF, when compared to the Human Microbiome Project (HMP) database and 15 bacterial microbiota were uniquely abundant in HMP only. Bacteroides spp., Escherichia/Shigella spp., and Acidaminococcus spp. which were predominant in PCF, while also a substantial Staphylococcus spp. and Fusobacterium spp. component was detected.

CONCLUSION: These results reveal and characterize an apparently specific bacterial ecosystem in pancreatic cyst fluid samples and may reflect the local microbiota in the pancreas. Some taxa with potential deleterious functions are present in the bacterial abundance profiles, suggesting that the unique microbiome in this specific niche may contribute to neoplastic processes in the pancreas. Further studies are needed to explore the intricate relationship between pathophysiological status in the host pancreas and its microbiota.}, } @article {pmid29106667, year = {2018}, author = {Oliveira, FS and Brestelli, J and Cade, S and Zheng, J and Iodice, J and Fischer, S and Aurrecoechea, C and Kissinger, JC and Brunk, BP and Stoeckert, CJ and Fernandes, GR and Roos, DS and Beiting, DP}, title = {MicrobiomeDB: a systems biology platform for integrating, mining and analyzing microbiome experiments.}, journal = {Nucleic acids research}, volume = {46}, number = {D1}, pages = {D684-D691}, pmid = {29106667}, issn = {1362-4962}, mesh = {Animals ; Computer Simulation ; Data Mining/*methods ; *Databases, Genetic ; Datasets as Topic ; Environmental Microbiology ; Genetic Variation ; Humans ; Internet ; *Microbiota ; Mobile Applications ; *Systems Biology ; User-Computer Interface ; Workflow ; }, abstract = {MicrobiomeDB (http://microbiomeDB.org) is a data discovery and analysis platform that empowers researchers to fully leverage experimental variables to interrogate microbiome datasets. MicrobiomeDB was developed in collaboration with the Eukaryotic Pathogens Bioinformatics Resource Center (http://EuPathDB.org) and leverages the infrastructure and user interface of EuPathDB, which allows users to construct in silico experiments using an intuitive graphical 'strategy' approach. The current release of the database integrates microbial census data with sample details for nearly 14 000 samples originating from human, animal and environmental sources, including over 9000 samples from healthy human subjects in the Human Microbiome Project (http://portal.ihmpdcc.org/). Query results can be statistically analyzed and graphically visualized via interactive web applications launched directly in the browser, providing insight into microbial community diversity and allowing users to identify taxa associated with any experimental covariate.}, } @article {pmid29088705, year = {2017}, author = {Thompson, LR and Sanders, JG and McDonald, D and Amir, A and Ladau, J and Locey, KJ and Prill, RJ and Tripathi, A and Gibbons, SM and Ackermann, G and Navas-Molina, JA and Janssen, S and Kopylova, E and Vázquez-Baeza, Y and González, A and Morton, JT and Mirarab, S and Zech Xu, Z and Jiang, L and Haroon, MF and Kanbar, J and Zhu, Q and Jin Song, S and Kosciolek, T and Bokulich, NA and Lefler, J and Brislawn, CJ and Humphrey, G and Owens, SM and Hampton-Marcell, J and Berg-Lyons, D and McKenzie, V and Fierer, N and Fuhrman, JA and Clauset, A and Stevens, RL and Shade, A and Pollard, KS and Goodwin, KD and Jansson, JK and Gilbert, JA and Knight, R and , }, title = {A communal catalogue reveals Earth's multiscale microbial diversity.}, journal = {Nature}, volume = {551}, number = {7681}, pages = {457-463}, pmid = {29088705}, issn = {1476-4687}, support = {R01 AI123037/AI/NIAID NIH HHS/United States ; R01 DE024463/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Archaea/genetics/isolation & purification ; Bacteria/genetics/isolation & purification ; *Biodiversity ; *Earth, Planet ; Ecology/methods ; Gene Dosage ; Geographic Mapping ; Humans ; Microbiota/*genetics ; Plants/microbiology ; RNA, Ribosomal, 16S/analysis/genetics ; }, abstract = {Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.}, } @article {pmid29062070, year = {2018}, author = {Cookson, WOCM and Cox, MJ and Moffatt, MF}, title = {New opportunities for managing acute and chronic lung infections.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {111-120}, pmid = {29062070}, issn = {1740-1534}, support = {G1000758/MRC_/Medical Research Council/United Kingdom ; }, mesh = {Acute Disease ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*drug therapy/*microbiology ; Chronic Disease ; Drug Resistance, Bacterial ; Global Health ; Humans ; Lung/microbiology ; Lung Diseases/*drug therapy/*microbiology ; Microbiota ; }, abstract = {Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.}, } @article {pmid29038470, year = {2017}, author = {Ma, ZS and Ye, D}, title = {Trios-promising in silico biomarkers for differentiating the effect of disease on the human microbiome network.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {13259}, pmid = {29038470}, issn = {2045-2322}, mesh = {Biomarkers/*metabolism ; Humans ; Microbiota/genetics/*physiology ; *Models, Theoretical ; }, abstract = {Recent advances in the HMP (human microbiome project) research have revealed profound implications of the human microbiome to our health and diseases. We postulated that there should be distinctive features associated with healthy and/or diseased microbiome networks. Following Occam's razor principle, we further hypothesized that triangle motifs or trios, arguably the simplest motif in a complex network of the human microbiome, should be sufficient to detect changes that occurred in the diseased microbiome. Here we test our hypothesis with six HMP datasets that cover five major human microbiome sites (gut, lung, oral, skin, and vaginal). The tests confirm our hypothesis and demonstrate that the trios involving the special nodes (e.g., most abundant OTU or MAO, and most dominant OTU or MDO, etc.) and interactions types (positive vs. negative) can be a powerful tool to differentiate between healthy and diseased microbiome samples. Our findings suggest that 12 kinds of trios (especially, dominantly inhibitive trio with mixed strategy, dominantly inhibitive trio with pure strategy, and fully facilitative strategy) may be utilized as in silico biomarkers for detecting disease-associated changes in the human microbiome, and may play an important role in personalized precision diagnosis of the human microbiome associated diseases.}, } @article {pmid29028892, year = {2018}, author = {Weber, N and Liou, D and Dommer, J and MacMenamin, P and Quiñones, M and Misner, I and Oler, AJ and Wan, J and Kim, L and Coakley McCarthy, M and Ezeji, S and Noble, K and Hurt, DE}, title = {Nephele: a cloud platform for simplified, standardized and reproducible microbiome data analysis.}, journal = {Bioinformatics (Oxford, England)}, volume = {34}, number = {8}, pages = {1411-1413}, pmid = {29028892}, issn = {1367-4811}, mesh = {*Cloud Computing ; Computational Biology/*methods ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA ; *Software ; }, abstract = {MOTIVATION: Widespread interest in the study of the microbiome has resulted in data proliferation and the development of powerful computational tools. However, many scientific researchers lack the time, training, or infrastructure to work with large datasets or to install and use command line tools.

RESULTS: The National Institute of Allergy and Infectious Diseases (NIAID) has created Nephele, a cloud-based microbiome data analysis platform with standardized pipelines and a simple web interface for transforming raw data into biological insights. Nephele integrates common microbiome analysis tools as well as valuable reference datasets like the healthy human subjects cohort of the Human Microbiome Project (HMP). Nephele is built on the Amazon Web Services cloud, which provides centralized and automated storage and compute capacity, thereby reducing the burden on researchers and their institutions.

https://nephele.niaid.nih.gov and https://github.com/niaid/Nephele.

CONTACT: darrell.hurt@nih.gov.}, } @article {pmid29022944, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {551}, number = {7679}, pages = {256}, pmid = {29022944}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23889.}, } @article {pmid29020741, year = {2017}, author = {Moitinho-Silva, L and Nielsen, S and Amir, A and Gonzalez, A and Ackermann, GL and Cerrano, C and Astudillo-Garcia, C and Easson, C and Sipkema, D and Liu, F and Steinert, G and Kotoulas, G and McCormack, GP and Feng, G and Bell, JJ and Vicente, J and Björk, JR and Montoya, JM and Olson, JB and Reveillaud, J and Steindler, L and Pineda, MC and Marra, MV and Ilan, M and Taylor, MW and Polymenakou, P and Erwin, PM and Schupp, PJ and Simister, RL and Knight, R and Thacker, RW and Costa, R and Hill, RT and Lopez-Legentil, S and Dailianis, T and Ravasi, T and Hentschel, U and Li, Z and Webster, NS and Thomas, T}, title = {The sponge microbiome project.}, journal = {GigaScience}, volume = {6}, number = {10}, pages = {1-7}, pmid = {29020741}, issn = {2047-217X}, mesh = {Animals ; *Microbiota ; Porifera/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Marine sponges (phylum Porifera) are a diverse, phylogenetically deep-branching clade known for forming intimate partnerships with complex communities of microorganisms. To date, 16S rRNA gene sequencing studies have largely utilised different extraction and amplification methodologies to target the microbial communities of a limited number of sponge species, severely limiting comparative analyses of sponge microbial diversity and structure. Here, we provide an extensive and standardised dataset that will facilitate sponge microbiome comparisons across large spatial, temporal, and environmental scales. Samples from marine sponges (n = 3569 specimens), seawater (n = 370), marine sediments (n = 65) and other environments (n = 29) were collected from different locations across the globe. This dataset incorporates at least 268 different sponge species, including several yet unidentified taxa. The V4 region of the 16S rRNA gene was amplified and sequenced from extracted DNA using standardised procedures. Raw sequences (total of 1.1 billion sequences) were processed and clustered with (i) a standard protocol using QIIME closed-reference picking resulting in 39 543 operational taxonomic units (OTU) at 97% sequence identity, (ii) a de novo clustering using Mothur resulting in 518 246 OTUs, and (iii) a new high-resolution Deblur protocol resulting in 83 908 unique bacterial sequences. Abundance tables, representative sequences, taxonomic classifications, and metadata are provided. This dataset represents a comprehensive resource of sponge-associated microbial communities based on 16S rRNA gene sequences that can be used to address overarching hypotheses regarding host-associated prokaryotes, including host specificity, convergent evolution, environmental drivers of microbiome structure, and the sponge-associated rare biosphere.}, } @article {pmid28978331, year = {2017}, author = {Shamarina, D and Stoyantcheva, I and Mason, CE and Bibby, K and Elhaik, E}, title = {Communicating the promise, risks, and ethics of large-scale, open space microbiome and metagenome research.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {132}, pmid = {28978331}, issn = {2049-2618}, mesh = {Environment Design ; *Ethics, Research ; Humans ; *Metagenome ; Metagenomics ; *Microbiota ; Public Opinion ; *Public Relations ; *Research ; }, abstract = {The public commonly associates microorganisms with pathogens. This suspicion of microorganisms is understandable, as historically microorganisms have killed more humans than any other agent while remaining largely unknown until the late seventeenth century with the works of van Leeuwenhoek and Kircher. Despite our improved understanding regarding microorganisms, the general public are apt to think of diseases rather than of the majority of harmless or beneficial species that inhabit our bodies and the built and natural environment. As long as microbiome research was confined to labs, the public's exposure to microbiology was limited. The recent launch of global microbiome surveys, such as the Earth Microbiome Project and MetaSUB (Metagenomics and Metadesign of Subways and Urban Biomes) project, has raised ethical, financial, feasibility, and sustainability concerns as to the public's level of understanding and potential reaction to the findings, which, done improperly, risk negative implications for ongoing and future investigations, but done correctly, can facilitate a new vision of "smart cities." To facilitate improved future research, we describe here the major concerns that our discussions with ethics committees, community leaders, and government officials have raised, and we expound on how to address them. We further discuss ethical considerations of microbiome surveys and provide practical recommendations for public engagement.}, } @article {pmid28961122, year = {2020}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Clustering and Integrating of Heterogeneous Microbiome Data by Joint Symmetric Nonnegative Matrix Factorization with Laplacian Regularization.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {17}, number = {3}, pages = {788-795}, doi = {10.1109/TCBB.2017.2756628}, pmid = {28961122}, issn = {1557-9964}, mesh = {*Cluster Analysis ; Computational Biology/*methods ; Databases, Genetic ; Humans ; Microbiota/*genetics ; Phylogeny ; Statistics as Topic ; }, abstract = {Many datasets that exists in the real world are often comprised of different representations or views which provide complementary information to each other. To integrate information from multiple views, data integration approaches such as nonnegative matrix factorization (NMF) have been developed to combine multiple heterogeneous data simultaneously to obtain a comprehensive representation. In this paper, we proposed a novel variant of symmetric nonnegative matrix factorization (SNMF), called Laplacian regularization based joint symmetric nonnegative matrix factorization (LJ-SNMF) for clustering multi-view data. We conduct extensive experiments on several realistic datasets including Human Microbiome Project data. The experimental results show that the proposed method outperforms other variants of NMF, which suggests the potential application of LJ-SNMF in clustering multi-view datasets. Additionally, we also demonstrate the capability of LJ-SNMF in community finding.}, } @article {pmid28953883, year = {2017}, author = {Lloyd-Price, J and Mahurkar, A and Rahnavard, G and Crabtree, J and Orvis, J and Hall, AB and Brady, A and Creasy, HH and McCracken, C and Giglio, MG and McDonald, D and Franzosa, EA and Knight, R and White, O and Huttenhower, C}, title = {Strains, functions and dynamics in the expanded Human Microbiome Project.}, journal = {Nature}, volume = {550}, number = {7674}, pages = {61-66}, pmid = {28953883}, issn = {1476-4687}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U01 HG006537/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Datasets as Topic ; Humans ; Metagenome/genetics/physiology ; Microbiota/genetics/*physiology ; Molecular Sequence Annotation ; National Institutes of Health (U.S.) ; Organ Specificity ; *Phylogeny ; Spatio-Temporal Analysis ; Time Factors ; United States ; }, abstract = {The characterization of baseline microbial and functional diversity in the human microbiome has enabled studies of microbiome-related disease, diversity, biogeography, and molecular function. The National Institutes of Health Human Microbiome Project has provided one of the broadest such characterizations so far. Here we introduce a second wave of data from the study, comprising 1,631 new metagenomes (2,355 total) targeting diverse body sites with multiple time points in 265 individuals. We applied updated profiling and assembly methods to provide new characterizations of microbiome personalization. Strain identification revealed subspecies clades specific to body sites; it also quantified species with phylogenetic diversity under-represented in isolate genomes. Body-wide functional profiling classified pathways into universal, human-enriched, and body site-enriched subsets. Finally, temporal analysis decomposed microbial variation into rapidly variable, moderately variable, and stable subsets. This study furthers our knowledge of baseline human microbial diversity and enables an understanding of personalized microbiome function and dynamics.}, } @article {pmid28915922, year = {2017}, author = {Winglee, K and Howard, AG and Sha, W and Gharaibeh, RZ and Liu, J and Jin, D and Fodor, AA and Gordon-Larsen, P}, title = {Recent urbanization in China is correlated with a Westernized microbiome encoding increased virulence and antibiotic resistance genes.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {121}, pmid = {28915922}, issn = {2049-2618}, support = {R01 DK104371/DK/NIDDK NIH HHS/United States ; R01 HL108427/HL/NHLBI NIH HHS/United States ; R24 HD050924/HD/NICHD NIH HHS/United States ; UL1 TR001111/TR/NCATS NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Bacteria/*genetics/pathogenicity ; China ; *Diet, Western ; Drug Resistance, Microbial/*genetics ; Escherichia coli/genetics/pathogenicity ; Feeding Behavior ; Female ; *Gastrointestinal Microbiome/genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metabolome ; Metagenomics ; Middle Aged ; Shigella/genetics/pathogenicity ; *Urbanization ; Virulence/genetics ; }, abstract = {BACKGROUND: Urbanization is associated with an increased risk for a number of diseases, including obesity, diabetes, and cancer, which all also show associations with the microbiome. While microbial community composition has been shown to vary across continents and in traditional versus Westernized societies, few studies have examined urban-rural differences in neighboring communities within a single country undergoing rapid urbanization. In this study, we compared the gut microbiome, plasma metabolome, dietary habits, and health biomarkers of rural and urban people from a single Chinese province.

RESULTS: We identified significant differences in the microbiota and microbiota-related plasma metabolites in rural versus recently urban subjects from the Hunan province of China. Microbes with higher relative abundance in Chinese urban samples have been associated with disease in other studies and were substantially more prevalent in the Human Microbiome Project cohort of American subjects. Furthermore, using whole metagenome sequencing, we found that urbanization was associated with a loss of microbial diversity and changes in the relative abundances of Viruses, Archaea, and Bacteria. Gene diversity, however, increased with urbanization, along with the proportion of reads associated with antibiotic resistance and virulence, which were strongly correlated with the presence of Escherichia and Shigella.

CONCLUSIONS: Our data suggest that urbanization has produced convergent evolution of the gut microbial composition in American and urban Chinese populations, resulting in similar compositional patterns of abundant microbes through similar lifestyles on different continents, including a loss of potentially beneficial bacteria and an increase in potentially harmful genes via increased relative abundance of Escherichia and Shigella.}, } @article {pmid28846702, year = {2017}, author = {Abdelmaksoud, AA and Girerd, PH and Garcia, EM and Brooks, JP and Leftwich, LM and Sheth, NU and Bradley, SP and Serrano, MG and Fettweis, JM and Huang, B and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0183765}, pmid = {28846702}, issn = {1932-6203}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*physiology ; Bacterial Toxins ; Cell Survival/*physiology ; Colony Count, Microbial ; Epithelial Cells/metabolism ; Female ; Gardnerella vaginalis/isolation & purification/*metabolism ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology ; Microbiota/*drug effects/genetics ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Simvastatin/*pharmacology ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome.

METHODS: To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity.

RESULTS: The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol.

CONCLUSIONS: In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.}, } @article {pmid28842845, year = {2017}, author = {Li, DY and Tang, WHW}, title = {Gut Microbiota and Atherosclerosis.}, journal = {Current atherosclerosis reports}, volume = {19}, number = {10}, pages = {39}, doi = {10.1007/s11883-017-0675-9}, pmid = {28842845}, issn = {1534-6242}, mesh = {Animals ; *Atherosclerosis/drug therapy/metabolism/microbiology ; Bile Acids and Salts/metabolism ; Carnitine/metabolism ; Diet ; Disease Models, Animal ; *Gastrointestinal Microbiome/immunology ; Humans ; Methylamines/*metabolism ; }, abstract = {PURPOSE OF REVIEW: Studies in microbiota-mediated health risks have gained traction in recent years since the compilation of the Human Microbiome Project. No longer do we believe that our gut microbiota is an inert set of microorganisms that reside in the body without consequence. In this review, we discuss the recent findings which further our understanding of the connection between the gut microbiota and the atherosclerosis.

RECENT FINDINGS: We evaluate studies which illustrate the current understanding of the relationship between infection, immunity, altered metabolism, and bacterial products such as immune activators or dietary metabolites and their contributions to the development of atherosclerosis. In particular, we critically examine rec ent clinical and mechanistic findings for the novel microbiota-dependent dietary metabolite, trimethylamine N-oxide (TMAO), which has been implicated in atherosclerosis. These discoveries are now becoming integrated with advances in microbiota profiling which enhance our ability to interrogate the functional role of the gut microbiome and develop strategies for targeted therapeutics. The gut microbiota is a multi-faceted system that is unraveling novel contributors to the development and progression of atherosclerosis. In this review, we discuss historic and novel contributors while highlighting the TMAO story mainly as an example of the various paths taken beyond deciphering microbial composition to elucidate downstream mechanisms that promote (or protect from) atherogenesis in the hopes of translating these findings from bench to bedside.}, } @article {pmid28771841, year = {2017}, author = {Boost, M and Cho, P and Wang, Z}, title = {Disturbing the balance: effect of contact lens use on the ocular proteome and microbiome.}, journal = {Clinical & experimental optometry}, volume = {100}, number = {5}, pages = {459-472}, doi = {10.1111/cxo.12582}, pmid = {28771841}, issn = {1444-0938}, mesh = {Contact Lenses/*statistics & numerical data ; Cornea/*metabolism ; Humans ; Microbiota/*physiology ; Proteome/*metabolism ; Proteostasis/*physiology ; Refractive Errors/therapy ; Tears/*metabolism ; Vision Disorders/therapy ; }, abstract = {Contact lens wear is a popular, convenient and effective method for vision correction. In recent years, contact lens practice has expanded to include new paradigms, including orthokeratology; however, their use is not entirely without risk, as the incidence of infection has consistently been reported to be higher in contact lens wearers. The explanations for this increased susceptibility have largely focused on physical damage, especially to the cornea, due to a combination of hypoxia, mechanical trauma, deposits and solution cytotoxicity, as well as poor compliance with care routines leading to introduction of pathogens into the ocular environment. However, in recent years, with the increasing availability and reduced cost of molecular techniques, the ocular environment has received greater attention with in-depth studies of proteins and other components. Numerous proteins were found to be present in the tears and their functions and interactions indicate that the tears are far more complex than formerly presumed. In addition, the concept of a sterile or limited microbial population on the ocular surface has been challenged by analysis of the microbiome. Ocular microbiome was not considered as one of the key sites for the Human Microbiome Project, as it was thought to be limited compared to other body sites. This was proven to be fallacious, as a wide variety of micro-organisms were identified in the analyses of human tears. Thus, the ocular environment is now recognised to be more complicated and interference with this ecological balance may lead to adverse effects. The use of contact lenses clearly changes the situation at the ocular surface, which may result in consequences which disturb the balance in the healthy eye.}, } @article {pmid28769875, year = {2017}, author = {Vecchio-Pagan, B and Bewick, S and Mainali, K and Karig, DK and Fagan, WF}, title = {A Stoichioproteomic Analysis of Samples from the Human Microbiome Project.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1119}, pmid = {28769875}, issn = {1664-302X}, abstract = {Ecological stoichiometry (ES) uses organism-specific elemental content to explain differences in species life histories, species interactions, community organization, environmental constraints and even ecosystem function. Although ES has been successfully applied to a range of different organisms, most emphasis on microbial ecological stoichiometry focuses on lake, ocean, and soil communities. With the recent advances in human microbiome research, however, large amounts of data are being generated that describe differences in community composition across body sites and individuals. We suggest that ES may provide a framework for beginning to understand the structure, organization, and function of human microbial communities, including why certain organisms exist at certain locations, and how they interact with both the other microbes in their environment and their human host. As a first step, we undertake a stoichioproteomic analysis of microbial communities from different body sites. Specifically, we compare and contrast the elemental composition of microbial protein samples using annotated sequencing data from 690 gut, vaginal, oral, nares, and skin samples currently available through the Human Microbiome Project. Our results suggest significant differences in both the median and variance of the carbon, oxygen, nitrogen, and sulfur contents of microbial protein samples from different locations. For example, whereas proteins from vaginal sites are high in carbon, proteins from skin and nasal sites are high in nitrogen and oxygen. Meanwhile, proteins from stool (the gut) are particularly high in sulfur content. We interpret these differences in terms of the local environments at different human body sites, including atmospheric exposure and food intake rates.}, } @article {pmid28761932, year = {2017}, author = {Dheilly, NM and Bolnick, D and Bordenstein, S and Brindley, PJ and Figuères, C and Holmes, EC and Martínez Martínez, J and Phillips, AJ and Poulin, R and Rosario, K}, title = {Parasite Microbiome Project: Systematic Investigation of Microbiome Dynamics within and across Parasite-Host Interactions.}, journal = {mSystems}, volume = {2}, number = {4}, pages = {}, pmid = {28761932}, issn = {2379-5077}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; }, abstract = {Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and allow reliable comparative analyses across model systems. It is also an invitation to foundations and national funding agencies to propel the field of parasitology into the microbiome/metagenomic era.}, } @article {pmid28730144, year = {2017}, author = {Yu, G and Torres, J and Hu, N and Medrano-Guzman, R and Herrera-Goepfert, R and Humphrys, MS and Wang, L and Wang, C and Ding, T and Ravel, J and Taylor, PR and Abnet, CC and Goldstein, AM}, title = {Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {302}, pmid = {28730144}, issn = {2235-2988}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/*isolation & purification ; China ; Female ; *Gastrointestinal Microbiome ; Helicobacter pylori/classification/genetics/isolation & purification ; Humans ; Male ; Mexico ; Middle Aged ; Stomach/*microbiology ; Stomach Neoplasms/*microbiology ; Young Adult ; }, abstract = {Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.}, } @article {pmid28578872, year = {2017}, author = {Pollet, RM and D'Agostino, EH and Walton, WG and Xu, Y and Little, MS and Biernat, KA and Pellock, SJ and Patterson, LM and Creekmore, BC and Isenberg, HN and Bahethi, RR and Bhatt, AP and Liu, J and Gharaibeh, RZ and Redinbo, MR}, title = {An Atlas of β-Glucuronidases in the Human Intestinal Microbiome.}, journal = {Structure (London, England : 1993)}, volume = {25}, number = {7}, pages = {967-977.e5}, pmid = {28578872}, issn = {1878-4186}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; R01 HL094463/HL/NHLBI NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 GM102137/GM/NIGMS NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/classification/genetics/metabolism ; *Gastrointestinal Microbiome ; Glucuronidase/*chemistry/classification/genetics/metabolism ; Humans ; }, abstract = {Microbiome-encoded β-glucuronidase (GUS) enzymes play important roles in human health by metabolizing drugs in the gastrointestinal (GI) tract. The numbers, types, and diversity of these proteins in the human GI microbiome, however, remain undefined. We present an atlas of GUS enzymes comprehensive for the Human Microbiome Project GI database. We identify 3,013 total and 279 unique microbiome-encoded GUS proteins clustered into six unique structural categories. We assign their taxonomy, assess cellular localization, reveal the inter-individual variability within the 139 individuals sampled, and discover 112 novel microbial GUS enzymes. A representative in vitro panel of the most common GUS proteins by read abundances highlights structural and functional variabilities within the family, including their differential processing of smaller glucuronides and larger carbohydrates. These data provide a sequencing-to-molecular roadmap for examining microbiome-encoded enzymes essential to human health.}, } @article {pmid28533766, year = {2017}, author = {Moitinho-Silva, L and Steinert, G and Nielsen, S and Hardoim, CCP and Wu, YC and McCormack, GP and López-Legentil, S and Marchant, R and Webster, N and Thomas, T and Hentschel, U}, title = {Predicting the HMA-LMA Status in Marine Sponges by Machine Learning.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {752}, pmid = {28533766}, issn = {1664-302X}, abstract = {The dichotomy between high microbial abundance (HMA) and low microbial abundance (LMA) sponges has been observed in sponge-microbe symbiosis, although the extent of this pattern remains poorly unknown. We characterized the differences between the microbiomes of HMA (n = 19) and LMA (n = 17) sponges (575 specimens) present in the Sponge Microbiome Project. HMA sponges were associated with richer and more diverse microbiomes than LMA sponges, as indicated by the comparison of alpha diversity metrics. Microbial community structures differed between HMA and LMA sponges considering Operational Taxonomic Units (OTU) abundances and across microbial taxonomic levels, from phylum to species. The largest proportion of microbiome variation was explained by the host identity. Several phyla, classes, and OTUs were found differentially abundant in either group, which were considered "HMA indicators" and "LMA indicators." Machine learning algorithms (classifiers) were trained to predict the HMA-LMA status of sponges. Among nine different classifiers, higher performances were achieved by Random Forest trained with phylum and class abundances. Random Forest with optimized parameters predicted the HMA-LMA status of additional 135 sponge species (1,232 specimens) without a priori knowledge. These sponges were grouped in four clusters, from which the largest two were composed of species consistently predicted as HMA (n = 44) and LMA (n = 74). In summary, our analyses shown distinct features of the microbial communities associated with HMA and LMA sponges. The prediction of the HMA-LMA status based on the microbiome profiles of sponges demonstrates the application of machine learning to explore patterns of host-associated microbial communities.}, } @article {pmid28506279, year = {2017}, author = {Rath, S and Heidrich, B and Pieper, DH and Vital, M}, title = {Uncovering the trimethylamine-producing bacteria of the human gut microbiota.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {54}, pmid = {28506279}, issn = {2049-2618}, mesh = {Bacteria/*classification/enzymology/isolation & purification/metabolism ; Bacterial Proteins/genetics ; Biosynthetic Pathways ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/*methods ; Methylamines/*metabolism ; Multilocus Sequence Typing ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Trimethylamine (TMA), produced by the gut microbiota from dietary quaternary amines (mainly choline and carnitine), is associated with atherosclerosis and severe cardiovascular disease. Currently, little information on the composition of TMA producers in the gut is available due to their low abundance and the requirement of specific functional-based detection methods as many taxa show disparate abilities to produce that compound.

RESULTS: In order to examine the TMA-forming potential of microbial communities, we established databases for the key genes of the main TMA-synthesis pathways, encoding choline TMA-lyase (cutC) and carnitine oxygenase (cntA), using a multi-level screening approach on 67,134 genomes revealing 1107 and 6738 candidates to exhibit cutC and cntA, respectively. Gene-targeted assays enumerating the TMA-producing community by quantitative PCR and characterizing its composition via Illumina sequencing were developed and applied on human fecal samples (n = 50) where all samples contained potential TMA producers (cutC was detected in all individuals, whereas only 26% harbored cntA) constituting, however, only a minor part of the total community (below 1% in most samples). Obtained cutC amplicons were associated with various taxa, in particular with Clostridium XIVa strains and Eubacterium sp. strain AB3007, though a bulk of sequences displayed low nucleotide identities to references (average 86% ± 7%) indicating that key human TMA producers are yet to be isolated. Co-occurrence analysis revealed specific groups governing the community structure of cutC-exhibiting taxa across samples. CntA amplicons displayed high identities (~99%) to Gammaproteobacteria-derived references, primarily from Escherichia coli. Metagenomic analysis of samples provided by the Human Microbiome Project (n = 154) confirmed the abundance patterns as well as overall taxonomic compositions obtained with our assays, though at much lower resolution, whereas 16S ribosomal RNA gene sequence analysis could not adequately uncover the TMA-producing potential.

CONCLUSIONS: In this study, we developed a diagnostic framework that enabled the quantification and comprehensive characterization of the TMA-producing potential in human fecal samples. The key players were identified, and together with predictions on their environmental niches using functional genomics on most closely related reference strains, we provide crucial information for the development of specific treatment strategies to restrain TMA producers and limit their proliferation.}, } @article {pmid28480145, year = {2017}, author = {Santiago-Rodriguez, TM and Narganes-Storde, Y and Chanlatte-Baik, L and Toranzos, GA and Cano, RJ}, title = {Insights of the dental calculi microbiome of pre-Columbian inhabitants from Puerto Rico.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3277}, pmid = {28480145}, issn = {2167-8359}, abstract = {BACKGROUND: The study of ancient microorganisms in mineralized dental plaque or calculi is providing insights into microbial evolution, as well as lifestyles and disease states of extinct cultures; yet, little is still known about the oral microbial community structure and function of pre-Columbian Caribbean cultures. In the present study, we investigated the dental calculi microbiome and predicted function of one of these cultures, known as the Saladoid. The Saladoids were horticulturalists that emphasized root-crop production. Fruits, as well as small marine and terrestrial animals were also part of the Saladoid diet.

METHODS: Dental calculi samples were recovered from the archaeological site of Sorcé, in the municipal island of Vieques, Puerto Rico, characterized using 16S rRNA gene high-throughput sequencing, and compared to the microbiome of previously characterized coprolites of the same culture, as well modern plaque, saliva and stool microbiomes available from the Human Microbiome Project.

RESULTS: Actinobacteria, Proteobacteria and Firmicutes comprised the majority of the Saladoid dental calculi microbiome. The Saladoid dental calculi microbiome was distinct when compared to those of modern saliva and dental plaque, but showed the presence of common inhabitants of modern oral cavities including Streptococcus sp., Veillonella dispar and Rothia mucilaginosa. Cell motility, signal transduction and biosynthesis of other secondary metabolites may be unique features of the Saladoid microbiome.

DISCUSSION: Results suggest that the Saladoid dental calculi microbiome structure and function may possibly reflect a horticulturalist lifestyle and distinct dietary habits. Results also open the opportunity to further elucidate oral disease states in extinct Caribbean cultures and extinct indigenous cultures with similar lifestyles.}, } @article {pmid28473000, year = {2017}, author = {Lee, STM and Kahn, SA and Delmont, TO and Shaiber, A and Esen, ÖC and Hubert, NA and Morrison, HG and Antonopoulos, DA and Rubin, DT and Eren, AM}, title = {Tracking microbial colonization in fecal microbiota transplantation experiments via genome-resolved metagenomics.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {50}, pmid = {28473000}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/*growth & development ; Clostridium Infections/microbiology/*therapy ; DNA, Bacterial/genetics ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Living Donors ; Male ; Metagenomics/*methods ; Phylogeny ; Sequence Analysis, DNA/methods ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection and shows promise for treating other medical conditions associated with intestinal dysbioses. However, we lack a sufficient understanding of which microbial populations successfully colonize the recipient gut, and the widely used approaches to study the microbial ecology of FMT experiments fail to provide enough resolution to identify populations that are likely responsible for FMT-derived benefits.

METHODS: We used shotgun metagenomics together with assembly and binning strategies to reconstruct metagenome-assembled genomes (MAGs) from fecal samples of a single FMT donor. We then used metagenomic mapping to track the occurrence and distribution patterns of donor MAGs in two FMT recipients.

RESULTS: Our analyses revealed that 22% of the 92 highly complete bacterial MAGs that we identified from the donor successfully colonized and remained abundant in two recipients for at least 8 weeks. Most MAGs with a high colonization rate belonged to the order Bacteroidales. The vast majority of those that lacked evidence of colonization belonged to the order Clostridiales, and colonization success was negatively correlated with the number of genes related to sporulation. Our analysis of 151 publicly available gut metagenomes showed that the donor MAGs that colonized both recipients were prevalent, and the ones that colonized neither were rare across the participants of the Human Microbiome Project. Although our dataset showed a link between taxonomy and the colonization ability of a given MAG, we also identified MAGs that belong to the same taxon with different colonization properties, highlighting the importance of an appropriate level of resolution to explore the functional basis of colonization and to identify targets for cultivation, hypothesis generation, and testing in model systems.

CONCLUSIONS: The analytical strategy adopted in our study can provide genomic insights into bacterial populations that may be critical to the efficacy of FMT due to their success in gut colonization and metabolic properties, and guide cultivation efforts to investigate mechanistic underpinnings of this procedure beyond associations.}, } @article {pmid28462050, year = {2017}, author = {Walsh, CJ and Guinane, CM and O' Toole, PW and Cotter, PD}, title = {A Profile Hidden Markov Model to investigate the distribution and frequency of LanB-encoding lantibiotic modification genes in the human oral and gut microbiome.}, journal = {PeerJ}, volume = {5}, number = {}, pages = {e3254}, pmid = {28462050}, issn = {2167-8359}, abstract = {BACKGROUND: The human microbiota plays a key role in health and disease, and bacteriocins, which are small, bacterially produced, antimicrobial peptides, are likely to have an important function in the stability and dynamics of this community. Here we examined the density and distribution of the subclass I lantibiotic modification protein, LanB, in human oral and stool microbiome datasets using a specially constructed profile Hidden Markov Model (HMM).

METHODS: The model was validated by correctly identifying known lanB genes in the genomes of known bacteriocin producers more effectively than other methods, while being sensitive enough to differentiate between different subclasses of lantibiotic modification proteins. This approach was compared with two existing methods to screen both genomic and metagenomic datasets obtained from the Human Microbiome Project (HMP).

RESULTS: Of the methods evaluated, the new profile HMM identified the greatest number of putative LanB proteins in the stool and oral metagenome data while BlastP identified the fewest. In addition, the model identified more LanB proteins than a pre-existing Pfam lanthionine dehydratase model. Searching the gastrointestinal tract subset of the HMP reference genome database with the new HMM identified seven putative subclass I lantibiotic producers, including two members of the Coprobacillus genus.

CONCLUSIONS: These findings establish custom profile HMMs as a potentially powerful tool in the search for novel bioactive producers with the power to benefit human health, and reinforce the repertoire of apparent bacteriocin-encoding gene clusters that may have been overlooked by culture-dependent mining efforts to date.}, } @article {pmid28448493, year = {2017}, author = {Fisher, CK and Mora, T and Walczak, AM}, title = {Variable habitat conditions drive species covariation in the human microbiota.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005435}, pmid = {28448493}, issn = {1553-7358}, mesh = {Computational Biology ; *Ecosystem ; Humans ; Microbiota/*genetics/*physiology ; Models, Biological ; Species Specificity ; }, abstract = {Two species with similar resource requirements respond in a characteristic way to variations in their habitat-their abundances rise and fall in concert. We use this idea to learn how bacterial populations in the microbiota respond to habitat conditions that vary from person-to-person across the human population. Our mathematical framework shows that habitat fluctuations are sufficient for explaining intra-bodysite correlations in relative species abundances from the Human Microbiome Project. We explicitly show that the relative abundances of closely related species are positively correlated and can be predicted from taxonomic relationships. We identify a small set of functional pathways related to metabolism and maintenance of the cell wall that form the basis of a common resource sharing niche space of the human microbiota.}, } @article {pmid28437450, year = {2017}, author = {Cai, Y and Zheng, W and Yao, J and Yang, Y and Mai, V and Mao, Q and Sun, Y}, title = {ESPRIT-Forest: Parallel clustering of massive amplicon sequence data in subquadratic time.}, journal = {PLoS computational biology}, volume = {13}, number = {4}, pages = {e1005518}, pmid = {28437450}, issn = {1553-7358}, support = {R01 AI125982/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; *Cluster Analysis ; Computational Biology ; Databases, Genetic ; Humans ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment/*methods ; Sequence Analysis, RNA/*methods ; }, abstract = {The rapid development of sequencing technology has led to an explosive accumulation of genomic sequence data. Clustering is often the first step to perform in sequence analysis, and hierarchical clustering is one of the most commonly used approaches for this purpose. However, it is currently computationally expensive to perform hierarchical clustering of extremely large sequence datasets due to its quadratic time and space complexities. In this paper we developed a new algorithm called ESPRIT-Forest for parallel hierarchical clustering of sequences. The algorithm achieves subquadratic time and space complexity and maintains a high clustering accuracy comparable to the standard method. The basic idea is to organize sequences into a pseudo-metric based partitioning tree for sub-linear time searching of nearest neighbors, and then use a new multiple-pair merging criterion to construct clusters in parallel using multiple threads. The new algorithm was tested on the human microbiome project (HMP) dataset, currently one of the largest published microbial 16S rRNA sequence dataset. Our experiment demonstrated that with the power of parallel computing it is now compu- tationally feasible to perform hierarchical clustering analysis of tens of millions of sequences. The software is available at http://www.acsu.buffalo.edu/∼yijunsun/lab/ESPRIT-Forest.html.}, } @article {pmid28435844, year = {2016}, author = {Stanley, N and Shai, S and Taylor, D and Mucha, PJ}, title = {Clustering network layers with the strata multilayer stochastic block model.}, journal = {IEEE transactions on network science and engineering}, volume = {3}, number = {2}, pages = {95-105}, pmid = {28435844}, issn = {2327-4697}, support = {R01 HD075712/HD/NICHD NIH HHS/United States ; }, abstract = {Multilayer networks are a useful data structure for simultaneously capturing multiple types of relationships between a set of nodes. In such networks, each relational definition gives rise to a layer. While each layer provides its own set of information, community structure across layers can be collectively utilized to discover and quantify underlying relational patterns between nodes. To concisely extract information from a multilayer network, we propose to identify and combine sets of layers with meaningful similarities in community structure. In this paper, we describe the "strata multilayer stochastic block model" (sMLSBM), a probabilistic model for multilayer community structure. The central extension of the model is that there exist groups of layers, called "strata", which are defined such that all layers in a given stratum have community structure described by a common stochastic block model (SBM). That is, layers in a stratum exhibit similar node-to-community assignments and SBM probability parameters. Fitting the sMLSBM to a multilayer network provides a joint clustering that yields node-to-community and layer-to-stratum assignments, which cooperatively aid one another during inference. We describe an algorithm for separating layers into their appropriate strata and an inference technique for estimating the SBM parameters for each stratum. We demonstrate our method using synthetic networks and a multilayer network inferred from data collected in the Human Microbiome Project.}, } @article {pmid28391505, year = {2017}, author = {Somboonna, N and Wilantho, A and Srisuttiyakorn, C and Assawamakin, A and Tongsima, S}, title = {Bacterial communities on facial skin of teenage and elderly Thai females.}, journal = {Archives of microbiology}, volume = {199}, number = {7}, pages = {1035-1042}, doi = {10.1007/s00203-017-1375-0}, pmid = {28391505}, issn = {1432-072X}, support = {RSA58-80061//Thailand Research Fund/ ; }, mesh = {Acne Vulgaris/*microbiology ; Adult ; *Bacteria/classification/genetics/isolation & purification ; Base Sequence ; Female ; Humans ; Microbiota/*genetics ; Middle Aged ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Skin/*microbiology ; Thailand ; Young Adult ; }, abstract = {The Human Microbiome Project was first established to understand the roles of human-associated microbes to human health and disease. This study presents preliminary findings of Thai female facial skin microbiome using three pooled samples from groups of skin microbiome profiles, namely (1) healthy and (2) acne-prone young adults (teenage.hea and teenage.acn) and (3) healthy elderly adults (elderly.hea) based on standard dermatological criteria. These samples were sequenced using 454-pyrosequencing targeting 16S rRNA (V3-V4 regions). Good's coverage index of greater than 92% shows sufficient sampling of our data for each group. Three unique OTUs for each microbiome profile (43, 258 and 59 for teenage.hea, teenage.acn and ederly.hea, respectively) were obtained with 134 shared OTUs among the three datasets. Based on Morisita-Horn similarity coefficient, age is the major factor that brings the community relationship factor closer. The comparison among the three datasets reveal majority of Gemmatimonadetes, Planctomycetes and Nitrospirae in the teenage.hea, whereas Firmicutes are more prevalent in teenage.acn and elderly.hea skin types. In addition, when comparing Thai facial microbial diversity with the 16S data from U.S. forehead female database, significant differences were found among orders of bacteria, pointing to possible differences in human ecto-flora.}, } @article {pmid28383789, year = {2017}, author = {Acharya, A and Chan, Y and Kheur, S and Kheur, M and Gopalakrishnan, D and Watt, RM and Mattheos, N}, title = {Salivary microbiome of an urban Indian cohort and patterns linked to subclinical inflammation.}, journal = {Oral diseases}, volume = {23}, number = {7}, pages = {926-940}, doi = {10.1111/odi.12676}, pmid = {28383789}, issn = {1601-0825}, mesh = {Adult ; Aged ; *Asymptomatic Diseases ; Female ; Humans ; India ; Inflammation/*microbiology ; Interleukin-1beta/metabolism ; Male ; *Microbiota ; Middle Aged ; Saliva/metabolism/*microbiology ; Urban Population ; }, abstract = {OBJECTIVE: To profile salivary microbiomes of an urban-living, healthy Indian cohort and explore associations with proinflammatory status.

METHODS: Fifty-one clinically healthy Indian subjects' salivary microbiomes were analyzed using 16S rRNA Illumina MiSeq sequencing. Community distribution was compared with salivary data from the Human Microbiome Project (HMP). Indian subjects were clustered using microbiome-based "partitioning along medoids" (PAM), and relationships of interleukin-1 beta levels with community composition were analyzed.

RESULTS: Indian subjects presented higher phylogenetic diversity than HMP. Several taxa associated with traditional societies gut microbiomes (Bacteroidales, Paraprevotellaceae, and Spirochaetaceae) were raised. Bifidobacteriaceae and Lactobacillaceae were approximately fourfold greater. A PAM cluster enriched in several Proteobacteria, Actinobacteria, and Bacilli taxa and having almost twofold higher Prevotella to Bacteroides ratio showed significant overrepresentation of subjects within the highest quartile of salivary interleukin-1 beta levels. Abiotrophia, Anaerobacillus, Micrococcus, Aggregatibacter, Halomonas, Propionivivrio, Paracoccus, Mannhemia, unclassified Bradyrhizobiaceae, and Caulobacteraceae were each significant indicators of presence in the highest interleukin-1 beta quartile. 2 OTUs representing Lactobacillus fermentum and Cardiobacterium hominis significantly correlated with interleukin-1 beta levels.

CONCLUSION: The salivary microbiome of this urban-dwelling Indian cohort differed significantly from that of a well-studied Western cohort. Specific community patterns were putatively associated with subclinical inflammation levels.}, } @article {pmid28375407, year = {2017}, author = {Lacy, BE}, title = {Hot Topics in Primary Care: Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome.}, journal = {The Journal of family practice}, volume = {66}, number = {4 Suppl}, pages = {S40-S45}, pmid = {28375407}, issn = {1533-7294}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Education, Medical, Continuing ; Gastrointestinal Microbiome/*drug effects ; Humans ; Irritable Bowel Syndrome/*diagnosis/*drug therapy/microbiology/physiopathology ; *Practice Guidelines as Topic ; Primary Health Care/*standards ; Probiotics/*therapeutic use ; United States ; }, abstract = {Dietary and some other treatments for IBS are supported by a growing body of evidence, much of which comes from programs such as the Human Microbiome Project and Human Gut Microbiome Initiative, which were intended to identify and characterize microorganisms found in association with both healthy and diseased humans. These programs used state-of-the-art technology to characterize the human microbiome from multiple body sites. This evidence indicates that the gut microbiome plays an important role in IBS and some other gastrointestinal (GI) disorders.}, } @article {pmid28357466, year = {2017}, author = {Steinhagen, PR and Baumgart, DC}, title = {[Fundamentals of the microbiome].}, journal = {Der Internist}, volume = {58}, number = {5}, pages = {429-434}, pmid = {28357466}, issn = {1432-1289}, mesh = {Disease ; Humans ; *Microbial Consortia ; }, abstract = {Until the middle of the 20th century, clinical microbiology was limited to bacterial cultures enabling the detection of pathogenic microorganisms. Knowledge about the mutual relationship between humans and microorganisms has increased slowly. With the introduction of culture-independent analysis methods, comprehensive cataloging of the human microbiome was possible for the first time. Since then, compositional changes in relation to diseases have been studied. The goals of the Human Microbiome Project and MetaHIT include comparative studies of healthy and diseased individuals. Numerous libraries on time- and location-dependent changes of the microbiota composition in human diseases have been created. However, a mathematical correlation does not equal biological or medical relevance. Future research needs to validate the hypotheses generated in these studies in functional experiments and evaluate their true impact on clinical practice.}, } @article {pmid28337070, year = {2017}, author = {Tighe, S and Afshinnekoo, E and Rock, TM and McGrath, K and Alexander, N and McIntyre, A and Ahsanuddin, S and Bezdan, D and Green, SJ and Joye, S and Stewart Johnson, S and Baldwin, DA and Bivens, N and Ajami, N and Carmical, JR and Herriott, IC and Colwell, R and Donia, M and Foox, J and Greenfield, N and Hunter, T and Hoffman, J and Hyman, J and Jorgensen, E and Krawczyk, D and Lee, J and Levy, S and Garcia-Reyero, N and Settles, M and Thomas, K and Gómez, F and Schriml, L and Kyrpides, N and Zaikova, E and Penterman, J and Mason, CE}, title = {Genomic Methods and Microbiological Technologies for Profiling Novel and Extreme Environments for the Extreme Microbiome Project (XMP).}, journal = {Journal of biomolecular techniques : JBT}, volume = {28}, number = {1}, pages = {31-39}, pmid = {28337070}, issn = {1943-4731}, support = {R01 AI125416/AI/NIAID NIH HHS/United States ; R01 ES021006/ES/NIEHS NIH HHS/United States ; R01 NS076465/NS/NINDS NIH HHS/United States ; R25 EB020393/EB/NIBIB NIH HHS/United States ; }, mesh = {DNA, Bacterial/genetics/isolation & purification ; *Environmental Microbiology ; Extreme Environments ; Metagenome ; Microbiota/*genetics ; Molecular Typing/standards ; RNA, Bacterial/genetics/isolation & purification ; Reference Standards ; Sequence Analysis, DNA/standards ; }, abstract = {The Extreme Microbiome Project (XMP) is a project launched by the Association of Biomolecular Resource Facilities Metagenomics Research Group (ABRF MGRG) that focuses on whole genome shotgun sequencing of extreme and unique environments using a wide variety of biomolecular techniques. The goals are multifaceted, including development and refinement of new techniques for the following: 1) the detection and characterization of novel microbes, 2) the evaluation of nucleic acid techniques for extremophilic samples, and 3) the identification and implementation of the appropriate bioinformatics pipelines. Here, we highlight the different ongoing projects that we have been working on, as well as details on the various methods we use to characterize the microbiome and metagenome of these complex samples. In particular, we present data of a novel multienzyme extraction protocol that we developed, called Polyzyme or MetaPolyZyme. Presently, the XMP is characterizing sample sites around the world with the intent of discovering new species, genes, and gene clusters. Once a project site is complete, the resulting data will be publically available. Sites include Lake Hillier in Western Australia, the "Door to Hell" crater in Turkmenistan, deep ocean brine lakes of the Gulf of Mexico, deep ocean sediments from Greenland, permafrost tunnels in Alaska, ancient microbial biofilms from Antarctica, Blue Lagoon Iceland, Ethiopian toxic hot springs, and the acidic hypersaline ponds in Western Australia.}, } @article {pmid28216014, year = {2017}, author = {Bhattacharyya, M and Ghosh, T and Shankar, S and Tomar, N}, title = {The conserved phylogeny of blood microbiome.}, journal = {Molecular phylogenetics and evolution}, volume = {109}, number = {}, pages = {404-408}, doi = {10.1016/j.ympev.2017.02.001}, pmid = {28216014}, issn = {1095-9513}, mesh = {Archaea/classification ; Bacteria/*classification ; Bacterial Proteins/genetics ; *Biological Evolution ; Blood/*microbiology ; Fungal Proteins/genetics ; Humans ; *Microbiota ; Phylogeny ; }, abstract = {The proliferation and intensification of diseases have forced every researcher to take actions for a robust understanding of the organisms. This demands deep knowledge about the cells and tissues in an organ and its entire surroundings, more precisely the microbiome community which involves viruses, bacteria, archaea, among others. They play an important role in the function of our body, and act both as a deterrent as well as shelter for diseases. Therefore, it is pertinent to study the relation within the microbiome in a human body. In this work, we analyze the sequence data provided through the Human Microbiome Project to explore evolutionary relations within blood microbiome. The objective is to analyze the common proteins present in the different microbes in the blood and find their phylogeny. The analysis of the phylogenetic relation between these species provides important insights about the conservedness of phylogeny of blood microbiome. Interestingly, the co-existence of five of those common proteins is observed in human too.}, } @article {pmid28178947, year = {2017}, author = {Wadsworth, WD and Argiento, R and Guindani, M and Galloway-Pena, J and Shelburne, SA and Vannucci, M}, title = {An integrative Bayesian Dirichlet-multinomial regression model for the analysis of taxonomic abundances in microbiome data.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {94}, pmid = {28178947}, issn = {1471-2105}, support = {L30 CA209245/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA096520/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification ; Bayes Theorem ; Computer Simulation ; Humans ; *Linear Models ; Markov Chains ; *Microbiota ; Monte Carlo Method ; }, abstract = {BACKGROUND: The Human Microbiome has been variously associated with the immune-regulatory mechanisms involved in the prevention or development of many non-infectious human diseases such as autoimmunity, allergy and cancer. Integrative approaches which aim at associating the composition of the human microbiome with other available information, such as clinical covariates and environmental predictors, are paramount to develop a more complete understanding of the role of microbiome in disease development.

RESULTS: In this manuscript, we propose a Bayesian Dirichlet-Multinomial regression model which uses spike-and-slab priors for the selection of significant associations between a set of available covariates and taxa from a microbiome abundance table. The approach allows straightforward incorporation of the covariates through a log-linear regression parametrization of the parameters of the Dirichlet-Multinomial likelihood. Inference is conducted through a Markov Chain Monte Carlo algorithm, and selection of the significant covariates is based upon the assessment of posterior probabilities of inclusions and the thresholding of the Bayesian false discovery rate. We design a simulation study to evaluate the performance of the proposed method, and then apply our model on a publicly available dataset obtained from the Human Microbiome Project which associates taxa abundances with KEGG orthology pathways. The method is implemented in specifically developed R code, which has been made publicly available.

CONCLUSIONS: Our method compares favorably in simulations to several recently proposed approaches for similarly structured data, in terms of increased accuracy and reduced false positive as well as false negative rates. In the application to the data from the Human Microbiome Project, a close evaluation of the biological significance of our findings confirms existing associations in the literature.}, } @article {pmid28146577, year = {2017}, author = {Traykova, D and Schneider, B and Chojkier, M and Buck, M}, title = {Blood Microbiome Quantity and the Hyperdynamic Circulation in Decompensated Cirrhotic Patients.}, journal = {PloS one}, volume = {12}, number = {2}, pages = {e0169310}, pmid = {28146577}, issn = {1932-6203}, support = {R01 DK084139/DK/NIDDK NIH HHS/United States ; R41 HL122022/HL/NHLBI NIH HHS/United States ; R41 HL127919/HL/NHLBI NIH HHS/United States ; RC1 DK087031/DK/NIDDK NIH HHS/United States ; }, mesh = {Aged ; Bacteria/classification/genetics ; Biomarkers ; Case-Control Studies ; Cytokines/genetics/metabolism ; Gastrointestinal Microbiome ; Gene Expression Regulation ; *Hemodynamics ; Humans ; Liver Cirrhosis/*complications/diagnosis/etiology/*physiopathology ; Liver Function Tests ; Macrophages/immunology/metabolism ; Male ; Metagenome ; Metagenomics/methods ; *Microbiota ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide/metabolism ; Sepsis/*etiology ; }, abstract = {BACKGROUND: Recently, a complex microbiome was comprehensibly characterized in the serum and ascitic fluid of cirrhotic patients. In the current study, we investigated for the first time the induction of inflammatory pathways and Nitric Oxide, as well as the systemic hemodynamics in conjunction with the blood microbiome in a Child-Pugh class B cirrhotic cohort.

METHODS AND FINDINGS: We used the Intestinal Infections Microbial DNA qPCR Array to screen for 53 bacterial DNA from the gut in the blood. Assays were designed using the 16S rRNA gene as a target, and PCR amplification primers (based on the Human Microbiome Project) and hydrolysis-probe detection. Eighteen systemic hemodynamic parameters were measured non-invasively by impedance cardiography using the BioZ ICG monitor. The inflammatory response was assessed by measuring blood cytokines, Nitric Oxide RNA arrays, and Nitric Oxide. In the blood of this cirrhotic cohort, we detected 19 of 53 bacterial species tested. The number of bacterial species was markedly increased in the blood of cirrhotic patients compared to control individuals (0.2+/-0.4 vs 3.1+/-2.3; 95% CI: 1.3 to 4.9; P = 0.0030). The total bacterial DNA was also increased in the blood of cirrhotic subjects compared to control subjects (0.2+/- 1.1 vs 41.8+/-132.1; 95% CI: 6.0 to 77.2; P = 0.0022). In the cirrhotic cohort, the Cardiac Output increased by 37% and the Systemic Vascular Resistance decreased by 40% (P< 0.00001 for both compared to control subjects). Systemic Vascular Resistance was inversely correlated to blood bacterial DNA quantity (- 0.621; 95% CI -0.843 to -0.218; P = 0.0060), blood bacterial species number (- 0.593; 95% CI -0.83 to -0.175; P = 0.0095; logistic regression: Chi Square = 5.8877; P = 0.0152), and serum Nitric Oxide (- 0.705; 95% CI -0.881 to -0.355; P = 0.0011). Many members of the Nitric Oxide signaling pathway gene family were increased in cirrhotic subjects.

CONCLUSIONS: Our study identified blood bacterial DNA in ~ 90% of the cirrhotic patients without clinical evidences of infection, and suggests that the quantity of bacterial DNA in blood may stimulate signaling pathways, including Nitric Oxide, that could decrease systemic vascular resistance and increase cardiac output.}, } @article {pmid28111075, year = {2017}, author = {Guo, CJ and Chang, FY and Wyche, TP and Backus, KM and Acker, TM and Funabashi, M and Taketani, M and Donia, MS and Nayfach, S and Pollard, KS and Craik, CS and Cravatt, BF and Clardy, J and Voigt, CA and Fischbach, MA}, title = {Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases.}, journal = {Cell}, volume = {168}, number = {3}, pages = {517-526.e18}, pmid = {28111075}, issn = {1097-4172}, support = {R01 GM104659/GM/NIGMS NIH HHS/United States ; R37 CA087660/CA/NCI NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 AT009874/AT/NCCIH NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; F32 GM111012/GM/NIGMS NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacillus subtilis/genetics ; Bacteria/classification/genetics/*metabolism ; Escherichia coli/genetics ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; Peptide Synthases/genetics/*metabolism ; Phylogeny ; Pyrazines/*metabolism ; }, abstract = {The gut microbiota modulate host biology in numerous ways, but little is known about the molecular mediators of these interactions. Previously, we found a widely distributed family of nonribosomal peptide synthetase gene clusters in gut bacteria. Here, by expressing a subset of these clusters in Escherichia coli or Bacillus subtilis, we show that they encode pyrazinones and dihydropyrazinones. At least one of the 47 clusters is present in 88% of the National Institutes of Health Human Microbiome Project (NIH HMP) stool samples, and they are transcribed under conditions of host colonization. We present evidence that the active form of these molecules is the initially released peptide aldehyde, which bears potent protease inhibitory activity and selectively targets a subset of cathepsins in human cell proteomes. Our findings show that an approach combining bioinformatics, synthetic biology, and heterologous gene cluster expression can rapidly expand our knowledge of the metabolic potential of the microbiota while avoiding the challenges of cultivating fastidious commensals.}, } @article {pmid28028549, year = {2016}, author = {Lynch, MD and Neufeld, JD}, title = {SSUnique: Detecting Sequence Novelty in Microbiome Surveys.}, journal = {mSystems}, volume = {1}, number = {6}, pages = {}, pmid = {28028549}, issn = {2379-5077}, abstract = {High-throughput sequencing of small-subunit (SSU) rRNA genes has revolutionized understanding of microbial communities and facilitated investigations into ecological dynamics at unprecedented scales. Such extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain a substantial proportion of unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. Indeed, these novel taxonomic lineages are associated with so-called microbial "dark matter," which is the genomic potential of these lineages. Unfortunately, characterization beyond "unclassified" is challenging due to relatively short read lengths and large data set sizes. Here we demonstrate how mining of phylogenetically novel sequences from microbial ecosystems can be automated using SSUnique, a software pipeline that filters unclassified and/or rare operational taxonomic units (OTUs) from 16S rRNA gene sequence libraries by screening against consensus structural models for SSU rRNA. Phylogenetic position is inferred against a reference data set, and additional characterization of novel clades is also included, such as targeted probe/primer design and mining of assembled metagenomes for genomic context. We show how SSUnique reproduced a previous analysis of phylogenetic novelty from an Arctic tundra soil and demonstrate the recovery of highly novel clades from data sets associated with both the Earth Microbiome Project (EMP) and Human Microbiome Project (HMP). We anticipate that SSUnique will add to the expanding computational toolbox supporting high-throughput sequencing approaches for the study of microbial ecology and phylogeny. IMPORTANCE Extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain many unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. This novelty is poorly explored in standard workflows, which narrows the breadth and discovery potential of such studies. Here we present the SSUnique analysis pipeline, which will promote the exploration of unclassified diversity in microbiome research and, importantly, enable the discovery of substantial novel taxonomic lineages through the analysis of a large variety of existing data sets.}, } @article {pmid27997751, year = {2017}, author = {Jackrel, SL and Owens, SM and Gilbert, JA and Pfister, CA}, title = {Identifying the plant-associated microbiome across aquatic and terrestrial environments: the effects of amplification method on taxa discovery.}, journal = {Molecular ecology resources}, volume = {17}, number = {5}, pages = {931-942}, doi = {10.1111/1755-0998.12645}, pmid = {27997751}, issn = {1755-0998}, mesh = {Bacteria/*classification/*genetics ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Metagenomics/*methods ; *Microbiota ; Plants/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Plants in terrestrial and aquatic environments contain a diverse microbiome. Yet, the chloroplast and mitochondria organelles of the plant eukaryotic cell originate from free-living cyanobacteria and Rickettsiales. This represents a challenge for sequencing the plant microbiome with universal primers, as ~99% of 16S rRNA sequences may consist of chloroplast and mitochondrial sequences. Peptide nucleic acid clamps offer a potential solution by blocking amplification of host-associated sequences. We assessed the efficacy of chloroplast and mitochondria-blocking clamps against a range of microbial taxa from soil, freshwater and marine environments. While we found that the mitochondrial blocking clamps appear to be a robust method for assessing animal-associated microbiota, Proteobacterial 16S rRNA binds to the chloroplast-blocking clamp, resulting in a strong sequencing bias against this group. We attribute this bias to a conserved 14-bp sequence in the Proteobacteria that matches the 17-bp chloroplast-blocking clamp sequence. By scanning the Greengenes database, we provide a reference list of nearly 1500 taxa that contain this 14-bp sequence, including 48 families such as the Rhodobacteraceae, Phyllobacteriaceae, Rhizobiaceae, Kiloniellaceae and Caulobacteraceae. To determine where these taxa are found in nature, we mapped this taxa reference list against the Earth Microbiome Project database. These taxa are abundant in a variety of environments, particularly aquatic and semiaquatic freshwater and marine habitats. To facilitate informed decisions on effective use of organelle-blocking clamps, we provide a searchable database of microbial taxa in the Greengenes and Silva databases matching various n-mer oligonucleotides of each PNA sequence.}, } @article {pmid27913230, year = {2017}, author = {Brooks, JP and Edwards, DJ and Blithe, DL and Fettweis, JM and Serrano, MG and Sheth, NU and Strauss, JF and Buck, GA and Jefferson, KK}, title = {Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome.}, journal = {Contraception}, volume = {95}, number = {4}, pages = {405-413}, pmid = {27913230}, issn = {1879-0518}, support = {P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Condoms ; Contraception/*methods ; Contraceptives, Oral, Combined/*pharmacology ; Female ; Humans ; Intrauterine Devices ; Levonorgestrel/*pharmacology ; Medroxyprogesterone Acetate/*pharmacology ; Microbiota/*drug effects ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Retrospective Studies ; Sexually Transmitted Diseases, Bacterial/prevention & control ; Vagina/*drug effects ; Vaginosis, Bacterial/prevention & control ; Young Adult ; }, abstract = {OBJECTIVES: Prior studies suggest that the composition of the vaginal microbiome may positively or negatively affect susceptibility to sexually transmitted infections (STIs) and bacterial vaginosis (BV). Some female hormonal contraceptive methods also appear to positively or negatively influence STI transmission and BV. Therefore, changes in the vaginal microbiome that are associated with different contraceptive methods may explain, in part, effects on STI transmission and BV.

STUDY DESIGN: We performed a retrospective study of 16S rRNA gene survey data of vaginal samples from a subset of participants from the Human Vaginal Microbiome Project at Virginia Commonwealth University. The subset included 682 women who reported using a single form of birth control that was condoms, combined oral contraceptives (COCs), depot medroxyprogesterone acetate (DMPA) or the levonorgestrel-releasing intrauterine system (LNG-IUS).

RESULTS: Women using COCs [adjusted odds ratio (aOR) 0.29, 95% confidence interval (CI) 0.13-0.64] and DMPA (aOR 0.34, 95% CI 0.13-0.89), but not LNG-IUS (aOR 1.55, 95% CI 0.72-3.35), were less likely to be colonized by BV-associated bacteria relative to women who used condoms. Women using COCs (aOR 1.94, 95% CI 1.25-3.02) were more likely to be colonized by beneficial H2O2-producing Lactobacillus species compared with women using condoms, while women using DMPA (aOR 1.09, 95% CI 0.63-1.86) and LNG-IUS (aOR 0.74, 95% CI 0.48-1.15) were not.

CONCLUSIONS: Use of COCs is significantly associated with increased vaginal colonization by healthy lactobacilli and reduced BV-associated taxa.

IMPLICATIONS: COC use may positively influence gynecologic health through an increase in healthy lactobacilli and a decrease in BV-associated bacterial taxa.}, } @article {pmid27856569, year = {2016}, author = {Hartman, MR and Harrington, KT and Etson, CM and Fierman, MB and Slonim, DK and Walt, DR}, title = {Personal microbiomes and next-generation sequencing for laboratory-based education.}, journal = {FEMS microbiology letters}, volume = {363}, number = {23}, pages = {}, pmid = {27856569}, issn = {1574-6968}, support = {K12 GM074869/GM/NIGMS NIH HHS/United States ; R25 OD010547/OD/NIH HHS/United States ; }, mesh = {Computational Biology/*education ; *Curriculum ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microbiota/*genetics ; Schools ; Students ; }, abstract = {Sequencing and bioinformatics technologies have advanced rapidly in recent years, driven largely by developments in next-generation sequencing (NGS) technology. Given the increasing importance of these advances, there is a growing need to incorporate concepts and practices relating to NGS into undergraduate and high school science curricula. We believe that direct access to sequencing and bioinformatics will improve the ability of students to understand the information obtained through these increasingly ubiquitous research tools. In this commentary, we discuss approaches and challenges for bringing NGS into the classroom based on our experiences in developing and running a microbiome project in high school and undergraduate courses. We describe strategies for maximizing student engagement through establishing personal relevance and utilizing an inquiry-based structure. Additionally, we address the practical issues of incorporating cutting edge technologies into an established curriculum. Looking forward, we anticipate that NGS educational experiments will become more commonplace as sequencing costs continue to decrease and the workflow becomes more user friendly.}, } @article {pmid27822515, year = {2016}, author = {Kopylova, E and Navas-Molina, JA and Mercier, C and Xu, ZZ and Mahé, F and He, Y and Zhou, HW and Rognes, T and Caporaso, JG and Knight, R}, title = {Open-Source Sequence Clustering Methods Improve the State Of the Art.}, journal = {mSystems}, volume = {1}, number = {1}, pages = {}, pmid = {27822515}, issn = {2379-5077}, abstract = {Sequence clustering is a common early step in amplicon-based microbial community analysis, when raw sequencing reads are clustered into operational taxonomic units (OTUs) to reduce the run time of subsequent analysis steps. Here, we evaluated the performance of recently released state-of-the-art open-source clustering software products, namely, OTUCLUST, Swarm, SUMACLUST, and SortMeRNA, against current principal options (UCLUST and USEARCH) in QIIME, hierarchical clustering methods in mothur, and USEARCH's most recent clustering algorithm, UPARSE. All the latest open-source tools showed promising results, reporting up to 60% fewer spurious OTUs than UCLUST, indicating that the underlying clustering algorithm can vastly reduce the number of these derived OTUs. Furthermore, we observed that stringent quality filtering, such as is done in UPARSE, can cause a significant underestimation of species abundance and diversity, leading to incorrect biological results. Swarm, SUMACLUST, and SortMeRNA have been included in the QIIME 1.9.0 release. IMPORTANCE Massive collections of next-generation sequencing data call for fast, accurate, and easily accessible bioinformatics algorithms to perform sequence clustering. A comprehensive benchmark is presented, including open-source tools and the popular USEARCH suite. Simulated, mock, and environmental communities were used to analyze sensitivity, selectivity, species diversity (alpha and beta), and taxonomic composition. The results demonstrate that recent clustering algorithms can significantly improve accuracy and preserve estimated diversity without the application of aggressive filtering. Moreover, these tools are all open source, apply multiple levels of multithreading, and scale to the demands of modern next-generation sequencing data, which is essential for the analysis of massive multidisciplinary studies such as the Earth Microbiome Project (EMP) (J. A. Gilbert, J. K. Jansson, and R. Knight, BMC Biol 12:69, 2014, http://dx.doi.org/10.1186/s12915-014-0069-1).}, } @article {pmid27612939, year = {2016}, author = {Nelson, DB and Rockwell, LC and Prioleau, MD and Goetzl, L}, title = {The role of the bacterial microbiota on reproductive and pregnancy health.}, journal = {Anaerobe}, volume = {42}, number = {}, pages = {67-73}, doi = {10.1016/j.anaerobe.2016.09.001}, pmid = {27612939}, issn = {1095-8274}, mesh = {Actinobacteria/growth & development/pathogenicity ; Female ; Humans ; Lactobacillus/*physiology ; Leptotrichia/growth & development/pathogenicity ; Male ; Microbiota/physiology ; Pregnancy ; Pregnancy Complications, Infectious/*microbiology/pathology/prevention & control ; Reproduction/*physiology ; Sexual Behavior/physiology ; Sexual Partners ; Urethritis/*microbiology/pathology/prevention & control ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology/pathology/prevention & control ; }, abstract = {Recent assessments have examined the composition of bacterial communities influencing reproductive, pregnancy and infant health. The Microbiome Project has made great strides in sequencing the microbiome and identifying the vast communities of microorganisms that inhabit our bodies and much work continues to examine the individual contribution of bacteria on health and disease to inform future therapies. This review explores the current literature outlining the contribution of important bacteria on reproductive health among sexually active men and women, outlines gaps in current research to determine causal and interventional relationships, and suggests future research initiatives. Novel treatments options to reduce adverse outcomes must recognize the heterogeneity of the bacteria within the microbiome and adequately assess long-term benefits in reducing disease burden and re-establishing a healthy Lactobacillus-dominant state. Recognizing other reservoirs outside of the lower genital track and within sexual partners as well as genetic and individual moderators may be most important for long-term cure and reduction of disease. It will be important to develop useful screening tools and comprehensively examine novel therapeutic options to promote the long-term reduction of high-risk bacteria and the re-establishment of healthy bacterial levels to considerably improve outcomes among pregnant women and sexually active men and women.}, } @article {pmid27781166, year = {2016}, author = {Joseph, SJ and Li, B and Petit Iii, RA and Qin, ZS and Darrow, L and Read, TD}, title = {The single-species metagenome: subtyping Staphylococcus aureus core genome sequences from shotgun metagenomic data.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e2571}, pmid = {27781166}, issn = {2167-8359}, support = {R21 AI121860/AI/NIAID NIH HHS/United States ; }, abstract = {In this study we developed a genome-based method for detecting Staphylococcus aureus subtypes from metagenome shotgun sequence data. We used a binomial mixture model and the coverage counts at >100,000 known S. aureus SNP (single nucleotide polymorphism) sites derived from prior comparative genomic analysis to estimate the proportion of 40 subtypes in metagenome samples. We were able to obtain >87% sensitivity and >94% specificity at 0.025X coverage for S. aureus. We found that 321 and 149 metagenome samples from the Human Microbiome Project and metaSUB analysis of the New York City subway, respectively, contained S. aureus at genome coverage >0.025. In both projects, CC8 and CC30 were the most common S. aureus clonal complexes encountered. We found evidence that the subtype composition at different body sites of the same individual were more similar than random sampling and more limited evidence that certain body sites were enriched for particular subtypes. One surprising finding was the apparent high frequency of CC398, a lineage often associated with livestock, in samples from the tongue dorsum. Epidemiologic analysis of the HMP subject population suggested that high BMI (body mass index) and health insurance are possibly associated with S. aureus carriage but there was limited power to identify factors linked to carriage of even the most common subtype. In the NYC subway data, we found a small signal of geographic distance affecting subtype clustering but other unknown factors influence taxonomic distribution of the species around the city.}, } @article {pmid27770008, year = {2017}, author = {Yu, G and Phillips, S and Gail, MH and Goedert, JJ and Humphrys, M and Ravel, J and Ren, Y and Caporaso, NE}, title = {Evaluation of Buccal Cell Samples for Studies of Oral Microbiota.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {26}, number = {2}, pages = {249-253}, doi = {10.1158/1055-9965.EPI-16-0538}, pmid = {27770008}, issn = {1538-7755}, mesh = {Adult ; Aged ; Feasibility Studies ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Male ; Microbiota/*genetics ; Middle Aged ; Mouth Diseases/diagnosis/genetics/microbiology ; Mouth Mucosa/cytology/*microbiology ; Prospective Studies ; RNA, Bacterial/*analysis ; RNA, Ribosomal, 16S/analysis/*genetics ; }, abstract = {BACKGROUND: The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk.

METHODS: We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3-V4 region.

RESULTS: Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum.

CONCLUSIONS: Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease.

IMPACT: The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249-53. ©2016 AACR.}, } @article {pmid27734124, year = {2017}, author = {Tu, Q and Li, J and Shi, Z and Chen, Y and Lin, L and Li, J and Wang, H and Yan, J and Zhou, Q and Li, X and Li, L and Zhou, J and He, Z}, title = {HuMiChip2 for strain level identification and functional profiling of human microbiomes.}, journal = {Applied microbiology and biotechnology}, volume = {101}, number = {1}, pages = {423-435}, doi = {10.1007/s00253-016-7910-0}, pmid = {27734124}, issn = {1432-0614}, mesh = {Humans ; Liver Cirrhosis ; Metagenomics/*methods ; Microarray Analysis/*methods ; Microbiological Techniques/*methods ; *Microbiota ; Nucleic Acid Hybridization/*methods ; Sensitivity and Specificity ; }, abstract = {With the massive data generated by the Human Microbiome Project, how to transform such data into useful information and knowledge remains challenging. Here, with currently available sequencing information (reference genomes and metagenomes), we have developed a comprehensive microarray, HuMiChip2, for strain-level identification and functional characterization of human microbiomes. HuMiChip2 was composed of 29,467 strain-specific probes targeting 2063 microbial strains/species and 133,924 sequence- and group-specific probes targeting 157 key functional gene families involved in various metabolic pathways and host-microbiome interaction processes. Computational evaluation of strain-specific probes suggested that they were not only specific to mock communities of sequenced microorganisms and metagenomes from different human body sites but also to non-sequenced microbial strains. Experimental evaluation of strain-specific probes using single strains/species and mock communities suggested a high specificity of these probes with their corresponding targets. Application of HuMiChip2 to human gut microbiome samples showed the patient microbiomes of alcoholic liver cirrhosis significantly (p < 0.05) shifted their functional structure from the healthy individuals, and the relative abundance of 21 gene families significantly (p < 0.1) differed between the liver cirrhosis patients and healthy individuals. At the strain level, five Bacteroides strains were significantly (p < 0.1) and more frequently detected in liver cirrhosis patients. These results suggest that the developed HuMiChip2 is a useful microbial ecological microarray for both strain-level identification and functional profiling of human microbiomes.}, } @article {pmid27698613, year = {2016}, author = {Jones, RM}, title = {The Influence of the Gut Microbiota on Host Physiology: In Pursuit of Mechanisms.}, journal = {The Yale journal of biology and medicine}, volume = {89}, number = {3}, pages = {285-297}, pmid = {27698613}, issn = {1551-4056}, support = {R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/microbiology ; Probiotics/metabolism ; Stem Cells/immunology/metabolism ; }, abstract = {The results generated from the NIH funded Human Microbiome Project (HMP) are necessarily tied to the overall mission of the agency, which is to foster scientific discoveries as a basis for protecting and improving health. The investment in the HMP phase 1 accomplished many of its goals including the preliminary characterization of the human microbiome and the identification of links between microbiome diversity and disease states. Going forward, the next step in these studies must involve the identification of the functional molecular elements that mediate the positive influence of a eubiotic microbiome on health and disease. This review will focus on recent advances describing mechanistic events in the intestine elicited by the microbiome. These include symbiotic bacteria-induced activation of redox-dependent cell signaling, the bacterial production of short chain fatty acids and ensuing cellular responses, and the secretion of bacteriocins by bacteria that have anti-microbial activities against potential pathogens.}, } @article {pmid27697111, year = {2016}, author = {Moon, JH and Lee, JH}, title = {Probing the diversity of healthy oral microbiome with bioinformatics approaches.}, journal = {BMB reports}, volume = {49}, number = {12}, pages = {662-670}, pmid = {27697111}, issn = {1976-670X}, mesh = {Aging ; Bacteria/genetics ; Climate ; *Computational Biology ; Databases, Genetic ; Humans ; *Microbiota ; Mouth/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The human oral cavity contains a highly personalized microbiome essential to maintaining health, but capable of causing oral and systemic diseases. Thus, an in-depth definition of "healthy oral microbiome" is critical to understanding variations in disease states from preclinical conditions, and disease onset through progressive states of disease. With rapid advances in DNA sequencing and analytical technologies, population-based studies have documented the range and diversity of both taxonomic compositions and functional potentials observed in the oral microbiome in healthy individuals. Besides factors specific to the host, such as age and race/ethnicity, environmental factors also appear to contribute to the variability of the healthy oral microbiome. Here, we review bioinformatic techniques for metagenomic datasets, including their strengths and limitations. In addition, we summarize the interpersonal and intrapersonal diversity of the oral microbiome, taking into consideration the recent large-scale and longitudinal studies, including the Human Microbiome Project. [BMB Reports 2016; 49(12): 662-670].}, } @article {pmid27668170, year = {2016}, author = {Sung, J and Hale, V and Merkel, AC and Kim, PJ and Chia, N}, title = {Metabolic modeling with Big Data and the gut microbiome.}, journal = {Applied & translational genomics}, volume = {10}, number = {}, pages = {10-15}, pmid = {27668170}, issn = {2212-0661}, support = {R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The recent advances in high-throughput omics technologies have enabled researchers to explore the intricacies of the human microbiome. On the clinical front, the gut microbial community has been the focus of many biomarker-discovery studies. While the recent deluge of high-throughput data in microbiome research has been vastly informative and groundbreaking, we have yet to capture the full potential of omics-based approaches. Realizing the promise of multi-omics data will require integration of disparate omics data, as well as a biologically relevant, mechanistic framework - or metabolic model - on which to overlay these data. Also, a new paradigm for metabolic model evaluation is necessary. Herein, we outline the need for multi-omics data integration, as well as the accompanying challenges. Furthermore, we present a framework for characterizing the ecology of the gut microbiome based on metabolic network modeling.}, } @article {pmid27602409, year = {2016}, author = {McDonald, D and Ackermann, G and Khailova, L and Baird, C and Heyland, D and Kozar, R and Lemieux, M and Derenski, K and King, J and Vis-Kampen, C and Knight, R and Wischmeyer, PE}, title = {Extreme Dysbiosis of the Microbiome in Critical Illness.}, journal = {mSphere}, volume = {1}, number = {4}, pages = {}, pmid = {27602409}, issn = {2379-5042}, abstract = {Critical illness is hypothesized to associate with loss of "health-promoting" commensal microbes and overgrowth of pathogenic bacteria (dysbiosis). This dysbiosis is believed to increase susceptibility to nosocomial infections, sepsis, and organ failure. A trial with prospective monitoring of the intensive care unit (ICU) patient microbiome using culture-independent techniques to confirm and characterize this dysbiosis is thus urgently needed. Characterizing ICU patient microbiome changes may provide first steps toward the development of diagnostic and therapeutic interventions using microbiome signatures. To characterize the ICU patient microbiome, we collected fecal, oral, and skin samples from 115 mixed ICU patients across four centers in the United States and Canada. Samples were collected at two time points: within 48 h of ICU admission, and at ICU discharge or on ICU day 10. Sample collection and processing were performed according to Earth Microbiome Project protocols. We applied SourceTracker to assess the source composition of ICU patient samples by using Qiita, including samples from the American Gut Project (AGP), mammalian corpse decomposition samples, childhood (Global Gut study), and house surfaces. Our results demonstrate that critical illness leads to significant and rapid dysbiosis. Many taxons significantly depleted from ICU patients versus AGP healthy controls are key "health-promoting" organisms, and overgrowth of known pathogens was frequent. Source compositions of ICU patient samples are largely uncharacteristic of the expected community type. Between time points and within a patient, the source composition changed dramatically. Our initial results show great promise for microbiome signatures as diagnostic markers and guides to therapeutic interventions in the ICU to repopulate the normal, "health-promoting" microbiome and thereby improve patient outcomes. IMPORTANCE Critical illness may be associated with the loss of normal, "health promoting" bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially "illness-promoting" dysbiosis with probiotics or with targeted, multimicrobe synthetic "stool pills" that restore a healthy microbiome in the ICU setting to improve patient outcomes.}, } @article {pmid27572971, year = {2016}, author = {Donati, C and Zolfo, M and Albanese, D and Tin Truong, D and Asnicar, F and Iebba, V and Cavalieri, D and Jousson, O and De Filippo, C and Huttenhower, C and Segata, N}, title = {Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.}, journal = {Nature microbiology}, volume = {1}, number = {7}, pages = {16070}, pmid = {27572971}, issn = {2058-5276}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; }, mesh = {Computers, Molecular ; Genome, Bacterial ; Gingiva/microbiology ; Humans ; *Metagenome ; Metagenomics/methods ; Microbiota ; Mouth/*microbiology ; Multilocus Sequence Typing ; Neisseria/classification/genetics/isolation & purification/*physiology ; Pharynx/microbiology ; Phylogeny ; Polymorphism, Single Nucleotide ; *Sequence Analysis, DNA ; Tongue/microbiology ; *Viral Tropism ; }, abstract = {Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments.}, } @article {pmid27527985, year = {2016}, author = {Li, L and Ma, ZS}, title = {Testing the Neutral Theory of Biodiversity with Human Microbiome Datasets.}, journal = {Scientific reports}, volume = {6}, number = {}, pages = {31448}, pmid = {27527985}, issn = {2045-2322}, mesh = {Bacteria/*classification ; *Biota ; Humans ; *Microbiota ; Models, Biological ; }, abstract = {The human microbiome project (HMP) has made it possible to test important ecological theories for arguably the most important ecosystem to human health-the human microbiome. Existing limited number of studies have reported conflicting evidence in the case of the neutral theory; the present study aims to comprehensively test the neutral theory with extensive HMP datasets covering all five major body sites inhabited by the human microbiome. Utilizing 7437 datasets of bacterial community samples, we discovered that only 49 communities (less than 1%) satisfied the neutral theory, and concluded that human microbial communities are not neutral in general. The 49 positive cases, although only a tiny minority, do demonstrate the existence of neutral processes. We realize that the traditional doctrine of microbial biogeography "Everything is everywhere, but the environment selects" first proposed by Baas-Becking resolves the apparent contradiction. The first part of Baas-Becking doctrine states that microbes are not dispersal-limited and therefore are neutral prone, and the second part reiterates that the freely dispersed microbes must endure selection by the environment. Therefore, in most cases, it is the host environment that ultimately shapes the community assembly and tip the human microbiome to niche regime.}, } @article {pmid27496318, year = {2017}, author = {Twigg, HL and Weinstock, GM and Knox, KS}, title = {Lung microbiome in human immunodeficiency virus infection.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {179}, number = {}, pages = {97-107}, pmid = {27496318}, issn = {1878-1810}, support = {U01 HL098960/HL/NHLBI NIH HHS/United States ; U01 HL121831/HL/NHLBI NIH HHS/United States ; }, mesh = {HIV Infections/*microbiology/virology ; Humans ; Lung/immunology/*microbiology/pathology/*virology ; *Microbiota ; Pneumonia/microbiology/pathology ; Treatment Outcome ; }, abstract = {The lung microbiome plays a significant role in normal lung function and disease. Because microbial colonization is likely influenced by immunodeficiency, one would speculate that infection with human immunodeficiency virus (HIV) alters the lung microbiome. Furthermore, how this alteration might impact pulmonary complications now seen in HIV-infected patients on antiretroviral therapy (ART), which has shifted from opportunistic infections to diseases associated with chronic inflammation, is not known. There have been limited publications on the lung microbiome in HIV infection, many of them emanating from the Lung HIV Microbiome Project. Current evidence suggests that the lung microbiome in healthy HIV-infected individuals with preserved CD4 counts is similar to uninfected individuals. However, in individuals with more advanced disease, there is an altered alveolar microbiome characterized by a loss of richness and evenness (alpha diversity) within individuals. Furthermore, as a group the taxa making up the HIV-infected and uninfected lung microbiome are different (differences in beta diversity), and the HIV-infected population is more spread out (greater dispersion) than the uninfected population. These differences decline with ART, but even after effective therapy the alveolar microbiome in HIV-infected individuals contains increased amounts of signature bacteria, some of which have previously been associated with chronic lung inflammation. Furthermore, more recent investigations into the lung virome in HIV infection suggest that perturbations in lung viral communities also exist in HIV infection, and that these too are associated with evidence of lung inflammation. Thus, it is likely both microbiome and virome alterations in HIV infection contribute to lung inflammation in these individuals, which has important implications on the changing spectrum of pulmonary complications in patients living with HIV.}, } @article {pmid27363992, year = {2016}, author = {Lau, JT and Whelan, FJ and Herath, I and Lee, CH and Collins, SM and Bercik, P and Surette, MG}, title = {Capturing the diversity of the human gut microbiota through culture-enriched molecular profiling.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {72}, pmid = {27363992}, issn = {1756-994X}, mesh = {Aerobiosis ; Anaerobiosis ; Bacteria/classification/*genetics/isolation & purification ; Biodiversity ; *Cell Culture Techniques ; Clostridiales/classification/*genetics/growth & development/isolation & purification ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/microbiology ; *Genes, Bacterial ; Healthy Volunteers ; Humans ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The human gut microbiota has been implicated in most aspects of health and disease; however, most of the bacteria in this community are considered unculturable, so studies have relied on molecular-based methods. These methods generally do not permit the isolation of organisms, which is required to fully explore the functional roles of bacteria for definitive association with host phenotypes. Using a combination of culture and 16S rRNA gene sequencing, referred to as culture-enriched molecular profiling, we show that the majority of the bacteria identified by 16S sequencing of the human gut microbiota can be cultured.

METHODS: Five fresh, anaerobic fecal samples were cultured using 33 media and incubation of plates anaerobically and aerobically resulted in 66 culture conditions for culture-enriched molecular profiling. The cultivable portion of the fecal microbiota was determined by comparing the operational taxonomic units (OTUs) recovered by 16S sequencing of the culture plates to OTUs from culture-independent sequencing of the fecal sample. Targeted isolation of Lachnospiraceae strains using conditions defined by culture-enriched molecular profiling was carried out on two fresh stool samples.

RESULTS: We show that culture-enriched molecular profiling, utilizing 66 culture conditions combined with 16S rRNA gene sequencing, allowed for the culturing of an average of 95 % of the OTUs present at greater than 0.1 % abundance in fecal samples. Uncultured OTUs were low abundance in stool. Importantly, comparing culture-enrichment to culture-independent sequencing revealed that the majority of OTUs were detected only by culture, highlighting the advantage of culture for studying the diversity of the gut microbiota. Applying culture-enriched molecular profiling to target Lachnospiraceae strains resulted in the recovery of 79 isolates, 12 of which are on the Human Microbiome Project's "Most Wanted" list.

CONCLUSIONS: We show that, through culture-enriched molecular profiling, the majority of the bacteria in the human gut microbiota can be cultured and this method revealed greater bacterial diversity compared to culture-independent sequencing. Additionally, this method could be applied for the targeted recovery of a specific bacterial group. This approach allows for the isolation of bacteria of interest from the gut microbiota, providing new opportunities to explore mechanisms of microbiota-host interactions and the diversity of the human microbiota.}, } @article {pmid27350143, year = {2016}, author = {Proctor, LM}, title = {The National Institutes of Health Human Microbiome Project.}, journal = {Seminars in fetal & neonatal medicine}, volume = {21}, number = {6}, pages = {368-372}, doi = {10.1016/j.siny.2016.05.002}, pmid = {27350143}, issn = {1878-0946}, mesh = {Humans ; *Microbiota ; National Institutes of Health (U.S.) ; United States ; }, abstract = {This overview describes the impetus for and the goals of the National Institutes of Health (NIH)'s Human Microbiome Project (HMP) and the research resources available through the HMP. As the HMP also serves as a catalyst for human microbiome research at the NIH, NIH Institutes and Centers support for this field is also briefly addressed.}, } @article {pmid27339941, year = {2016}, author = {Ma, Y and Hu, X and He, T and Jiang, X}, title = {Hessian regularization based symmetric nonnegative matrix factorization for clustering gene expression and microbiome data.}, journal = {Methods (San Diego, Calif.)}, volume = {111}, number = {}, pages = {80-84}, doi = {10.1016/j.ymeth.2016.06.017}, pmid = {27339941}, issn = {1095-9130}, mesh = {*Algorithms ; *Cluster Analysis ; Gene Expression/genetics ; Gene Expression Profiling/*methods/statistics & numerical data ; Humans ; Microbiota/*genetics ; }, abstract = {Nonnegative matrix factorization (NMF) has received considerable attention due to its interpretation of observed samples as combinations of different components, and has been successfully used as a clustering method. As an extension of NMF, Symmetric NMF (SNMF) inherits the advantages of NMF. Unlike NMF, however, SNMF takes a nonnegative similarity matrix as an input, and two lower rank nonnegative matrices (H, H[T]) are computed as an output to approximate the original similarity matrix. Laplacian regularization has improved the clustering performance of NMF and SNMF. However, Laplacian regularization (LR), as a classic manifold regularization method, suffers some problems because of its weak extrapolating ability. In this paper, we propose a novel variant of SNMF, called Hessian regularization based symmetric nonnegative matrix factorization (HSNMF), for this purpose. In contrast to Laplacian regularization, Hessian regularization fits the data perfectly and extrapolates nicely to unseen data. We conduct extensive experiments on several datasets including text data, gene expression data and HMP (Human Microbiome Project) data. The results show that the proposed method outperforms other methods, which suggests the potential application of HSNMF in biological data clustering.}, } @article {pmid27303377, year = {2016}, author = {Jeraldo, P and Hernandez, A and Nielsen, HB and Chen, X and White, BA and Goldenfeld, N and Nelson, H and Alhquist, D and Boardman, L and Chia, N}, title = {Capturing One of the Human Gut Microbiome's Most Wanted: Reconstructing the Genome of a Novel Butyrate-Producing, Clostridial Scavenger from Metagenomic Sequence Data.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {783}, pmid = {27303377}, issn = {1664-302X}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; }, abstract = {The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent among healthy volunteers and distantly related to any sequenced organisms. Unfortunately, the challenge of assembling high-quality genomes from a tangle of metagenomic reads has slowed progress in learning about these uncultured bacteria. Here, we describe how recent advances in sequencing and analysis allowed us to assemble "most wanted" genomes from metagenomic data collected from four stool samples. Using a combination of both de novo and guided assembly methods, we assembled and binned over 100 genomes from an initial data set of over 1,300 Gbp. One of these genome bins, which met HMP's criteria for a "most wanted" taxa, contained three essentially complete genomes belonging to a previously uncultivated species. This species is most closely related to Eubacterium desmolans and the clostridial cluster IV/Clostridium leptum subgroup species Butyricicoccus pullicaecorum (71-76% average nucleotide identity). Gene function analysis indicates that the species is an obligate anaerobe, forms spores, and produces the anti-inflammatory short-chain fatty acids acetate and butyrate. It also appears to take up metabolically costly molecules such as cobalamin, methionine, and branch-chained amino acids from the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient-scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases such as colon cancer and inflammatory bowel disease. In conclusion, we have assembled essentially complete genomes from stool metagenomic data, yielding valuable information about uncultured organisms' metabolic and ecologic niches, factors that may be required to successfully culture these bacteria, and their role in maintaining health and causing disease.}, } @article {pmid27279224, year = {2016}, author = {Bashan, A and Gibson, TE and Friedman, J and Carey, VJ and Weiss, ST and Hohmann, EL and Liu, YY}, title = {Universality of human microbial dynamics.}, journal = {Nature}, volume = {534}, number = {7606}, pages = {259-262}, pmid = {27279224}, issn = {1476-4687}, support = {R01 HL091528/HL/NHLBI NIH HHS/United States ; }, mesh = {Clostridioides difficile/physiology ; Clostridium Infections/microbiology ; Computer Simulation ; Cross-Sectional Studies ; Datasets as Topic ; *Ecosystem ; Environment ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Healthy Volunteers ; Humans ; Intestines/microbiology ; Metagenomics ; Microbiota/*physiology ; Mouth/microbiology ; Organ Specificity ; Skin/microbiology ; Species Specificity ; }, abstract = {Human-associated microbial communities have a crucial role in determining our health and well-being, and this has led to the continuing development of microbiome-based therapies such as faecal microbiota transplantation. These microbial communities are very complex, dynamic and highly personalized ecosystems, exhibiting a high degree of inter-individual variability in both species assemblages and abundance profiles. It is not known whether the underlying ecological dynamics of these communities, which can be parameterized by growth rates, and intra- and inter-species interactions in population dynamics models, are largely host-independent (that is, universal) or host-specific. If the inter-individual variability reflects host-specific dynamics due to differences in host lifestyle, physiology or genetics, then generic microbiome manipulations may have unintended consequences, rendering them ineffective or even detrimental. Alternatively, microbial ecosystems of different subjects may exhibit universal dynamics, with the inter-individual variability mainly originating from differences in the sets of colonizing species. Here we develop a new computational method to characterize human microbial dynamics. By applying this method to cross-sectional data from two large-scale metagenomic studies--the Human Microbiome Project and the Student Microbiome Project--we show that gut and mouth microbiomes display pronounced universal dynamics, whereas communities associated with certain skin sites are probably shaped by differences in the host environment. Notably, the universality of gut microbial dynamics is not observed in subjects with recurrent Clostridium difficile infection but is observed in the same set of subjects after faecal microbiota transplantation. These results fundamentally improve our understanding of the processes that shape human microbial ecosystems, and pave the way to designing general microbiome-based therapies.}, } @article {pmid27245597, year = {2018}, author = {Cundell, AM}, title = {Microbial Ecology of the Human Skin.}, journal = {Microbial ecology}, volume = {76}, number = {1}, pages = {113-120}, pmid = {27245597}, issn = {1432-184X}, mesh = {Age Factors ; Anti-Bacterial Agents ; Axilla/microbiology ; Bacteria/classification/genetics ; Bacterial Physiological Phenomena ; *Biodiversity ; Cosmetics ; *Ecology ; *Ecosystem ; Fungi/classification/genetics/physiology ; Genes, Bacterial/genetics ; Genes, Fungal/genetics ; Health Status ; Homeostasis ; Humans ; Injections ; Microbiota/genetics/*physiology ; Perineum/microbiology ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; Skin/*microbiology ; Toe Joint/microbiology ; Vaccination ; }, abstract = {This review article on the skin microbiota was written in response to recent advances that transitioned from culture methods to PCR amplification and sequencing of bacterial and fungal genes as a result of the Human Microbiome Project. This transition enables the investigation of the full diversity of microorganisms inhabiting human skin. The skin provides a range of habitats with different microbiota associated with the three major regions of the skin, namely the moist axilla, perineum, and toe webs; oily or sebaceous head, neck, and trunk; and dry forearms and legs. These new culture-independent tools are revealing the diversity of the human skin microbiota in the different locations of the body and with skin depth. These tools should lead to a better understanding of the state of homeostasis between the microbiota and the host and the overall functionality of that microbiota.}, } @article {pmid29878736, year = {2016}, author = {Lin, Z and Zu, XP and Xie, HS and Jin, HZ and Yang, N and Liu, XR and Zhang, WD}, title = {[Research progress in mechanism of intestinal microorganisms in human diseases].}, journal = {Yao xue xue bao = Acta pharmaceutica Sinica}, volume = {51}, number = {6}, pages = {843-852}, pmid = {29878736}, issn = {0513-4870}, mesh = {*Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; *Metagenomics ; Symbiosis ; }, abstract = {The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.}, } @article {pmid27220974, year = {2016}, author = {Pylro, VS and Morais, DK and de Oliveira, FS and Dos Santos, FG and Lemos, LN and Oliveira, G and Roesch, LF}, title = {BMPOS: a Flexible and User-Friendly Tool Sets for Microbiome Studies.}, journal = {Microbial ecology}, volume = {72}, number = {2}, pages = {443-447}, pmid = {27220974}, issn = {1432-184X}, mesh = {Bacteriological Techniques ; Brazil ; Databases, Genetic ; Genetic Markers ; High-Throughput Nucleotide Sequencing/*methods ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA ; *Software ; }, abstract = {Recent advances in science and technology are leading to a revision and re-orientation of methodologies, addressing old and current issues under a new perspective. Advances in next generation sequencing (NGS) are allowing comparative analysis of the abundance and diversity of whole microbial communities, generating a large amount of data and findings at a systems level. The current limitation for biologists has been the increasing demand for computational power and training required for processing of NGS data. Here, we describe the deployment of the Brazilian Microbiome Project Operating System (BMPOS), a flexible and user-friendly Linux distribution dedicated to microbiome studies. The Brazilian Microbiome Project (BMP) has developed data analyses pipelines for metagenomic studies (phylogenetic marker genes), conducted using the two main high-throughput sequencing platforms (Ion Torrent and Illumina MiSeq). The BMPOS is freely available and possesses the entire requirement of bioinformatics packages and databases to perform all the pipelines suggested by the BMP team. The BMPOS may be used as a bootable live USB stick or installed in any computer with at least 1 GHz CPU and 512 MB RAM, independent of the operating system previously installed. The BMPOS has proved to be effective for sequences processing, sequences clustering, alignment, taxonomic annotation, statistical analysis, and plotting of metagenomic data. The BMPOS has been used during several metagenomic analyses courses, being valuable as a tool for training, and an excellent starting point to anyone interested in performing metagenomic studies. The BMPOS and its documentation are available at http://www.brmicrobiome.org .}, } @article {pmid27182288, year = {2016}, author = {Thomas-White, K and Brady, M and Wolfe, AJ and Mueller, ER}, title = {The bladder is not sterile: History and current discoveries on the urinary microbiome.}, journal = {Current bladder dysfunction reports}, volume = {11}, number = {1}, pages = {18-24}, pmid = {27182288}, issn = {1931-7212}, support = {R01 DK104718/DK/NIDDK NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; }, abstract = {In the human body, there are 10 bacterial cells for every one human cell. This fact highlights the importance of the National institutes of Health's initiative to map the human microbiome. The Human Microbiome Project was the first large-scale mapping of the human microbiome of 5 body sites: GI tract, mouth, vagina, skin and nasal cavity using culture-independent methods. The bladder was not originally tested because it was considered to be sterile and there were complexities regarding sample collection. Over the last couple years our team along with other investigators have shown that a urinary microbiome exists and for most individuals it plays a protective role.}, } @article {pmid27152251, year = {2016}, author = {Cross, B and Faustoferri, RC and Quivey, RG}, title = {What are We Learning and What Can We Learn from the Human Oral Microbiome Project?.}, journal = {Current oral health reports}, volume = {3}, number = {1}, pages = {56-63}, pmid = {27152251}, issn = {2196-3002}, support = {R01 DE013683/DE/NIDCR NIH HHS/United States ; R01 DE017157/DE/NIDCR NIH HHS/United States ; T90 DE021985/DE/NIDCR NIH HHS/United States ; }, abstract = {Extraordinary technological advances have greatly accelerated our ability to identify bacteria, at the species level, present in clinical samples taken from the human mouth. In addition, technologies are evolving such that the oral samples can be analyzed for their protein and metabolic products. As a result, pictures are the advent of personalized dental medicine is becoming closer to reality.}, } @article {pmid27148241, year = {2016}, author = {Utter, DR and Mark Welch, JL and Borisy, GG}, title = {Individuality, Stability, and Variability of the Plaque Microbiome.}, journal = {Frontiers in microbiology}, volume = {7}, number = {}, pages = {564}, pmid = {27148241}, issn = {1664-302X}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; }, abstract = {Dental plaque is a bacterial biofilm composed of a characteristic set of organisms. Relatively little information from cultivation-independent, high-throughput analyses has been published on the temporal dynamics of the dental plaque microbiome. We used Minimum Entropy Decomposition, an information theory-based approach similar to oligotyping that provides single-nucleotide resolution, to analyze a previously published time series data set and investigate the dynamics of the plaque microbiome at various analytic and taxonomic levels. At both the genus and 97% Operational Taxonomic Unit (OTU) levels of resolution, the range of variation within each individual overlapped that of other individuals in the data set. When analyzed at the oligotype level, however, the overlap largely disappeared, showing that single-nucleotide resolution enables differentiation of individuals from one another without ambiguity. The overwhelming majority of the plaque community in all samples was made up of bacteria from a moderate number of plaque-typical genera, indicating that the overall community framework is shared among individuals. Each of these genera fluctuated in abundance around a stable mean that varied between individuals, with some genera having higher inter-individual variability than others. Thus, at the genus level, differences between individuals lay not in the identity of the major genera but in consistently differing proportions of these genera from mouth to mouth. However, at the oligotype level, we detected oligotype "fingerprints," a highly individual-specific set of persistently abundant oligotypes fluctuating around a stable mean over time. For example, within the genus Corynebacterium, more than a dozen oligotypes were detectable in each individual, of which a different subset reached high abundance in any given person. This pattern suggests that each mouth contains a subtly different community of organisms. We also compared the Chinese plaque community characterized here to previously characterized Western plaque communities, as represented by analyses of data emerging from the Human Microbiome Project, and found no major differences between Chinese and Western supragingival plaque. In conclusion, we found the plaque microbiome to be highly individualized at the oligotype level and characterized by stability of community membership, with variability in the relative abundance of community members between individuals and over time.}, } @article {pmid27143475, year = {2016}, author = {Gloor, GB and Wu, JR and Pawlowsky-Glahn, V and Egozcue, JJ}, title = {It's all relative: analyzing microbiome data as compositions.}, journal = {Annals of epidemiology}, volume = {26}, number = {5}, pages = {322-329}, doi = {10.1016/j.annepidem.2016.03.003}, pmid = {27143475}, issn = {1873-2585}, support = {//CIHR/Canada ; }, mesh = {Datasets as Topic ; Female ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics ; Sensitivity and Specificity ; }, abstract = {PURPOSE: The ability to properly analyze and interpret large microbiome data sets has lagged behind our ability to acquire such data sets from environmental or clinical samples. Sequencing instruments impose a structure on these data: the natural sample space of a 16S rRNA gene sequencing data set is a simplex, which is a part of real space that is restricted to nonnegative values with a constant sum. Such data are compositional and should be analyzed using compositionally appropriate tools and approaches. However, most of the tools for 16S rRNA gene sequencing analysis assume these data are unrestricted.

METHODS: We show that existing tools for compositional data (CoDa) analysis can be readily adapted to analyze high-throughput sequencing data sets.

RESULTS: The Human Microbiome Project tongue versus buccal mucosa data set shows how the CoDa approach can address the major elements of microbiome analysis. Reanalysis of a publicly available autism microbiome data set shows that the CoDa approach in concert with multiple hypothesis test corrections prevent false positive identifications.

CONCLUSIONS: The CoDa approach is readily scalable to microbiome-sized analyses. We provide example code and make recommendations to improve the analysis and reporting of microbiome data sets.}, } @article {pmid27124399, year = {2016}, author = {Tandon, D and Haque, MM and Mande, SS}, title = {Inferring Intra-Community Microbial Interaction Patterns from Metagenomic Datasets Using Associative Rule Mining Techniques.}, journal = {PloS one}, volume = {11}, number = {4}, pages = {e0154493}, pmid = {27124399}, issn = {1932-6203}, mesh = {Algorithms ; Data Mining/*methods ; Databases, Genetic ; Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Microbial Interactions ; Web Browser ; }, abstract = {The nature of inter-microbial metabolic interactions defines the stability of microbial communities residing in any ecological niche. Deciphering these interaction patterns is crucial for understanding the mode/mechanism(s) through which an individual microbial community transitions from one state to another (e.g. from a healthy to a diseased state). Statistical correlation techniques have been traditionally employed for mining microbial interaction patterns from taxonomic abundance data corresponding to a given microbial community. In spite of their efficiency, these correlation techniques can capture only 'pair-wise interactions'. Moreover, their emphasis on statistical significance can potentially result in missing out on several interactions that are relevant from a biological standpoint. This study explores the applicability of one of the earliest association rule mining algorithm i.e. the 'Apriori algorithm' for deriving 'microbial association rules' from the taxonomic profile of given microbial community. The classical Apriori approach derives association rules by analysing patterns of co-occurrence/co-exclusion between various '(subsets of) features/items' across various samples. Using real-world microbiome data, the efficiency/utility of this rule mining approach in deciphering multiple (biologically meaningful) association patterns between 'subsets/subgroups' of microbes (constituting microbiome samples) is demonstrated. As an example, association rules derived from publicly available gut microbiome datasets indicate an association between a group of microbes (Faecalibacterium, Dorea, and Blautia) that are known to have mutualistic metabolic associations among themselves. Application of the rule mining approach on gut microbiomes (sourced from the Human Microbiome Project) further indicated similar microbial association patterns in gut microbiomes irrespective of the gender of the subjects. A Linux implementation of the Association Rule Mining (ARM) software (customised for deriving 'microbial association rules' from microbiome data) is freely available for download from the following link: http://metagenomics.atc.tcs.com/arm.}, } @article {pmid27123663, year = {2016}, author = {Wolf, PG and Biswas, A and Morales, SE and Greening, C and Gaskins, HR}, title = {H2 metabolism is widespread and diverse among human colonic microbes.}, journal = {Gut microbes}, volume = {7}, number = {3}, pages = {235-245}, pmid = {27123663}, issn = {1949-0984}, mesh = {Bacteria/*classification/*metabolism ; Carbohydrate Metabolism ; Colon/*microbiology ; Feces/microbiology ; Fermentation ; Healthy Volunteers ; Humans ; Hydrogen/*metabolism ; Hydrogenase/metabolism ; Metabolic Networks and Pathways ; }, abstract = {Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon.}, } @article {pmid27122046, year = {2016}, author = {Lloyd-Price, J and Abu-Ali, G and Huttenhower, C}, title = {The healthy human microbiome.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {51}, pmid = {27122046}, issn = {1756-994X}, mesh = {Bacteria/*classification/*genetics ; Genetic Variation ; Healthy Volunteers ; Humans ; Metagenome ; *Microbiota ; Phylogeny ; Phylogeography ; }, abstract = {Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome-the total DNA content of microbes inhabiting our bodies-is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the "healthy microbiome" has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a 'healthy microbiome' that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future.}, } @article {pmid27114874, year = {2016}, author = {Trembath-Reichert, E and Case, DH and Orphan, VJ}, title = {Characterization of microbial associations with methanotrophic archaea and sulfate-reducing bacteria through statistical comparison of nested Magneto-FISH enrichments.}, journal = {PeerJ}, volume = {4}, number = {}, pages = {e1913}, pmid = {27114874}, issn = {2167-8359}, support = {T32 GM007616/GM/NIGMS NIH HHS/United States ; }, abstract = {Methane seep systems along continental margins host diverse and dynamic microbial assemblages, sustained in large part through the microbially mediated process of sulfate-coupled Anaerobic Oxidation of Methane (AOM). This methanotrophic metabolism has been linked to consortia of anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB). These two groups are the focus of numerous studies; however, less is known about the wide diversity of other seep associated microorganisms. We selected a hierarchical set of FISH probes targeting a range of Deltaproteobacteria diversity. Using the Magneto-FISH enrichment technique, we then magnetically captured CARD-FISH hybridized cells and their physically associated microorganisms from a methane seep sediment incubation. DNA from nested Magneto-FISH experiments was analyzed using Illumina tag 16S rRNA gene sequencing (iTag). Enrichment success and potential bias with iTag was evaluated in the context of full-length 16S rRNA gene clone libraries, CARD-FISH, functional gene clone libraries, and iTag mock communities. We determined commonly used Earth Microbiome Project (EMP) iTAG primers introduced bias in some common methane seep microbial taxa that reduced the ability to directly compare OTU relative abundances within a sample, but comparison of relative abundances between samples (in nearly all cases) and whole community-based analyses were robust. The iTag dataset was subjected to statistical co-occurrence measures of the most abundant OTUs to determine which taxa in this dataset were most correlated across all samples. Many non-canonical microbial partnerships were statistically significant in our co-occurrence network analysis, most of which were not recovered with conventional clone library sequencing, demonstrating the utility of combining Magneto-FISH and iTag sequencing methods for hypothesis generation of associations within complex microbial communities. Network analysis pointed to many co-occurrences containing putatively heterotrophic, candidate phyla such as OD1, Atribacteria, MBG-B, and Hyd24-12 and the potential for complex sulfur cycling involving Epsilon-, Delta-, and Gammaproteobacteria in methane seep ecosystems.}, } @article {pmid27110483, year = {2016}, author = {Heiman, ML and Greenway, FL}, title = {A healthy gastrointestinal microbiome is dependent on dietary diversity.}, journal = {Molecular metabolism}, volume = {5}, number = {5}, pages = {317-320}, pmid = {27110483}, issn = {2212-8778}, abstract = {BACKGROUND: Like all healthy ecosystems, richness of microbiota species characterizes the GI microbiome in healthy individuals. Conversely, a loss in species diversity is a common finding in several disease states. This biome is flooded with energy in the form of undigested and partially digested foods, and in some cases drugs and dietary supplements. Each microbiotic species in the biome transforms that energy into new molecules, which may signal messages to physiological systems of the host.

SCOPE OF REVIEW: Dietary choices select substrates for species, providing a competitive advantage over other GI microbiota. The more diverse the diet, the more diverse the microbiome and the more adaptable it will be to perturbations. Unfortunately, dietary diversity has been lost during the past 50 years and dietary choices that exclude food products from animals or plants will narrow the GI microbiome further.

MAJOR CONCLUSION: Additional research into expanding gut microbial richness by dietary diversity is likely to expand concepts in healthy nutrition, stimulate discovery of new diagnostics, and open up novel therapeutic possibilities.}, } @article {pmid27102203, year = {2016}, author = {Grassl, N and Kulak, NA and Pichler, G and Geyer, PE and Jung, J and Schubert, S and Sinitcyn, P and Cox, J and Mann, M}, title = {Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome.}, journal = {Genome medicine}, volume = {8}, number = {1}, pages = {44}, pmid = {27102203}, issn = {1756-994X}, mesh = {Adult ; Bacteria/classification/genetics/metabolism ; Bacterial Proteins ; Biodiversity ; Chromatography, Liquid ; Female ; Humans ; Male ; Mass Spectrometry ; Metagenome ; Metagenomics ; *Microbiota ; Mouth/*microbiology ; Peptides/metabolism ; Phylogeny ; *Proteome ; *Proteomics/methods ; Saliva/*metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Young Adult ; }, abstract = {BACKGROUND: The oral cavity is home to one of the most diverse microbial communities of the human body and a major entry portal for pathogens. Its homeostasis is maintained by saliva, which fulfills key functions including lubrication of food, pre-digestion, and bacterial defense. Consequently, disruptions in saliva secretion and changes in the oral microbiome contribute to conditions such as tooth decay and respiratory tract infections. Here we set out to quantitatively map the saliva proteome in great depth with a rapid and in-depth mass spectrometry-based proteomics workflow.

METHODS: We used recent improvements in mass spectrometry (MS)-based proteomics to develop a rapid workflow for mapping the saliva proteome quantitatively and at great depth. Standard clinical cotton swabs were used to collect saliva form eight healthy individuals at two different time points, allowing us to study inter-individual differences and interday changes of the saliva proteome. To accurately identify microbial proteins, we developed a method called "split by taxonomy id" that prevents peptides shared by humans and bacteria or between different bacterial phyla to contribute to protein identification.

RESULTS: Microgram protein amounts retrieved from cotton swabs resulted in more than 3700 quantified human proteins in 100-min gradients or 5500 proteins after simple fractionation. Remarkably, our measurements also quantified more than 2000 microbial proteins from 50 bacterial genera. Co-analysis of the proteomics results with next-generation sequencing data from the Human Microbiome Project as well as a comparison to MALDI-TOF mass spectrometry on microbial cultures revealed strong agreement. The oral microbiome differs between individuals and changes drastically upon eating and tooth brushing.

CONCLUSION: Rapid shotgun and robust technology can now simultaneously characterize the human and microbiome contributions to the proteome of a body fluid and is therefore a valuable complement to genomic studies. This opens new frontiers for the study of host-pathogen interactions and clinical saliva diagnostics.}, } @article {pmid28721243, year = {2016}, author = {Nguyen, NP and Warnow, T and Pop, M and White, B}, title = {A perspective on 16S rRNA operational taxonomic unit clustering using sequence similarity.}, journal = {NPJ biofilms and microbiomes}, volume = {2}, number = {}, pages = {16004}, pmid = {28721243}, issn = {2055-5008}, abstract = {The standard pipeline for 16S amplicon analysis starts by clustering sequences within a percent sequence similarity threshold (typically 97%) into 'Operational Taxonomic Units' (OTUs). From each OTU, a single sequence is selected as a representative. This representative sequence is annotated, and that annotation is applied to all remaining sequences within that OTU. This perspective paper will discuss the known shortcomings of this standard approach using results obtained from the Human Microbiome Project. In particular, we will show that the traditional approach of using pairwise sequence alignments to compute sequence similarity can result in poorly clustered OTUs. As OTUs are typically annotated based upon a single representative sequence, poorly clustered OTUs can have significant impact on downstream analyses. These results suggest that we need to move beyond simple clustering techniques for 16S analysis.}, } @article {pmid27051943, year = {2015}, author = {Xin, X and Junzhi, H and Xuedong, Z}, title = {[Oral microbiota: a promising predictor of human oral and systemic diseases].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {33}, number = {6}, pages = {555-560}, pmid = {27051943}, issn = {1000-1182}, mesh = {*Biomarkers ; Cardiovascular Diseases/microbiology ; Dental Caries/microbiology ; Diabetes Mellitus/microbiology ; Humans ; Metagenomics ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/microbiology ; Neoplasms/microbiology ; Oral Health ; Periodontal Diseases/microbiology ; }, abstract = {A human oral microbiota is the ecological community of commensal, symbiotic, and pathogenic microorganisms found in human oral cavity. Oral microbiota exists mostly in the form of a biofilm and maintains a dynamic ecological equilibrium with the host body. However, the disturbance of this ecological balance inevitably causes oral infectious diseases, such as dental caries, apical periodontitis, periodontal diseases, pericoronitis, and craniofacial bone osteomyelitis. Oral microbiota is also correlated with many systemic diseases, including cancer, diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, and preterm birth. Hence, oral microbiota has been considered as a potential biomarker of human diseases. The "Human Microbiome Project" and other metagenomic projects worldwide have advanced our knowledge of the human oral microbiota. The integration of these metadata has been the frontier of oral microbiology to improve clinical translation. By reviewing recent progress on studies involving oral microbiota-related oral and systemic diseases, we aimed to propose the essential role of oral microbiota in the prediction of the onset, progression, and prognosis of oral and systemic diseases. An oral microbiota-based prediction model helps develop a new paradigm of personalized medicine and benefits the human health in the post-metagenomics era.}, } @article {pmid27025836, year = {2016}, author = {Millan, B and Park, H and Hotte, N and Mathieu, O and Burguiere, P and Tompkins, TA and Kao, D and Madsen, KL}, title = {Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {62}, number = {12}, pages = {1479-1486}, pmid = {27025836}, issn = {1537-6591}, support = {93675//CIHR/Canada ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology ; Clostridioides difficile/*drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes.

METHODS: In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes.

RESULTS: RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT.

CONCLUSIONS: RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes.}, } @article {pmid26982053, year = {2016}, author = {Gearry, RB}, title = {IBD and Environment: Are There Differences between East and West.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {34}, number = {1-2}, pages = {84-89}, doi = {10.1159/000442933}, pmid = {26982053}, issn = {1421-9875}, mesh = {*Environment ; Gastroenterology ; Humans ; Inflammatory Bowel Diseases/*epidemiology/*pathology ; *Internationality ; Risk Factors ; }, abstract = {BACKGROUND: The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC) occur worldwide with differences in epidemiology, etiology and phenotype between regions. Breakthroughs have occurred in IBD genetics, although the genes that predispose to IBD differ between racial groups. What do we know about the 'envirotype' of those who develop IBD, and are there differences between the East and the West?

KEY MESSAGES: The strongest IBD risk factor identified to date is a family history of IBD. Whilst likely representing an underlying genetic predisposition, it may also reflect shared environmental factors amongst family members. Cigarette smoking increases the risk of developing CD, whilst smoking is less common in those who develop UC. Having ceased smoking increases the risk of developing UC subsequently. Unlike the West, cigarette smoking appears to play a lesser role in the East. Other environmental risk factors are inconsistent. Studies of migrant populations moving from regions of low to high IBD incidence point to early life as a key time for environmental triggers. In these populations, it is the second generation (those born in the high incidence region) with higher IBD incidence rates than their parents. Early life environmental exposures have been studied exhaustively but, except for having been breastfed, few putative early childhood environmental risk factors have been shown consistently to alter the risk of developing IBD.

CONCLUSIONS: The identification of IBD environmental risk factors remains elusive in both the East and West. In the West, case-control studies are unlikely to move the field forward without multi-level (phenotype, genotype, diet history, 'envirotype' and microbiome) data, ideally collected prospectively. Cohort studies (such as the Genes, Environment, Microbiome project) may address some of these issues. However, in the East where IBD incidence is still increasing, well-designed comprehensive case-control studies may identify differences that give an insight into the 'envirotype' driving IBD incidence.}, } @article {pmid26943627, year = {2016}, author = {Almeida, M and Pop, M and Le Chatelier, E and Prifti, E and Pons, N and Ghozlane, A and Ehrlich, SD}, title = {Capturing the most wanted taxa through cross-sample correlations.}, journal = {The ISME journal}, volume = {10}, number = {10}, pages = {2459-2467}, pmid = {26943627}, issn = {1751-7370}, support = {R01 AI100947/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Humans ; Metagenomics ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The Human Microbiome Project (HMP) identified the 16S rRNA gene sequences of 'most wanted' taxa-prevalent in the healthy human microbiota but distant from previously known sequences. Since 2012, few of the corresponding genomes have been isolated and sequenced, and only through advanced isolation techniques. We demonstrate that the genomes of the most wanted taxa can be identified computationally through their correlation in abundance across multiple public metagenomic data sets. We link over 200 most wanted sequences with nearly complete genome sequences, including half of the taxa identified as high-priority targets by the HMP. The genomes we identify have strong similarity to genomes reconstructed through expensive isolation techniques, and provide a more complete functional characterization of these organisms than can be extrapolated from their 16S rRNA gene. We also provide insights into the function of organisms for which 16S rRNA gene signatures were recently reported to be associated with health and host genetic factors.}, } @article {pmid26932765, year = {2016}, author = {Rampelli, S and Soverini, M and Turroni, S and Quercia, S and Biagi, E and Brigidi, P and Candela, M}, title = {ViromeScan: a new tool for metagenomic viral community profiling.}, journal = {BMC genomics}, volume = {17}, number = {}, pages = {165}, pmid = {26932765}, issn = {1471-2164}, mesh = {Computational Biology ; DNA, Viral ; *Genome, Viral ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; *Microbiota ; RNA, Viral/isolation & purification ; Sequence Analysis, DNA ; *Software ; Viruses/*classification/isolation & purification ; }, abstract = {BACKGROUND: Bioinformatics tools available for metagenomic sequencing analysis are principally devoted to the identification of microorganisms populating an ecological niche, but they usually do not consider viruses. Only some software have been designed to profile the viral sequences, however they are not efficient in the characterization of viruses in the context of complex communities, like the intestinal microbiota, containing bacteria, archeabacteria, eukaryotic microorganisms and viruses. In any case, a comprehensive description of the host-microbiota interactions can not ignore the profile of eukaryotic viruses within the virome, as viruses are definitely critical for the regulation of the host immunophenotype.

RESULTS: ViromeScan is an innovative metagenomic analysis tool that characterizes the taxonomy of the virome directly from raw data of next-generation sequencing. The tool uses hierarchical databases for eukaryotic viruses to unambiguously assign reads to viral species more accurately and >1000 fold faster than other existing approaches. We validated ViromeScan on synthetic microbial communities and applied it on metagenomic samples of the Human Microbiome Project, providing a sensitive eukaryotic virome profiling of different human body sites.

CONCLUSIONS: ViromeScan allows the user to explore and taxonomically characterize the virome from metagenomic reads, efficiently denoising samples from reads of other microorganisms. This implies that users can fully characterize the microbiome, including bacteria and viruses, by shotgun metagenomic sequencing followed by different bioinformatic pipelines.}, } @article {pmid26914164, year = {2016}, author = {O'Brien, SL and Gibbons, SM and Owens, SM and Hampton-Marcell, J and Johnston, ER and Jastrow, JD and Gilbert, JA and Meyer, F and Antonopoulos, DA}, title = {Spatial scale drives patterns in soil bacterial diversity.}, journal = {Environmental microbiology}, volume = {18}, number = {6}, pages = {2039-2051}, pmid = {26914164}, issn = {1462-2920}, support = {T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Bacteria/*classification/isolation & purification ; *Biodiversity ; *Grassland ; Panicum ; *Soil Microbiology ; }, abstract = {Soil microbial communities are essential for ecosystem function, but linking community composition to biogeochemical processes is challenging because of high microbial diversity and large spatial variability of most soil characteristics. We investigated soil bacterial community structure in a switchgrass stand planted on soil with a history of grassland vegetation at high spatial resolution to determine whether biogeographic trends occurred at the centimeter scale. Moreover, we tested whether such heterogeneity, if present, influenced community structure within or among ecosystems. Pronounced heterogeneity was observed at centimeter scales, with abrupt changes in relative abundance of phyla from sample to sample. At the ecosystem scale (> 10 m), however, bacterial community composition and structure were subtly, but significantly, altered by fertilization, with higher alpha diversity in fertilized plots. Moreover, by comparing these data with data from 1772 soils from the Earth Microbiome Project, it was found that 20% of bacterial taxa were shared between their site and diverse globally sourced soil samples, while grassland soils shared approximately 40% of their operational taxonomic units with the current study. By spanning several orders of magnitude, the analysis suggested that extreme patchiness characterized community structure at smaller scales but that coherent patterns emerged at larger length scales.}, } @article {pmid26852737, year = {2016}, author = {Mammen, MJ and Sethi, S}, title = {COPD and the microbiome.}, journal = {Respirology (Carlton, Vic.)}, volume = {21}, number = {4}, pages = {590-599}, doi = {10.1111/resp.12732}, pmid = {26852737}, issn = {1440-1843}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bronchoalveolar Lavage Fluid ; Disease Progression ; Female ; Gastrointestinal Tract/immunology/*microbiology ; Humans ; Lung/*microbiology/physiopathology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/immunology/microbiology/*physiopathology/therapy ; RNA, Ribosomal, 16S/chemistry ; Risk Factors ; Severity of Illness Index ; Smoking ; United States ; }, abstract = {Traditional culture techniques confirm that bacteria have an important role in Chronic Obstructive Pulmonary Disease (COPD). In individuals with COPD, acquisition of novel bacterial strains is associated with onset of acute exacerbation of COPD, which leads to further lung dysfunction and enormous health-care costs. Recent study of the human microbiome, the total composite of the bacteria on the human body, posited the microbiome as the last human organ studied, as the microbiome performs a multitude of metabolic functions absent in the human genome. The largest project to study the human microbiome was the National Institutes of Health (NIH) human microbiome project (HMP) started in 2007 to understand the 'normal' microbiome. However due to the presumption that the healthy human lung was sterile, the respiratory tract was not included in that study. The advent of next-generation sequencing technologies has allowed the investigation of the human respiratory microbiome, which revealed that the healthy lung does have a robust microbiome. Subsequent studies in individuals with COPD revealed that the microbiome composition fluctuates with severity of COPD, composition of the individual aero-digestive tract microbiomes, age, during an acute exacerbation of COPD and with the use of steroids and/or antibiotics. Understanding the impact of the microbiome on COPD progression and risk of exacerbation will lead to directed therapies for prevention of COPD progression and exacerbation.}, } @article {pmid26833346, year = {2016}, author = {Jaillard, M and Tournoud, M and Meynier, F and Veyrieras, JB}, title = {Optimization of alignment-based methods for taxonomic binning of metagenomics reads.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {12}, pages = {1779-1787}, doi = {10.1093/bioinformatics/btw040}, pmid = {26833346}, issn = {1367-4811}, mesh = {Algorithms ; Humans ; Metagenome ; *Metagenomics ; Microbiota ; Models, Theoretical ; }, abstract = {MOTIVATION: Alignment-based taxonomic binning for metagenome characterization proceeds in two steps: reads mapping against a reference database (RDB) and taxonomic assignment according to the best hits. Beyond the sequencing technology and the completeness of the RDB, selecting the optimal configuration of the workflow, in particular the mapper parameters and the best hit selection threshold, to get the highest binning performance remains quite empirical.

RESULTS: We developed a statistical framework to perform such optimization at a minimal computational cost. Using an optimization experimental design and simulated datasets for three sequencing technologies, we built accurate prediction models for five performance indicators and then derived the parameter configuration providing the optimal performance. Whatever the mapper and the dataset, we observed that the optimal configuration yielded better performance than the default configuration and that the best hit selection threshold had a large impact on performance. Finally, on a reference dataset from the Human Microbiome Project, we confirmed that the optimized configuration increased the performance compared with the default configuration.

Not applicable.

CONTACT: magali.dancette@biomerieux.com

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid26778967, year = {2015}, author = {Savidge, TC}, title = {Epigenetic Regulation of Enteric Neurotransmission by Gut Bacteria.}, journal = {Frontiers in cellular neuroscience}, volume = {9}, number = {}, pages = {503}, pmid = {26778967}, issn = {1662-5102}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AI100914/AI/NIAID NIH HHS/United States ; R21 DK096323/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Project defined microbial community interactions with the human host, and provided important molecular insight into how epigenetic factors can influence intestinal ecosystems. Given physiological context, changes in gut microbial community structure are increasingly found to associate with alterations in enteric neurotransmission and disease. At present, it is not known whether shifts in microbial community dynamics represent cause or consequence of disease pathogenesis. The discovery of bacterial-derived neurotransmitters suggests further studies are needed to establish their role in enteric neuropathy. This mini-review highlights recent advances in bacterial communications to the autonomic nervous system and discusses emerging epigenetic data showing that diet, probiotic and antibiotic use may regulate enteric neurotransmission through modulation of microbial communities. A particular emphasis is placed on bacterial metabolite regulation of enteric nervous system function in the intestine.}, } @article {pmid26664362, year = {2015}, author = {Riiser, A}, title = {The human microbiome, asthma, and allergy.}, journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology}, volume = {11}, number = {}, pages = {35}, pmid = {26664362}, issn = {1710-1484}, abstract = {The human microbiome can be defined as the microorganisms that reside within and on our bodies and how they interact with the environment. Recent research suggests that numerous mutually beneficial interactions occur between a human and their microbiome, including those that are essential for good health. Modern microbiological detection techniques have contributed to new knowledge about microorganisms in their human environment. These findings reveal that the microbiomes of the lung and gut contribute to the pathogenesis of asthma and allergy. For example, evidence indicates that the microbiome of the gut regulates the activities of helper T cell subsets (Th1 and Th2) that affect the development of immune tolerance. Moreover, recent studies demonstrate differences between the lung microbiomes of healthy and asthmatic subjects. The hygiene and biodiversity hypotheses explain how exposure to microorganisms is associated with asthma and allergy. Although those living in developed countries are exposed to fewer and less diverse microorganisms compared with the inhabitants of developing countries, they are experiencing an increase in the incidence of asthma and allergies. Detailed analyses of the human microbiome, as are being conducted under the auspices of the Human Microbiome Project initiated in 2007, promise to contribute insights into the mechanisms and factors that cause asthma and allergy that may lead to the development of strategies to prevent and treat these diseases.}, } @article {pmid26597628, year = {2015}, author = {Franasiak, JM and Scott, RT}, title = {Reproductive tract microbiome in assisted reproductive technologies.}, journal = {Fertility and sterility}, volume = {104}, number = {6}, pages = {1364-1371}, doi = {10.1016/j.fertnstert.2015.10.012}, pmid = {26597628}, issn = {1556-5653}, mesh = {Anti-Infective Agents/therapeutic use ; Bacteria/classification/drug effects/*growth & development ; Female ; Fertility ; Genitalia/*microbiology/physiopathology ; Host-Pathogen Interactions ; Humans ; Infertility/microbiology/physiopathology/*therapy ; Male ; *Microbiota ; *Reproduction ; *Reproductive Techniques, Assisted ; Ribotyping ; Risk Factors ; Treatment Outcome ; }, abstract = {The human microbiome has gained much attention recently for its role in health and disease. This interest has come as we have begun to scratch the surface of the complexity of what has been deemed to be our "second genome" through initiatives such as the Human Microbiome Project. Microbes have been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction since before the first success in IVF. Although the data supporting or refuting this hypothesis remain somewhat sparse, thanks to sequencing data from the 16S rRNA subunit, we have begun to characterize the microbiome in the male and female reproductive tracts and understand how this may play a role in reproductive competence. In this review, we discuss what is known about the microbiome of the reproductive tract as it pertains to assisted reproductive technologies.}, } @article {pmid26579434, year = {2015}, author = {Ridlon, JM and Bajaj, JS}, title = {The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics.}, journal = {Acta pharmaceutica Sinica. B}, volume = {5}, number = {2}, pages = {99-105}, pmid = {26579434}, issn = {2211-3835}, support = {R01 DK087913/DK/NIDDK NIH HHS/United States ; }, abstract = {The human body is now viewed as a complex ecosystem that on a cellular and gene level is mainly prokaryotic. The mammalian liver synthesizes and secretes hydrophilic primary bile acids, some of which enter the colon during the enterohepatic circulation, and are converted into numerous hydrophobic metabolites which are capable of entering the portal circulation, returned to the liver, and in humans, accumulating in the biliary pool. Bile acids are hormones that regulate their own synthesis, transport, in addition to glucose and lipid homeostasis, and energy balance. The gut microbial community through their capacity to produce bile acid metabolites distinct from the liver can be thought of as an "endocrine organ" with potential to alter host physiology, perhaps to their own favor. We propose the term "sterolbiome" to describe the genetic potential of the gut microbiome to produce endocrine molecules from endogenous and exogenous steroids in the mammalian gut. The affinity of secondary bile acid metabolites to host nuclear receptors is described, the potential of secondary bile acids to promote tumors, and the potential of bile acids to serve as therapeutic agents are discussed.}, } @article {pmid26576770, year = {2015}, author = {Fernandez, M and Riveros, JD and Campos, M and Mathee, K and Narasimhan, G}, title = {Microbial "social networks".}, journal = {BMC genomics}, volume = {16 Suppl 11}, number = {Suppl 11}, pages = {S6}, pmid = {26576770}, issn = {1471-2164}, mesh = {Bacteria/classification/*genetics ; *Bacterial Physiological Phenomena ; Female ; Humans ; Male ; Metagenomics/*methods ; Microbiota ; Middle Aged ; Smoking ; }, abstract = {BACKGROUND: It is well understood that distinct communities of bacteria are present at different sites of the body, and that changes in the structure of these communities have strong implications for human health. Yet, challenges remain in understanding the complex interconnections between the bacterial taxa within these microbial communities and how they change during the progression of diseases. Many recent studies attempt to analyze the human microbiome using traditional ecological measures and cataloging differences in bacterial community membership. In this paper, we show how to push metagenomic analyses beyond mundane questions related to the bacterial taxonomic profiles that differentiate one sample from another.

METHODS: We develop tools and techniques that help us to investigate the nature of social interactions in microbial communities, and demonstrate ways of compactly capturing extensive information about these networks and visually conveying them in an effective manner. We define the concept of bacterial "social clubs", which are groups of taxa that tend to appear together in many samples. More importantly, we define the concept of "rival clubs", entire groups that tend to avoid occurring together in many samples. We show how to efficiently compute social clubs and rival clubs and demonstrate their utility with the help of examples including a smokers' dataset and a dataset from the Human Microbiome Project (HMP).

RESULTS: The tools developed provide a framework for analyzing relationships between bacterial taxa modeled as bacterial co-occurrence networks. The computational techniques also provide a framework for identifying clubs and rival clubs and for studying differences in the microbiomes (and their interactions) of two or more collections of samples.

CONCLUSIONS: Microbial relationships are similar to those found in social networks. In this work, we assume that strong (positive or negative) tendencies to co-occur or co-infect is likely to have biological, physiological, or ecological significance, possibly as a result of cooperation or competition. As a consequence of the analysis, a variety of biological interpretations are conjectured. In the human microbiome context, the pattern of strength of interactions between bacterial taxa is unique to body site.}, } @article {pmid26568626, year = {2016}, author = {Biggs, MB and Papin, JA}, title = {Metabolic network-guided binning of metagenomic sequence fragments.}, journal = {Bioinformatics (Oxford, England)}, volume = {32}, number = {6}, pages = {867-874}, pmid = {26568626}, issn = {1367-4811}, support = {R01 GM108501/GM/NIGMS NIH HHS/United States ; T32 GM008715/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Cluster Analysis ; Humans ; Metabolic Networks and Pathways ; *Metagenomics ; Microbiota ; }, abstract = {MOTIVATION: Most microbes on Earth have never been grown in a laboratory, and can only be studied through DNA sequences. Environmental DNA sequence samples are complex mixtures of fragments from many different species, often unknown. There is a pressing need for methods that can reliably reconstruct genomes from complex metagenomic samples in order to address questions in ecology, bioremediation, and human health.

RESULTS: We present the SOrting by NEtwork Completion (SONEC) approach for assigning reactions to incomplete metabolic networks based on a metabolite connectivity score. We successfully demonstrate proof of concept in a set of 100 genome-scale metabolic network reconstructions, and delineate the variables that impact reaction assignment accuracy. We further demonstrate the integration of SONEC with existing approaches (such as cross-sample scaffold abundance profile clustering) on a set of 94 metagenomic samples from the Human Microbiome Project. We show that not only does SONEC aid in reconstructing species-level genomes, but it also improves functional predictions made with the resulting metabolic networks.

The datasets and code presented in this work are available at: https://bitbucket.org/mattbiggs/sorting_by_network_completion/

CONTACT: papin@virginia.edu

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid26523201, year = {2015}, author = {Lagier, JC and Khelaifia, S and Azhar, EI and Croce, O and Bibi, F and Jiman-Fatani, AA and Yasir, M and Helaby, HB and Robert, C and Fournier, PE and Raoult, D}, title = {Genome sequence of Oceanobacillus picturae strain S1, an halophilic bacterium first isolated in human gut.}, journal = {Standards in genomic sciences}, volume = {10}, number = {}, pages = {91}, pmid = {26523201}, issn = {1944-3277}, abstract = {Oceanobacillus picturae is a strain of a moderately halophilic bacterium, first isolated from a mural painting. We demonstrate, for the first time, the culture of human Oceanobacillus picturae, strain S1(T), whose genome is described here, from a stool sample collected from a 25-year-old Saoudian healthy individual. We used a slightly modified standard culture medium adding 100 g/L of NaCl. We provide a short description of this strain including its MALDI-TOF spectrum, the main identification tool currently used in clinical microbiology. The 3,675,175 bp long genome exhibits a G + C content of 39.15 % and contains 3666 protein-coding and 157 RNA genes. The draft genome sequence of Oceanobacillus picturae has a similar size to the Oceanobacillus kimchii (respectively 3.67 Mb versus 3.83 Mb). The G + C content was higher compared with Oceanobacillus kimchii (respectively 39.15 % and 35.2 %). Oceanobacillus picturae shared almost identical number of genes (3823 genes versus 3879 genes), with a similar ratio of genes per Mb (1041 genes/Mb versus 1012 genes/Mb). The genome sequencing of Oceanobacillus picturae strain S1 isolated for the first time in a human, will be added to the 778 genome projects from the gastrointestinal tract listed by the international consortium Human Microbiome Project.}, } @article {pmid26500804, year = {2015}, author = {Davis, C and Kota, K and Baldhandapani, V and Gong, W and Abubucker, S and Becker, E and Martin, J and Wylie, KM and Khetani, R and Hudson, ME and Weinstock, GM and Mitreva, M}, title = {mBLAST: Keeping up with the sequencing explosion for (meta)genome analysis.}, journal = {Journal of data mining in genomics & proteomics}, volume = {4}, number = {3}, pages = {}, pmid = {26500804}, issn = {2153-0602}, support = {U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {Recent advances in next-generation sequencing technologies require alignment algorithms and software that can keep pace with the heightened data production. Standard algorithms, especially protein similarity searches, represent significant bottlenecks in analysis pipelines. For metagenomic approaches in particular, it is now often necessary to search hundreds of millions of sequence reads against large databases. Here we describe mBLAST, an accelerated search algorithm for translated and/or protein alignments to large datasets based on the Basic Local Alignment Search Tool (BLAST) and retaining the high sensitivity of BLAST. The mBLAST algorithms achieve substantial speed up over the National Center for Biotechnology Information (NCBI) programs BLASTX, TBLASTX and BLASTP for large datasets, allowing analysis within reasonable timeframes on standard computer architectures. In this article, the impact of mBLAST is demonstrated with sequences originating from the microbiota of healthy humans from the Human Microbiome Project. mBLAST is designed as a plug-in replacement for BLAST for any study that involves short-read sequences and includes high-throughput analysis. The mBLAST software is freely available to academic users at www.multicorewareinc.com.}, } @article {pmid26500616, year = {2015}, author = {Belizário, JE and Napolitano, M}, title = {Human microbiomes and their roles in dysbiosis, common diseases, and novel therapeutic approaches.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {1050}, pmid = {26500616}, issn = {1664-302X}, abstract = {The human body is the residence of a large number of commensal (non-pathogenic) and pathogenic microbial species that have co-evolved with the human genome, adaptive immune system, and diet. With recent advances in DNA-based technologies, we initiated the exploration of bacterial gene functions and their role in human health. The main goal of the human microbiome project is to characterize the abundance, diversity and functionality of the genes present in all microorganisms that permanently live in different sites of the human body. The gut microbiota expresses over 3.3 million bacterial genes, while the human genome expresses only 20 thousand genes. Microbe gene-products exert pivotal functions via the regulation of food digestion and immune system development. Studies are confirming that manipulation of non-pathogenic bacterial strains in the host can stimulate the recovery of the immune response to pathogenic bacteria causing diseases. Different approaches, including the use of nutraceutics (prebiotics and probiotics) as well as phages engineered with CRISPR/Cas systems and quorum sensing systems have been developed as new therapies for controlling dysbiosis (alterations in microbial community) and common diseases (e.g., diabetes and obesity). The designing and production of pharmaceuticals based on our own body's microbiome is an emerging field and is rapidly growing to be fully explored in the near future. This review provides an outlook on recent findings on the human microbiomes, their impact on health and diseases, and on the development of targeted therapies.}, } @article {pmid26437943, year = {2015}, author = {Ning, J and Beiko, RG}, title = {Phylogenetic approaches to microbial community classification.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {47}, pmid = {26437943}, issn = {2049-2618}, mesh = {Biodiversity ; Dental Plaque/microbiology ; Humans ; *Metagenome ; *Microbiota ; Mouth/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Supervised Machine Learning ; }, abstract = {BACKGROUND: The microbiota from different body sites are dominated by different major groups of microbes, but the variations within a body site such as the mouth can be more subtle. Accurate predictive models can serve as useful tools for distinguishing sub-sites and understanding key organisms and their roles and can highlight deviations from expected distributions of microbes. Good classification depends on choosing the right combination of classifier, feature representation, and learning model. Machine-learning procedures have been used in the past for supervised classification, but increased attention to feature representation and selection may produce better models and predictions.

RESULTS: We focused our attention on the classification of nine oral sites and dental plaque in particular, using data collected from the Human Microbiome Project. A key focus of our representations was the use of phylogenetic information, both as the basis for custom kernels and as a way to represent sets of microbes to the classifier. We also used the PICRUSt software, which draws on phylogenetic relationships to predict molecular functions and to generate additional features for the classifier. Custom kernels based on the UniFrac measure of community dissimilarity did not improve performance. However, feature representation was vital to classification accuracy, with microbial clade and function representations providing useful information to the classifier; combining the two types of features did not yield increased prediction accuracy. Many of the best-performing clades and functions had clear associations with oral microflora.

CONCLUSIONS: The classification of oral microbiota remains a challenging problem; our best accuracy on the plaque dataset was approximately 81 %. Perfect accuracy may be unattainable due to the close proximity of the sites and intra-individual variation. However, further exploration of the space of both classifiers and feature representations is likely to increase the accuracy of predictive models.}, } @article {pmid26431583, year = {2016}, author = {Song, H and Yoo, Y and Hwang, J and Na, YC and Kim, HS}, title = {Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.}, journal = {The Journal of allergy and clinical immunology}, volume = {137}, number = {3}, pages = {852-860}, doi = {10.1016/j.jaci.2015.08.021}, pmid = {26431583}, issn = {1097-6825}, mesh = {*Clostridiales/classification/genetics/metabolism ; Cluster Analysis ; Computational Biology/methods ; Dermatitis, Atopic/*etiology ; *Dysbiosis ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Metagenome ; Metagenomics ; Models, Biological ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a serious global epidemic associated with a modern lifestyle.

OBJECTIVE: Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, the nature of the microbiome dysfunction underlying the disease remains unclear.

METHODS: The gut microbiome from 132 subjects, including 90 patients with AD, was analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference genomes from the Human Microbiome Project and the KEGG Orthology database were used for metagenome analyses. Short-chain fatty acids in fecal samples were compared by using gas chromatographic-mass spectrometric analyses.

RESULTS: We show that enrichment of a subspecies of the major gut species Faecalibacterium prausnitzii is strongly associated with AD. In addition, the AD microbiome was enriched in genes encoding the use of various nutrients that could be released from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal samples from patients with AD showed decreased levels of butyrate and propionate, which have anti-inflammatory effects. This is likely a consequence of an intraspecies compositional change in F prausnitzii that reduces the number of high butyrate and propionate producers, including those related to the strain A2-165, a lack of which has been implicated in patients with Crohn disease.

CONCLUSIONS: The data suggest that feedback interactions between dysbiosis in F prausnitzii and dysregulation of gut epithelial inflammation might underlie the chronic progression of AD by resulting in impairment of the gut epithelial barrier, which ultimately leads to aberrant TH2-type immune responses to allergens in the skin.}, } @article {pmid26409790, year = {2015}, author = {Jun, SR and Robeson, MS and Hauser, LJ and Schadt, CW and Gorin, AA}, title = {PanFP: pangenome-based functional profiles for microbial communities.}, journal = {BMC research notes}, volume = {8}, number = {}, pages = {479}, pmid = {26409790}, issn = {1756-0500}, mesh = {*Algorithms ; Bacteria/*genetics ; Metagenome/*genetics ; Metagenomics/*methods ; Sequence Analysis, DNA ; Statistics, Nonparametric ; }, abstract = {BACKGROUND: For decades there has been increasing interest in understanding the relationships between microbial communities and ecosystem functions. Current DNA sequencing technologies allows for the exploration of microbial communities in two principle ways: targeted rRNA gene surveys and shotgun metagenomics. For large study designs, it is often still prohibitively expensive to sequence metagenomes at both the breadth and depth necessary to statistically capture the true functional diversity of a community. Although rRNA gene surveys provide no direct evidence of function, they do provide a reasonable estimation of microbial diversity, while being a very cost-effective way to screen samples of interest for later shotgun metagenomic analyses. However, there is a great deal of 16S rRNA gene survey data currently available from diverse environments, and thus a need for tools to infer functional composition of environmental samples based on 16S rRNA gene survey data.

RESULTS: We present a computational method called pangenome-based functional profiles (PanFP), which infers functional profiles of microbial communities from 16S rRNA gene survey data for Bacteria and Archaea. PanFP is based on pangenome reconstruction of a 16S rRNA gene operational taxonomic unit (OTU) from known genes and genomes pooled from the OTU's taxonomic lineage. From this lineage, we derive an OTU functional profile by weighting a pangenome's functional profile with the OTUs abundance observed in a given sample. We validated our method by comparing PanFP to the functional profiles obtained from the direct shotgun metagenomic measurement of 65 diverse communities via Spearman correlation coefficients. These correlations improved with increasing sequencing depth, within the range of 0.8-0.9 for the most deeply sequenced Human Microbiome Project mock community samples. PanFP is very similar in performance to another recently released tool, PICRUSt, for almost all of survey data analysed here. But, our method is unique in that any OTU building method can be used, as opposed to being limited to closed-reference OTU picking strategies against specific reference sequence databases.

CONCLUSIONS: We developed an automated computational method, which derives an inferred functional profile based on the 16S rRNA gene surveys of microbial communities. The inferred functional profile provides a cost effective way to study complex ecosystems through predicted comparative functional metagenomes and metadata analysis. All PanFP source code and additional documentation are freely available online at GitHub (https://github.com/srjun/PanFP).}, } @article {pmid26407082, year = {2015}, author = {Ma, ZS}, title = {Power law analysis of the human microbiome.}, journal = {Molecular ecology}, volume = {24}, number = {21}, pages = {5428-5445}, doi = {10.1111/mec.13394}, pmid = {26407082}, issn = {1365-294X}, mesh = {Bacteria/*classification ; Humans ; *Microbiota ; *Models, Biological ; Population Dynamics ; }, abstract = {Taylor's (1961, Nature, 189:732) power law, a power function (V = am(b)) describing the scaling relationship between the mean and variance of population abundances of organisms, has been found to govern the population abundance distributions of single species in both space and time in macroecology. It is regarded as one of few generalities in ecology, and its parameter b has been widely applied to characterize spatial aggregation (i.e. heterogeneity) and temporal stability of single-species populations. Here, we test its applicability to bacterial populations in the human microbiome using extensive data sets generated by the US-NIH Human Microbiome Project (HMP). We further propose extending Taylor's power law from the population to the community level, and accordingly introduce four types of power-law extensions (PLEs): type I PLE for community spatial aggregation (heterogeneity), type II PLE for community temporal aggregation (stability), type III PLE for mixed-species population spatial aggregation (heterogeneity) and type IV PLE for mixed-species population temporal aggregation (stability). Our results show that fittings to the four PLEs with HMP data were statistically extremely significant and their parameters are ecologically sound, hence confirming the validity of the power law at both the population and community levels. These findings not only provide a powerful tool to characterize the aggregations of population and community in both time and space, offering important insights into community heterogeneity in space and/or stability in time, but also underscore the three general properties of power laws (scale invariance, no average and universality) and their specific manifestations in our four PLEs.}, } @article {pmid26377179, year = {2015}, author = {Walsh, CJ and Guinane, CM and Hill, C and Ross, RP and O'Toole, PW and Cotter, PD}, title = {In silico identification of bacteriocin gene clusters in the gastrointestinal tract, based on the Human Microbiome Project's reference genome database.}, journal = {BMC microbiology}, volume = {15}, number = {}, pages = {183}, pmid = {26377179}, issn = {1471-2180}, mesh = {Bacteriocins/*biosynthesis/*genetics ; Biosynthetic Pathways/*genetics ; Computational Biology ; Computer Simulation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; *Multigene Family ; }, abstract = {BACKGROUND: The human gut microbiota comprises approximately 100 trillion microbial cells which significantly impact many aspects of human physiology - including metabolism, nutrient absorption and immune function. Disturbances in this population have been implicated in many conditions and diseases, including obesity, type-2 diabetes and inflammatory bowel disease. This suggests that targeted manipulation or shaping of the gut microbiota, by bacteriocins and other antimicrobials, has potential as a therapeutic tool for the prevention or treatment of these conditions. With this in mind, several studies have used traditional culture-dependent approaches to successfully identify bacteriocin-producers from the mammalian gut. In silico-based approaches to identify novel gene clusters are now also being utilised to take advantage of the vast amount of data currently being generated by next generation sequencing technologies. In this study, we employed an in silico screening approach to mine potential bacteriocin clusters in genome-sequenced isolates from the gastrointestinal tract (GIT). More specifically, the bacteriocin genome-mining tool BAGEL3 was used to identify potential bacteriocin producers in the genomes of the GIT subset of the Human Microbiome Project's reference genome database. Each of the identified gene clusters were manually annotated and potential bacteriocin-associated genes were evaluated.

RESULTS: We identified 74 clusters of note from 59 unique members of the Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria and Synergistetes. The most commonly identified class of bacteriocin was the >10 kDa class, formerly known as bacteriolysins, followed by lantibiotics and sactipeptides.

CONCLUSIONS: Multiple bacteriocin gene clusters were identified in a dataset representative of the human gut microbiota. Interestingly, many of these were associated with species and genera which are not typically associated with bacteriocin production.}, } @article {pmid26374288, year = {2015}, author = {Blekhman, R and Goodrich, JK and Huang, K and Sun, Q and Bukowski, R and Bell, JT and Spector, TD and Keinan, A and Ley, RE and Gevers, D and Clark, AG}, title = {Host genetic variation impacts microbiome composition across human body sites.}, journal = {Genome biology}, volume = {16}, number = {1}, pages = {191}, pmid = {26374288}, issn = {1474-760X}, support = {R01 DK093595/DK/NIDDK NIH HHS/United States ; T32 GM007617/GM/NIGMS NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/classification/isolation & purification ; *Genetic Variation ; Genome, Human ; Humans ; Metagenomics ; *Microbiota ; }, abstract = {BACKGROUND: The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale.

RESULTS: Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes.

CONCLUSIONS: Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.}, } @article {pmid26336898, year = {2015}, author = {Kumar, V and Kumar, P and Sharma, V}, title = {Xenobiotic and non-xenobiotic interventions in the microbiome therapeutics.}, journal = {Current drug metabolism}, volume = {16}, number = {4}, pages = {284-293}, doi = {10.2174/138920021604150902180008}, pmid = {26336898}, issn = {1875-5453}, mesh = {Animals ; Humans ; *Microbiota ; Probiotics/therapeutic use ; Xenobiotics/*therapeutic use ; }, abstract = {It is now very much clear that the microbiome plays an important part in human health. Microbiome is associated with several diseases and targeting the whole microbiome is certainly a challenge before the scientists. The "Human Microbiome Project" is continually exploring certain therapeutic targets inside microbiome landscape that could be utilized for the treatment of microbiome associated diseases. Additionally, associated research across the globe is going on and now some potential targets are available that might be beneficial for the designing and synthesis of novel drugs. In this review, we made an effort to discuss all the potential targets and corresponding possible drugs/treatments available for each of them. However, it is not possible to treat all microbiome associated diseases with a single drug/drug combination. Therefore, for different diseases, different treatments/drugs (whether xenobiotic or non-xenobiotic) could be used for better therapeutic efficacy.}, } @article {pmid26311042, year = {2015}, author = {Hugon, P and Dufour, JC and Colson, P and Fournier, PE and Sallah, K and Raoult, D}, title = {A comprehensive repertoire of prokaryotic species identified in human beings.}, journal = {The Lancet. Infectious diseases}, volume = {15}, number = {10}, pages = {1211-1219}, doi = {10.1016/S1473-3099(15)00293-5}, pmid = {26311042}, issn = {1474-4457}, mesh = {Archaea/*classification/*isolation & purification ; Bacteria/*classification/*isolation & purification ; Bacterial Infections/*microbiology ; Carrier State/*microbiology ; Databases, Factual ; Humans ; *Microbiota ; }, abstract = {The compilation of the complete prokaryotic repertoire associated with human beings as commensals or pathogens is a major goal for the scientific and medical community. The use of bacterial culture techniques remains a crucial step to describe new prokaryotic species. The large number of officially acknowledged bacterial species described since 1980 and the recent increase in the number of recognised pathogenic species have highlighted the absence of an exhaustive compilation of species isolated in human beings. By means of a thorough investigation of several large culture databases and a search of the scientific literature, we built an online database containing all human-associated prokaryotic species described, whether or not they had been validated and have standing in nomenclature. We list 2172 species that have been isolated in human beings. They were classified in 12 different phyla, mostly in the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes phyla. Our online database is useful for both clinicians and microbiologists and forms part of the Human Microbiome Project, which aims to characterise the whole human microbiota and help improve our understanding of the human predisposition and susceptibility to infectious agents.}, } @article {pmid26292041, year = {2016}, author = {Barnett, C and Nazzal, L and Goldfarb, DS and Blaser, MJ}, title = {The Presence of Oxalobacter formigenes in the Microbiome of Healthy Young Adults.}, journal = {The Journal of urology}, volume = {195}, number = {2}, pages = {499-506}, pmid = {26292041}, issn = {1527-3792}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; U54 DK 083908/DK/NIDDK NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Feces/microbiology ; Female ; Healthy Volunteers ; Humans ; Male ; Metagenome/genetics ; *Microbiota ; Oxalobacter formigenes/classification/genetics/*isolation & purification ; United States ; }, abstract = {PURPOSE: Oxalobacter formigenes, a member of the human colonic microbiota with a major role in net colonic oxalate transport and secretion, is protective against the formation of calcium oxalate kidney stones. We describe the prevalence, relative abundance and stability of O. formigenes in healthy young adults in the United States.

MATERIALS AND METHODS: We used HMP (Human Microbiome Project) data on fecal samples from 242 healthy young adults who had 1 to 3 study visits. Samples underwent whole genomic shotgun sequencing and/or 16S rRNA sequencing. Three data sets available from the processed sequence data were studied, including whole genomic shotgun metagenomic analysis by alignment to reference genomes using shotgun community profiling, or MetaPhlAn (http://huttenhower.sph.harvard.edu/metaphlan) or QIIME (http://qiime.org/) analysis of the V1-3 or V3-5 16S sequences.

RESULTS: O. formigenes was detected in fecal samples using whole genomic shotgun and 16S rRNA data. Analysis of the whole genomic shotgun data set using shotgun community profiling showed that 29 of 94 subjects (31%) were O. formigenes positive. V1-3 and V3-5 analyses were less sensitive for O. formigenes detection. When present, O. formigenes relative abundance varied over 3 log10 and was normally distributed. All assays agreed in 58 of 66 samples (88%) studied by all 3 methods. Of 14 subjects who were O. formigenes positive at baseline 13 (93%) were positive at the followup visit, indicating the stability of colonization.

CONCLUSIONS: O. formigenes appears to be stably present in fewer than half of healthy young adults in the United States. It is most sensitively detected by whole genomic shotgun.}, } @article {pmid26247840, year = {2015}, author = {Beck, JM and Schloss, PD and Venkataraman, A and Twigg, H and Jablonski, KA and Bushman, FD and Campbell, TB and Charlson, ES and Collman, RG and Crothers, K and Curtis, JL and Drews, KL and Flores, SC and Fontenot, AP and Foulkes, MA and Frank, I and Ghedin, E and Huang, L and Lynch, SV and Morris, A and Palmer, BE and Schmidt, TM and Sodergren, E and Weinstock, GM and Young, VB and , }, title = {Multicenter Comparison of Lung and Oral Microbiomes of HIV-infected and HIV-uninfected Individuals.}, journal = {American journal of respiratory and critical care medicine}, volume = {192}, number = {11}, pages = {1335-1344}, pmid = {26247840}, issn = {1535-4970}, support = {U01HL098958/HL/NHLBI NIH HHS/United States ; T32 HL007749/HL/NHLBI NIH HHS/United States ; U01HL098964/HL/NHLBI NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01 HL098958/HL/NHLBI NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; U01HL098960/HL/NHLBI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; U01HL098996/HL/NHLBI NIH HHS/United States ; R01 HL090342/HL/NHLBI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; U01HL98961/HL/NHLBI NIH HHS/United States ; UL1 TR001108/TR/NCATS NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL102245/HL/NHLBI NIH HHS/United States ; U01HL098957/HL/NHLBI NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; R0100417746//PHS HHS/United States ; U01 HL098957/HL/NHLBI NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; UL1 TR000424/TR/NCATS NIH HHS/United States ; R01HL090342/HL/NHLBI NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01 HL098996/HL/NHLBI NIH HHS/United States ; U01HL098962/HL/NHLBI NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Antiretroviral Therapy, Highly Active ; Bronchoalveolar Lavage Fluid/*microbiology ; Cohort Studies ; Female ; HIV Infections/drug therapy/*microbiology ; Humans ; Lung/*microbiology ; Male ; *Microbiota ; Middle Aged ; Mouth/*microbiology ; Prospective Studies ; }, abstract = {RATIONALE: Improved understanding of the lung microbiome in HIV-infected individuals could lead to better strategies for diagnosis, therapy, and prophylaxis of HIV-associated pneumonias. Differences in the oral and lung microbiomes in HIV-infected and HIV-uninfected individuals are not well defined. Whether highly active antiretroviral therapy influences these microbiomes is unclear.

OBJECTIVES: We determined whether oral and lung microbiomes differed in clinically healthy groups of HIV-infected and HIV-uninfected subjects.

METHODS: Participating sites in the Lung HIV Microbiome Project contributed bacterial 16S rRNA sequencing data from oral washes and bronchoalveolar lavages (BALs) obtained from HIV-uninfected individuals (n = 86), HIV-infected individuals who were treatment naive (n = 18), and HIV-infected individuals receiving antiretroviral therapy (n = 38).

MEASUREMENTS AND MAIN RESULTS: Microbial populations differed in the oral washes among the subject groups (Streptococcus, Actinomyces, Rothia, and Atopobium), but there were no individual taxa that differed among the BALs. Comparison of oral washes and BALs demonstrated similar patterns from HIV-uninfected individuals and HIV-infected individuals receiving antiretroviral therapy, with multiple taxa differing in abundance. The pattern observed from HIV-infected individuals who were treatment naive differed from the other two groups, with differences limited to Veillonella, Rothia, and Granulicatella. CD4 cell counts did not influence the oral or BAL microbiome in these relatively healthy, HIV-infected subjects.

CONCLUSIONS: The overall similarity of the microbiomes in participants with and without HIV infection was unexpected, because HIV-infected individuals with relatively preserved CD4 cell counts are at higher risk for lower respiratory tract infections, indicating impaired local immune function.}, } @article {pmid26246894, year = {2015}, author = {Wang, Q and Fish, JA and Gilman, M and Sun, Y and Brown, CT and Tiedje, JM and Cole, JR}, title = {Xander: employing a novel method for efficient gene-targeted metagenomic assembly.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {32}, pmid = {26246894}, issn = {2049-2618}, support = {P42 ES004911/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: Metagenomics can provide important insight into microbial communities. However, assembling metagenomic datasets has proven to be computationally challenging. Current methods often assemble only fragmented partial genes.

RESULTS: We present a novel method for targeting assembly of specific protein-coding genes. This method combines a de Bruijn graph, as used in standard assembly approaches, and a protein profile hidden Markov model (HMM) for the gene of interest, as used in standard annotation approaches. These are used to create a novel combined weighted assembly graph. Xander performs both assembly and annotation concomitantly using information incorporated in this graph. We demonstrate the utility of this approach by assembling contigs for one phylogenetic marker gene and for two functional marker genes, first on Human Microbiome Project (HMP)-defined community Illumina data and then on 21 rhizosphere soil metagenomic datasets from three different crops totaling over 800 Gbp of unassembled data. We compared our method to a recently published bulk metagenome assembly method and a recently published gene-targeted assembler and found our method produced more, longer, and higher quality gene sequences.

CONCLUSION: Xander combines gene assignment with the rapid assembly of full-length or near full-length functional genes from metagenomic data without requiring bulk assembly or post-processing to find genes of interest. HMMs used for assembly can be tailored to the targeted genes, allowing flexibility to improve annotation over generic annotation pipelines. This method is implemented as open source software and is available at https://github.com/rdpstaff/Xander_assembler.}, } @article {pmid26220947, year = {2016}, author = {Rodrigues Hoffmann, A and Proctor, LM and Surette, MG and Suchodolski, JS}, title = {The Microbiome: The Trillions of Microorganisms That Maintain Health and Cause Disease in Humans and Companion Animals.}, journal = {Veterinary pathology}, volume = {53}, number = {1}, pages = {10-21}, doi = {10.1177/0300985815595517}, pmid = {26220947}, issn = {1544-2217}, mesh = {Animals ; Gastrointestinal Tract/microbiology ; Humans ; Lung/microbiology ; *Microbiota ; Pets ; Respiratory System/microbiology ; Skin/microbiology ; }, abstract = {The microbiome is the complex collection of microorganisms, their genes, and their metabolites, colonizing the human and animal mucosal surfaces, digestive tract, and skin. It is now well known that the microbiome interacts with its host, assisting in digestion and detoxification, supporting immunity, protecting against pathogens, and maintaining health. Studies published to date have demonstrated that healthy individuals are often colonized with different microbiomes than those with disease involving various organ systems. This review covers a brief history of the development of the microbiome field, the main objectives of the Human Microbiome Project, and the most common microbiomes inhabiting the human respiratory tract, companion animal digestive tract, and skin in humans and companion animals. The main changes in the microbiomes in patients with pulmonary, gastrointestinal, and cutaneous lesions are described.}, } @article {pmid26203331, year = {2015}, author = {Mukherjee, S and Huntemann, M and Ivanova, N and Kyrpides, NC and Pati, A}, title = {Large-scale contamination of microbial isolate genomes by Illumina PhiX control.}, journal = {Standards in genomic sciences}, volume = {10}, number = {}, pages = {18}, pmid = {26203331}, issn = {1944-3277}, abstract = {With the rapid growth and development of sequencing technologies, genomes have become the new go-to for exploring solutions to some of the world's biggest challenges such as searching for alternative energy sources and exploration of genomic dark matter. However, progress in sequencing has been accompanied by its share of errors that can occur during template or library preparation, sequencing, imaging or data analysis. In this study we screened over 18,000 publicly available microbial isolate genome sequences in the Integrated Microbial Genomes database and identified more than 1000 genomes that are contaminated with PhiX, a control frequently used during Illumina sequencing runs. Approximately 10% of these genomes have been published in literature and 129 contaminated genomes were sequenced under the Human Microbiome Project. Raw sequence reads are prone to contamination from various sources and are usually eliminated during downstream quality control steps. Detection of PhiX contaminated genomes indicates a lapse in either the application or effectiveness of proper quality control measures. The presence of PhiX contamination in several publicly available isolate genomes can result in additional errors when such data are used in comparative genomics analyses. Such contamination of public databases have far-reaching consequences in the form of erroneous data interpretation and analyses, and necessitates better measures to proofread raw sequences before releasing them to the broader scientific community.}, } @article {pmid26048598, year = {2015}, author = {Fang, H and Huang, C and Zhao, H and Deng, M}, title = {CCLasso: correlation inference for compositional data through Lasso.}, journal = {Bioinformatics (Oxford, England)}, volume = {31}, number = {19}, pages = {3172-3180}, pmid = {26048598}, issn = {1367-4811}, support = {GM59507/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Bacteria/*classification/genetics ; Computational Biology/*methods ; Computer Simulation ; Genomics/methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {MOTIVATION: Direct analysis of microbial communities in the environment and human body has become more convenient and reliable owing to the advancements of high-throughput sequencing techniques for 16S rRNA gene profiling. Inferring the correlation relationship among members of microbial communities is of fundamental importance for genomic survey study. Traditional Pearson correlation analysis treating the observed data as absolute abundances of the microbes may lead to spurious results because the data only represent relative abundances. Special care and appropriate methods are required prior to correlation analysis for these compositional data.

RESULTS: In this article, we first discuss the correlation definition of latent variables for compositional data. We then propose a novel method called CCLasso based on least squares with [Formula: see text] penalty to infer the correlation network for latent variables of compositional data from metagenomic data. An effective alternating direction algorithm from augmented Lagrangian method is used to solve the optimization problem. The simulation results show that CCLasso outperforms existing methods, e.g. SparCC, in edge recovery for compositional data. It also compares well with SparCC in estimating correlation network of microbe species from the Human Microbiome Project.

CCLasso is open source and freely available from https://github.com/huayingfang/CCLasso under GNU LGPL v3.

CONTACT: dengmh@pku.edu.cn

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid25977840, year = {2015}, author = {Zhao, Y and Dua, P and Lukiw, WJ}, title = {Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's Disease (AD).}, journal = {Journal of Alzheimer's disease & Parkinsonism}, volume = {5}, number = {1}, pages = {177}, pmid = {25977840}, issn = {2161-0460}, support = {R01 EY006311/EY/NEI NIH HHS/United States ; R01 AG018031/AG/NIA NIH HHS/United States ; P50 AG016573/AG/NIA NIH HHS/United States ; R01 AG038834/AG/NIA NIH HHS/United States ; P30 GM103340/GM/NIGMS NIH HHS/United States ; }, abstract = {Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~10[14] microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest 'diffuse organ system' in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer's disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.}, } @article {pmid25970595, year = {2015}, author = {McKenney, EA and Rodrigo, A and Yoder, AD}, title = {Patterns of gut bacterial colonization in three primate species.}, journal = {PloS one}, volume = {10}, number = {5}, pages = {e0124618}, pmid = {25970595}, issn = {1932-6203}, mesh = {Animals ; Animals, Newborn ; DNA, Bacterial/classification/*genetics ; Diet ; Feces/microbiology ; Female ; Fruit/chemistry ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/growth & development/microbiology/physiology ; Lemur/growth & development/*microbiology/physiology ; Lemuridae/growth & development/*microbiology/physiology ; Male ; Molecular Sequence Annotation ; Phylogeny ; Plant Leaves/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Species Specificity ; Strepsirhini/growth & development/*microbiology/physiology ; Symbiosis/physiology ; Weaning ; }, abstract = {Host fitness is impacted by trillions of bacteria in the gastrointestinal tract that facilitate development and are inextricably tied to life history. During development, microbial colonization primes the gut metabolism and physiology, thereby setting the stage for adult nutrition and health. However, the ecological rules governing microbial succession are poorly understood. In this study, we examined the relationship between host lineage, captive diet, and life stage and gut microbiota characteristics in three primate species (infraorder, Lemuriformes). Fecal samples were collected from captive lemur mothers and their infants, from birth to weaning. Microbial DNA was extracted and the v4 region of 16S rDNA was sequenced on the Illumina platform using protocols from the Earth Microbiome Project. Here, we show that colonization proceeds along different successional trajectories in developing infants from species with differing dietary regimes and ecological profiles: frugivorous (fruit-eating) Varecia variegata, generalist Lemur catta, and folivorous (leaf-eating) Propithecus coquereli. Our analyses reveal community membership and succession patterns consistent with previous studies of human infants, suggesting that lemurs may serve as a useful model of microbial ecology in the primate gut. Each lemur species exhibits distinct species-specific bacterial diversity signatures correlating to life stages and life history traits, implying that gut microbial community assembly primes developing infants at species-specific rates for their respective adult feeding strategies.}, } @article {pmid25964341, year = {2015}, author = {Franzosa, EA and Huang, K and Meadow, JF and Gevers, D and Lemon, KP and Bohannan, BJ and Huttenhower, C}, title = {Identifying personal microbiomes using metagenomic codes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, number = {22}, pages = {E2930-8}, pmid = {25964341}, issn = {1091-6490}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; P50 GM098911/GM/NIGMS NIH HHS/United States ; HHSN272200900018C//PHS HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; P50GM098911/GM/NIGMS NIH HHS/United States ; }, mesh = {Confidentiality/standards/trends ; Genetic Markers/*genetics ; *Genetic Variation ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; Precision Medicine/*methods ; }, abstract = {Community composition within the human microbiome varies across individuals, but it remains unknown if this variation is sufficient to uniquely identify individuals within large populations or stable enough to identify them over time. We investigated this by developing a hitting set-based coding algorithm and applying it to the Human Microbiome Project population. Our approach defined body site-specific metagenomic codes: sets of microbial taxa or genes prioritized to uniquely and stably identify individuals. Codes capturing strain variation in clade-specific marker genes were able to distinguish among 100s of individuals at an initial sampling time point. In comparisons with follow-up samples collected 30-300 d later, ∼30% of individuals could still be uniquely pinpointed using metagenomic codes from a typical body site; coincidental (false positive) matches were rare. Codes based on the gut microbiome were exceptionally stable and pinpointed >80% of individuals. The failure of a code to match its owner at a later time point was largely explained by the loss of specific microbial strains (at current limits of detection) and was only weakly associated with the length of the sampling interval. In addition to highlighting patterns of temporal variation in the ecology of the human microbiome, this work demonstrates the feasibility of microbiome-based identifiability-a result with important ethical implications for microbiome study design. The datasets and code used in this work are available for download from huttenhower.sph.harvard.edu/idability.}, } @article {pmid25926546, year = {2015}, author = {Ames, SK and Gardner, SN and Marti, JM and Slezak, TR and Gokhale, MB and Allen, JE}, title = {Using populations of human and microbial genomes for organism detection in metagenomes.}, journal = {Genome research}, volume = {25}, number = {7}, pages = {1056-1067}, pmid = {25926546}, issn = {1549-5469}, mesh = {Computational Biology/methods ; Databases, Nucleic Acid ; *Genome, Microbial ; Humans ; *Metagenome ; Metagenomics/*methods ; *Microbiota ; ROC Curve ; }, abstract = {Identifying causative disease agents in human patients from shotgun metagenomic sequencing (SMS) presents a powerful tool to apply when other targeted diagnostics fail. Numerous technical challenges remain, however, before SMS can move beyond the role of research tool. Accurately separating the known and unknown organism content remains difficult, particularly when SMS is applied as a last resort. The true amount of human DNA that remains in a sample after screening against the human reference genome and filtering nonbiological components left from library preparation has previously been underreported. In this study, we create the most comprehensive collection of microbial and reference-free human genetic variation available in a database optimized for efficient metagenomic search by extracting sequences from GenBank and the 1000 Genomes Project. The results reveal new human sequences found in individual Human Microbiome Project (HMP) samples. Individual samples contain up to 95% human sequence, and 4% of the individual HMP samples contain 10% or more human reads. Left unidentified, human reads can complicate and slow down further analysis and lead to inaccurately labeled microbial taxa and ultimately lead to privacy concerns as more human genome data is collected.}, } @article {pmid25888481, year = {2015}, author = {Wang, T and Mori, H and Zhang, C and Kurokawa, K and Xing, XH and Yamada, T}, title = {DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe.}, journal = {BMC bioinformatics}, volume = {16}, number = {}, pages = {96}, pmid = {25888481}, issn = {1471-2105}, mesh = {Databases, Protein ; Enzymes/*chemistry ; Genome, Bacterial ; Humans ; Metagenomics ; Molecular Sequence Annotation/*methods ; Protein Structure, Tertiary ; Sequence Analysis, Protein ; *Software ; }, abstract = {BACKGROUND: Computational predictions of catalytic function are vital for in-depth understanding of enzymes. Because several novel approaches performing better than the common BLAST tool are rarely applied in research, we hypothesized that there is a large gap between the number of known annotated enzymes and the actual number in the protein universe, which significantly limits our ability to extract additional biologically relevant functional information from the available sequencing data. To reliably expand the enzyme space, we developed DomSign, a highly accurate domain signature-based enzyme functional prediction tool to assign Enzyme Commission (EC) digits.

RESULTS: DomSign is a top-down prediction engine that yields results comparable, or superior, to those from many benchmark EC number prediction tools, including BLASTP, when a homolog with an identity >30% is not available in the database. Performance tests showed that DomSign is a highly reliable enzyme EC number annotation tool. After multiple tests, the accuracy is thought to be greater than 90%. Thus, DomSign can be applied to large-scale datasets, with the goal of expanding the enzyme space with high fidelity. Using DomSign, we successfully increased the percentage of EC-tagged enzymes from 12% to 30% in UniProt-TrEMBL. In the Kyoto Encyclopedia of Genes and Genomes bacterial database, the percentage of EC-tagged enzymes for each bacterial genome could be increased from 26.0% to 33.2% on average. Metagenomic mining was also efficient, as exemplified by the application of DomSign to the Human Microbiome Project dataset, recovering nearly one million new EC-labeled enzymes.

CONCLUSIONS: Our results offer preliminarily confirmation of the existence of the hypothesized huge number of "hidden enzymes" in the protein universe, the identification of which could substantially further our understanding of the metabolisms of diverse organisms and also facilitate bioengineering by providing a richer enzyme resource. Furthermore, our results highlight the necessity of using more advanced computational tools than BLAST in protein database annotations to extract additional biologically relevant functional information from the available biological sequences.}, } @article {pmid25883569, year = {2015}, author = {Braundmeier, AG and Lenz, KM and Inman, KS and Chia, N and Jeraldo, P and Walther-António, MR and Berg Miller, ME and Yang, F and Creedon, DJ and Nelson, H and White, BA}, title = {Individualized medicine and the microbiome in reproductive tract.}, journal = {Frontiers in physiology}, volume = {6}, number = {}, pages = {97}, pmid = {25883569}, issn = {1664-042X}, abstract = {Humans have evolved along with the millions of microorganisms that populate their bodies. These microbes (10(14)) outnumber human cells by 10 to 1 and account for 3 × 10(6) genes, more than ten times the 25,000 human genes. This microbial metagenome acts as our "other genome" and like our own genes, is unique to the individual. Recent international efforts such as the Human Microbiome Project (HMP) and the MetaHIT Project have helped catalog these microbial genomes using culture-independent, high-throughput, next-generation sequencing. This manuscript will describe recent efforts to define microbial diversity in the female reproductive tract because of the impact that microbial function has on reproductive efficiency. In this review, we will discuss current evidence that microbial communities are critical for maintaining reproductive health and how perturbations of microbial community structures can impact reproductive health from the aspect of infection, reproductive cyclicity, pregnancy, and disease states. Investigations of the human microbiome are propelling interventional strategies from treating medical populations to treating individual patients. In particular, we highlight how understanding and defining microbial community structures in different disease and physiological states have lead to the discovery of biomarkers and, more importantly, the development and implementation of microbial intervention strategies (probiotics) into modern day medicine. Finally this review will conclude with a literature summary of the effectiveness of microbial intervention strategies that have been implemented in animal and human models of disease and the potential for integrating these microbial intervention strategies into standard clinical practice.}, } @article {pmid25842007, year = {2015}, author = {Imangaliyev, S and Keijser, B and Crielaard, W and Tsivtsivadze, E}, title = {Personalized microbial network inference via co-regularized spectral clustering.}, journal = {Methods (San Diego, Calif.)}, volume = {83}, number = {}, pages = {28-35}, doi = {10.1016/j.ymeth.2015.03.017}, pmid = {25842007}, issn = {1095-9130}, mesh = {Algorithms ; *Cluster Analysis ; Computational Biology/*methods ; Humans ; *Microbial Consortia ; Microbiota/*genetics ; }, abstract = {We use Human Microbiome Project (HMP) cohort (Peterson et al., 2009) to infer personalized oral microbial networks of healthy individuals. To determine clustering of individuals with similar microbial profiles, co-regularized spectral clustering algorithm is applied to the dataset. For each cluster we discovered, we compute co-occurrence relationships among the microbial species that determine microbial network per cluster of individuals. The results of our study suggest that there are several differences in microbial interactions on personalized network level in healthy oral samples acquired from various niches. Based on the results of co-regularized spectral clustering we discover two groups of individuals with different topology of their microbial interaction network. The results of microbial network inference suggest that niche-wise interactions are different in these two groups. Our study shows that healthy individuals have different microbial clusters according to their oral microbiota. Such personalized microbial networks open a better understanding of the microbial ecology of healthy oral cavities and new possibilities for future targeted medication. The scripts written in scientific Python and in Matlab, which were used for network visualization, are provided for download on the website http://learning-machines.com/.}, } @article {pmid25825673, year = {2015}, author = {Weingarden, A and González, A and Vázquez-Baeza, Y and Weiss, S and Humphry, G and Berg-Lyons, D and Knights, D and Unno, T and Bobr, A and Kang, J and Khoruts, A and Knight, R and Sadowsky, MJ}, title = {Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {10}, pmid = {25825673}, issn = {2049-2618}, support = {R21 AI091907/AI/NIAID NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.

RESULTS: Here we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.

CONCLUSIONS: Dynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.}, } @article {pmid25763184, year = {2015}, author = {Ross, MC and Muzny, DM and McCormick, JB and Gibbs, RA and Fisher-Hoch, SP and Petrosino, JF}, title = {16S gut community of the Cameron County Hispanic Cohort.}, journal = {Microbiome}, volume = {3}, number = {}, pages = {7}, pmid = {25763184}, issn = {2049-2618}, support = {P20 MD000170/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Obesity and type 2 diabetes (T2D) are major public health concerns worldwide, and their prevalence has only increased in recent years. Mexican Americans are disproportionately afflicted by obesity and T2D, and rates are even higher in the United States-Mexico border region. To determine the factors associated with the increased risk of T2D, obesity, and other diseases in this population, the Cameron County Hispanic Cohort was established in 2004.

RESULTS: In this study, we characterized the 16S gut community of a subset of 63 subjects from this unique cohort. We found that these communities, when compared to Human Microbiome Project subjects, exhibit community shifts often observed in obese and T2D individuals in published studies. We also examined microbial network relationships between operational taxonomic units (OTUs) in the Cameron County Hispanic Cohort (CCHC) and three additional datasets. We identified a group of seven genera that form a tightly interconnected network present in all four tested datasets, dominated by butyrate producers, which are often increased in obese individuals while being depleted in T2D patients.

CONCLUSIONS: Through a combination of increased disease prevalence and relatively high gut microbial homogeneity in the subset of CCHC members we examined, we believe that the CCHC may represent an ideal community to dissect mechanisms underlying the role of the gut microbiome in human health and disease. The lack of CCHC subject gut community segregation based on all tested metadata suggests that the community structure we observe in the CCHC likely occurs early in life, and endures. This persistent 'disease'-related gut microbial community in CCHC subjects may enhance existing genetic or lifestyle predispositions to the prevalent diseases of the CCHC, leading to increased attack rates of obesity, T2D, non-alcoholic fatty liver disease, and others.}, } @article {pmid25755571, year = {2014}, author = {Shalimar, }, title = {Gut microbiome and liver diseases.}, journal = {Journal of clinical and experimental hepatology}, volume = {4}, number = {3}, pages = {267-268}, pmid = {25755571}, issn = {0973-6883}, abstract = {Nan Qin(1,2), Fengling Yang(1), Ang Li(1), Edi Prifti(3), Yanfei Chen(1), Li Shao(1,2), Jing Guo(1), Emmanuelle Le Chatelier(3), Jian Yao(1,2), Lingjiao Wu(1), Jiawei Zhou(1), Shujun Ni(1), Lin Liu(1), Nicolas Pons(3), Jean Michel Batto(3), Sean P. Kennedy(3), Pierre Leonard(3), Chunhui Yuan(1), Wenchao Ding(1), Yuanting Chen(1), Xinjun Hu(1), Beiwen Zheng(1,2), Guirong Qian(1), Wei Xu(1), S. Dusko Ehrlich(3,4), Shusen Zheng(2,5) and Lanjuan Li(1,2) Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014 Jul 23 [Epub ahead of print]. (1) State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003 Hangzhou, China; (2) Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, 310003 Hangzhou, China; (3) Metagenopolis, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France; (4) King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London Bridge, London SE1 9RT, UK; (5) Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University, 310003 Hangzhou, China.}, } @article {pmid25741335, year = {2015}, author = {Wagner Mackenzie, B and Waite, DW and Taylor, MW}, title = {Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.}, journal = {Frontiers in microbiology}, volume = {6}, number = {}, pages = {130}, pmid = {25741335}, issn = {1664-302X}, abstract = {The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.}, } @article {pmid25729898, year = {2015}, author = {Ramos, T and Dedesko, S and Siegel, JA and Gilbert, JA and Stephens, B}, title = {Spatial and temporal variations in indoor environmental conditions, human occupancy, and operational characteristics in a new hospital building.}, journal = {PloS one}, volume = {10}, number = {3}, pages = {e0118207}, pmid = {25729898}, issn = {1932-6203}, mesh = {Air Pollution, Indoor/prevention & control ; Carbon Dioxide/analysis ; Environmental Microbiology ; *Environmental Monitoring ; Hospitals/*standards ; Humans ; Humidity ; Temperature ; Ventilation ; }, abstract = {The dynamics of indoor environmental conditions, human occupancy, and operational characteristics of buildings influence human comfort and indoor environmental quality, including the survival and progression of microbial communities. A suite of continuous, long-term environmental and operational parameters were measured in ten patient rooms and two nurse stations in a new hospital building in Chicago, IL to characterize the indoor environment in which microbial samples were taken for the Hospital Microbiome Project. Measurements included environmental conditions (indoor dry-bulb temperature, relative humidity, humidity ratio, and illuminance) in the patient rooms and nurse stations; differential pressure between the patient rooms and hallways; surrogate measures for human occupancy and activity in the patient rooms using both indoor air CO2 concentrations and infrared doorway beam-break counters; and outdoor air fractions in the heating, ventilating, and air-conditioning systems serving the sampled spaces. Measurements were made at 5-minute intervals over consecutive days for nearly one year, providing a total of ∼8×106 data points. Indoor temperature, illuminance, and human occupancy/activity were all weakly correlated between rooms, while relative humidity, humidity ratio, and outdoor air fractions showed strong temporal (seasonal) patterns and strong spatial correlations between rooms. Differential pressure measurements confirmed that all patient rooms were operated at neutral pressure. The patient rooms averaged about 100 combined entrances and exits per day, which suggests they were relatively lightly occupied compared to higher traffic environments (e.g., retail buildings) and more similar to lower traffic office environments. There were also clear differences in several environmental parameters before and after the hospital was occupied with patients and staff. Characterizing and understanding factors that influence these building dynamics is vital for hospital environments, where they can impact patient health and the survival and spread of healthcare associated infections.}, } @article {pmid25702727, year = {2015}, author = {Walker, B and Kassim, K and Stokes, LD}, title = {The microbiome: a contributor to health and disease.}, journal = {Journal of health care for the poor and underserved}, volume = {26}, number = {1}, pages = {62-72}, doi = {10.1353/hpu.2015.0025}, pmid = {25702727}, issn = {1548-6869}, mesh = {Cardiovascular Diseases/microbiology ; Human Genome Project ; Humans ; Intestines/microbiology ; Irritable Bowel Syndrome/microbiology ; *Metagenome ; *Microbiota ; Neoplasms/microbiology ; Obesity/microbiology ; Renal Insufficiency, Chronic/microbiology ; }, abstract = {As the 21st century unfolds there is substantial evidence that biological research is experiencing extraordinary scientific and technological advances. Prominent among these advances are the completion of the Human Genome Project, which laid the foundation for the second advance, the Human Microbiome Project. Emerging from these advances are two overarching conclusions: a) genomics is no longer the sole domain of the geneticist, and b) we each are hosts to trillions of microorganisms. Genomics and other technologies have enhanced efforts to characterize the structure, composition, and functions of the microbiome. This characterization has fueled progress in understanding the role of the microbiome in health and disease. In this review, we highlight developments that have helped illuminate the microbiome-health connection. This information can improve an understanding of connections and relationships among multiple factors (or determinants) of health.}, } @article {pmid25695334, year = {2015}, author = {Youmans, BP and Ajami, NJ and Jiang, ZD and Campbell, F and Wadsworth, WD and Petrosino, JF and DuPont, HL and Highlander, SK}, title = {Characterization of the human gut microbiome during travelers' diarrhea.}, journal = {Gut microbes}, volume = {6}, number = {2}, pages = {110-119}, pmid = {25695334}, issn = {1949-0984}, support = {F31 DK094596/DK/NIDDK NIH HHS/United States ; R21DK099573/DK/NIDDK NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; 2T32CA096520/CA/NCI NIH HHS/United States ; F31DK094596/DK/NIDDK NIH HHS/United States ; R25GM056929/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Caliciviridae Infections/*microbiology ; Diarrhea/*microbiology ; *Dysbiosis ; Escherichia coli Infections/*microbiology ; *Gastrointestinal Microbiome ; Humans ; *Travel ; }, abstract = {Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.}, } @article {pmid25671105, year = {2014}, author = {Hanshew, AS and Jetté, ME and Thibeault, SL}, title = {Characterization and comparison of bacterial communities in benign vocal fold lesions.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {43}, pmid = {25671105}, issn = {2049-2618}, support = {R01 DC009600/DC/NIDCD NIH HHS/United States ; T32 DC009401/DC/NIDCD NIH HHS/United States ; }, abstract = {BACKGROUND: Benign vocal fold lesions, including cysts, nodules, polyps, and Reinke's edema, are common causes of hoarseness and subsequent voice disorders. Given the prevalence of these lesions, disease etiology and pathophysiology remain unclear and their microbiota has not been studied to date secondary to the paucity of available biopsies for investigation. We sought to characterize and compare the bacterial communities in biopsies of cysts, nodules, polyps, and Reinke's edema collected from patients in Germany and Wisconsin. These samples were then compared to the communities found in healthy saliva and throat samples from the Human Microbiome Project (HMP).

RESULTS: 454 pyrosequencing of the V3-V5 regions of the 16S rRNA gene revealed five phyla that explained most of the bacterial diversity, including Firmicutes (73.8%), Proteobacteria (12.7%), Bacteroidetes (9.2%), Actinobacteria (2.1%), and Fusobacteria (1.9%). Every lesion sample, regardless of diagnosis, had operational taxonomic units (OTUs) identified as Streptococcus, with a mean abundance of 68.7%. Most of the lesions, 31 out of 44, were indistinguishable in a principal coordinates analysis (PCoA) due to dominance by OTUs phylogenetically similar to Streptococcus pseudopneumoniae. Thirteen lesions not dominated by S. pseudopneumoniae were more similar to HMP throat and saliva samples, though 12 of them contained Pseudomonas, which was not present in any of the HMP samples. Community structure and abundance could not be correlated with lesion diagnosis or any other documented patient factor, including age, sex, or country of origin.

CONCLUSIONS: Dominance by S. pseudopneumoniae could be a factor in disease etiology, as could the presence of Pseudomonas in some samples. Likewise, decreased diversity, as compared to healthy saliva and throat samples, may be associated with disease, similar to disease models in other mucosal sites.}, } @article {pmid25653214, year = {2015}, author = {Mao, B and Li, D and Zhao, J and Liu, X and Gu, Z and Chen, YQ and Zhang, H and Chen, W}, title = {In vitro fermentation of fructooligosaccharides with human gut bacteria.}, journal = {Food & function}, volume = {6}, number = {3}, pages = {947-954}, doi = {10.1039/c4fo01082e}, pmid = {25653214}, issn = {2042-650X}, mesh = {Adult ; Bacterial Proteins/chemistry/genetics/metabolism ; Carrier Proteins/chemistry/genetics/metabolism ; China ; Clostridiales/classification/growth & development/isolation & purification/metabolism ; Cronobacter sakazakii/classification/growth & development/isolation & purification/metabolism ; Databases, Genetic ; Feces/microbiology ; Fermentation ; *Gastrointestinal Microbiome ; Glycoside Hydrolases/chemistry/genetics/metabolism ; Humans ; *Models, Biological ; Molecular Typing ; Oligosaccharides/adverse effects/*metabolism ; Open Reading Frames ; *Prebiotics/adverse effects ; Ruminococcus/classification/growth & development/isolation & purification/metabolism ; Sequence Alignment ; Weissella/classification/growth & development/isolation & purification/metabolism ; }, abstract = {Fructooligosaccharides (FOS) are one of the most studied prebiotics, selectively stimulating the growth of health-promoting bacteria in the host. However, there is increasing evidence that commensal gut bacteria, such as Bacteroides fragilis, Clostridium butyricum, Enterobacter cloacae, and even the pathogenic Escherichia coli BEN2908, are also able to metabolize FOS in vitro, and in some cases, FOS displayed adverse effects. Therefore, it is necessary to identify FOS-metabolizing species that are present in the gut. Unlike previous studies focusing on individual strains, this study used the traditional culture method combined with an alignment search on the gut bacteria database established from the Human Microbiome Project (HMP). The alignment results showed that homologous proteins for FOS transporters and glycosidases were distributed in 237 of the 453 strains of gut bacteria. La506 msmK encoding the ATP-binding protein and Aec45 fosGH1 encoding glycoside hydrolase were most widely distributed, in 155 and 55 strains, respectively. Seven of eight strains with both transporters and glycosidases were proven to be capable of metabolizing FOS, while five strains without either transporters or glycosidases were not. Fifteen species isolated from human feces and 11 species from the alignment search were identified to be FOS-metabolizing, of which Cronobacter sakazakii, Marvinbryantia formatexigens, Ruminococcus gnavus, and Weissella paramesenteroides are reported here for the first time. Thus, alignment search combined with the culture method is an effective method for obtaining a global view of the FOS-metabolizing bacteria in the gut and will be helpful in further investigating the relationship between FOS and human gut bacteria.}, } @article {pmid25621279, year = {2014}, author = {Thompson, JR and Rivera, HE and Closek, CJ and Medina, M}, title = {Microbes in the coral holobiont: partners through evolution, development, and ecological interactions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {4}, number = {}, pages = {176}, pmid = {25621279}, issn = {2235-2988}, mesh = {Animals ; Anthozoa/genetics/*microbiology ; Bacteria/classification/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; *Ecosystem ; Symbiosis ; }, abstract = {In the last two decades, genetic and genomic studies have revealed the astonishing diversity and ubiquity of microorganisms. Emergence and expansion of the human microbiome project has reshaped our thinking about how microbes control host health-not only as pathogens, but also as symbionts. In coral reef environments, scientists have begun to examine the role that microorganisms play in coral life history. Herein, we review the current literature on coral-microbe interactions within the context of their role in evolution, development, and ecology. We ask the following questions, first posed by McFall-Ngai et al. (2013) in their review of animal evolution, with specific attention to how coral-microbial interactions may be affected under future environmental conditions: (1) How do corals and their microbiome affect each other's genomes? (2) How does coral development depend on microbial partners? (3) How is homeostasis maintained between corals and their microbial symbionts? (4) How can ecological approaches deepen our understanding of the multiple levels of coral-microbial interactions? Elucidating the role that microorganisms play in the structure and function of the holobiont is essential for understanding how corals maintain homeostasis and acclimate to changing environmental conditions.}, } @article {pmid25577384, year = {2015}, author = {Bruno, F and Marinella, M and Santamaria, M}, title = {e-DNA meta-barcoding: from NGS raw data to taxonomic profiling.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {1269}, number = {}, pages = {257-278}, doi = {10.1007/978-1-4939-2291-8_16}, pmid = {25577384}, issn = {1940-6029}, mesh = {Animals ; Computational Biology/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {In recent years, thanks to the essential support provided by the Next-Generation Sequencing (NGS) technologies, Metagenomics is enabling the direct access to the taxonomic and functional composition of mixed microbial communities living in any environmental niche, without the prerequisite to isolate or culture the single organisms. This approach has already been successfully applied for the analysis of many habitats, such as water or soil natural environments, also characterized by extreme physical and chemical conditions, food supply chains, and animal organisms, including humans. A shotgun sequencing approach can lead to investigate both organisms and genes diversity. Anyway, if the purpose is limited to explore the taxonomic complexity, an amplicon-based approach, based on PCR-targeted sequencing of selected genetic species markers, commonly named "meta-barcodes", is desirable. Among the genomic regions most widely used for the discrimination of bacterial organisms, in some cases up to the species level, some hypervariable domains of the gene coding for the 16S rRNA occupy a prominent place. The amplification of a certain meta-barcode from a microbial community through the use of PCR primers able to work in the entire considered taxonomic group is the first task after the extraction of the total DNA. Generally, this step is followed by the high-throughput sequencing of the resulting amplicons libraries by means of a selected NGS platform. Finally, the interpretation of the huge amount of produced data requires appropriate bioinformatics tools and know-how in addition to efficient computational resources. Here a computational methodology suitable for the taxonomic characterization of 454 meta-barcode sequences is described in detail. In particular, a dataset covering the V1-V3 region belonging to the bacterial 16S rRNA coding gene and produced in the Human Microbiome Project (HMP) from a palatine tonsils sample is analyzed. The proposed exercise includes the basic steps to manage raw sequencing data, remove amplification and pyrosequencing errors, and finally map sequences on the taxonomy.}, } @article {pmid25557805, year = {2015}, author = {Starr, M}, title = {Paediatric infectious diseases: the last 50 years.}, journal = {Journal of paediatrics and child health}, volume = {51}, number = {1}, pages = {12-15}, doi = {10.1111/jpc.12795}, pmid = {25557805}, issn = {1440-1754}, mesh = {Anti-Bacterial Agents/therapeutic use ; Australia ; Child ; Communicable Disease Control/*history ; Communicable Diseases/diagnosis/drug therapy/epidemiology/*history ; Drug Resistance, Bacterial ; Global Health ; History, 20th Century ; History, 21st Century ; Humans ; Pediatrics/*history ; }, abstract = {Many advances and challenges have occurred in the field of paediatric infectious diseases during the past 50 years. It is impossible to cover all of these in a short review, but a few highlights and lowlights will be covered. These include virtual disappearance of some infectious diseases, emergence of new ones, infections in the immunocompromised, antimicrobial resistance, development of new and improved antimicrobials, improved diagnostic tests and the Human Microbiome Project.}, } @article {pmid36119463, year = {2015}, author = {Darling, KW and Boyce, AM and Cho, MK and Sankar, PL}, title = {"What is the FDA Going to Think?": Negotiating Values through Reflective and Strategic Category Work in Microbiome Science.}, journal = {Science, technology & human values}, volume = {40}, number = {1}, pages = {71-95}, pmid = {36119463}, issn = {0162-2439}, support = {P50 HG003389/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; }, abstract = {The US National Institute of Health's Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable from the reflective and strategic category work (i.e., the work of anticipating and strategizing around divergent sets of institutional categories) that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated "values levers" and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research.}, } @article {pmid25544325, year = {2014}, author = {Schneider, GW and Winslow, R}, title = {Parts and wholes: the human microbiome, ecological ontology, and the challenges of community.}, journal = {Perspectives in biology and medicine}, volume = {57}, number = {2}, pages = {208-223}, doi = {10.1353/pbm.2014.0016}, pmid = {25544325}, issn = {1529-8795}, mesh = {Ethics, Research ; Humans ; *Metagenome ; *Microbiota ; National Institutes of Health (U.S.) ; Politics ; United States ; }, abstract = {The early results of the Human Microbiome Project, released in June 2012, add to the overwhelming data that show that there are literally trillions of microbes that live in and on each human individual. This research raises profound questions about what it means to be an individual organism, human or otherwise. In this paper, we ask two broad questions: (1) how might we conceive of an individual organism, given these results? and (2) in light of this emerging conception of the individual organism, what are the implications for how humans conceive of their own self-sufficiency and interact with other members of the living world? We highlight the ontological and political presuppositions animating this research and return to Aristotle for insights into how to conceive of and how to behave towards and within a diverse community of interdependent living parts that function together as one.}, } @article {pmid25517115, year = {2014}, author = {Labbé, A and Ganopolsky, JG and Martoni, CJ and Prakash, S and Jones, ML}, title = {Bacterial bile metabolising gene abundance in Crohn's, ulcerative colitis and type 2 diabetes metagenomes.}, journal = {PloS one}, volume = {9}, number = {12}, pages = {e115175}, pmid = {25517115}, issn = {1932-6203}, mesh = {Amidohydrolases/genetics ; Animals ; Bacteria/enzymology ; Bile Acids and Salts/*metabolism ; Colitis, Ulcerative/*enzymology/genetics/microbiology ; Crohn Disease/*enzymology/genetics/microbiology ; Databases, Factual ; Diabetes Mellitus, Type 2/*enzymology/genetics/microbiology ; Feces/enzymology/microbiology ; Gastrointestinal Tract/*enzymology/microbiology ; Genes, Bacterial/*genetics ; Humans ; Hydroxysteroid Dehydrogenases/genetics ; *Metagenome ; Metagenomics ; Mice ; Microbiota ; Phylogeny ; }, abstract = {We performed an analysis to determine the importance of bile acid modification genes in the gut microbiome of inflammatory bowel disease and type 2 diabetic patients. We used publicly available metagenomic datasets from the Human Microbiome Project and the MetaHIT consortium, and determined the abundance of bile salt hydrolase gene (bsh), 7 alpha-dehydroxylase gene (adh) and 7-alpha hydroxysteroid dehydrogenase gene (hsdh) in fecal bacteria in diseased populations of Crohn's disease (CD), Ulcerative Colitis (UC) and Type 2 diabetes mellitus (T2DM). Phylum level abundance analysis showed a significant reduction in Firmicute-derived bsh in UC and T2DM patients but not in CD patients, relative to healthy controls. Reduction of adh and hsdh genes was also seen in UC and T2DM patients, while an increase was observed in the CD population as compared to healthy controls. A further analysis of the bsh genes showed significant differences in the correlations of certain Firmicutes families with disease or healthy populations. From this observation we proceeded to analyse BSH protein sequences and identified BSH proteins clusters representing the most abundant strains in our analysis of Firmicute bsh genes. The abundance of the bsh genes corresponding to one of these protein clusters was significantly reduced in all disease states relative to healthy controls. This cluster includes bsh genes derived from Lachospiraceae, Clostridiaceae, Erysipelotrichaceae and Ruminococcaceae families. This metagenomic analysis provides evidence of the importance of bile acid modifying enzymes in health and disease. It further highlights the importance of identifying gene and protein clusters, as the same gene may be associated with health or disease, depending on the strains expressing the enzyme, and differences in the enzymes themselves.}, } @article {pmid25484919, year = {2014}, author = {Zhou, Y and Holland, MJ and Makalo, P and Joof, H and Roberts, CH and Mabey, DC and Bailey, RL and Burton, MJ and Weinstock, GM and Burr, SE}, title = {The conjunctival microbiome in health and trachomatous disease: a case control study.}, journal = {Genome medicine}, volume = {6}, number = {11}, pages = {99}, pmid = {25484919}, issn = {1756-994X}, support = {/WT_/Wellcome Trust/United Kingdom ; U54 HG004968/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection.

METHODS: We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project.

RESULTS: The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only.

CONCLUSIONS: Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown.}, } @article {pmid25484632, year = {2014}, author = {Huss, J}, title = {Methodology and Ontology in Microbiome Research.}, journal = {Biological theory}, volume = {9}, number = {4}, pages = {392-400}, pmid = {25484632}, issn = {1555-5542}, support = {P50 HG003390/HG/NHGRI NIH HHS/United States ; R03 HG006029/HG/NHGRI NIH HHS/United States ; }, abstract = {Research on the human microbiome has generated a staggering amount of sequence data, revealing variation in microbial diversity at the community, species (or phylotype), and genomic levels. In order to make this complexity more manageable and easier to interpret, new units-the metagenome, core microbiome, and enterotype-have been introduced in the scientific literature. Here, I argue that analytical tools and exploratory statistical methods, coupled with a translational imperative, are the primary drivers of this new ontology. By reducing the dimensionality of variation in the human microbiome, these new units render it more tractable and easier to interpret, and hence serve an important heuristic role. Nonetheless, there are several reasons to be cautious about these new categories prematurely "hardening" into natural units: a lack of constraints on what can be sequenced metagenomically, freedom of choice in taxonomic level in defining a "core microbiome," typological framing of some of the concepts, and possible reification of statistical constructs. Finally, lessons from the Human Genome Project have led to a translational imperative: a drive to derive results from the exploration of microbiome variation that can help to articulate the emerging paradigm of personalized genomic medicine (PGM). There is a tension between the typologizing inherent in much of this research and the personal in PGM.}, } @article {pmid25452698, year = {2014}, author = {Isokpehi, RD and Udensi, UK and Simmons, SS and Hollman, AL and Cain, AE and Olofinsae, SA and Hassan, OA and Kashim, ZA and Enejoh, OA and Fasesan, DE and Nashiru, O}, title = {Evaluative profiling of arsenic sensing and regulatory systems in the human microbiome project genomes.}, journal = {Microbiology insights}, volume = {7}, number = {}, pages = {25-34}, pmid = {25452698}, issn = {1178-6361}, support = {G12 MD007581/MD/NIMHD NIH HHS/United States ; P20 MD006899/MD/NIMHD NIH HHS/United States ; T36 GM095335/GM/NIGMS NIH HHS/United States ; U41 HG006941/HG/NHGRI NIH HHS/United States ; }, abstract = {The influence of environmental chemicals including arsenic, a type 1 carcinogen, on the composition and function of the human-associated microbiota is of significance in human health and disease. We have developed a suite of bioinformatics and visual analytics methods to evaluate the availability (presence or absence) and abundance of functional annotations in a microbial genome for seven Pfam protein families: As(III)-responsive transcriptional repressor (ArsR), anion-transporting ATPase (ArsA), arsenical pump membrane protein (ArsB), arsenate reductase (ArsC), arsenical resistance operon transacting repressor (ArsD), water/glycerol transport protein (aquaporins), and universal stress protein (USP). These genes encode function for sensing and/or regulating arsenic content in the bacterial cell. The evaluative profiling strategy was applied to 3,274 genomes from which 62 genomes from 18 genera were identified to contain genes for the seven protein families. Our list included 12 genomes in the Human Microbiome Project (HMP) from the following genera: Citrobacter, Escherichia, Lactobacillus, Providencia, Rhodococcus, and Staphylococcus. Gene neighborhood analysis of the arsenic resistance operon in the genome of Bacteroides thetaiotaomicron VPI-5482, a human gut symbiont, revealed the adjacent arrangement of genes for arsenite binding/transfer (ArsD) and cytochrome c biosynthesis (DsbD_2). Visual analytics facilitated evaluation of protein annotations in 367 genomes in the phylum Bacteroidetes identified multiple genomes in which genes for ArsD and DsbD_2 were adjacently arranged. Cytochrome c, produced by a posttranslational process, consists of heme-containing proteins important for cellular energy production and signaling. Further research is desired to elucidate arsenic resistance and arsenic-mediated cellular energy production in the Bacteroidetes.}, } @article {pmid25426106, year = {2014}, author = {Mark Welch, JL and Utter, DR and Rossetti, BJ and Mark Welch, DB and Eren, AM and Borisy, GG}, title = {Dynamics of tongue microbial communities with single-nucleotide resolution using oligotyping.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {568}, pmid = {25426106}, issn = {1664-302X}, support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; }, abstract = {The human mouth is an excellent system to study the dynamics of microbial communities and their interactions with their host. We employed oligotyping to analyze, with single-nucleotide resolution, oral microbial 16S ribosomal RNA (rRNA) gene sequence data from a time course sampled from the tongue of two individuals, and we interpret our results in the context of oligotypes that we previously identified in the oral data from the Human Microbiome Project. Our previous work established that many of these oligotypes had dramatically different distributions between individuals and across oral habitats, suggesting that they represented functionally different organisms. Here we demonstrate the presence of a consistent tongue microbiome but with rapidly fluctuating proportions of the characteristic taxa. In some cases closely related oligotypes representing strains or variants within a single species displayed fluctuating relative abundances over time, while in other cases an initially dominant oligotype was replaced by another oligotype of the same species. We use this high temporal and taxonomic level of resolution to detect correlated changes in oligotype abundance that could indicate which taxa likely interact synergistically or occupy similar habitats, and which likely interact antagonistically or prefer distinct habitats. For example, we found a strong correlation in abundance over time between two oligotypes from different families of Gamma Proteobacteria, suggesting a close functional or ecological relationship between them. In summary, the tongue is colonized by a microbial community of moderate complexity whose proportional abundance fluctuates widely on time scales of days. The drivers and functional consequences of these community dynamics are not known, but we expect they will prove tractable to future, targeted studies employing taxonomically resolved analysis of high-throughput sequencing data sampled at appropriate temporal intervals and spatial scales.}, } @article {pmid25368606, year = {2014}, author = {Easson, CG and Thacker, RW}, title = {Phylogenetic signal in the community structure of host-specific microbiomes of tropical marine sponges.}, journal = {Frontiers in microbiology}, volume = {5}, number = {}, pages = {532}, pmid = {25368606}, issn = {1664-302X}, abstract = {Sponges (Porifera) can host diverse and abundant communities of microbial symbionts that make crucial contributions to host metabolism. Although these communities are often host-specific and hypothesized to co-evolve with their hosts, correlations between host phylogeny and microbiome community structure are rarely tested. As part of the Earth Microbiome Project (EMP), we surveyed the microbiomes associated with 20 species of tropical marine sponges collected over a narrow geographic range. We tested whether (1) univariate metrics of microbiome diversity displayed significant phylogenetic signal across the host phylogeny; (2) host identity and host phylogeny were significant factors in multivariate analyses of taxonomic and phylogenetic dissimilarity; and (3) different minimum read thresholds impacted these results. We observed significant differences in univariate metrics of diversity among host species for all read thresholds, with strong phylogenetic signal in the inverse Simpson's index of diversity (D). We observed a surprisingly wide range of variability in community dissimilarity within host species (4-73%); this variability was not related to microbial abundance within a host species. Taxonomic and phylogenetic dissimilarity were significantly impacted by host identity and host phylogeny when these factors were considered individually; when tested together, the effect of host phylogeny was reduced, but remained significant. In our dataset, this outcome is largely due to closely related host sponges harboring distinct microbial taxa. Host identity maintained a strong statistical signal at all minimum read thresholds. Although the identity of specific microbial taxa varied substantially among host sponges, closely related hosts tended to harbor microbial communities with similar patterns of relative abundance. We hypothesize that microbiomes with low D might be structured by regulation of the microbial community by the host or by the presence of competitively dominant symbionts that are themselves under selection for host specificity.}, } @article {pmid25303278, year = {2015}, author = {Sherman, MP and Zaghouani, H and Niklas, V}, title = {Gut microbiota, the immune system, and diet influence the neonatal gut-brain axis.}, journal = {Pediatric research}, volume = {77}, number = {1-2}, pages = {127-135}, doi = {10.1038/pr.2014.161}, pmid = {25303278}, issn = {1530-0447}, mesh = {Brain/*physiology ; Dysbiosis/microbiology ; Enterocolitis, Necrotizing/microbiology ; Gastrointestinal Tract/*microbiology/*physiology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology ; Infant, Very Low Birth Weight ; Microbiota/*physiology ; *Models, Biological ; Sepsis/microbiology ; Signal Transduction/*physiology ; }, abstract = {The conceptual framework for a gut-brain axis has existed for decades. The Human Microbiome Project is responsible for establishing intestinal dysbiosis as a mediator of inflammatory bowel disease, obesity, and neurodevelopmental disorders in adults. Recent advances in metagenomics implicate gut microbiota and diet as key modulators of the bidirectional signaling pathways between the gut and brain that underlie neurodevelopmental and psychiatric disorders in adults. Evidence linking intestinal dysbiosis to neurodevelopmental disease outcomes in preterm infants is emerging. Recent clinical studies show that intestinal dysbiosis precedes late-onset neonatal sepsis and necrotizing enterocolitis in intensive care nurseries. Moreover, strong epidemiologic evidence links late-onset neonatal sepsis and necrotizing enterocolitis in long-term psychomotor disabilities of very-low-birth-weight infants. The notion of the gut-brain axis thereby supports that intestinal microbiota can indirectly harm the brain of preterm infants. In this review, we highlight the anatomy and physiology of the gut-brain axis and describe transmission of stress signals caused by immune-microbial dysfunction in the gut. These messengers initiate neurologic disease in preterm infants. Understanding neural and humoral signaling through the gut-brain axis will offer insight into therapeutic and dietary approaches that may improve the outcomes of very-low-birth-weight infants.}, } @article {pmid25291122, year = {2014}, author = {Robles-Alonso, V and Guarner, F}, title = {From basic to applied research: lessons from the human microbiome projects.}, journal = {Journal of clinical gastroenterology}, volume = {48 Suppl 1}, number = {}, pages = {S3-4}, doi = {10.1097/MCG.0000000000000242}, pmid = {25291122}, issn = {1539-2031}, mesh = {Bacteria/*classification/genetics ; DNA, Bacterial/genetics ; Dysbiosis ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Metagenome ; Metagenomics/methods ; *Microbiota ; Ribotyping ; }, abstract = {Two large-scale initiatives of major funding agencies aimed at deciphering the structure and function of the human gut microbiota, namely the NIH's Human Microbiome project and the European MetaHIT project, finalized their research program in 2012.}, } @article {pmid25263219, year = {2014}, author = {Williams, BB and Van Benschoten, AH and Cimermancic, P and Donia, MS and Zimmermann, M and Taketani, M and Ishihara, A and Kashyap, PC and Fraser, JS and Fischbach, MA}, title = {Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.}, journal = {Cell host & microbe}, volume = {16}, number = {4}, pages = {495-503}, pmid = {25263219}, issn = {1934-6069}, support = {DP2 OD007290/OD/NIH HHS/United States ; GM081879/GM/NIGMS NIH HHS/United States ; T32 EB009383/EB/NIBIB NIH HHS/United States ; K08 DK100638/DK/NIDDK NIH HHS/United States ; OD009180/OD/NIH HHS/United States ; DP5 OD009180/OD/NIH HHS/United States ; K08DK100638/DK/NIDDK NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; OD007290/OD/NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacteria/enzymology/genetics ; Biotransformation ; Carboxy-Lyases/chemistry/*genetics/metabolism ; Crystallography, X-Ray ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; *Microbiota ; Models, Molecular ; Molecular Sequence Data ; Neurotransmitter Agents/*metabolism ; Phylogeny ; Protein Conformation ; Sequence Homology ; Tryptamines/*metabolism ; Tryptophan/metabolism ; }, abstract = {Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.}, } @article {pmid25257543, year = {2014}, author = {Rubin, BE and Sanders, JG and Hampton-Marcell, J and Owens, SM and Gilbert, JA and Moreau, CS}, title = {DNA extraction protocols cause differences in 16S rRNA amplicon sequencing efficiency but not in community profile composition or structure.}, journal = {MicrobiologyOpen}, volume = {3}, number = {6}, pages = {910-921}, pmid = {25257543}, issn = {2045-8827}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Ants/*microbiology ; Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; DNA, Bacterial/*genetics/*isolation & purification ; High-Throughput Nucleotide Sequencing ; Microbiota ; RNA, Ribosomal, 16S/*genetics/isolation & purification ; }, abstract = {The recent development of methods applying next-generation sequencing to microbial community characterization has led to the proliferation of these studies in a wide variety of sample types. Yet, variation in the physical properties of environmental samples demands that optimal DNA extraction techniques be explored for each new environment. The microbiota associated with many species of insects offer an extraction challenge as they are frequently surrounded by an armored exoskeleton, inhibiting disruption of the tissues within. In this study, we examine the efficacy of several commonly used protocols for extracting bacterial DNA from ants. While bacterial community composition recovered using Illumina 16S rRNA amplicon sequencing was not detectably biased by any method, the quantity of bacterial DNA varied drastically, reducing the number of samples that could be amplified and sequenced. These results indicate that the concentration necessary for dependable sequencing is around 10,000 copies of target DNA per microliter. Exoskeletal pulverization and tissue digestion increased the reliability of extractions, suggesting that these steps should be included in any study of insect-associated microorganisms that relies on obtaining microbial DNA from intact body segments. Although laboratory and analysis techniques should be standardized across diverse sample types as much as possible, minimal modifications such as these will increase the number of environments in which bacterial communities can be successfully studied.}, } @article {pmid25228989, year = {2014}, author = {Hang, J and Desai, V and Zavaljevski, N and Yang, Y and Lin, X and Satya, RV and Martinez, LJ and Blaylock, JM and Jarman, RG and Thomas, SJ and Kuschner, RA}, title = {16S rRNA gene pyrosequencing of reference and clinical samples and investigation of the temperature stability of microbiome profiles.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {31}, pmid = {25228989}, issn = {2049-2618}, abstract = {BACKGROUND: Sample storage conditions, extraction methods, PCR primers, and parameters are major factors that affect metagenomics analysis based on microbial 16S rRNA gene sequencing. Most published studies were limited to the comparison of only one or two types of these factors. Systematic multi-factor explorations are needed to evaluate the conditions that may impact validity of a microbiome analysis. This study was aimed to improve methodological options to facilitate the best technical approaches in the design of a microbiome study. Three readily available mock bacterial community materials and two commercial extraction techniques, Qiagen DNeasy and MO BIO PowerSoil DNA purification methods, were used to assess procedures for 16S ribosomal DNA amplification and pyrosequencing-based analysis. Primers were chosen for 16S rDNA quantitative PCR and amplification of region V3 to V1. Swabs spiked with mock bacterial community cells and clinical oropharyngeal swabs were incubated at respective temperatures of -80°C, -20°C, 4°C, and 37°C for 4 weeks, then extracted with the two methods, and subjected to pyrosequencing and taxonomic and statistical analyses to investigate microbiome profile stability.

RESULTS: The bacterial compositions for the mock community DNA samples determined in this study were consistent with the projected levels and agreed with the literature. The quantitation accuracy of abundances for several genera was improved with changes made to the standard Human Microbiome Project (HMP) procedure. The data for the samples purified with DNeasy and PowerSoil methods were statistically distinct; however, both results were reproducible and in good agreement with each other. The temperature effect on storage stability was investigated by using mock community cells and showed that the microbial community profiles were altered with the increase in incubation temperature. However, this phenomenon was not detected when clinical oropharyngeal swabs were used in the experiment.

CONCLUSIONS: Mock community materials originated from the HMP study are valuable controls in developing 16S metagenomics analysis procedures. Long-term exposure to a high temperature may introduce variation into analysis for oropharyngeal swabs, suggestive of storage at 4°C or lower. The observed variations due to sample storage temperature are in a similar range as the intrapersonal variability among different clinical oropharyngeal swab samples.}, } @article {pmid25215495, year = {2014}, author = {Donia, MS and Cimermancic, P and Schulze, CJ and Wieland Brown, LC and Martin, J and Mitreva, M and Clardy, J and Linington, RG and Fischbach, MA}, title = {A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.}, journal = {Cell}, volume = {158}, number = {6}, pages = {1402-1414}, pmid = {25215495}, issn = {1097-4172}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; DP2 OD007290/OD/NIH HHS/United States ; R01 DK101674/DK/NIDDK NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; R21 AI101722/AI/NIAID NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; U01 TW006634/TW/FIC NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacteria/*chemistry/classification/*genetics/metabolism ; Biosynthetic Pathways ; Gastrointestinal Tract/microbiology ; Humans ; Metagenomics/*methods ; *Microbiota ; Molecular Sequence Data ; Mouth/microbiology ; Multigene Family ; Peptide Biosynthesis, Nucleic Acid-Independent ; Polyketides/analysis ; }, abstract = {In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:}, } @article {pmid25212266, year = {2014}, author = {Wylie, KM and Mihindukulasuriya, KA and Zhou, Y and Sodergren, E and Storch, GA and Weinstock, GM}, title = {Metagenomic analysis of double-stranded DNA viruses in healthy adults.}, journal = {BMC biology}, volume = {12}, number = {}, pages = {71}, pmid = {25212266}, issn = {1741-7007}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; DNA Viruses/classification/*genetics/isolation & purification ; DNA, Viral/*analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Metagenome ; Missouri ; Sequence Analysis, DNA ; Texas ; Young Adult ; }, abstract = {BACKGROUND: The Human Microbiome Project (HMP) was undertaken with the goal of defining microbial communities in and on the bodies of healthy individuals using high-throughput, metagenomic sequencing analysis. The viruses present in these microbial communities, the 'human virome', are an important aspect of the human microbiome that is particularly understudied in the absence of overt disease. We analyzed eukaryotic double-stranded DNA (dsDNA) viruses, together with dsDNA replicative intermediates of single-stranded DNA viruses, in metagenomic sequence data generated by the HMP. 706 samples from 102 subjects were studied, with each subject sampled at up to five major body habitats: nose, skin, mouth, vagina, and stool. Fifty-one individuals had samples taken at two or three time points 30 to 359 days apart from at least one of the body habitats.

RESULTS: We detected an average of 5.5 viral genera in each individual. At least 1 virus was detected in 92% of the individuals sampled. These viruses included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and circoviruses. Each individual had a distinct viral profile, demonstrating the high interpersonal diversity of the virome. Some components of the virome were stable over time.

CONCLUSIONS: This study is the first to use high-throughput DNA sequencing to describe the diversity of eukaryotic dsDNA viruses in a large cohort of normal individuals who were sampled at multiple body sites. Our results show that the human virome is a complex component of the microbial flora. Some viruses establish long-term infections that may be associated with increased risk or possibly with protection from disease. A better understanding of the composition and dynamics of the virome may hold important keys to human health.}, } @article {pmid25211071, year = {2014}, author = {, }, title = {The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease.}, journal = {Cell host & microbe}, volume = {16}, number = {3}, pages = {276-289}, pmid = {25211071}, issn = {1934-6069}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; 8U54DK102557/DK/NIDDK NIH HHS/United States ; U19 AG063744/AG/NIA NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54 DK102556/DK/NIDDK NIH HHS/United States ; 8U54HD080784/HD/NICHD NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; 8U54DK102556/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; Diabetes Mellitus, Type 2/*microbiology ; Health ; Humans ; Inflammatory Bowel Diseases/*microbiology ; *Microbiota ; Premature Birth/*microbiology ; }, abstract = {Much has been learned about the diversity and distribution of human-associated microbial communities, but we still know little about the biology of the microbiome, how it interacts with the host, and how the host responds to its resident microbiota. The Integrative Human Microbiome Project (iHMP, http://hmp2.org), the second phase of the NIH Human Microbiome Project, will study these interactions by analyzing microbiome and host activities in longitudinal studies of disease-specific cohorts and by creating integrated data sets of microbiome and host functional properties. These data sets will serve as experimental test beds to evaluate new models, methods, and analyses on the interactions of host and microbiome. Here we describe the three models of microbiome-associated human conditions, on the dynamics of preterm birth, inflammatory bowel disease, and type 2 diabetes, and their underlying hypotheses, as well as the multi-omic data types to be collected, integrated, and distributed through public repositories as a community resource.}, } @article {pmid25208106, year = {2014}, author = {Landsman, MJ and Sultan, M and Stevens, M and Charabaty, A and Mattar, MC}, title = {Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn's disease patients.}, journal = {Inflammatory bowel diseases}, volume = {20}, number = {12}, pages = {2503-2510}, doi = {10.1097/MIB.0000000000000140}, pmid = {25208106}, issn = {1536-4844}, mesh = {Anti-Infective Agents/*therapeutic use ; Colitis, Ulcerative/*complications ; Crohn Disease/*complications ; Disease Management ; Gastrointestinal Diseases/*diagnosis/*drug therapy/etiology ; Humans ; Prognosis ; }, abstract = {Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohn's and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.}, } @article {pmid25196521, year = {2014}, author = {Ye, Y}, title = {Identification of diversity-generating retroelements in human microbiomes.}, journal = {International journal of molecular sciences}, volume = {15}, number = {8}, pages = {14234-14246}, pmid = {25196521}, issn = {1422-0067}, mesh = {Humans ; Microbiota/*genetics ; RNA-Directed DNA Polymerase/genetics ; Retroelements/*genetics ; }, abstract = {Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by accelerating the evolution of target genes through a specialized, error-prone, reverse transcription process. First identified in a Bordetella phage (BPP-1), which mediates the phage tropism specificity by generating variability in an involved gene, DGRs were predicted to be present in a larger collection of viral and bacterial species. A minimal DGR system is comprised of a reverse transcriptase (RTase) gene, a template sequence (TR) and a variable region (VR) within a target gene. We developed a computational tool, DGRscan, to allow either de novo identification (based on the prediction of potential template-variable region pairs) or similarity-based searches of DGR systems using known template sequences as the reference. The application of DGRscan to the human microbiome project (HMP) datasets resulted in the identification of 271 non-redundant DGR systems, doubling the size of the collection of known DGR systems. We further identified a large number of putative target genes (651, which share no more than 90% sequence identity at the amino acid level) that are potentially under diversification by the DGR systems. Our study provides the first survey of the DGR systems in the human microbiome, showing that the DGR systems are frequently found in human-associated bacterial communities, although they are of low incidence in individual genomes. Our study also provides functional clues for a large number of genes (reverse transcriptases and target genes) that were previously annotated as proteins of unknown functions or nonspecific functions.}, } @article {pmid25184604, year = {2014}, author = {Gilbert, JA and Jansson, JK and Knight, R}, title = {The Earth Microbiome project: successes and aspirations.}, journal = {BMC biology}, volume = {12}, number = {}, pages = {69}, pmid = {25184604}, issn = {1741-7007}, mesh = {Archaea/classification/*genetics ; Bacteria/classification/*genetics ; *Biodiversity ; Ecosystem ; *Microbiota ; }, } @article {pmid25177538, year = {2014}, author = {Rideout, JR and He, Y and Navas-Molina, JA and Walters, WA and Ursell, LK and Gibbons, SM and Chase, J and McDonald, D and Gonzalez, A and Robbins-Pianka, A and Clemente, JC and Gilbert, JA and Huse, SM and Zhou, HW and Knight, R and Caporaso, JG}, title = {Subsampled open-reference clustering creates consistent, comprehensive OTU definitions and scales to billions of sequences.}, journal = {PeerJ}, volume = {2}, number = {}, pages = {e545}, pmid = {25177538}, issn = {2167-8359}, support = {T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, abstract = {We present a performance-optimized algorithm, subsampled open-reference OTU picking, for assigning marker gene (e.g., 16S rRNA) sequences generated on next-generation sequencing platforms to operational taxonomic units (OTUs) for microbial community analysis. This algorithm provides benefits over de novo OTU picking (clustering can be performed largely in parallel, reducing runtime) and closed-reference OTU picking (all reads are clustered, not only those that match a reference database sequence with high similarity). Because more of our algorithm can be run in parallel relative to "classic" open-reference OTU picking, it makes open-reference OTU picking tractable on massive amplicon sequence data sets (though on smaller data sets, "classic" open-reference OTU clustering is often faster). We illustrate that here by applying it to the first 15,000 samples sequenced for the Earth Microbiome Project (1.3 billion V4 16S rRNA amplicons). To the best of our knowledge, this is the largest OTU picking run ever performed, and we estimate that our new algorithm runs in less than 1/5 the time than would be required of "classic" open reference OTU picking. We show that subsampled open-reference OTU picking yields results that are highly correlated with those generated by "classic" open-reference OTU picking through comparisons on three well-studied datasets. An implementation of this algorithm is provided in the popular QIIME software package, which uses uclust for read clustering. All analyses were performed using QIIME's uclust wrappers, though we provide details (aided by the open-source code in our GitHub repository) that will allow implementation of subsampled open-reference OTU picking independently of QIIME (e.g., in a compiled programming language, where runtimes should be further reduced). Our analyses should generalize to other implementations of these OTU picking algorithms. Finally, we present a comparison of parameter settings in QIIME's OTU picking workflows and make recommendations on settings for these free parameters to optimize runtime without reducing the quality of the results. These optimized parameters can vastly decrease the runtime of uclust-based OTU picking in QIIME.}, } @article {pmid29405744, year = {2014}, author = {Proctor, LM}, title = {Mycins v Microbes Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues by Martin J. Blaser (2014) Holt New York, USA.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {28}, number = {9}, pages = {3821-3822}, doi = {10.1096/fj.14-0901ufm}, pmid = {29405744}, issn = {1530-6860}, } @article {pmid25153520, year = {2014}, author = {Honsa, ES and Maresso, AW and Highlander, SK}, title = {Molecular and evolutionary analysis of NEAr-iron Transporter (NEAT) domains.}, journal = {PloS one}, volume = {9}, number = {8}, pages = {e104794}, pmid = {25153520}, issn = {1932-6203}, support = {A1069697//PHS HHS/United States ; A1097167//PHS HHS/United States ; R21 AI146481/AI/NIAID NIH HHS/United States ; R01 AI097167/AI/NIAID NIH HHS/United States ; R21 AI109465/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/*chemistry/genetics ; Binding Sites ; Gram-Positive Bacteria/*genetics ; Phylogeny ; Protein Structure, Tertiary ; }, abstract = {Iron is essential for bacterial survival, being required for numerous biological processes. NEAr-iron Transporter (NEAT) domains have been studied in pathogenic Gram-positive bacteria to understand how their proteins obtain heme as an iron source during infection. While a 2002 study initially discovered and annotated the NEAT domain encoded by the genomes of several Gram-positive bacteria, there remains a scarcity of information regarding the conservation and distribution of NEAT domains throughout the bacterial kingdom, and whether these domains are restricted to pathogenic bacteria. This study aims to expand upon initial bioinformatics analysis of predicted NEAT domains, by exploring their evolution and conserved function. This information was used to identify new candidate domains in both pathogenic and nonpathogenic organisms. We also searched metagenomic datasets, specifically sequence from the Human Microbiome Project. Here, we report a comprehensive phylogenetic analysis of 343 NEAT domains, encoded by Gram-positive bacteria, mostly within the phylum Firmicutes, with the exception of Eggerthella sp. (Actinobacteria) and an unclassified Mollicutes bacterium (Tenericutes). No new NEAT sequences were identified in the HMP dataset. We detected specific groups of NEAT domains based on phylogeny of protein sequences, including a cluster of novel clostridial NEAT domains. We also identified environmental and soil organisms that encode putative NEAT proteins. Biochemical analysis of heme binding by a NEAT domain from a protein encoded by the soil-dwelling organism Paenibacillus polymyxa demonstrated that the domain is homologous in function to NEAT domains encoded by pathogenic bacteria. Together, this study provides the first global bioinformatics analysis and phylogenetic evidence that NEAT domains have a strong conservation of function, despite group-specific differences at the amino acid level. These findings will provide information useful for future projects concerning the structure and function of NEAT domains, particularly in pathogens where they have yet to be studied.}, } @article {pmid25136443, year = {2014}, author = {Wu, YW and Tang, YH and Tringe, SG and Simmons, BA and Singer, SW}, title = {MaxBin: an automated binning method to recover individual genomes from metagenomes using an expectation-maximization algorithm.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {26}, pmid = {25136443}, issn = {2049-2618}, abstract = {BACKGROUND: Recovering individual genomes from metagenomic datasets allows access to uncultivated microbial populations that may have important roles in natural and engineered ecosystems. Understanding the roles of these uncultivated populations has broad application in ecology, evolution, biotechnology and medicine. Accurate binning of assembled metagenomic sequences is an essential step in recovering the genomes and understanding microbial functions.

RESULTS: We have developed a binning algorithm, MaxBin, which automates the binning of assembled metagenomic scaffolds using an expectation-maximization algorithm after the assembly of metagenomic sequencing reads. Binning of simulated metagenomic datasets demonstrated that MaxBin had high levels of accuracy in binning microbial genomes. MaxBin was used to recover genomes from metagenomic data obtained through the Human Microbiome Project, which demonstrated its ability to recover genomes from real metagenomic datasets with variable sequencing coverages. Application of MaxBin to metagenomes obtained from microbial consortia adapted to grow on cellulose allowed genomic analysis of new, uncultivated, cellulolytic bacterial populations, including an abundant myxobacterial population distantly related to Sorangium cellulosum that possessed a much smaller genome (5 MB versus 13 to 14 MB) but has a more extensive set of genes for biomass deconstruction. For the cellulolytic consortia, the MaxBin results were compared to binning using emergent self-organizing maps (ESOMs) and differential coverage binning, demonstrating that it performed comparably to these methods but had distinct advantages in automation, resolution of related genomes and sensitivity.

CONCLUSIONS: The automatic binning software that we developed successfully classifies assembled sequences in metagenomic datasets into recovered individual genomes. The isolation of dozens of species in cellulolytic microbial consortia, including a novel species of myxobacteria that has the smallest genome among all sequenced aerobic myxobacteria, was easily achieved using the binning software. This work demonstrates that the processes required for recovering genomes from assembled metagenomic datasets can be readily automated, an important advance in understanding the metabolic potential of microbes in natural environments. MaxBin is available at https://sourceforge.net/projects/maxbin/.}, } @article {pmid25118239, year = {2014}, author = {Eilam, O and Zarecki, R and Oberhardt, M and Ursell, LK and Kupiec, M and Knight, R and Gophna, U and Ruppin, E}, title = {Glycan degradation (GlyDeR) analysis predicts mammalian gut microbiota abundance and host diet-specific adaptations.}, journal = {mBio}, volume = {5}, number = {4}, pages = {}, pmid = {25118239}, issn = {2150-7511}, support = {T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*metabolism ; *Diet ; Gastrointestinal Tract/*microbiology ; Genomics ; Humans ; Linear Models ; Metagenomics ; *Microbiota ; Polysaccharides/*metabolism ; Prebiotics ; }, abstract = {UNLABELLED: Glycans form the primary nutritional source for microbes in the human gut, and understanding their metabolism is a critical yet understudied aspect of microbiome research. Here, we present a novel computational pipeline for modeling glycan degradation (GlyDeR) which predicts the glycan degradation potency of 10,000 reference glycans based on either genomic or metagenomic data. We first validated GlyDeR by comparing degradation profiles for genomes in the Human Microbiome Project against KEGG reaction annotations. Next, we applied GlyDeR to the analysis of human and mammalian gut microbial communities, which revealed that the glycan degradation potential of a community is strongly linked to host diet and can be used to predict diet with higher accuracy than sequence data alone. Finally, we show that a microbe's glycan degradation potential is significantly correlated (R = 0.46) with its abundance, with even higher correlations for potential pathogens such as the class Clostridia (R = 0.76). GlyDeR therefore represents an important tool for advancing our understanding of bacterial metabolism in the gut and for the future development of more effective prebiotics for microbial community manipulation.

IMPORTANCE: The increased availability of high-throughput sequencing data has positioned the gut microbiota as a major new focal point for biomedical research. However, despite the expenditure of huge efforts and resources, sequencing-based analysis of the microbiome has uncovered mostly associative relationships between human health and diet, rather than a causal, mechanistic one. In order to utilize the full potential of systems biology approaches, one must first characterize the metabolic requirements of gut bacteria, specifically, the degradation of glycans, which are their primary nutritional source. We developed a computational framework called GlyDeR for integrating expert knowledge along with high-throughput data to uncover important new relationships within glycan metabolism. GlyDeR analyzes particular bacterial (meta)genomes and predicts the potency by which they degrade a variety of different glycans. Based on GlyDeR, we found a clear connection between microbial glycan degradation and human diet, and we suggest a method for the rational design of novel prebiotics.}, } @article {pmid25102107, year = {2014}, author = {Daley, D}, title = {The evolution of the hygiene hypothesis: the role of early-life exposures to viruses and microbes and their relationship to asthma and allergic diseases.}, journal = {Current opinion in allergy and clinical immunology}, volume = {14}, number = {5}, pages = {390-396}, doi = {10.1097/ACI.0000000000000101}, pmid = {25102107}, issn = {1473-6322}, mesh = {Airway Remodeling ; Asthma/etiology/*immunology ; Bacteria/*immunology ; Environmental Exposure/adverse effects ; Gene-Environment Interaction ; Host-Pathogen Interactions ; Humans ; *Hygiene Hypothesis ; Hypersensitivity/etiology/*immunology ; Immunity, Mucosal ; Infant ; Infant, Newborn ; Infections/complications/*immunology ; Microbiota ; Viruses/*immunology ; }, abstract = {PURPOSE OF REVIEW: Understanding the mechanisms involved in the development of asthma and allergic diseases is expanding, due in part to sequencing advances that have led to the identification of new viral strains such as human rhinovirus strain C (HRV-C) and the human microbiome project.

RECENT FINDINGS: Recent studies have identified new ways in which viral and microbial exposures in early life interact with host genetic background/variants to modify the risk for developing asthma and allergic diseases. Recent research suggests that HRV-C is the main pathogenic agent associated with infant wheeze, hospitalizations and likely the subsequent development of asthma. Pulmonary He MRI suggests that HRV infection in early childhood and subsequent immune responses initiate airway remodeling. Numerous studies of the microbiome indicate that intestinal and airway microbiome diversity and composition contribute to the cause of asthma and allergic diseases.

SUMMARY: Susceptibility to asthma and allergic diseases is complex and involves genetic variants and environmental exposures (bacteria, viruses, smoking, and pet ownership), alteration of our microbiome and potentially large-scale manipulation of the environment over the past century.}, } @article {pmid25091187, year = {2014}, author = {Can, I and Javan, GT and Pozhitkov, AE and Noble, PA}, title = {Distinctive thanatomicrobiome signatures found in the blood and internal organs of humans.}, journal = {Journal of microbiological methods}, volume = {106}, number = {}, pages = {1-7}, doi = {10.1016/j.mimet.2014.07.026}, pmid = {25091187}, issn = {1872-8359}, mesh = {Adult ; Aged ; Blood/*microbiology ; Brain/*microbiology ; *Cadaver ; Cluster Analysis ; DNA, Ribosomal/chemistry/genetics ; Heart/*microbiology ; Humans ; Liver/*microbiology ; Male ; *Microbiota ; Middle Aged ; Molecular Sequence Data ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spleen/*microbiology ; Young Adult ; }, abstract = {According to the Human Microbiome Project, 90% of the cells in a healthy adult body are microorganisms. What happens to these cells after human host death, defined here as the thanatomicrobiome (i.e., thanatos-, Greek defn., death), is not clear. To fill the void, we examined the thanatomicrobiome of the spleen, liver, brain, heart and blood of human cadavers. These organs are thought to be devoid of microorganisms in a healthy adult host. We report that the thanatomicrobiome was highly similar among organ tissues from the same cadaver but very different among the cadavers possibly due to differences in the elapsed time since death and/or environmental factors. Isolation of microbial DNA from cadavers is known to be a challenge. We compared the effectiveness of two methods by amplifying the 16S rRNA genes and sequencing the amplicons from four cadavers. Paired comparisons revealed that the conventional DNA extraction method (bead-beating in phenol/chloroform/bead-beating followed by ethanol precipitation) yielded more 16S rRNA amplicons (28 of 30 amplicons) than a second method (repeated cycles of heating/cooling followed by centrifugation to remove cellular debris) (19 of 30 amplicons). Shannon diversity index of the 16S rRNA genes revealed no significant difference by extraction method. The present report provides a proof of principle that the thanatomicrobiome may be an efficient biomarker to study postmortem transformations of cadavers.}, } @article {pmid25073854, year = {2014}, author = {Fettweis, JM and Brooks, JP and Serrano, MG and Sheth, NU and Girerd, PH and Edwards, DJ and Strauss, JF and The Vaginal Microbiome Consortium, and Jefferson, KK and Buck, GA}, title = {Differences in vaginal microbiome in African American women versus women of European ancestry.}, journal = {Microbiology (Reading, England)}, volume = {160}, number = {Pt 10}, pages = {2272-2282}, pmid = {25073854}, issn = {1465-2080}, support = {4UH3AI083263/AI/NIAID NIH HHS/United States ; P60 MD002256/MD/NIMHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54 DE023786/DE/NIDCR NIH HHS/United States ; }, mesh = {Black or African American ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Female ; Humans ; *Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vagina/*microbiology ; Virginia ; White People ; }, abstract = {Women of European ancestry are more likely to harbour a Lactobacillus-dominated microbiome, whereas African American women are more likely to exhibit a diverse microbial profile. African American women are also twice as likely to be diagnosed with bacterial vaginosis and are twice as likely to experience preterm birth. The objective of this study was to further characterize and contrast the vaginal microbial profiles in African American versus European ancestry women. Through the Vaginal Human Microbiome Project at Virginia Commonwealth University, 16S rRNA gene sequence analysis was used to compare the microbiomes of vaginal samples from 1268 African American women and 416 women of European ancestry. The results confirmed significant differences in the vaginal microbiomes of the two groups and identified several taxa relevant to these differences. Major community types were dominated by Gardnerella vaginalis and the uncultivated bacterial vaginosis-associated bacterium-1 (BVAB1) that were common among African Americans. Moreover, the prevalence of multiple bacterial taxa that are associated with microbial invasion of the amniotic cavity and preterm birth, including Mycoplasma, Gardnerella, Prevotella and Sneathia, differed between the two ethnic groups. We investigated the contributions of intrinsic and extrinsic factors, including pregnancy, body mass index, diet, smoking and alcohol use, number of sexual partners, and household income, to vaginal community composition. Ethnicity, pregnancy and alcohol use correlated significantly with the relative abundance of bacterial vaginosis-associated species. Trends between microbial profiles and smoking and number of sexual partners were observed; however, these associations were not statistically significant. These results support and extend previous findings that there are significant differences in the vaginal microbiome related to ethnicity and demonstrate that these differences are pronounced even in healthy women.}, } @article {pmid25052396, year = {2014}, author = {Aujoulat, F and Bouvet, P and Jumas-Bilak, E and Jean-Pierre, H and Marchandin, H}, title = {Veillonella seminalis sp. nov., a novel anaerobic Gram-stain-negative coccus from human clinical samples, and emended description of the genus Veillonella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {64}, number = {Pt 10}, pages = {3526-3531}, doi = {10.1099/ijs.0.064451-0}, pmid = {25052396}, issn = {1466-5034}, mesh = {Abscess/*microbiology ; Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Female ; Genes, Bacterial ; Humans ; Infant ; Male ; Middle Aged ; Molecular Sequence Data ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Semen/*microbiology ; Sequence Analysis, DNA ; Veillonella/*classification/genetics/isolation & purification ; Young Adult ; }, abstract = {Ten isolates of unknown, Gram-stain-negative, anaerobic cocci were recovered from human clinical samples, mainly from semen. On the basis of their phenotypic features, including morphology, main metabolic end products, gas production, nitrate reduction and decarboxylation of succinate, the strains were identified as members of the genus Veillonella. Multi-locus sequence analysis and corresponding phylogenies were based on 16S rRNA, dnaK and rpoB genes, and on the newly proposed gltA gene. The strains shared high levels of genetic sequence similarity and were related most closely to Veillonella ratti. The strains could not be differentiated from V. ratti on the basis of 16S rRNA gene sequence analysis while gltA, rpoB and dnaK gene sequences showed 85.1, 93.5 and 90.2% similarity with those of the type strain of V. ratti, respectively. Phylogenetic analyses revealed that the isolates formed a robust clade in the V. ratti-Veillonella criceti-Veillonella magna subgroup of the genus Veillonella. As observed for V. criceti, the isolates were able to ferment fructose. In contrast to other members of the genus Veillonella, the 10 strains were not able to metabolize lactate. Cellular fatty acid composition was consistent with that of other species of the genus Veillonella. From these data, the 10 isolates are considered to belong to a novel species in the genus Veillonella, for which the name Veillonella seminalis sp. nov. is proposed. The type strain is ADV 4313.2(T) (= CIP 107810(T) = LMG 28162(T)). Veillonella strain ACS-216-V-Col6b subjected to whole genome sequencing as part as the Human Microbiome Project is another representative of V. seminalis sp. nov. An emended description of the genus Veillonella is also proposed.}, } @article {pmid24965364, year = {2014}, author = {Ma, L and Kim, J and Hatzenpichler, R and Karymov, MA and Hubert, N and Hanan, IM and Chang, EB and Ismagilov, RF}, title = {Gene-targeted microfluidic cultivation validated by isolation of a gut bacterium listed in Human Microbiome Project's Most Wanted taxa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {27}, pages = {9768-9773}, pmid = {24965364}, issn = {1091-6490}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; R01HG005826/HG/NHGRI NIH HHS/United States ; R01 HG005826/HG/NHGRI NIH HHS/United States ; R37 DK047722/DK/NIDDK NIH HHS/United States ; R01 DK047722/DK/NIDDK NIH HHS/United States ; }, mesh = {*Gene Targeting ; Humans ; Intestines/*microbiology ; *Microbiota ; *Microfluidic Analytical Techniques ; Molecular Sequence Data ; }, abstract = {This paper describes a microfluidics-based workflow for genetically targeted isolation and cultivation of microorganisms from complex clinical samples. Data sets from high-throughput sequencing suggest the existence of previously unidentified bacterial taxa and functional genes with high biomedical importance. Obtaining isolates of these targets, preferably in pure cultures, is crucial for advancing understanding of microbial genetics and physiology and enabling physical access to microbes for further applications. However, the majority of microbes have not been cultured, due in part to the difficulties of both identifying proper growth conditions and characterizing and isolating each species. We describe a method that enables genetically targeted cultivation of microorganisms through a combination of microfluidics and on- and off-chip assays. This method involves (i) identification of cultivation conditions for microbes using growth substrates available only in small quantities as well as the correction of sampling bias using a "chip wash" technique; and (ii) performing on-chip genetic assays while also preserving live bacterial cells for subsequent scale-up cultivation of desired microbes, by applying recently developed technology to create arrays of individually addressable replica microbial cultures. We validated this targeted approach by cultivating a bacterium, here referred to as isolate microfluidicus 1, from a human cecal biopsy. Isolate microfluidicus 1 is, to our knowledge, the first successful example of targeted cultivation of a microorganism from the high-priority group of the Human Microbiome Project's "Most Wanted" list, and, to our knowledge, the first cultured representative of a previously unidentified genus of the Ruminococcaceae family.}, } @article {pmid24965363, year = {2014}, author = {Eren, AM and Borisy, GG and Huse, SM and Mark Welch, JL}, title = {Oligotyping analysis of the human oral microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, number = {28}, pages = {E2875-84}, pmid = {24965363}, issn = {1091-6490}, support = {DE022586/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; DK083993/DK/NIDDK NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; R01 DE022586/DE/NIDCR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Bacteria/classification/genetics ; *Databases, Nucleic Acid ; Female ; *Genes, Bacterial ; *Genes, rRNA ; Humans ; Male ; Microbiota ; Mouth Mucosa/*microbiology ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The Human Microbiome Project provided a census of bacterial populations in healthy individuals, but an understanding of the biomedical significance of this census has been hindered by limited taxonomic resolution. A high-resolution method termed oligotyping overcomes this limitation by evaluating individual nucleotide positions using Shannon entropy to identify the most information-rich nucleotide positions, which then define oligotypes. We have applied this method to comprehensively analyze the oral microbiome. Using Human Microbiome Project 16S rRNA gene sequence data for the nine sites in the oral cavity, we identified 493 oligotypes from the V1-V3 data and 360 oligotypes from the V3-V5 data. We associated these oligotypes with species-level taxon names by comparison with the Human Oral Microbiome Database. We discovered closely related oligotypes, differing sometimes by as little as a single nucleotide, that showed dramatically different distributions among oral sites and among individuals. We also detected potentially pathogenic taxa in high abundance in individual samples. Numerous oligotypes were preferentially located in plaque, others in keratinized gingiva or buccal mucosa, and some oligotypes were characteristic of habitat groupings such as throat, tonsils, tongue dorsum, hard palate, and saliva. The differing habitat distributions of closely related oligotypes suggest a level of ecological and functional biodiversity not previously recognized. We conclude that the Shannon entropy approach of oligotyping has the capacity to analyze entire microbiomes, discriminate between closely related but distinct taxa and, in combination with habitat analysis, provide deep insight into the microbial communities in health and disease.}, } @article {pmid24957091, year = {2014}, author = {Barzegari, A and Saeedi, N and Saei, AA}, title = {Shrinkage of the human core microbiome and a proposal for launching microbiome biobanks.}, journal = {Future microbiology}, volume = {9}, number = {5}, pages = {639-656}, doi = {10.2217/fmb.14.22}, pmid = {24957091}, issn = {1746-0921}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; *Biodiversity ; *Biological Specimen Banks ; Diet ; Gastrointestinal Tract/*microbiology ; Humans ; Metabolic Syndrome/immunology ; Mice ; *Microbiota ; Obesity/immunology ; Probiotics/therapeutic use ; }, abstract = {The Human Microbiome Project (HMP) revealed the significance of the gut microbiome in promoting health. Disruptions in microbiome composition are associated with the pathogenesis of numerous diseases. The indigenous microflora has co-evolved with humans for millions of years and humans have preserved the inherited microbiomes through consumption of fermented foods and interactions with environmental microbes. Through modernization, traditional foods were abandoned, native food starters were substituted with industrial products, vaccines and antibiotics were used, extreme hygiene measures were taken, the rate of cesarean section increased, and breast feeding changed into formula. These factors have reduced human exposure to microbial symbionts and led to shrinkage of the core microbiome. Reduction in microbiome biodiversity can compromise the human immune system and predispose individuals to several modern diseases. This article suggests launching microbiome biobanks for archiving native microbiomes, supervising antibiotic use, probiotic design and native starter production, as well as advertising a revisit to native lifestyles.}, } @article {pmid24949196, year = {2014}, author = {Wesolowska-Andersen, A and Bahl, MI and Carvalho, V and Kristiansen, K and Sicheritz-Pontén, T and Gupta, R and Licht, TR}, title = {Choice of bacterial DNA extraction method from fecal material influences community structure as evaluated by metagenomic analysis.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {19}, pmid = {24949196}, issn = {2049-2618}, abstract = {BACKGROUND: In recent years, studies on the human intestinal microbiota have attracted tremendous attention. Application of next generation sequencing for mapping of bacterial phylogeny and function has opened new doors to this field of research. However, little attention has been given to the effects of choice of methodology on the output resulting from such studies.

RESULTS: IN THIS STUDY WE CONDUCTED A SYSTEMATIC COMPARISON OF THE DNA EXTRACTION METHODS USED BY THE TWO MAJOR COLLABORATIVE EFFORTS: The European MetaHIT and the American Human Microbiome Project (HMP). Additionally, effects of homogenizing the samples before extraction were addressed. We observed significant differences in distribution of bacterial taxa depending on the method. While eukaryotic DNA was most efficiently extracted by the MetaHIT protocol, DNA from bacteria within the Bacteroidetes phylum was most efficiently extracted by the HMP protocol.

CONCLUSIONS: Whereas it is comforting that the inter-individual variation clearly exceeded the variation resulting from choice of extraction method, our data highlight the challenge of comparing data across studies applying different methodologies.}, } @article {pmid24910773, year = {2014}, author = {Fernandes, AD and Reid, JN and Macklaim, JM and McMurrough, TA and Edgell, DR and Gloor, GB}, title = {Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis.}, journal = {Microbiome}, volume = {2}, number = {}, pages = {15}, pmid = {24910773}, issn = {2049-2618}, abstract = {BACKGROUND: Experimental designs that take advantage of high-throughput sequencing to generate datasets include RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), sequencing of 16S rRNA gene fragments, metagenomic analysis and selective growth experiments. In each case the underlying data are similar and are composed of counts of sequencing reads mapped to a large number of features in each sample. Despite this underlying similarity, the data analysis methods used for these experimental designs are all different, and do not translate across experiments. Alternative methods have been developed in the physical and geological sciences that treat similar data as compositions. Compositional data analysis methods transform the data to relative abundances with the result that the analyses are more robust and reproducible.

RESULTS: Data from an in vitro selective growth experiment, an RNA-seq experiment and the Human Microbiome Project 16S rRNA gene abundance dataset were examined by ALDEx2, a compositional data analysis tool that uses Bayesian methods to infer technical and statistical error. The ALDEx2 approach is shown to be suitable for all three types of data: it correctly identifies both the direction and differential abundance of features in the differential growth experiment, it identifies a substantially similar set of differentially expressed genes in the RNA-seq dataset as the leading tools and it identifies as differential the taxa that distinguish the tongue dorsum and buccal mucosa in the Human Microbiome Project dataset. The design of ALDEx2 reduces the number of false positive identifications that result from datasets composed of many features in few samples.

CONCLUSION: Statistical analysis of high-throughput sequencing datasets composed of per feature counts showed that the ALDEx2 R package is a simple and robust tool, which can be applied to RNA-seq, 16S rRNA gene sequencing and differential growth datasets, and by extension to other techniques that use a similar approach.}, } @article {pmid24898946, year = {2014}, author = {Aruni, W and Chioma, O and Fletcher, HM}, title = {Filifactor alocis: The Newly Discovered Kid on the Block with Special Talents.}, journal = {Journal of dental research}, volume = {93}, number = {8}, pages = {725-732}, pmid = {24898946}, issn = {1544-0591}, support = {R21 DE022724/DE/NIDCR NIH HHS/United States ; R01 DE022508/DE/NIDCR NIH HHS/United States ; DE019730 04S1/DE/NIDCR NIH HHS/United States ; DE13664/DE/NIDCR NIH HHS/United States ; R01 DE013664/DE/NIDCR NIH HHS/United States ; R56 DE013664/DE/NIDCR NIH HHS/United States ; DE019730/DE/NIDCR NIH HHS/United States ; DE022724/DE/NIDCR NIH HHS/United States ; DE022508/DE/NIDCR NIH HHS/United States ; R01 DE019730/DE/NIDCR NIH HHS/United States ; }, mesh = {Biofilms ; Coinfection/microbiology ; Gram-Positive Bacterial Infections/*diagnosis ; Gram-Positive Rods/*pathogenicity/physiology ; Host-Pathogen Interactions ; Humans ; Microbial Consortia/physiology ; Periodontitis/*microbiology ; Virulence ; }, abstract = {Infection-induced periodontal disease has been primarily focused on a small group of periodontal pathogens. A paradigm shift, based on data emerging from the oral microbiome project, now suggests the involvement of as-yet-unculturable and fastidious organisms. Collectively, these studies have demonstrated that there are changes in the periodontal status associated with shifts in the composition of the bacterial community in the periodontal pocket. In addition, it is likely that the emerging new pathogens may play a more significant role in the disease. One of the organisms previously unrecognized is Filifactor alocis. While this Gram-positive anaerobic rod has been identified in peri-implantitis, in endodontic infections, and in patients with localized aggressive periodontitis, its presence is now observed at significantly higher levels in patients with adult periodontitis or refractory periodontitis. Its colonization properties and its potential virulence attributes support the proposal that F. alocis should be included as a diagnostic indicator of periodontal disease. Moreover, these emerging characteristics would be consistent with the polymicrobial synergy and dysbiosis (PSD) periodontal pathogenesis model. Here, unique characteristics of F. alocis are discussed. F. alocis has specific factors that can modulate multiple changes in the microbial community and host cell proteome. It is likely that such variations at the molecular level are responsible for the functional changes required to mediate the pathogenic process.}, } @article {pmid24887286, year = {2014}, author = {Zhou, Y and Mihindukulasuriya, KA and Gao, H and La Rosa, PS and Wylie, KM and Martin, JC and Kota, K and Shannon, WD and Mitreva, M and Sodergren, E and Weinstock, GM}, title = {Exploration of bacterial community classes in major human habitats.}, journal = {Genome biology}, volume = {15}, number = {5}, pages = {R66}, pmid = {24887286}, issn = {1474-760X}, support = {U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Demography ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Mouth/microbiology ; Nose/microbiology ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {BACKGROUND: Determining bacterial abundance variation is the first step in understanding bacterial similarity between individuals. Categorization of bacterial communities into groups or community classes is the subsequent step in describing microbial distribution based on abundance patterns. Here, we present an analysis of the groupings of bacterial communities in stool, nasal, skin, vaginal and oral habitats in a healthy cohort of 236 subjects from the Human Microbiome Project.

RESULTS: We identify distinct community group patterns in the anterior nares, four skin sites, and vagina at the genus level. We also confirm three enterotypes previously identified in stools. We identify two clusters with low silhouette values in most oral sites, in which bacterial communities are more homogeneous. Subjects sharing a community class in one habitat do not necessarily share a community class in another, except in the three vaginal sites and the symmetric habitats of the left and right retroauricular creases. Demographic factors, including gender, age, and ethnicity, significantly influence community composition in several habitats. Community classes in the vagina, retroauricular crease and stool are stable over approximately 200 days.

CONCLUSION: The community composition, association of demographic factors with community classes, and demonstration of community stability deepen our understanding of the variability and dynamics of human microbiomes. This also has significant implications for experimental designs that seek microbial correlations with clinical phenotypes.}, } @article {pmid24846174, year = {2014}, author = {Hasan, NA and Young, BA and Minard-Smith, AT and Saeed, K and Li, H and Heizer, EM and McMillan, NJ and Isom, R and Abdullah, AS and Bornman, DM and Faith, SA and Choi, SY and Dickens, ML and Cebula, TA and Colwell, RR}, title = {Microbial community profiling of human saliva using shotgun metagenomic sequencing.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e97699}, pmid = {24846174}, issn = {1932-6203}, support = {1R01A139129-01//PHS HHS/United States ; 2R01A1039129-11A2//PHS HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Male ; *Metagenome ; Metagenomics/*methods ; Microbiota/*genetics ; Saliva/*microbiology ; Sequence Analysis, DNA/*methods ; }, abstract = {Human saliva is clinically informative of both oral and general health. Since next generation shotgun sequencing (NGS) is now widely used to identify and quantify bacteria, we investigated the bacterial flora of saliva microbiomes of two healthy volunteers and five datasets from the Human Microbiome Project, along with a control dataset containing short NGS reads from bacterial species representative of the bacterial flora of human saliva. GENIUS, a system designed to identify and quantify bacterial species using unassembled short NGS reads was used to identify the bacterial species comprising the microbiomes of the saliva samples and datasets. Results, achieved within minutes and at greater than 90% accuracy, showed more than 175 bacterial species comprised the bacterial flora of human saliva, including bacteria known to be commensal human flora but also Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae, and Gamma proteobacteria. Basic Local Alignment Search Tool (BLASTn) analysis in parallel, reported ca. five times more species than those actually comprising the in silico sample. Both GENIUS and BLAST analyses of saliva samples identified major genera comprising the bacterial flora of saliva, but GENIUS provided a more precise description of species composition, identifying to strain in most cases and delivered results at least 10,000 times faster. Therefore, GENIUS offers a facile and accurate system for identification and quantification of bacterial species and/or strains in metagenomic samples.}, } @article {pmid24845653, year = {2014}, author = {Seth, S and Välimäki, N and Kaski, S and Honkela, A}, title = {Exploration and retrieval of whole-metagenome sequencing samples.}, journal = {Bioinformatics (Oxford, England)}, volume = {30}, number = {17}, pages = {2471-2479}, pmid = {24845653}, issn = {1367-4811}, mesh = {Algorithms ; Data Mining ; Diabetes Mellitus, Type 2/microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/microbiology ; Metagenomics/*methods ; Microbiota ; Sequence Analysis, DNA ; }, abstract = {MOTIVATION: Over the recent years, the field of whole-metagenome shotgun sequencing has witnessed significant growth owing to the high-throughput sequencing technologies that allow sequencing genomic samples cheaper, faster and with better coverage than before. This technical advancement has initiated the trend of sequencing multiple samples in different conditions or environments to explore the similarities and dissimilarities of the microbial communities. Examples include the human microbiome project and various studies of the human intestinal tract. With the availability of ever larger databases of such measurements, finding samples similar to a given query sample is becoming a central operation.

RESULTS: In this article, we develop a content-based exploration and retrieval method for whole-metagenome sequencing samples. We apply a distributed string mining framework to efficiently extract all informative sequence k-mers from a pool of metagenomic samples and use them to measure the dissimilarity between two samples. We evaluate the performance of the proposed approach on two human gut metagenome datasets as well as human microbiome project metagenomic samples. We observe significant enrichment for diseased gut samples in results of queries with another diseased sample and high accuracy in discriminating between different body sites even though the method is unsupervised.

A software implementation of the DSM framework is available at https://github.com/HIITMetagenomics/dsm-framework.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, } @article {pmid24841417, year = {2014}, author = {Gibbons, SM and Jones, E and Bearquiver, A and Blackwolf, F and Roundstone, W and Scott, N and Hooker, J and Madsen, R and Coleman, ML and Gilbert, JA}, title = {Human and environmental impacts on river sediment microbial communities.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e97435}, pmid = {24841417}, issn = {1932-6203}, support = {T32 EB009412/EB/NIBIB NIH HHS/United States ; }, mesh = {Biodiversity ; Geologic Sediments/*microbiology ; Humans ; RNA, Ribosomal, 16S/genetics ; Rivers ; }, abstract = {Sediment microbial communities are responsible for a majority of the metabolic activity in river and stream ecosystems. Understanding the dynamics in community structure and function across freshwater environments will help us to predict how these ecosystems will change in response to human land-use practices. Here we present a spatiotemporal study of sediments in the Tongue River (Montana, USA), comprising six sites along 134 km of river sampled in both spring and fall for two years. Sequencing of 16S rRNA amplicons and shotgun metagenomes revealed that these sediments are the richest (∼ 65,000 microbial 'species' identified) and most novel (93% of OTUs do not match known microbial diversity) ecosystems analyzed by the Earth Microbiome Project to date, and display more functional diversity than was detected in a recent review of global soil metagenomes. Community structure and functional potential have been significantly altered by anthropogenic drivers, including increased pathogenicity and antibiotic metabolism markers near towns and metabolic signatures of coal and coalbed methane extraction byproducts. The core (OTUs shared across all samples) and the overall microbial community exhibited highly similar structure, and phylogeny was weakly coupled with functional potential. Together, these results suggest that microbial community structure is shaped by environmental drivers and niche filtering, though stochastic assembly processes likely play a role as well. These results indicate that sediment microbial communities are highly complex and sensitive to changes in land use practices.}, } @article {pmid24827833, year = {2014}, author = {Kraal, L and Abubucker, S and Kota, K and Fischbach, MA and Mitreva, M}, title = {The prevalence of species and strains in the human microbiome: a resource for experimental efforts.}, journal = {PloS one}, volume = {9}, number = {5}, pages = {e97279}, pmid = {24827833}, issn = {1932-6203}, support = {DP2 OD007290/OD/NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; T32 EB009383/EB/NIBIB NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Genome, Bacterial/*genetics ; Humans ; Metagenome/genetics ; Metagenomics/methods ; Microbiota/*genetics ; Phylogeny ; Prevalence ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {Experimental efforts to characterize the human microbiota often use bacterial strains that were chosen for historical rather than biological reasons. Here, we report an analysis of 380 whole-genome shotgun samples from 100 subjects from the NIH Human Microbiome Project. By mapping their reads to 1,751 reference genome sequences and analyzing the resulting relative strain abundance in each sample we present metrics and visualizations that can help identify strains of interest for experimentalists. We also show that approximately 14 strains of 10 species account for 80% of the mapped reads from a typical stool sample, indicating that the function of a community may not be irreducibly complex. Some of these strains account for >20% of the sequence reads in a subset of samples but are absent in others, a dichotomy that could underlie biological differences among subjects. These data should serve as an important strain selection resource for the community of researchers who take experimental approaches to studying the human microbiota.}, } @article {pmid24797966, year = {2014}, author = {Blum, HE}, title = {Advances in individualized and regenerative medicine.}, journal = {Advances in medical sciences}, volume = {59}, number = {1}, pages = {7-12}, doi = {10.1016/j.advms.2013.12.001}, pmid = {24797966}, issn = {1898-4002}, mesh = {Adult ; *Genetic Therapy ; *Genome, Human ; Humans ; Induced Pluripotent Stem Cells/*cytology ; *Precision Medicine ; *Regenerative Medicine ; }, abstract = {Molecular and cell biology have resulted in major advances in our understanding of disease pathogenesis as well as in novel strategies for the diagnosis, therapy and prevention of human diseases. Based on modern molecular, genetic and biochemical methodologies it is on the one hand possible to identify for example disease-related point mutations and single nucleotide polymorphisms. On the other hand, using high throughput array and other technologies, it is for example possible to simultaneously analyze thousands of genes or gene products (RNA and proteins), resulting in an individual gene or gene expression profile ('signature'). Such data increasingly allow to define the individual disposition for a given disease and to predict disease prognosis as well as the efficacy of therapeutic strategies in the individual patient ('individualized medicine'). At the same time, the basic discoveries in cell biology, including embryonic and adult stem cells, induced pluripotent stem cells, genetically modified cells and others, have moved regenerative medicine into the center of biomedical research worldwide with a major translational impact on tissue engineering as well as transplantation medicine. All these aspects have greatly contributed to the recent advances in regenerative medicine and the development novel concepts for the treatment of many human diseases, including liver diseases.}, } @article {pmid24785449, year = {2014}, author = {ElRakaiby, M and Dutilh, BE and Rizkallah, MR and Boleij, A and Cole, JN and Aziz, RK}, title = {Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics.}, journal = {Omics : a journal of integrative biology}, volume = {18}, number = {7}, pages = {402-414}, pmid = {24785449}, issn = {1557-8100}, mesh = {Animals ; Anti-Infective Agents/pharmacology/therapeutic use ; Biodiversity ; Genomics ; Humans ; *Metagenome ; Microbiology/trends ; *Microbiota ; *Pharmacogenetics ; *Precision Medicine ; }, abstract = {The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.}, } @article {pmid24757212, year = {2014}, author = {Vital, M and Howe, AC and Tiedje, JM}, title = {Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e00889}, pmid = {24757212}, issn = {2150-7511}, support = {UH3 DK083993/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*genetics/*metabolism ; Butyrates/*metabolism ; Feces/*microbiology ; Healthy Volunteers ; Humans ; Metabolic Networks and Pathways/*genetics ; *Metagenomics ; *Microbiota ; }, abstract = {Butyrate-producing bacteria have recently gained attention, since they are important for a healthy colon and when altered contribute to emerging diseases, such as ulcerative colitis and type II diabetes. This guild is polyphyletic and cannot be accurately detected by 16S rRNA gene sequencing. Consequently, approaches targeting the terminal genes of the main butyrate-producing pathway have been developed. However, since additional pathways exist and alternative, newly recognized enzymes catalyzing the terminal reaction have been described, previous investigations are often incomplete. We undertook a broad analysis of butyrate-producing pathways and individual genes by screening 3,184 sequenced bacterial genomes from the Integrated Microbial Genome database. Genomes of 225 bacteria with a potential to produce butyrate were identified, including many previously unknown candidates. The majority of candidates belong to distinct families within the Firmicutes, but members of nine other phyla, especially from Actinobacteria, Bacteroidetes, Fusobacteria, Proteobacteria, Spirochaetes, and Thermotogae, were also identified as potential butyrate producers. The established gene catalogue (3,055 entries) was used to screen for butyrate synthesis pathways in 15 metagenomes derived from stool samples of healthy individuals provided by the HMP (Human Microbiome Project) consortium. A high percentage of total genomes exhibited a butyrate-producing pathway (mean, 19.1%; range, 3.2% to 39.4%), where the acetyl-coenzyme A (CoA) pathway was the most prevalent (mean, 79.7% of all pathways), followed by the lysine pathway (mean, 11.2%). Diversity analysis for the acetyl-CoA pathway showed that the same few firmicute groups associated with several Lachnospiraceae and Ruminococcaceae were dominating in most individuals, whereas the other pathways were associated primarily with Bacteroidetes. IMPORTANCE Microbiome research has revealed new, important roles of our gut microbiota for maintaining health, but an understanding of effects of specific microbial functions on the host is in its infancy, partly because in-depth functional microbial analyses are rare and publicly available databases are often incomplete/misannotated. In this study, we focused on production of butyrate, the main energy source for colonocytes, which plays a critical role in health and disease. We have provided a complete database of genes from major known butyrate-producing pathways, using in-depth genomic analysis of publicly available genomes, filling an important gap to accurately assess the butyrate-producing potential of complex microbial communities from "-omics"-derived data. Furthermore, a reference data set containing the abundance and diversity of butyrate synthesis pathways from the healthy gut microbiota was established through a metagenomics-based assessment. This study will help in understanding the role of butyrate producers in health and disease and may assist the development of treatments for functional dysbiosis.}, } @article {pmid24739969, year = {2014}, author = {Ding, T and Schloss, PD}, title = {Dynamics and associations of microbial community types across the human body.}, journal = {Nature}, volume = {509}, number = {7500}, pages = {357-360}, pmid = {24739969}, issn = {1476-4687}, support = {R01 HG005975/HG/NHGRI NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; R01GM099514/GM/NIGMS NIH HHS/United States ; P30DK034933/DK/NIDDK NIH HHS/United States ; R01 GM099514/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Feeding ; Disease Susceptibility ; Educational Status ; Feces/microbiology ; Female ; Gastrointestinal Tract/microbiology ; Health ; *Human Body ; Humans ; Life Style ; Male ; Metagenome/genetics ; *Microbiota/genetics ; Mouth/microbiology ; *Organ Specificity ; Precision Medicine ; RNA, Ribosomal, 16S/genetics ; Sex Characteristics ; Time Factors ; Vagina/microbiology ; }, abstract = {A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.}, } @article {pmid24708091, year = {2014}, author = {Kidd, JM and Sharpton, TJ and Bobo, D and Norman, PJ and Martin, AR and Carpenter, ML and Sikora, M and Gignoux, CR and Nemat-Gorgani, N and Adams, A and Guadalupe, M and Guo, X and Feng, Q and Li, Y and Liu, X and Parham, P and Hoal, EG and Feldman, MW and Pollard, KS and Wall, JD and Bustamante, CD and Henn, BM}, title = {Exome capture from saliva produces high quality genomic and metagenomic data.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {262}, pmid = {24708091}, issn = {1471-2164}, support = {R01HG003229/HG/NHGRI NIH HHS/United States ; T32HG000044/HG/NHGRI NIH HHS/United States ; GM007790/GM/NIGMS NIH HHS/United States ; R01 AI017892/AI/NIAID NIH HHS/United States ; T32GM007175/GM/NIGMS NIH HHS/United States ; R01HG400409/HG/NHGRI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; T32 GM007790/GM/NIGMS NIH HHS/United States ; DP5 OD009154/OD/NIH HHS/United States ; AI17892/AI/NIAID NIH HHS/United States ; 1DP5OD009154/OD/NIH HHS/United States ; }, mesh = {*Exome ; Genome, Human ; *Genomics ; Genotype ; HLA Antigens/genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Metagenomics ; Microbiota ; Molecular Sequence Data ; Mouth/microbiology ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Receptors, KIR/genetics ; Saliva/*chemistry/*microbiology ; }, abstract = {BACKGROUND: Targeted capture of genomic regions reduces sequencing cost while generating higher coverage by allowing biomedical researchers to focus on specific loci of interest, such as exons. Targeted capture also has the potential to facilitate the generation of genomic data from DNA collected via saliva or buccal cells. DNA samples derived from these cell types tend to have a lower human DNA yield, may be degraded from age and/or have contamination from bacteria or other ambient oral microbiota. However, thousands of samples have been previously collected from these cell types, and saliva collection has the advantage that it is a non-invasive and appropriate for a wide variety of research.

RESULTS: We demonstrate successful enrichment and sequencing of 15 South African KhoeSan exomes and 2 full genomes with samples initially derived from saliva. The expanded exome dataset enables us to characterize genetic diversity free from ascertainment bias for multiple KhoeSan populations, including new exome data from six HGDP Namibian San, revealing substantial population structure across the Kalahari Desert region. Additionally, we discover and independently verify thirty-one previously unknown KIR alleles using methods we developed to accurately map and call the highly polymorphic HLA and KIR loci from exome capture data. Finally, we show that exome capture of saliva-derived DNA yields sufficient non-human sequences to characterize oral microbial communities, including detection of bacteria linked to oral disease (e.g. Prevotella melaninogenica). For comparison, two samples were sequenced using standard full genome library preparation without exome capture and we found no systematic bias of metagenomic information between exome-captured and non-captured data.

CONCLUSIONS: DNA from human saliva samples, collected and extracted using standard procedures, can be used to successfully sequence high quality human exomes, and metagenomic data can be derived from non-human reads. We find that individuals from the Kalahari carry a higher oral pathogenic microbial load than samples surveyed in the Human Microbiome Project. Additionally, rare variants present in the exomes suggest strong population structure across different KhoeSan populations.}, } @article {pmid24694284, year = {2014}, author = {Ma, J and Coarfa, C and Qin, X and Bonnen, PE and Milosavljevic, A and Versalovic, J and Aagaard, K}, title = {mtDNA haplogroup and single nucleotide polymorphisms structure human microbiome communities.}, journal = {BMC genomics}, volume = {15}, number = {}, pages = {257}, pmid = {24694284}, issn = {1471-2164}, mesh = {DNA, Mitochondrial/*genetics ; *Haplotypes ; Humans ; *Microbiota ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale framework with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria's role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest.

RESULTS: We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDNA variants. 15 haplogroups and 631 mtDNA nucleotide polymorphisms (mean sequencing depth of 280X on the mitochondria genome) from 89 individuals participating in the HMP were accurately identified. 16S rRNA (V3-V5 region) sequencing generated microbiome taxonomy profiles and whole genome shotgun sequencing generated metabolic profiles from various body sites were treated as traits to conduct association analysis between haplogroups and host clinical metadata through linear regression. The mtSNPs of individuals with European haplogroups were associated with microbiome profiles using PLINK quantitative trait associations with permutation and adjusted for multiple comparisons. We observe that among 139 stool and 59 vaginal posterior fornix samples, several haplogroups show significant association with specific microbiota (q-value < 0.05) as well as their aggregate community structure (Chi-square with Monte Carlo, p < 0.005), which confirmed and expanded previous research on the association of race and ethnicity with microbiome profile. Our results further indicate that mtDNA variations may render different microbiome profiles, possibly through an inflammatory response to different levels of reactive oxygen species activity.

CONCLUSIONS: These data provide initial evidence for the association between host ancestral genome with the structure of its microbiome.}, } @article {pmid24692635, year = {2014}, author = {Jorth, P and Turner, KH and Gumus, P and Nizam, N and Buduneli, N and Whiteley, M}, title = {Metatranscriptomics of the human oral microbiome during health and disease.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e01012-14}, pmid = {24692635}, issn = {2150-7511}, support = {F31 DE021633/DE/NIDCR NIH HHS/United States ; R01 DE023193/DE/NIDCR NIH HHS/United States ; 5F31DE021633-02/DE/NIDCR NIH HHS/United States ; 1R01DE020100/DE/NIDCR NIH HHS/United States ; R01 DE020100/DE/NIDCR NIH HHS/United States ; }, mesh = {Adult ; Dysbiosis ; Female ; Humans ; Male ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; Periodontitis/microbiology ; *Transcriptome ; }, abstract = {The human microbiome plays important roles in health, but when disrupted, these same indigenous microbes can cause disease. The composition of the microbiome changes during the transition from health to disease; however, these changes are often not conserved among patients. Since microbiome-associated diseases like periodontitis cause similar patient symptoms despite interpatient variability in microbial community composition, we hypothesized that human-associated microbial communities undergo conserved changes in metabolism during disease. Here, we used patient-matched healthy and diseased samples to compare gene expression of 160,000 genes in healthy and diseased periodontal communities. We show that health- and disease-associated communities exhibit defined differences in metabolism that are conserved between patients. In contrast, the metabolic gene expression of individual species was highly variable between patients. These results demonstrate that despite high interpatient variability in microbial composition, disease-associated communities display conserved metabolic profiles that are generally accomplished by a patient-specific cohort of microbes. IMPORTANCE The human microbiome project has shown that shifts in our microbiota are associated with many diseases, including obesity, Crohn's disease, diabetes, and periodontitis. While changes in microbial populations are apparent during these diseases, the species associated with each disease can vary from patient to patient. Taking into account this interpatient variability, we hypothesized that specific microbiota-associated diseases would be marked by conserved microbial community behaviors. Here, we use gene expression analyses of patient-matched healthy and diseased human periodontal plaque to show that microbial communities have highly conserved metabolic gene expression profiles, whereas individual species within the community do not. Furthermore, disease-associated communities exhibit conserved changes in metabolic and virulence gene expression.}, } @article {pmid24676219, year = {2014}, author = {Pyles, RB and Vincent, KL and Baum, MM and Elsom, B and Miller, AL and Maxwell, C and Eaves-Pyles, TD and Li, G and Popov, VL and Nusbaum, RJ and Ferguson, MR}, title = {Cultivated vaginal microbiomes alter HIV-1 infection and antiretroviral efficacy in colonized epithelial multilayer cultures.}, journal = {PloS one}, volume = {9}, number = {3}, pages = {e93419}, pmid = {24676219}, issn = {1932-6203}, support = {UL1TR000071/TR/NCATS NIH HHS/United States ; R01AI100744/AI/NIAID NIH HHS/United States ; UL1 TR000071/TR/NCATS NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; R01 AI100744/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Anti-HIV Agents/pharmacology ; Cell Culture Techniques ; Cell Line ; Cytokines/biosynthesis/metabolism ; Epithelial Cells/drug effects/*microbiology/virology ; Female ; HIV-1/*physiology ; Host-Pathogen Interactions ; Humans ; Microbiota/*physiology ; Models, Biological ; Mucous Membrane/drug effects/*microbiology/virology ; Vagina/microbiology/virology ; Virus Replication/drug effects ; }, abstract = {There is a pressing need for modeling of the symbiotic and at times dysbiotic relationship established between bacterial microbiomes and human mucosal surfaces. In particular clinical studies have indicated that the complex vaginal microbiome (VMB) contributes to the protection against sexually-transmitted pathogens including the life-threatening human immunodeficiency virus (HIV-1). The human microbiome project has substantially increased our understanding of the complex bacterial communities in the vagina however, as is the case for most microbiomes, very few of the community member species have been successfully cultivated in the laboratory limiting the types of studies that can be completed. A genetically controlled ex vivo model system is critically needed to study the complex interactions and associated molecular dialog. We present the first vaginal mucosal culture model that supports colonization by both healthy and dysbiotic VMB from vaginal swabs collected from routine gynecological patients. The immortalized vaginal epithelial cells used in the model and VMB cryopreservation methods provide the opportunity to reproducibly create replicates for lab-based evaluations of this important mucosal/bacterial community interface. The culture system also contains HIV-1 susceptible cells allowing us to study the impact of representative microbiomes on replication. Our results show that our culture system supports stable and reproducible colonization by VMB representing distinct community state types and that the selected representatives have significantly different effects on the replication of HIV-1. Further, we show the utility of the system to predict unwanted alterations in efficacy or bacterial community profiles following topical application of a front line antiretroviral.}, } @article {pmid24643867, year = {2014}, author = {Quinn, RA and Lim, YW and Maughan, H and Conrad, D and Rohwer, F and Whiteson, KL}, title = {Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung.}, journal = {mBio}, volume = {5}, number = {2}, pages = {e00956-13}, pmid = {24643867}, issn = {2150-7511}, support = {R01 GM095384/GM/NIGMS NIH HHS/United States ; R01 GM095384-01/GM/NIGMS NIH HHS/United States ; R01GM095384-01S1/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Infections/*microbiology ; *Biota ; Cystic Fibrosis/*complications ; High-Throughput Nucleotide Sequencing ; Humans ; Lung/*microbiology ; Metabolic Networks and Pathways/genetics ; Metagenome ; Sputum/microbiology ; Transcriptome ; }, abstract = {The cystic fibrosis (CF) lung contains thick mucus colonized by opportunistic pathogens which adapt to the CF lung environment over decades. The difficulty associated with sampling airways has impeded a thorough examination of the biochemical microhabitats these pathogens are exposed to. An indirect approach is to study the responses of microbial communities to these microhabitats, facilitated by high-throughput sequencing of microbial DNA and RNA from sputum samples. Microbial metagenomes and metatranscriptomes were sequenced from multiple CF patients, and the reads were assigned taxonomy and function through sequence homology to NCBI and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database hierarchies. For a comparison, saliva microbial metagenomes from the Human Microbiome Project (HMP) were also analyzed. These analyses identified that functions encoded and expressed by CF microbes were significantly enriched for amino acid catabolism, folate biosynthesis, and lipoic acid biosynthesis. The data indicate that the community uses oxidative phosphorylation as a major energy source but that terminal electron acceptors were diverse. Nitrate reduction was the most abundant anaerobic respiratory pathway, and genes for nitrate reductase were largely assigned to Pseudomonas and Rothia. Although many reductive pathways of the nitrogen cycle were present, the cycle was incomplete, because the oxidative pathways were absent. Due to the abundant amino acid catabolism and incomplete nitrogen cycle, the CF microbial community appears to accumulate ammonia. This finding was verified experimentally using a CF bronchiole culture model system. The data also revealed abundant sensing and transport of iron, ammonium, zinc, and other metals along with a low-oxygen environment. This study reveals the core biochemistry and physiology of the CF microbiome. IMPORTANCE The cystic fibrosis (CF) microbial community is complex and adapts to the environmental conditions of the lung over the lifetime of a CF patient. This analysis illustrates the core functions of the CF microbial community in the context of CF lung biochemistry. There are many studies of the metabolism and physiology of individual microbes within the CF lung, but none that collectively analyze data from the whole microbiome. Understanding the core metabolism of microbes that inhabit the CF lung can provide new targets for novel therapies. The fundamental processes that CF pathogens rely on for survival may represent an Achilles heel for this pathogenic community. Novel therapies that are designed to disrupt understudied survival strategies of the CF microbial community may succeed against otherwise untreatable or antibiotic-resistant microbes.}, } @article {pmid24601676, year = {2014}, author = {Whelan, FJ and Verschoor, CP and Stearns, JC and Rossi, L and Luinstra, K and Loeb, M and Smieja, M and Johnstone, J and Surette, MG and Bowdish, DM}, title = {The loss of topography in the microbial communities of the upper respiratory tract in the elderly.}, journal = {Annals of the American Thoracic Society}, volume = {11}, number = {4}, pages = {513-521}, doi = {10.1513/AnnalsATS.201310-351OC}, pmid = {24601676}, issn = {2325-6621}, support = {//Canadian Institutes of Health Research/Canada ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; DNA, Bacterial/*genetics ; Female ; Humans ; Male ; Microbiota/*genetics/immunology ; Nasal Cavity/immunology/*microbiology ; Oropharynx/immunology/*microbiology ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/*genetics ; Respiratory Tract Infections/immunology/*microbiology ; Sequence Analysis, DNA ; Streptococcus/*genetics ; Streptococcus pneumoniae/genetics ; Young Adult ; }, abstract = {RATIONALE: The microbial communities inhabiting the upper respiratory tract protect from respiratory infection. The maturity of the immune system is a major influence on the composition of the microbiome and, in youth, the microbiota and immune system are believed to mature in tandem. With age, immune function declines and susceptibility to respiratory infection increases. Whether these changes contribute to the microbial composition of the respiratory tract is unknown.

OBJECTIVES: Our goal was to determine whether the microbes of the upper respiratory tract differ between mid-aged adults (18-40 yr) and the elderly (>65 yr).

METHODS: Microbiomes of the anterior nares and oropharynx of elderly individuals were evaluated by 16S rRNA gene sequencing. These communities were compared with data on mid-aged adults obtained from the Human Microbiome Project.

MEASUREMENTS AND MAIN RESULTS: The microbiota of the elderly showed no associations with sex, comorbidities, residence, or vaccinations. Comparisons of mid-aged adults and the elderly demonstrated significant differences in the composition of the anterior nares and oropharynx, including a population in the anterior nares of the elderly that more closely resembled the oropharynx than the anterior nares of adults. The elderly oropharyngeal microbiota were characterized by increased abundance of streptococci, specifically, Streptococcus salivarius group species, but not Streptococcus pneumoniae, carriage of which was low (<3% of participants), as demonstrated by PCR (n = 4/123).

CONCLUSIONS: Microbial populations of the upper respiratory tract in mid-aged adults and the elderly differ; it is possible that these differences contribute to the increased risk of respiratory infections experienced by the elderly.}, } @article {pmid24591822, year = {2014}, author = {Sze, MA and Hogg, JC and Sin, DD}, title = {Bacterial microbiome of lungs in COPD.}, journal = {International journal of chronic obstructive pulmonary disease}, volume = {9}, number = {}, pages = {229-238}, pmid = {24591822}, issn = {1178-2005}, mesh = {Anti-Bacterial Agents/therapeutic use ; Disease Progression ; Gastrointestinal Tract/microbiology ; Humans ; Lung/drug effects/immunology/*microbiology/physiopathology ; *Microbiota ; Pulmonary Disease, Chronic Obstructive/drug therapy/epidemiology/immunology/*microbiology/physiopathology ; Risk Factors ; Smoking/adverse effects/epidemiology ; }, abstract = {Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death in the world. Although smoking is the main risk factor for this disease, only a minority of smokers develop COPD. Why this happens is largely unknown. Recent discoveries by the human microbiome project have shed new light on the importance and richness of the bacterial microbiota at different body sites in human beings. The microbiota plays a particularly important role in the development and functional integrity of the immune system. Shifts or perturbations in the microbiota can lead to disease. COPD is in part mediated by dysregulated immune responses to cigarette smoke and other environmental insults. Although traditionally the lung has been viewed as a sterile organ, by using highly sensitive genomic techniques, recent reports have identified diverse bacterial communities in the human lung that may change in COPD. This review summarizes the current knowledge concerning the lung microbiota in COPD and its potential implications for pathogenesis of the disease.}, } @article {pmid24522917, year = {2014}, author = {Ma, Y and Madupu, R and Karaoz, U and Nossa, CW and Yang, L and Yooseph, S and Yachimski, PS and Brodie, EL and Nelson, KE and Pei, Z}, title = {Human papillomavirus community in healthy persons, defined by metagenomics analysis of human microbiome project shotgun sequencing data sets.}, journal = {Journal of virology}, volume = {88}, number = {9}, pages = {4786-4797}, pmid = {24522917}, issn = {1098-5514}, support = {UH3 CA140233/CA/NCI NIH HHS/United States ; U01 CA182370/CA/NCI NIH HHS/United States ; UH3CA140233/CA/NCI NIH HHS/United States ; R01 CA159036/CA/NCI NIH HHS/United States ; U01CA18237/CA/NCI NIH HHS/United States ; }, mesh = {Coinfection/epidemiology/virology ; Female ; *Healthy Volunteers ; Humans ; Metagenomics ; *Microbiota ; Papillomaviridae/*classification/genetics/*isolation & purification ; Papillomavirus Infections/epidemiology/*virology ; Prevalence ; Sequence Analysis, DNA ; }, abstract = {UNLABELLED: Human papillomavirus (HPV) causes a number of neoplastic diseases in humans. Here, we show a complex normal HPV community in a cohort of 103 healthy human subjects, by metagenomics analysis of the shotgun sequencing data generated from the NIH Human Microbiome Project. The overall HPV prevalence was 68.9% and was highest in the skin (61.3%), followed by the vagina (41.5%), mouth (30%), and gut (17.3%). Of the 109 HPV types as well as additional unclassified types detected, most were undetectable by the widely used commercial kits targeting the vaginal/cervical HPV types. These HPVs likely represent true HPV infections rather than transitory exposure because of strong organ tropism and persistence of the same HPV types in repeat samples. Coexistence of multiple HPV types was found in 48.1% of the HPV-positive samples. Networking between HPV types, cooccurrence or exclusion, was detected in vaginal and skin samples. Large contigs assembled from short HPV reads were obtained from several samples, confirming their genuine HPV origin. This first large-scale survey of HPV using a shotgun sequencing approach yielded a comprehensive map of HPV infections among different body sites of healthy human subjects.

IMPORTANCE: This nonbiased survey indicates that the HPV community in healthy humans is much more complex than previously defined by widely used kits that are target selective for only a few high- and low-risk HPV types for cervical cancer. The importance of nononcogenic viruses in a mixed HPV infection could be for stimulating or inhibiting a coexisting oncogenic virus via viral interference or immune cross-reaction. Knowledge gained from this study will be helpful to guide the designing of epidemiological and clinical studies in the future to determine the impact of nononcogenic HPV types on the outcome of HPV infections.}, } @article {pmid24501640, year = {2013}, author = {Shogan, BD and Smith, DP and Packman, AI and Kelley, ST and Landon, EM and Bhangar, S and Vora, GJ and Jones, RM and Keegan, K and Stephens, B and Ramos, T and Kirkup, BC and Levin, H and Rosenthal, M and Foxman, B and Chang, EB and Siegel, J and Cobey, S and An, G and Alverdy, JC and Olsiewski, PJ and Martin, MO and Marrs, R and Hernandez, M and Christley, S and Morowitz, M and Weber, S and Gilbert, J}, title = {The Hospital Microbiome Project: Meeting report for the 2nd Hospital Microbiome Project, Chicago, USA, January 15(th), 2013.}, journal = {Standards in genomic sciences}, volume = {8}, number = {3}, pages = {571-579}, pmid = {24501640}, issn = {1944-3277}, } @article {pmid24486053, year = {2014}, author = {Morgan, XC and Huttenhower, C}, title = {Meta'omic analytic techniques for studying the intestinal microbiome.}, journal = {Gastroenterology}, volume = {146}, number = {6}, pages = {1437-1448.e1}, doi = {10.1053/j.gastro.2014.01.049}, pmid = {24486053}, issn = {1528-0012}, support = {R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/*genetics ; DNA, Bacterial/analysis ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Genotype ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestines/*microbiology ; *Metagenome ; *Metagenomics/methods ; Microbiota/*genetics ; Models, Statistical ; Phenotype ; Phylogeny ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Ribotyping ; Transcriptome ; }, abstract = {Nucleotide sequencing has become increasingly common and affordable, and is now a vital tool for studies of the human microbiome. Comprehensive microbial community surveys such as MetaHit and the Human Microbiome Project have described the composition and molecular functional profile of the healthy (normal) intestinal microbiome. This knowledge will increase our ability to analyze host and microbial DNA (genome) and RNA (transcriptome) sequences. Bioinformatic and statistical tools then can be used to identify dysbioses that might cause disease, and potential treatments. Analyses that identify perturbations in specific molecules can leverage thousands of culture-based isolate genomes to contextualize culture-independent sequences, or may integrate sequence data with whole-community functional assays such as metaproteomic or metabolomic analyses. We review the state of available systems-level models for studies of the intestinal microbiome, along with analytic techniques and tools that can be used to determine its functional capabilities in healthy and unhealthy individuals.}, } @article {pmid24451062, year = {2013}, author = {Edlund, A and Yang, Y and Hall, AP and Guo, L and Lux, R and He, X and Nelson, KE and Nealson, KH and Yooseph, S and Shi, W and McLean, JS}, title = {An in vitro biofilm model system maintaining a highly reproducible species and metabolic diversity approaching that of the human oral microbiome.}, journal = {Microbiome}, volume = {1}, number = {1}, pages = {25}, pmid = {24451062}, issn = {2049-2618}, support = {R01 GM095373/GM/NIGMS NIH HHS/United States ; T90 DE022734/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Our knowledge of microbial diversity in the human oral cavity has vastly expanded during the last two decades of research. However, much of what is known about the behavior of oral species to date derives from pure culture approaches and the studies combining several cultivated species, which likely does not fully reflect their function in complex microbial communities. It has been shown in studies with a limited number of cultivated species that early oral biofilm development occurs in a successional manner and that continuous low pH can lead to an enrichment of aciduric species. Observations that in vitro grown plaque biofilm microcosms can maintain similar pH profiles in response to carbohydrate addition as plaque in vivo suggests a complex microbial community can be established in the laboratory. In light of this, our primary goal was to develop a robust in vitro biofilm-model system from a pooled saliva inoculum in order to study the stability, reproducibility, and development of the oral microbiome, and its dynamic response to environmental changes from the community to the molecular level.

RESULTS: Comparative metagenomic analyses confirmed a high similarity of metabolic potential in biofilms to recently available oral metagenomes from healthy subjects as part of the Human Microbiome Project. A time-series metagenomic analysis of the taxonomic community composition in biofilms revealed that the proportions of major species at 3 hours of growth are maintained during 48 hours of biofilm development. By employing deep pyrosequencing of the 16S rRNA gene to investigate this biofilm model with regards to bacterial taxonomic diversity, we show a high reproducibility of the taxonomic carriage and proportions between: 1) individual biofilm samples; 2) biofilm batches grown at different dates; 3) DNA extraction techniques and 4) research laboratories.

CONCLUSIONS: Our study demonstrates that we now have the capability to grow stable oral microbial in vitro biofilms containing more than one hundred operational taxonomic units (OTU) which represent 60-80% of the original inoculum OTU richness. Previously uncultivated Human Oral Taxa (HOT) were identified in the biofilms and contributed to approximately one-third of the totally captured 16S rRNA gene diversity. To our knowledge, this represents the highest oral bacterial diversity reported for an in vitro model system so far. This robust model will help investigate currently uncultivated species and the known virulence properties for many oral pathogens not solely restricted to pure culture systems, but within multi-species biofilms.}, } @article {pmid24429191, year = {2013}, author = {Twigg, HL and Morris, A and Ghedin, E and Curtis, JL and Huffnagle, GB and Crothers, K and Campbell, TB and Flores, SC and Fontenot, AP and Beck, JM and Huang, L and Lynch, S and Knox, KS and Weinstock, G and , }, title = {Use of bronchoalveolar lavage to assess the respiratory microbiome: signal in the noise.}, journal = {The Lancet. Respiratory medicine}, volume = {1}, number = {5}, pages = {354-356}, doi = {10.1016/S2213-2600(13)70117-6}, pmid = {24429191}, issn = {2213-2619}, support = {R01 HL090342/HL/NHLBI NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; }, mesh = {Bronchoalveolar Lavage/methods ; Bronchoalveolar Lavage Fluid/*microbiology ; Humans ; Lung/*microbiology ; *Microbiota ; }, } @article {pmid24416266, year = {2014}, author = {Finucane, MM and Sharpton, TJ and Laurent, TJ and Pollard, KS}, title = {A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter.}, journal = {PloS one}, volume = {9}, number = {1}, pages = {e84689}, pmid = {24416266}, issn = {1932-6203}, mesh = {Adult ; Bacteria/classification ; Body Mass Index ; Case-Control Studies ; *Classification ; Gastrointestinal Tract/*microbiology ; Humans ; *Microbiota ; Obesity/*microbiology ; }, abstract = {Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic target. However, human and animal-model studies have yielded conflicting results about the precise nature of associations between microbiome composition and obesity. In this paper, we use publicly available data from the Human Microbiome Project (HMP) and MetaHIT, both surveys of healthy adults that include obese individuals, plus two smaller studies that specifically examined lean versus obese adults. We find that inter-study variability in the taxonomic composition of stool microbiomes far exceeds differences between lean and obese individuals within studies. Our analyses further reveal a high degree of variability in stool microbiome composition and diversity across individuals. While we confirm the previously published small, but statistically significant, differences in phylum-level taxonomic composition between lean and obese individuals in several cohorts, we find no association between BMI and taxonomic composition of stool microbiomes in the larger HMP and MetaHIT datasets. We explore a range of different statistical techniques and show that this result is robust to the choice of methodology. Differences between studies are likely due to a combination of technical and clinical factors. We conclude that there is no simple taxonomic signature of obesity in the microbiota of the human gut.}, } @article {pmid24390919, year = {2014}, author = {Sirota, I and Zarek, SM and Segars, JH}, title = {Potential influence of the microbiome on infertility and assisted reproductive technology.}, journal = {Seminars in reproductive medicine}, volume = {32}, number = {1}, pages = {35-42}, pmid = {24390919}, issn = {1526-4564}, support = {ZIE HD008737-12//Intramural NIH HHS/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Cytokines/physiology ; Embryo Implantation ; Embryo Transfer ; Estrogens/blood ; Female ; Humans ; Infertility, Female/*microbiology ; Lactobacillus ; Microbiota/*physiology ; Pregnancy ; Progesterone/blood ; *Reproductive Techniques, Assisted ; Vagina/microbiology ; Vaginosis, Bacterial/microbiology ; }, abstract = {Although an altered vaginal microbiota has been demonstrated to affect parturition, its role in assisted reproductive technologies is uncertain. Nevertheless, the effect of known pathogens such as Mycoplasma tuberculosis, Chlamydia trachomatis, and Neisseria gonorrhoeae is clear, causing subclinical changes thought to be risk factors in subfertility. The Human Microbiome Project (HMP) has allowed for metagenomic studies to aid in characterizing normal vaginal flora. Recent findings from the HMP demonstrate that many different species of Lactobacillus are present in the vaginal tract, with a few that predominate. Studies that characterize the vaginal microbiome in assisted reproductive technology support the hypothesis that colonizing the transfer-catheter tip with Lactobacillus crispatus at the time of embryo transfer may increase the rates of implantation and live birth rate while decreasing the rate of infection. In addition, there is some evidence that a progesterone-resistant endometrium might increase the risk of an abnormal vaginal microbiome.}, } @article {pmid24390916, year = {2014}, author = {Prince, AL and Antony, KM and Ma, J and Aagaard, KM}, title = {The microbiome and development: a mother's perspective.}, journal = {Seminars in reproductive medicine}, volume = {32}, number = {1}, pages = {14-22}, doi = {10.1055/s-0033-1361818}, pmid = {24390916}, issn = {1526-4564}, mesh = {Child Development/*physiology ; Female ; Humans ; Infant, Newborn ; Microbiota/*physiology ; *Mothers ; Placenta/microbiology ; Pregnancy ; Premature Birth ; }, abstract = {Dysbiosis of the microbiome has been associated with type II diabetes mellitus, obesity, inflammatory bowel disorders, and colorectal cancer, and recently, the Human Microbiome Project Consortium has helped to define a healthy microbiome. Now research has begun to investigate how the microbiome is established, and in this article, we will discuss the maternal influences on the establishment of the microbiome. The inoculation of an individual's microbiome is highly dependent on the maternal microbiome, and changes occur in the maternal microbiome during pregnancy that may help to shape the neonatal microbiome. Further, we consider how mode of delivery may shape the developing microbiome of a neonate, and we end by discussing how the microbiome may impact preterm birth and the possibility of bacterial colonization of the placenta. Although the current literature demonstrates that the transformation of the maternal microbiome during pregnancy effects the establishment of the neonatal microbiome, further research is needed to explore how the microbiome shapes our metabolism and developing immune system.}, } @article {pmid24386477, year = {2013}, author = {Ramakrishnan, VR and Feazel, LM and Gitomer, SA and Ir, D and Robertson, CE and Frank, DN}, title = {The microbiome of the middle meatus in healthy adults.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e85507}, pmid = {24386477}, issn = {1932-6203}, support = {R21 HG005964/HG/NHGRI NIH HHS/United States ; HG005964/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Female ; Gram-Positive Bacteria/classification/*genetics/isolation & purification ; Humans ; Male ; *Microbiota ; Middle Aged ; Nasal Cavity/*microbiology ; Paranasal Sinuses/*microbiology ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Rhinitis and rhinosinusitis are multifactorial disease processes in which bacteria may play a role either in infection or stimulation of the inflammatory process. Rhinosinusitis has been historically studied with culture-based techniques, which have implicated several common pathogens in disease states. More recently, the NIH Human Microbiome Project has examined the microbiome at a number of accessible body sites, and demonstrated differences among healthy and diseased patients. Recent DNA-based sinus studies have suggested that healthy sinuses are not sterile, as was previously believed, but the normal sinonasal microbiome has yet to be thoroughly examined. Middle meatus swab specimens were collected from 28 consecutive patients presenting with no signs or symptoms of rhinosinusitis. Bacterial colonization was assessed in these specimens using quantitative PCR and 16S rRNA pyrosequencing. All subjects were positive for bacterial colonization of the middle meatus. Staphylococcus aureus, Staphylococcus epidermidis and Propionibacterium acnes were the most prevalent and abundant microorganisms detected. Rich and diverse bacterial assemblages are present in the sinonasal cavity in the normal state, including opportunistic pathogens typically found in the nasopharynx. This work helps establish a baseline for understanding how the sinonasal microbiome may impact diseases of the upper airways.}, } @article {pmid24349412, year = {2013}, author = {Culligan, EP and Sleator, RD and Marchesi, JR and Hill, C}, title = {Functional environmental screening of a metagenomic library identifies stlA; a unique salt tolerance locus from the human gut microbiome.}, journal = {PloS one}, volume = {8}, number = {12}, pages = {e82985}, pmid = {24349412}, issn = {1932-6203}, mesh = {Adult ; Bacterial Proteins/*genetics ; Datasets as Topic ; *Genes, Bacterial ; *Genetic Loci ; Humans ; Intestines/*microbiology ; Male ; Metagenomics/methods ; Microbiota/*genetics ; Salt Tolerance/*genetics ; }, abstract = {Functional environmental screening of metagenomic libraries is a powerful means to identify and assign function to novel genes and their encoded proteins without any prior sequence knowledge. In the current study we describe the identification and subsequent analysis of a salt-tolerant clone from a human gut metagenomic library. Following transposon mutagenesis we identified an unknown gene (stlA, for "salt tolerance locus A") with no current known homologues in the databases. Subsequent cloning and expression in Escherichia coli MKH13 revealed that stlA confers a salt tolerance phenotype in its surrogate host. Furthermore, a detailed in silico analysis was also conducted to gain additional information on the properties of the encoded StlA protein. The stlA gene is rare when searched against human metagenome datasets such as MetaHit and the Human Microbiome Project and represents a novel and unique salt tolerance determinant which appears to be found exclusively in the human gut environment.}, } @article {pmid24298178, year = {2013}, author = {Landy, J and Hart, A}, title = {The microbiome in inflammatory bowel disease and beyond.}, journal = {Clinical medicine (London, England)}, volume = {13 Suppl 6}, number = {}, pages = {s29-31}, doi = {10.7861/clinmedicine.13-6-s29}, pmid = {24298178}, issn = {1473-4893}, mesh = {Anti-Bacterial Agents ; Colitis, Ulcerative ; Crohn Disease ; Humans ; *Inflammatory Bowel Diseases/immunology ; *Microbiota ; Probiotics ; }, abstract = {The diverse and complex community of microorganisms that has co-evolved with the human gut is vital to intestinal functioning, and disturbances in the microbiota and its relationship with the host immune system have been linked to inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. This has suggested several treatment options, including antibiotics, probiotics and faecal transplantation. The human microbiome project has been established to enable comprehensive characterisation of the human microbiota and in the coming years, knowledge in this area is expected to continue to expand.}, } @article {pmid24280061, year = {2013}, author = {Vázquez-Baeza, Y and Pirrung, M and Gonzalez, A and Knight, R}, title = {EMPeror: a tool for visualizing high-throughput microbial community data.}, journal = {GigaScience}, volume = {2}, number = {1}, pages = {16}, pmid = {24280061}, issn = {2047-217X}, abstract = {BACKGROUND: As microbial ecologists take advantage of high-throughput sequencing technologies to describe microbial communities across ever-increasing numbers of samples, new analysis tools are required to relate the distribution of microbes among larger numbers of communities, and to use increasingly rich and standards-compliant metadata to understand the biological factors driving these relationships. In particular, the Earth Microbiome Project drives these needs by profiling the genomic content of tens of thousands of samples across multiple environment types.

FINDINGS: Features of EMPeror include: ability to visualize gradients and categorical data, visualize different principal coordinates axes, present the data in the form of parallel coordinates, show taxa as well as environmental samples, dynamically adjust the size and transparency of the spheres representing the communities on a per-category basis, dynamically scale the axes according to the fraction of variance each explains, show, hide or recolor points according to arbitrary metadata including that compliant with the MIxS family of standards developed by the Genomic Standards Consortium, display jackknifed-resampled data to assess statistical confidence in clustering, perform coordinate comparisons (useful for procrustes analysis plots), and greatly reduce loading times and overall memory footprint compared with existing approaches. Additionally, ease of sharing, given EMPeror's small output file size, enables agile collaboration by allowing users to embed these visualizations via emails or web pages without the need for extra plugins.

CONCLUSIONS: Here we present EMPeror, an open source and web browser enabled tool with a versatile command line interface that allows researchers to perform rapid exploratory investigations of 3D visualizations of microbial community data, such as the widely used principal coordinates plots. EMPeror includes a rich set of controllers to modify features as a function of the metadata. By being specifically tailored to the requirements of microbial ecologists, EMPeror thus increases the speed with which insight can be gained from large microbiome datasets.}, } @article {pmid24225315, year = {2014}, author = {Caspi, R and Altman, T and Billington, R and Dreher, K and Foerster, H and Fulcher, CA and Holland, TA and Keseler, IM and Kothari, A and Kubo, A and Krummenacker, M and Latendresse, M and Mueller, LA and Ong, Q and Paley, S and Subhraveti, P and Weaver, DS and Weerasinghe, D and Zhang, P and Karp, PD}, title = {The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D459-71}, pmid = {24225315}, issn = {1362-4962}, support = {GM077678/GM/NIGMS NIH HHS/United States ; R01 GM080746/GM/NIGMS NIH HHS/United States ; GM088849/GM/NIGMS NIH HHS/United States ; U24 GM077678/GM/NIGMS NIH HHS/United States ; GM75742/GM/NIGMS NIH HHS/United States ; GM080746/GM/NIGMS NIH HHS/United States ; }, mesh = {*Databases, Chemical ; Enzymes/chemistry/classification/*metabolism ; Gene Ontology ; Genome ; Internet ; Kinetics ; *Metabolic Networks and Pathways/genetics ; Polysaccharides/metabolism ; Software ; }, abstract = {The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37,000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states.}, } @article {pmid24203705, year = {2014}, author = {Huang, K and Brady, A and Mahurkar, A and White, O and Gevers, D and Huttenhower, C and Segata, N}, title = {MetaRef: a pan-genomic database for comparative and community microbial genomics.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D617-24}, pmid = {24203705}, issn = {1362-4962}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; }, mesh = {Archaea/classification ; Bacteria/classification ; *Databases, Genetic ; *Genome, Archaeal ; *Genome, Bacterial ; Genomics ; Internet ; Metagenomics ; Microbiota ; Molecular Sequence Annotation ; Multigene Family ; Phylogeny ; }, abstract = {Microbial genome sequencing is one of the longest-standing areas of biological database development, but high-throughput, low-cost technologies have increased its throughput to an unprecedented number of new genomes per year. Several thousand microbial genomes are now available, necessitating new approaches to organizing information on gene function, phylogeny and microbial taxonomy to facilitate downstream biological interpretation. MetaRef, available at http://metaref.org, is a novel online resource systematically cataloguing a comprehensive pan-genome of all microbial clades with sequenced isolates. It organizes currently available draft and finished bacterial and archaeal genomes into quality-controlled clades, reports all core and pan gene families at multiple levels in the resulting taxonomy, and it annotates families' conservation, phylogeny and consensus functional information. MetaRef also provides a comprehensive non-redundant reference gene catalogue for metagenomic studies, including the abundance and prevalence of all gene families in the >700 shotgun metagenomic samples of the Human Microbiome Project. This constitutes a systematic mapping of clade-specific microbial functions within the healthy human microbiome across multiple body sites and can be used as reference for identifying potential functional biomarkers in disease-associate microbiomes. MetaRef provides all information both as an online browsable resource and as downloadable sequences and tabular data files that can be used for subsequent offline studies.}, } @article {pmid24180596, year = {2013}, author = {Amirian, ES and Petrosino, JF and Ajami, NJ and Liu, Y and Mims, MP and Scheurer, ME}, title = {Potential role of gastrointestinal microbiota composition in prostate cancer risk.}, journal = {Infectious agents and cancer}, volume = {8}, number = {1}, pages = {42}, pmid = {24180596}, issn = {1750-9378}, abstract = {BACKGROUND: Among men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk.

The composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents.

TESTING THE HYPOTHESIS: Because very little preliminary data exist on this potential association, a case-control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time.

Given the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host's risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies.}, } @article {pmid24178066, year = {2014}, author = {Hong, P and Liu, CM and Nordstrom, L and Lalwani, AK}, title = {The role of the human microbiome in otolaryngology-head and neck surgery: a contemporary review.}, journal = {The Laryngoscope}, volume = {124}, number = {6}, pages = {1352-1357}, pmid = {24178066}, issn = {1531-4995}, support = {R15 DE021194/DE/NIDCR NIH HHS/United States ; 1R15DE021194-01/DE/NIDCR NIH HHS/United States ; }, mesh = {Female ; Head/microbiology/surgery ; Humans ; Male ; *Microbiota ; Neck/microbiology/surgery ; Otorhinolaryngologic Diseases/*microbiology/*surgery ; Otorhinolaryngologic Surgical Procedures/*methods ; Risk Assessment ; Sensitivity and Specificity ; Treatment Outcome ; }, abstract = {OBJECTIVES/HYPOTHESIS: The human microbiome represents the collective genomes and gene products of microbes living within and on humans. The objective of this review is to provide a summary of the current microbiome literature pertaining to otolaryngology-head and neck surgery.

DATA SOURCE: Ovid MEDLINE.

METHODS: Scientific publications with clinical correlates.

RESULTS: Human microbiome studies have been facilitated by culture-independent, high-throughput sequencing methods. Data from the Human Microbiome Project has shown that the composition of the human microbiome is specific to each body site and that each individual has a unique microbiome. Alterations in the human microbiome are associated with some disease states; thus, novel therapeutic strategies are being developed based on concepts and findings stemming from microbiome research.

CONCLUSIONS: Although a growing body of research shows potential significance of the human microbiome for human health and disease, there is a paucity of microbiome studies in otolaryngology. More studies are required to increase our understanding of the indigenous microbiota and their effects on diseases of the head and neck.}, } @article {pmid24173537, year = {2014}, author = {Pylro, VS and Roesch, LF and Ortega, JM and do Amaral, AM and Tótola, MR and Hirsch, PR and Rosado, AS and Góes-Neto, A and da Costa da Silva, AL and Rosa, CA and Morais, DK and Andreote, FD and Duarte, GF and de Melo, IS and Seldin, L and Lambais, MR and Hungria, M and Peixoto, RS and Kruger, RH and Tsai, SM and Azevedo, V and , }, title = {Brazilian Microbiome Project: revealing the unexplored microbial diversity--challenges and prospects.}, journal = {Microbial ecology}, volume = {67}, number = {2}, pages = {237-241}, pmid = {24173537}, issn = {1432-184X}, mesh = {Advisory Committees/*organization & administration ; Animals ; *Biodiversity ; Brazil ; Databases, Factual ; *Metagenome ; *Microbiota ; Plants/microbiology ; Soil Microbiology ; }, abstract = {The Brazilian Microbiome Project (BMP) aims to assemble a Brazilian Metagenomic Consortium/Database. At present, many metagenomic projects underway in Brazil are widely known. Our goal in this initiative is to co-ordinate and standardize these together with new projects to come. It is estimated that Brazil hosts approximately 20 % of the entire world's macroorganism biological diversity. It is 1 of the 17 countries that share nearly 70 % of the world's catalogued animal and plant species, and is recognized as one of the most megadiverse countries. At the end of 2012, Brazil has joined GBIF (Global Biodiversity Information Facility), as associated member, to improve the access to the Brazilian biodiversity data in a free and open way. This was an important step toward increasing international collaboration and clearly shows the commitment of the Brazilian government in directing national policies toward sustainable development. Despite its importance, the Brazilian microbial diversity is still considered to be largely unknown, and it is clear that to maintain ecosystem dynamics and to sustainably manage land use, it is crucial to understand the biological and functional diversity of the system. This is the first attempt to collect and collate information about Brazilian microbial genetic and functional diversity in a systematic and holistic manner. The success of the BMP depends on a massive collaborative effort of both the Brazilian and international scientific communities, and therefore, we invite all colleagues to participate in this project.}, } @article {pmid24160697, year = {2014}, author = {Mani, S and Boelsterli, UA and Redinbo, MR}, title = {Understanding and modulating mammalian-microbial communication for improved human health.}, journal = {Annual review of pharmacology and toxicology}, volume = {54}, number = {}, pages = {559-580}, pmid = {24160697}, issn = {1545-4304}, support = {CA161879/CA/NCI NIH HHS/United States ; R01 CA161879/CA/NCI NIH HHS/United States ; CA98468/CA/NCI NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; R01 CA127231/CA/NCI NIH HHS/United States ; CA127231/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents/pharmacology ; Camptothecin/administration & dosage/adverse effects/analogs & derivatives ; Disease Models, Animal ; Enteritis/chemically induced/drug therapy ; Eosinophilia/chemically induced/drug therapy ; Gastritis/chemically induced/drug therapy ; Gastrointestinal Tract/*drug effects/*microbiology ; Glucuronidase/pharmacology ; Humans ; Irinotecan ; Lipopolysaccharides/pharmacology ; *Mammals ; Microbiota/*drug effects ; }, abstract = {The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.}, } @article {pmid24146609, year = {2013}, author = {Carr, R and Shen-Orr, SS and Borenstein, E}, title = {Reconstructing the genomic content of microbiome taxa through shotgun metagenomic deconvolution.}, journal = {PLoS computational biology}, volume = {9}, number = {10}, pages = {e1003292}, pmid = {24146609}, issn = {1553-7358}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; DP2AT00780201/AT/NCCIH NIH HHS/United States ; }, mesh = {Genome, Bacterial/*genetics ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; Sequence Analysis, DNA/*methods ; Tongue/microbiology ; }, abstract = {Metagenomics has transformed our understanding of the microbial world, allowing researchers to bypass the need to isolate and culture individual taxa and to directly characterize both the taxonomic and gene compositions of environmental samples. However, associating the genes found in a metagenomic sample with the specific taxa of origin remains a critical challenge. Existing binning methods, based on nucleotide composition or alignment to reference genomes allow only a coarse-grained classification and rely heavily on the availability of sequenced genomes from closely related taxa. Here, we introduce a novel computational framework, integrating variation in gene abundances across multiple samples with taxonomic abundance data to deconvolve metagenomic samples into taxa-specific gene profiles and to reconstruct the genomic content of community members. This assembly-free method is not bounded by various factors limiting previously described methods of metagenomic binning or metagenomic assembly and represents a fundamentally different approach to metagenomic-based genome reconstruction. An implementation of this framework is available at http://elbo.gs.washington.edu/software.html. We first describe the mathematical foundations of our framework and discuss considerations for implementing its various components. We demonstrate the ability of this framework to accurately deconvolve a set of metagenomic samples and to recover the gene content of individual taxa using synthetic metagenomic samples. We specifically characterize determinants of prediction accuracy and examine the impact of annotation errors on the reconstructed genomes. We finally apply metagenomic deconvolution to samples from the Human Microbiome Project, successfully reconstructing genus-level genomic content of various microbial genera, based solely on variation in gene count. These reconstructed genera are shown to correctly capture genus-specific properties. With the accumulation of metagenomic data, this deconvolution framework provides an essential tool for characterizing microbial taxa never before seen, laying the foundation for addressing fundamental questions concerning the taxa comprising diverse microbial communities.}, } @article {pmid24136997, year = {2014}, author = {Markowitz, VM and Chen, IM and Chu, K and Szeto, E and Palaniappan, K and Pillay, M and Ratner, A and Huang, J and Pagani, I and Tringe, S and Huntemann, M and Billis, K and Varghese, N and Tennessen, K and Mavromatis, K and Pati, A and Ivanova, NN and Kyrpides, NC}, title = {IMG/M 4 version of the integrated metagenome comparative analysis system.}, journal = {Nucleic acids research}, volume = {42}, number = {Database issue}, pages = {D568-73}, pmid = {24136997}, issn = {1362-4962}, support = {U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Gene Expression Profiling ; Genome, Archaeal ; Genome, Bacterial ; Genome, Viral ; Internet ; *Metagenome ; Metagenomics/standards ; Plasmids/genetics ; Reference Standards ; Sequence Analysis, Protein ; Software ; Systems Integration ; }, abstract = {IMG/M (http://img.jgi.doe.gov/m) provides support for comparative analysis of microbial community aggregate genomes (metagenomes) in the context of a comprehensive set of reference genomes from all three domains of life, as well as plasmids, viruses and genome fragments. IMG/M's data content and analytical tools have expanded continuously since its first version was released in 2007. Since the last report published in the 2012 NAR Database Issue, IMG/M's database architecture, annotation and data integration pipelines and analysis tools have been extended to copewith the rapid growth in the number and size of metagenome data sets handled by the system. IMG/M data marts provide support for the analysis of publicly available genomes, expert review of metagenome annotations (IMG/M ER: http://img.jgi.doe.gov/mer) and Human Microbiome Project (HMP)-specific metagenome samples (IMG/M HMP: http://img.jgi.doe.gov/imgm_hmp).}, } @article {pmid23997318, year = {2012}, author = {Rup, L}, title = {The human microbiome project.}, journal = {Indian journal of microbiology}, volume = {52}, number = {3}, pages = {315}, doi = {10.1007/s12088-012-0304-9}, pmid = {23997318}, issn = {0046-8991}, } @article {pmid23975157, year = {2013}, author = {Langille, MG and Zaneveld, J and Caporaso, JG and McDonald, D and Knights, D and Reyes, JA and Clemente, JC and Burkepile, DE and Vega Thurber, RL and Knight, R and Beiko, RG and Huttenhower, C}, title = {Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences.}, journal = {Nature biotechnology}, volume = {31}, number = {9}, pages = {814-821}, pmid = {23975157}, issn = {1546-1696}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; /CAPMC/CIHR/Canada ; U01HG004866/HG/NHGRI NIH HHS/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Genes, Bacterial/genetics/physiology ; Genetic Markers/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.}, } @article {pmid23961316, year = {2013}, author = {Smith, D and Alverdy, J and An, G and Coleman, M and Garcia-Houchins, S and Green, J and Keegan, K and Kelley, ST and Kirkup, BC and Kociolek, L and Levin, H and Landon, E and Olsiewski, P and Knight, R and Siegel, J and Weber, S and Gilbert, J}, title = {The Hospital Microbiome Project: Meeting Report for the 1st Hospital Microbiome Project Workshop on sampling design and building science measurements, Chicago, USA, June 7th-8th 2012.}, journal = {Standards in genomic sciences}, volume = {8}, number = {1}, pages = {112-117}, pmid = {23961316}, issn = {1944-3277}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, abstract = {This report details the outcome of the 1st Hospital Microbiome Project workshop held on June 7th-8th, 2012 at the University of Chicago, USA. The workshop was arranged to determine the most appropriate sampling strategy and approach to building science measurement to characterize the development of a microbial community within a new hospital pavilion being built at the University of Chicago Medical Center. The workshop made several recommendations and led to the development of a full proposal to the Alfred P. Sloan Foundation as well as to the creation of the Hospital Microbiome Consortium.}, } @article {pmid23949665, year = {2013}, author = {Tickle, TL and Segata, N and Waldron, L and Weingart, U and Huttenhower, C}, title = {Two-stage microbial community experimental design.}, journal = {The ISME journal}, volume = {7}, number = {12}, pages = {2330-2339}, pmid = {23949665}, issn = {1751-7370}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bias ; Ecology/*methods/standards ; Humans ; Metagenomics ; Microbiological Techniques/*methods/standards ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Research Design/*standards ; }, abstract = {Microbial community samples can be efficiently surveyed in high throughput by sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of samples is then selected for subsequent metagenomic, metabolomic or other follow-up. Two-stage study design has long been used in ecology but has not yet been studied in-depth for high-throughput microbial community investigations. To avoid ad hoc sample selection, we developed and validated several purposive sample selection methods for two-stage studies (that is, biological criteria) targeting differing types of microbial communities. These methods select follow-up samples from large community surveys, with criteria including samples typical of the initially surveyed population, targeting specific microbial clades or rare species, maximizing diversity, representing extreme or deviant communities, or identifying communities distinct or discriminating among environment or host phenotypes. The accuracies of each sampling technique and their influences on the characteristics of the resulting selected microbial community were evaluated using both simulated and experimental data. Specifically, all criteria were able to identify samples whose properties were accurately retained in 318 paired 16S amplicon and whole-community metagenomic (follow-up) samples from the Human Microbiome Project. Some selection criteria resulted in follow-up samples that were strongly non-representative of the original survey population; diversity maximization particularly undersampled community configurations. Only selection of intentionally representative samples minimized differences in the selected sample set from the original microbial survey. An implementation is provided as the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for two-stage study design of microbial communities.}, } @article {pmid23802897, year = {2013}, author = {Hoffmann, DE and Fortenberry, JD and Ravel, J}, title = {Are changes to the common rule necessary to address evolving areas of research? A case study focusing on the human microbiome project.}, journal = {The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics}, volume = {41}, number = {2}, pages = {454-469}, pmid = {23802897}, issn = {1748-720X}, support = {R01 HG005171/HG/NHGRI NIH HHS/United States ; }, mesh = {Human Experimentation/*legislation & jurisprudence ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Patient Selection ; Research Subjects/*legislation & jurisprudence ; Social Stigma ; United States ; }, abstract = {This article examines ways in which research conducted under the Human Microbiome Project, an effort to establish a "reference catalogue" of the micro-organisms present in the human body and determine how changes in those micro-organisms affect health and disease, raise challenging issues for regulation of human subject research. The article focuses on issues related to subject selection and recruitment, group stigma, and informational risks, and explores whether: (1) the Common Rule or proposed changes to the Rule adequately address these issues and (2) the Common Rule is the most appropriate vehicle to provide regulatory oversight and guidance on these topics.}, } @article {pmid23734710, year = {2013}, author = {Ander, C and Schulz-Trieglaff, OB and Stoye, J and Cox, AJ}, title = {metaBEETL: high-throughput analysis of heterogeneous microbial populations from shotgun DNA sequences.}, journal = {BMC bioinformatics}, volume = {14 Suppl 5}, number = {Suppl 5}, pages = {S2}, pmid = {23734710}, issn = {1471-2105}, mesh = {Algorithms ; Environmental Microbiology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; *Microbiota ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Environmental shotgun sequencing (ESS) has potential to give greater insight into microbial communities than targeted sequencing of 16S regions, but requires much higher sequence coverage. The advent of next-generation sequencing has made it feasible for the Human Microbiome Project and other initiatives to generate ESS data on a large scale, but computationally efficient methods for analysing such data sets are needed.Here we present metaBEETL, a fast taxonomic classifier for environmental shotgun sequences. It uses a Burrows-Wheeler Transform (BWT) index of the sequencing reads and an indexed database of microbial reference sequences. Unlike other BWT-based tools, our method has no upper limit on the number or the total size of the reference sequences in its database. By capturing sequence relationships between strains, our reference index also allows us to classify reads which are not unique to an individual strain but are nevertheless specific to some higher phylogenetic order.Tested on datasets with known taxonomic composition, metaBEETL gave results that are competitive with existing similarity-based tools: due to normalization steps which other classifiers lack, the taxonomic profile computed by metaBEETL closely matched the true environmental profile. At the same time, its moderate running time and low memory footprint allow metaBEETL to scale well to large data sets.Code to construct the BWT indexed database and for the taxonomic classification is part of the BEETL library, available as a github repository at git@github.com:BEETL/BEETL.git.}, } @article {pmid23704890, year = {2013}, author = {Boyd, PW and Rynearson, TA and Armstrong, EA and Fu, F and Hayashi, K and Hu, Z and Hutchins, DA and Kudela, RM and Litchman, E and Mulholland, MR and Passow, U and Strzepek, RF and Whittaker, KA and Yu, E and Thomas, MK}, title = {Marine phytoplankton temperature versus growth responses from polar to tropical waters--outcome of a scientific community-wide study.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63091}, pmid = {23704890}, issn = {1932-6203}, mesh = {Aquatic Organisms/*growth & development/isolation & purification ; *Ecosystem ; Humans ; Oceans and Seas ; Phytoplankton/*growth & development/isolation & purification ; Species Specificity ; *Temperature ; *Tropical Climate ; Water ; }, abstract = {"It takes a village to finish (marine) science these days" Paraphrased from Curtis Huttenhower (the Human Microbiome project) The rapidity and complexity of climate change and its potential effects on ocean biota are challenging how ocean scientists conduct research. One way in which we can begin to better tackle these challenges is to conduct community-wide scientific studies. This study provides physiological datasets fundamental to understanding functional responses of phytoplankton growth rates to temperature. While physiological experiments are not new, our experiments were conducted in many laboratories using agreed upon protocols and 25 strains of eukaryotic and prokaryotic phytoplankton isolated across a wide range of marine environments from polar to tropical, and from nearshore waters to the open ocean. This community-wide approach provides both comprehensive and internally consistent datasets produced over considerably shorter time scales than conventional individual and often uncoordinated lab efforts. Such datasets can be used to parameterise global ocean model projections of environmental change and to provide initial insights into the magnitude of regional biogeographic change in ocean biota in the coming decades. Here, we compare our datasets with a compilation of literature data on phytoplankton growth responses to temperature. A comparison with prior published data suggests that the optimal temperatures of individual species and, to a lesser degree, thermal niches were similar across studies. However, a comparison of the maximum growth rate across studies revealed significant departures between this and previously collected datasets, which may be due to differences in the cultured isolates, temporal changes in the clonal isolates in cultures, and/or differences in culture conditions. Such methodological differences mean that using particular trait measurements from the prior literature might introduce unknown errors and bias into modelling projections. Using our community-wide approach we can reduce such protocol-driven variability in culture studies, and can begin to address more complex issues such as the effect of multiple environmental drivers on ocean biota.}, } @article {pmid23671663, year = {2013}, author = {Li, K and Bihan, M and Methé, BA}, title = {Analyses of the stability and core taxonomic memberships of the human microbiome.}, journal = {PloS one}, volume = {8}, number = {5}, pages = {e63139}, pmid = {23671663}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics ; Feces/microbiology ; Female ; Humans ; *Microbiota ; Molecular Typing ; Mouth/microbiology ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {Analyses of the taxonomic diversity associated with the human microbiome continue to be an area of great importance. The study of the nature and extent of the commonly shared taxa ("core"), versus those less prevalent, establishes a baseline for comparing healthy and diseased groups by quantifying the variation among people, across body habitats and over time. The National Institutes of Health (NIH) sponsored Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine and better define what constitutes the taxonomic core within and across body habitats and individuals through pyrosequencing-based profiling of 16S rRNA gene sequences from oral, skin, distal gut (stool), and vaginal body habitats from over 200 healthy individuals. A two-parameter model is introduced to quantitatively identify the core taxonomic members of each body habitat's microbiota across the healthy cohort. Using only cutoffs for taxonomic ubiquity and abundance, core taxonomic members were identified for each of the 18 body habitats and also for the 4 higher-level body regions. Although many microbes were shared at low abundance, they exhibited a relatively continuous spread in both their abundance and ubiquity, as opposed to a more discretized separation. The numbers of core taxa members in the body regions are comparatively small and stable, reflecting the relatively high, but conserved, interpersonal variability within the cohort. Core sizes increased across the body regions in the order of: vagina, skin, stool, and oral cavity. A number of "minor" oral taxonomic core were also identified by their majority presence across the cohort, but with relatively low and stable abundances. A method for quantifying the difference between two cohorts was introduced and applied to samples collected on a second visit, revealing that over time, the oral, skin, and stool body regions tended to be more transient in their taxonomic structure than the vaginal body region.}, } @article {pmid23509275, year = {2013}, author = {Campbell, JH and O'Donoghue, P and Campbell, AG and Schwientek, P and Sczyrba, A and Woyke, T and Söll, D and Podar, M}, title = {UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {110}, number = {14}, pages = {5540-5545}, pmid = {23509275}, issn = {1091-6490}, support = {R01 GM022854/GM/NIGMS NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; R37 GM022854/GM/NIGMS NIH HHS/United States ; GM22854/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Base Sequence ; Codon, Terminator/*genetics ; Flow Cytometry ; Genetic Code/*genetics ; Genetic Variation ; Glycine/*genetics ; Humans ; Metagenome/*genetics ; Molecular Sequence Data ; Mouth/*microbiology ; Nucleic Acid Amplification Techniques ; Sequence Analysis, DNA ; }, abstract = {The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant β-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.}, } @article {pmid23491408, year = {2013}, author = {Morris, A and Beck, JM and Schloss, PD and Campbell, TB and Crothers, K and Curtis, JL and Flores, SC and Fontenot, AP and Ghedin, E and Huang, L and Jablonski, K and Kleerup, E and Lynch, SV and Sodergren, E and Twigg, H and Young, VB and Bassis, CM and Venkataraman, A and Schmidt, TM and Weinstock, GM and , }, title = {Comparison of the respiratory microbiome in healthy nonsmokers and smokers.}, journal = {American journal of respiratory and critical care medicine}, volume = {187}, number = {10}, pages = {1067-1075}, pmid = {23491408}, issn = {1535-4970}, support = {U01 AI035004/AI/NIAID NIH HHS/United States ; U01-AI-35004/AI/NIAID NIH HHS/United States ; R01 HL090335/HL/NHLBI NIH HHS/United States ; U01-AI-35039/AI/NIAID NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000004/TR/NCATS NIH HHS/United States ; U01HL098958/HL/NHLBI NIH HHS/United States ; U01 AI035042/AI/NIAID NIH HHS/United States ; T32 HL007749/HL/NHLBI NIH HHS/United States ; K24HL087713/HL/NHLBI NIH HHS/United States ; U01HL098964/HL/NHLBI NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; U01-AI-35043/AI/NIAID NIH HHS/United States ; U01-AI-35042/AI/NIAID NIH HHS/United States ; U01-AI-42590/AI/NIAID NIH HHS/United States ; U01 HL098958/HL/NHLBI NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01-HD-32632/HD/NICHD NIH HHS/United States ; U01HL098960/HL/NHLBI NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; U01HL098996/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; R01 HL090342/HL/NHLBI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; U01HL98961/HL/NHLBI NIH HHS/United States ; UL1TR000005/TR/NCATS NIH HHS/United States ; U01-AI-35041/AI/NIAID NIH HHS/United States ; U01-AI-34994/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL102245/HL/NHLBI NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; R0100417746//PHS HHS/United States ; U01-AI-31834/AI/NIAID NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; UL1-RR025005/RR/NCRR NIH HHS/United States ; U01-AI-35040/AI/NIAID NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; UL1TR000004/TR/NCATS NIH HHS/United States ; R01HL090342/HL/NHLBI NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; R01HL090335/HL/NHLBI NIH HHS/United States ; U01-AI-34993/AI/NIAID NIH HHS/United States ; R01HL090339/HL/NHLBI NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01 HL098996/HL/NHLBI NIH HHS/United States ; U01HL098962/HL/NHLBI NIH HHS/United States ; U01-AI-34989/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bronchoalveolar Lavage Fluid/microbiology ; Cohort Studies ; Female ; Humans ; Lung/microbiology ; Male ; *Metagenome ; Middle Aged ; Mouth/microbiology ; Prospective Studies ; Reference Values ; Respiratory System/*microbiology ; Sequence Analysis, DNA/methods ; *Smoking ; Young Adult ; }, abstract = {RATIONALE: Results from 16S rDNA-encoding gene sequence-based, culture-independent techniques have led to conflicting conclusions about the composition of the lower respiratory tract microbiome.

OBJECTIVES: To compare the microbiome of the upper and lower respiratory tract in healthy HIV-uninfected nonsmokers and smokers in a multicenter cohort.

METHODS: Participants were nonsmokers and smokers without significant comorbidities. Oral washes and bronchoscopic alveolar lavages were collected in a standardized manner. Sequence analysis of bacterial 16S rRNA-encoding genes was performed, and the neutral model in community ecology was used to identify bacteria that were the most plausible members of a lung microbiome.

MEASUREMENTS AND MAIN RESULTS: Sixty-four participants were enrolled. Most bacteria identified in the lung were also in the mouth, but specific bacteria such as Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia species were disproportionally represented in the lungs compared with values predicted by the neutral model. Tropheryma was also in the lung, but not the mouth. Mouth communities differed between nonsmokers and smokers in species such as Porphyromonas, Neisseria, and Gemella, but lung bacterial populations did not.

CONCLUSIONS: This study is the largest to examine composition of the lower respiratory tract microbiome in healthy individuals and the first to use the neutral model to compare the lung to the mouth. Specific bacteria appear in significantly higher abundance in the lungs than would be expected if they originated from the mouth, demonstrating that the lung microbiome does not derive entirely from the mouth. The mouth microbiome differs in nonsmokers and smokers, but lung communities were not significantly altered by smoking.}, } @article {pmid23444796, year = {2012}, author = {Błaszkowska, J and Wójcik, A}, title = {Current problems concerning parasitology and mycology with regard to diseases of the skin and its appendages.}, journal = {Annals of parasitology}, volume = {58}, number = {3}, pages = {111-123}, pmid = {23444796}, issn = {2299-0631}, mesh = {Animals ; Dermatomycoses/diagnosis/epidemiology/therapy/transmission ; Humans ; Mycoses/*diagnosis/epidemiology/*therapy/transmission ; Parasitic Diseases/*diagnosis/epidemiology/*therapy/transmission ; Zoonoses/microbiology/parasitology/transmission ; }, abstract = {Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).}, } @article {pmid23431991, year = {2013}, author = {Bakhtiar, SM and LeBlanc, JG and Salvucci, E and Ali, A and Martin, R and Langella, P and Chatel, JM and Miyoshi, A and Bermúdez-Humarán, LG and Azevedo, V}, title = {Implications of the human microbiome in inflammatory bowel diseases.}, journal = {FEMS microbiology letters}, volume = {342}, number = {1}, pages = {10-17}, doi = {10.1111/1574-6968.12111}, pmid = {23431991}, issn = {1574-6968}, mesh = {*Biota ; High-Throughput Nucleotide Sequencing ; Humans ; Inflammatory Bowel Diseases/*microbiology ; *Metagenome ; }, abstract = {The study of the human microbiome or community of microorganisms and collection of genomes found in the human body is one of the fastest growing research areas because many diseases are reported to be associated with microbiome imbalance or dysbiosis. With the improvement in novel sequencing techniques, researchers are now generating millions of sequences of different sites from the human body and evaluating specific differences in microbial communities. The importance of microbiome constituency is so relevant that several consortia like the Human Microbiome project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT) project are focusing mainly on the human microbiome. The aim of this review is to highlight points of research in this field, mainly focusing on particular factors that modulate the microbiome and important insights into its potential impact on our health and well-being.}, } @article {pmid23418187, year = {2013}, author = {Klingenberg, H and Aßhauer, KP and Lingner, T and Meinicke, P}, title = {Protein signature-based estimation of metagenomic abundances including all domains of life and viruses.}, journal = {Bioinformatics (Oxford, England)}, volume = {29}, number = {8}, pages = {973-980}, pmid = {23418187}, issn = {1367-4811}, mesh = {DNA, Archaeal/analysis ; DNA, Viral/analysis ; Humans ; Metagenome ; Metagenomics/*methods ; Phylogeny ; *Protein Structure, Tertiary ; }, abstract = {MOTIVATION: Metagenome analysis requires tools that can estimate the taxonomic abundances in anonymous sequence data over the whole range of biological entities. Because there is usually no prior knowledge about the data composition, not only all domains of life but also viruses have to be included in taxonomic profiling. Such a full-range approach, however, is difficult to realize owing to the limited coverage of available reference data. In particular, archaea and viruses are generally not well represented by current genome databases.

RESULTS: We introduce a novel approach to taxonomic profiling of metagenomes that is based on mixture model analysis of protein signatures. Our results on simulated and real data reveal the difficulties of the existing methods when measuring achaeal or viral abundances and show the overall good profiling performance of the protein-based mixture model. As an application example, we provide a large-scale analysis of data from the Human Microbiome Project. This demonstrates the utility of our method as a first instance profiling tool for a fast estimate of the community structure.

AVAILABILITY: http://gobics.de/TaxyPro.

SUPPLEMENTARY INFORMATION: Supplementary Material is available at Bioinformatics online.}, } @article {pmid23408395, year = {2012}, author = {Mead, DA and Lucas, S and Copeland, A and Lapidus, A and Cheng, JF and Bruce, DC and Goodwin, LA and Pitluck, S and Chertkov, O and Zhang, X and Detter, JC and Han, CS and Tapia, R and Land, M and Hauser, LJ and Chang, YJ and Kyrpides, NC and Ivanova, NN and Ovchinnikova, G and Woyke, T and Brumm, C and Hochstein, R and Schoenfeld, T and Brumm, P}, title = {Complete Genome Sequence of Paenibacillus strain Y4.12MC10, a Novel Paenibacillus lautus strain Isolated from Obsidian Hot Spring in Yellowstone National Park.}, journal = {Standards in genomic sciences}, volume = {6}, number = {3}, pages = {381-400}, pmid = {23408395}, issn = {1944-3277}, abstract = {Paenibacillus sp.Y412MC10 was one of a number of organisms isolated from Obsidian Hot Spring, Yellowstone National Park, Montana, USA under permit from the National Park Service. The isolate was initially classified as a Geobacillus sp. Y412MC10 based on its isolation conditions and similarity to other organisms isolated from hot springs at Yellowstone National Park. Comparison of 16 S rRNA sequences within the Bacillales indicated that Geobacillus sp.Y412MC10 clustered with Paenibacillus species, and the organism was most closely related to Paenibacillus lautus. Lucigen Corp. prepared genomic DNA and the genome was sequenced, assembled, and annotated by the DOE Joint Genome Institute. The genome sequence was deposited at the NCBI in October 2009 (NC_013406). The genome of Paenibacillus sp. Y412MC10 consists of one circular chromosome of 7,121,665 bp with an average G+C content of 51.2%. Comparison to other Paenibacillus species shows the organism lacks nitrogen fixation, antibiotic production and social interaction genes reported in other paenibacilli. The Y412MC10 genome shows a high level of synteny and homology to the draft sequence of Paenibacillus sp. HGF5, an organism from the Human Microbiome Project (HMP) Reference Genomes. This, combined with genomic CAZyme analysis, suggests an intestinal, rather than environmental origin for Y412MC10.}, } @article {pmid23406581, year = {2013}, author = {Renko, J and Koskela, KA and Lepp, PW and Oksala, N and Levula, M and Lehtimäki, T and Solakivi, T and Kunnas, T and Nikkari, S and Nikkari, ST}, title = {Bacterial DNA signatures in carotid atherosclerosis represent both commensals and pathogens of skin origin.}, journal = {European journal of dermatology : EJD}, volume = {23}, number = {1}, pages = {53-58}, doi = {10.1684/ejd.2012.1908}, pmid = {23406581}, issn = {1952-4013}, mesh = {Actinobacteria/*isolation & purification ; Aged ; Aged, 80 and over ; Carotid Artery Diseases/*microbiology ; DNA, Bacterial/*isolation & purification ; DNA, Ribosomal ; Female ; Humans ; Male ; *Metagenome ; Middle Aged ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {Infectious agents have been suggested to be involved in atherosclerosis. By using a novel subtraction broad-range PCR approach, we defined bacterial DNA signatures in surgically removed sterile carotid artery endarterectomy plaques of patients with carotid atherosclerosis. Eighty partial bacterial 16S rDNA nucleotide sequences from eight patients were studied. Furthermore, 34 clones representing 21 bacterial sequence-types from the reagents used for DNA extraction and PCR amplification were determined. After subtraction of these potential methodological contaminants, 23 bacterial sequence-types were considered as clinically relevant findings. The most prominent phylum, Actinobacteria, accounted for 74% of these relevant sequences. Furthermore, according to the Human Microbiome project database, interestingly, nearly all (94%) of the sequences were associated with the human skin microbiome.}, } @article {pmid23401286, year = {2013}, author = {Devaraj, S and Hemarajata, P and Versalovic, J}, title = {The human gut microbiome and body metabolism: implications for obesity and diabetes.}, journal = {Clinical chemistry}, volume = {59}, number = {4}, pages = {617-628}, pmid = {23401286}, issn = {1530-8561}, support = {R01 DK065075-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; P30 DK56338-06A2/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Carbohydrate Metabolism ; Diabetes Mellitus/metabolism/*microbiology ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Obesity/*microbiology ; }, abstract = {BACKGROUND: Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders.

CONTENT: Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways.

CONCLUSION: Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes.}, } @article {pmid23400224, year = {2013}, author = {Douglas-Escobar, M and Elliott, E and Neu, J}, title = {Effect of intestinal microbial ecology on the developing brain.}, journal = {JAMA pediatrics}, volume = {167}, number = {4}, pages = {374-379}, doi = {10.1001/jamapediatrics.2013.497}, pmid = {23400224}, issn = {2168-6211}, support = {R01 HD 059143/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Brain/growth & development/*physiology ; Child ; Child Development Disorders, Pervasive/epidemiology/microbiology ; Comorbidity ; Enteric Nervous System/physiology ; Gastrointestinal Diseases/epidemiology ; Humans ; Infant, Newborn ; Infant, Premature/physiology ; Intestines/immunology/*microbiology/*physiology ; Metagenome/immunology/*physiology ; Toll-Like Receptors/physiology ; }, abstract = {The mammalian gastrointestinal tract harbors a highly diverse microbial population that plays a major role in nutrition, metabolism, protection against pathogens, and development of the immune system. It is estimated that at least 1000 different bacterial species cohabit the human intestinal tract. Most recently, the Human Microbiome Project, using new genomic technologies, has started a catalog of specific microbiome composition and its correlation with health and specific diseases. Herein we provide a brief review of the intestinal microbiome, with a focus on new studies showing that there is an important link between the microbes that inhabit the intestinal tract and the developing brain. With future research, an understanding of this link may help us to treat various neurobehavioral problems such as autism, schizophrenia, and anxiety.}, } @article {pmid23392441, year = {2013}, author = {Lozupone, C and Cota-Gomez, A and Palmer, BE and Linderman, DJ and Charlson, ES and Sodergren, E and Mitreva, M and Abubucker, S and Martin, J and Yao, G and Campbell, TB and Flores, SC and Ackerman, G and Stombaugh, J and Ursell, L and Beck, JM and Curtis, JL and Young, VB and Lynch, SV and Huang, L and Weinstock, GM and Knox, KS and Twigg, H and Morris, A and Ghedin, E and Bushman, FD and Collman, RG and Knight, R and Fontenot, AP and , }, title = {Widespread colonization of the lung by Tropheryma whipplei in HIV infection.}, journal = {American journal of respiratory and critical care medicine}, volume = {187}, number = {10}, pages = {1110-1117}, pmid = {23392441}, issn = {1535-4970}, support = {U01 AI035042/AI/NIAID NIH HHS/United States ; UL1 RR024153/RR/NCRR NIH HHS/United States ; DK090285/DK/NIDDK NIH HHS/United States ; AI35004/AI/NIAID NIH HHS/United States ; AI35042/AI/NIAID NIH HHS/United States ; U01 HL098961/HL/NHLBI NIH HHS/United States ; U01 AI034993/AI/NIAID NIH HHS/United States ; UL1 TR000005/TR/NCATS NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; U01 AI031834/AI/NIAID NIH HHS/United States ; U01 AI035004/AI/NIAID NIH HHS/United States ; AI35039/AI/NIAID NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; U01 AI075410/AI/NIAID NIH HHS/United States ; AI35043/AI/NIAID NIH HHS/United States ; AI34993/AI/NIAID NIH HHS/United States ; U01 HL098960/HL/NHLBI NIH HHS/United States ; UL1 TR000154/TR/NCATS NIH HHS/United States ; HL098957/HL/NHLBI NIH HHS/United States ; HL098962/HL/NHLBI NIH HHS/United States ; UL1 RR024131/RR/NCRR NIH HHS/United States ; HL087713/HL/NHLBI NIH HHS/United States ; HD32632/HD/NICHD NIH HHS/United States ; U01 AI034989/AI/NIAID NIH HHS/United States ; HL102245/HL/NHLBI NIH HHS/United States ; UL1TR000005/TR/NCATS NIH HHS/United States ; K01 DK090285/DK/NIDDK NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; U01 HL098964/HL/NHLBI NIH HHS/United States ; K24 HL102245/HL/NHLBI NIH HHS/United States ; U01 AI035041/AI/NIAID NIH HHS/United States ; AI35040/AI/NIAID NIH HHS/United States ; UM1 AI035043/AI/NIAID NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; AI34989/AI/NIAID NIH HHS/United States ; U01 HL098957/HL/NHLBI NIH HHS/United States ; U01 AI034994/AI/NIAID NIH HHS/United States ; UL1-RR025005/RR/NCRR NIH HHS/United States ; R01 HL090339/HL/NHLBI NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; HL098961/HL/NHLBI NIH HHS/United States ; HL98996/HL/NHLBI NIH HHS/United States ; R01 HL090335/HL/NHLBI NIH HHS/United States ; AI34994/AI/NIAID NIH HHS/United States ; U01 AI035043/AI/NIAID NIH HHS/United States ; HL090339/HL/NHLBI NIH HHS/United States ; AI045008/AI/NIAID NIH HHS/United States ; HL098964/HL/NHLBI NIH HHS/United States ; U01 AI035040/AI/NIAID NIH HHS/United States ; HL098960/HL/NHLBI NIH HHS/United States ; AI35041/AI/NIAID NIH HHS/United States ; U01 AI035039/AI/NIAID NIH HHS/United States ; U01AI42590/AI/NIAID NIH HHS/United States ; HL090335/HL/NHLBI NIH HHS/United States ; U01 HL098996/HL/NHLBI NIH HHS/United States ; AI31834/AI/NIAID NIH HHS/United States ; AI075410/AI/NIAID NIH HHS/United States ; U01 HD032632/HD/NICHD NIH HHS/United States ; U01 AI042590/AI/NIAID NIH HHS/United States ; }, mesh = {Cohort Studies ; HIV Infections/*complications ; Humans ; Longitudinal Studies ; Lung/*microbiology ; *Tropheryma ; Whipple Disease/*complications/*microbiology ; }, abstract = {RATIONALE: Lung infections caused by opportunistic or virulent pathogens are a principal cause of morbidity and mortality in HIV infection. It is unknown whether HIV infection leads to changes in basal lung microflora, which may contribute to chronic pulmonary complications that increasingly are being recognized in individuals infected with HIV.

OBJECTIVES: To determine whether the immunodeficiency associated with HIV infection resulted in alteration of the lung microbiota.

METHODS: We used 16S ribosomal RNA targeted pyrosequencing and shotgun metagenomic sequencing to analyze bacterial gene sequences in bronchoalveolar lavage (BAL) and mouths of 82 HIV-positive and 77 HIV-negative subjects.

MEASUREMENTS AND MAIN RESULTS: Sequences representing Tropheryma whipplei, the etiologic agent of Whipple's disease, were significantly more frequent in BAL of HIV-positive compared with HIV-negative individuals. T. whipplei dominated the community (>50% of sequence reads) in 11 HIV-positive subjects, but only 1 HIV-negative individual (13.4 versus 1.3%; P = 0.0018). In 30 HIV-positive individuals sampled longitudinally, antiretroviral therapy resulted in a significantly reduced relative abundance of T. whipplei in the lung. Shotgun metagenomic sequencing was performed on eight BAL samples dominated by T. whipplei 16S ribosomal RNA. Whole genome assembly of pooled reads showed that uncultured lung-derived T. whipplei had similar gene content to two isolates obtained from subjects with Whipple's disease.

CONCLUSIONS: Asymptomatic subjects with HIV infection have unexpected colonization of the lung by T. whipplei, which is reduced by effective antiretroviral therapy and merits further study for a potential pathogenic role in chronic pulmonary complications of HIV infection.}, } @article {pmid23326225, year = {2013}, author = {Koren, O and Knights, D and Gonzalez, A and Waldron, L and Segata, N and Knight, R and Huttenhower, C and Ley, RE}, title = {A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets.}, journal = {PLoS computational biology}, volume = {9}, number = {1}, pages = {e1002863}, pmid = {23326225}, issn = {1553-7358}, support = {HG4872/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Biodiversity ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Recent analyses of human-associated bacterial diversity have categorized individuals into 'enterotypes' or clusters based on the abundances of key bacterial genera in the gut microbiota. There is a lack of consensus, however, on the analytical basis for enterotypes and on the interpretation of these results. We tested how the following factors influenced the detection of enterotypes: clustering methodology, distance metrics, OTU-picking approaches, sequencing depth, data type (whole genome shotgun (WGS) vs.16S rRNA gene sequence data), and 16S rRNA region. We included 16S rRNA gene sequences from the Human Microbiome Project (HMP) and from 16 additional studies and WGS sequences from the HMP and MetaHIT. In most body sites, we observed smooth abundance gradients of key genera without discrete clustering of samples. Some body habitats displayed bimodal (e.g., gut) or multimodal (e.g., vagina) distributions of sample abundances, but not all clustering methods and workflows accurately highlight such clusters. Because identifying enterotypes in datasets depends not only on the structure of the data but is also sensitive to the methods applied to identifying clustering strength, we recommend that multiple approaches be used and compared when testing for enterotypes.}, } @article {pmid23282177, year = {2012}, author = {Fettweis, JM and Serrano, MG and Sheth, NU and Mayer, CM and Glascock, AL and Brooks, JP and Jefferson, KK and , and Buck, GA}, title = {Species-level classification of the vaginal microbiome.}, journal = {BMC genomics}, volume = {13 Suppl 8}, number = {Suppl 8}, pages = {S17}, pmid = {23282177}, issn = {1471-2164}, support = {UH2/UH3AI083263/AI/NIAID NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification/genetics ; Databases, Genetic ; Female ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/genetics ; Vagina/*microbiology ; }, abstract = {BACKGROUND: The application of next-generation sequencing to the study of the vaginal microbiome is revealing the spectrum of microbial communities that inhabit the human vagina. High-resolution identification of bacterial taxa, minimally to the species level, is necessary to fully understand the association of the vaginal microbiome with bacterial vaginosis, sexually transmitted infections, pregnancy complications, menopause, and other physiological and infectious conditions. However, most current taxonomic assignment strategies based on metagenomic 16S rDNA sequence analysis provide at best a genus-level resolution. While surveys of 16S rRNA gene sequences are common in microbiome studies, few well-curated, body-site-specific reference databases of 16S rRNA gene sequences are available, and no such resource is available for vaginal microbiome studies.

RESULTS: We constructed the Vaginal 16S rDNA Reference Database, a comprehensive and non-redundant database of 16S rDNA reference sequences for bacterial taxa likely to be associated with vaginal health, and we developed STIRRUPS, a new method that employs the USEARCH algorithm with a curated reference database for rapid species-level classification of 16S rDNA partial sequences. The method was applied to two datasets of V1-V3 16S rDNA reads: one generated from a mock community containing DNA from six bacterial strains associated with vaginal health, and a second generated from over 1,000 mid-vaginal samples collected as part of the Vaginal Human Microbiome Project at Virginia Commonwealth University. In both datasets, STIRRUPS, used in conjunction with the Vaginal 16S rDNA Reference Database, classified more than 95% of processed reads to a species-level taxon using a 97% global identity threshold for assignment.

CONCLUSIONS: This database and method provide accurate species-level classifications of metagenomic 16S rDNA sequence reads that will be useful for analysis and comparison of microbiome profiles from vaginal samples. STIRRUPS can be used to classify 16S rDNA sequence reads from other ecological niches if an appropriate reference database of 16S rDNA sequences is available.}, } @article {pmid23281612, year = {2012}, author = {Harwich, MD and Serrano, MG and Fettweis, JM and Alves, JM and Reimers, MA and , and Buck, GA and Jefferson, KK}, title = {Genomic sequence analysis and characterization of Sneathia amnii sp. nov.}, journal = {BMC genomics}, volume = {13 Suppl 8}, number = {Suppl 8}, pages = {S4}, pmid = {23281612}, issn = {1471-2164}, support = {2P30 CA16059/CA/NCI NIH HHS/United States ; 4UH3AI083263/AI/NIAID NIH HHS/United States ; 5P30NS047463/NS/NINDS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Female ; *Genome, Bacterial ; Humans ; Leptotrichia/classification/drug effects/*genetics ; Metagenome ; Microbial Sensitivity Tests ; Phenotype ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; Vagina/microbiology ; Virulence/genetics ; }, abstract = {BACKGROUND: Bacteria of the genus Sneathia are emerging as potential pathogens of the female reproductive tract. Species of Sneathia, which were formerly grouped with Leptotrichia, can be part of the normal microbiota of the genitourinary tracts of men and women, but they are also associated with a variety of clinical conditions including bacterial vaginosis, preeclampsia, preterm labor, spontaneous abortion, post-partum bacteremia and other invasive infections. Sneathia species also exhibit a significant correlation with sexually transmitted diseases and cervical cancer. Because Sneathia species are fastidious and rarely cultured successfully in vitro; and the genomes of members of the genus had until now not been characterized, very little is known about the physiology or the virulence of these organisms.

RESULTS: Here, we describe a novel species, Sneathia amnii sp. nov, which closely resembles bacteria previously designated "Leptotrichia amnionii". As part of the Vaginal Human Microbiome Project at VCU, a vaginal isolate of S. amnii sp. nov. was identified, successfully cultured and bacteriologically cloned. The biochemical characteristics and virulence properties of the organism were examined in vitro, and the genome of the organism was sequenced, annotated and analyzed. The analysis revealed a reduced circular genome of ~1.34 Mbp, containing ~1,282 protein-coding genes. Metabolic reconstruction of the bacterium reflected its biochemical phenotype, and several genes potentially associated with pathogenicity were identified.

CONCLUSIONS: Bacteria with complex growth requirements frequently remain poorly characterized and, as a consequence, their roles in health and disease are unclear. Elucidation of the physiology and identification of genes putatively involved in the metabolism and virulence of S. amnii may lead to a better understanding of the role of this potential pathogen in bacterial vaginosis, preterm birth, and other issues associated with vaginal and reproductive health.}, } @article {pmid23296358, year = {2013}, author = {Foxman, B and Rosenthal, M}, title = {Implications of the human microbiome project for epidemiology.}, journal = {American journal of epidemiology}, volume = {177}, number = {3}, pages = {197-201}, pmid = {23296358}, issn = {1476-6256}, support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; T32 AI049816/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/genetics/isolation & purification ; Epidemiology/*organization & administration ; Fungi/genetics/isolation & purification ; Humans ; *Metagenome ; Microbial Consortia ; Polymerase Chain Reaction ; Risk Factors ; Time Factors ; Viruses/genetics/isolation & purification ; }, abstract = {The structure and function of microorganisms that live in and on us, the human microbiota, are a tremendous resource. Microbiota may help to explain individual variability in health outcomes and be a source of new biomarkers for environmental exposures and of novel prognostic and diagnostic indicators. The increase in availability of low-cost, high-throughput techniques makes it relatively straightforward to include microbiota assessments in epidemiologic studies. With the recent joint publications of the findings of the Human Microbiome Consortium and related studies, the consequent surge of interest in microbiome research, and remarkable media attention, the time is ripe for epidemiologists to contribute their expertise to and translate results of microbiota research for population health.}, } @article {pmid23223587, year = {2013}, author = {Mitsuma, SF and Mansour, MK and Dekker, JP and Kim, J and Rahman, MZ and Tweed-Kent, A and Schuetz, P}, title = {Promising new assays and technologies for the diagnosis and management of infectious diseases.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {56}, number = {7}, pages = {996-1002}, pmid = {23223587}, issn = {1537-6591}, support = {T32 AI007061/AI/NIAID NIH HHS/United States ; T32-AI007061-35/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Laboratory Techniques/*methods/trends ; Communicable Diseases/*diagnosis ; Humans ; }, abstract = {In the first decade of the 21st century, we have seen the completion of the human genome project and marked progress in the human microbiome project. The vast amount of data generated from these efforts combined with advances in molecular and biomedical technologies have led to the development of a multitude of assays and technologies that may be useful in the diagnosis and management of infectious diseases. Here, we identify several new assays and technologies that have recently come into clinical use or have potential for clinical use in the near future. The scope of this review is broad and includes topics such as the serum marker procalcitonin, gene expression profiling, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and nucleic acid aptamers. Principles that underlie each assay or technology, their clinical applications, and potential strengths and limitations are addressed.}, } @article {pmid23216677, year = {2012}, author = {Tyakht, AV and Popenko, AS and Belenikin, MS and Altukhov, IA and Pavlenko, AV and Kostryukova, ES and Selezneva, OV and Larin, AK and Karpova, IY and Alexeev, DG}, title = {MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads.}, journal = {Source code for biology and medicine}, volume = {7}, number = {1}, pages = {13}, pmid = {23216677}, issn = {1751-0473}, abstract = {MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors' knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded from http://hmpdacc.org). MALINA is made freely available on the web at http://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported.}, } @article {pmid23209389, year = {2012}, author = {Gevers, D and Pop, M and Schloss, PD and Huttenhower, C}, title = {Bioinformatics for the Human Microbiome Project.}, journal = {PLoS computational biology}, volume = {8}, number = {11}, pages = {e1002779}, pmid = {23209389}, issn = {1553-7358}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; }, mesh = {*Computational Biology ; Database Management Systems ; Databases, Factual ; Humans ; *Metagenome ; Metagenomics ; }, } @article {pmid23196853, year = {2013}, author = {Buccigrossi, V and Nicastro, E and Guarino, A}, title = {Functions of intestinal microflora in children.}, journal = {Current opinion in gastroenterology}, volume = {29}, number = {1}, pages = {31-38}, doi = {10.1097/MOG.0b013e32835a3500}, pmid = {23196853}, issn = {1531-7056}, mesh = {Child ; Enterocolitis, Necrotizing/microbiology/therapy ; Humans ; Inflammatory Bowel Diseases/microbiology ; Intestinal Diseases/*microbiology/therapy ; Intestines/*microbiology ; Irritable Bowel Syndrome/microbiology/therapy ; Metagenome/*physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: This review discusses the structural composition of intestinal microbiota, the functional relationship between the latter and the host, and the role of abnormal microflora in chronic diseases.

RECENT FINDINGS: A more complete view of the gut microbiota is being developed following the Human Microbiome Project. The microflora in children is plastic, susceptible to changes in response to diet modifications, antibiotic treatment and other events, providing the opportunity to study its functional role. Increasing evidence highlights the role of nutrition in the age-related development of microflora. Eubiosis, that is, a normal microflora structure, provides protection against infections, educates the immune system, ensures tolerance to foods, and contributes to nutrient digestion and energy harvest. Changes in microflora, consisting in the overpresence of harmful species or underpresence of commensal species, or dysbiosis produce dysfunctions, such as intestinal inflammation or dysmotility. Moreover abnormal pattern of microflora have been consistently detected in specific diseases.

SUMMARY: A relationship exists between eubiosis and functions and conversely between dysbiosis and dysfunctions or even diseases. Abnormalities in microflora composition may trigger or contribute to specific diseases. This raises the hypothesis to target microflora in order to restore eubiosis through the use of antibiotics, probiotics or nutrients.}, } @article {pmid23194438, year = {2012}, author = {Saad, R and Rizkallah, MR and Aziz, RK}, title = {Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.}, journal = {Gut pathogens}, volume = {4}, number = {1}, pages = {16}, pmid = {23194438}, issn = {1757-4749}, abstract = {The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.}, } @article {pmid23165986, year = {2013}, author = {Aagaard, K and Petrosino, J and Keitel, W and Watson, M and Katancik, J and Garcia, N and Patel, S and Cutting, M and Madden, T and Hamilton, H and Harris, E and Gevers, D and Simone, G and McInnes, P and Versalovic, J}, title = {The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {27}, number = {3}, pages = {1012-1022}, pmid = {23165986}, issn = {1530-6860}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; K23 HD070979/HD/NICHD NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Body Mass Index ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Skin/*microbiology ; Specimen Handling/*methods ; Vagina/*microbiology ; }, abstract = {The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.}, } @article {pmid23141757, year = {2013}, author = {Peyyala, R and Ebersole, JL}, title = {Multispecies biofilms and host responses: "discriminating the trees from the forest".}, journal = {Cytokine}, volume = {61}, number = {1}, pages = {15-25}, pmid = {23141757}, issn = {1096-0023}, support = {P20 GM103538/GM/NIGMS NIH HHS/United States ; R21 DE018177/DE/NIDCR NIH HHS/United States ; DE 018177/DE/NIDCR NIH HHS/United States ; }, mesh = {Biodiversity ; *Biofilms ; Host-Pathogen Interactions/*immunology/physiology ; Humans ; Metagenome/immunology ; Mouth/*microbiology/*pathology ; Periodontal Diseases/*microbiology ; }, abstract = {Periodontal diseases reflect a tissue destructive process of the hard and soft tissues of the periodontium that are initiated by the accumulation of multispecies bacterial biofilms in the subgingival sulcus. This accumulation, in both quantity and quality of bacteria, results in a chronic immunoinflammatory response of the host to control this noxious challenge, leading to collateral damage of the tissues. As knowledge of the characteristics of the host-bacterial interactions in the oral cavity has expanded, new knowledge has become available on the complexity of the microbial challenge and the repertoire of host responses to this challenge. Recent results from the Human Microbiome Project continue to extend the array of taxa, genera, and species of bacteria that inhabit the multiple niches in the oral cavity; however, there is rather sparse information regarding variations in how host cells discriminate commensal from pathogenic species, as well as how the host response is affected by the three-dimensional architecture and interbacterial interactions that occur in the oral biofilms. This review provides some insights into these processes by including existing literature on the biology of nonoral bacterial biofilms, and the more recent literature just beginning to document how the oral cavity responds to multispecies biofilms.}, } @article {pmid23140990, year = {2013}, author = {Morgan, XC and Segata, N and Huttenhower, C}, title = {Biodiversity and functional genomics in the human microbiome.}, journal = {Trends in genetics : TIG}, volume = {29}, number = {1}, pages = {51-58}, pmid = {23140990}, issn = {0168-9525}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; 1R01HG005969-01/HG/NHGRI NIH HHS/United States ; }, mesh = {*Biodiversity ; Computational Biology ; Gastrointestinal Tract/metabolism/*microbiology ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics/physiology ; Phylogeny ; }, abstract = {Over the course of our lives, humans are colonized by a tremendous diversity of commensal microbes, which comprise the human microbiome. The collective genetic potential (metagenome) of the human microbiome is orders of magnitude more than the human genome, and it profoundly affects human health and disease in ways we are only beginning to understand. Advances in computing and high-throughput sequencing have enabled population-level surveys such as MetaHIT and the recently released Human Microbiome Project, detailed investigations of the microbiome in human disease, and mechanistic studies employing gnotobiotic model organisms. The resulting knowledge of human microbiome composition, function, and range of variation across multiple body sites has begun to assemble a rich picture of commensal host-microbe and microbe-microbe interactions as well as their roles in human health and disease and their potential as diagnostic and therapeutic tools.}, } @article {pmid23131830, year = {2012}, author = {Rogers, GB and Bruce, KD}, title = {Exploring the parallel development of microbial systems in neonates with cystic fibrosis.}, journal = {mBio}, volume = {3}, number = {6}, pages = {e00408-12}, pmid = {23131830}, issn = {2150-7511}, mesh = {*Biota ; Cystic Fibrosis/*microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Respiratory System/*microbiology ; }, abstract = {Recent studies have greatly extended our understanding of the microbiota present in and on the human body. Here, advanced sequencing strategies have provided unprecedented analytical power. The important implications that the emerging data have for human health emphasize the need to intensify research in this area (D. A. Relman, Nature 486:194-195, 2012). It is already clear from these studies that the microbiotas characterized in different body locations of healthy individuals are both complex and diverse (The Human Microbiome Project Consortium, Nature 486:215-221). These studies also provide a point of contrast for investigations that aim to characterize the microbiota present in disease conditions. In this regard, Madan et al. (mBio 3(4):e00251-12, 2012) monitored the development over time of microbiota in the oropharynges and feces of neonates with cystic fibrosis and explored the potential for interactions between these complex microbial systems.}, } @article {pmid23071716, year = {2012}, author = {Conlan, S and Kong, HH and Segre, JA}, title = {Species-level analysis of DNA sequence data from the NIH Human Microbiome Project.}, journal = {PloS one}, volume = {7}, number = {10}, pages = {e47075}, pmid = {23071716}, issn = {1932-6203}, support = {UH3-AR057504/AR/NIAMS NIH HHS/United States ; //Intramural NIH HHS/United States ; }, mesh = {Databases, Nucleic Acid ; Drug Resistance, Bacterial ; Enterococcus faecalis/classification/*genetics ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Klebsiella pneumoniae/classification/*genetics ; *Metagenome ; Mouth/microbiology ; National Institutes of Health (U.S.) ; Phylogeny ; *RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; Skin/microbiology ; Staphylococcus aureus/classification/*genetics ; United States ; Vagina/microbiology ; }, abstract = {BACKGROUND: Outbreaks of antibiotic-resistant bacterial infections emphasize the importance of surveillance of potentially pathogenic bacteria. Genomic sequencing of clinical microbiological specimens expands our capacity to study cultivable, fastidious and uncultivable members of the bacterial community. Herein, we compared the primary data collected by the NIH's Human Microbiome Project (HMP) with published epidemiological surveillance data of Staphylococcus aureus.

METHODS: The HMP's initial dataset contained microbial survey data from five body regions (skin, nares, oral cavity, gut and vagina) of 242 healthy volunteers. A significant component of the HMP dataset was deep sequencing of the 16S ribosomal RNA gene, which contains variable regions enabling taxonomic classification. Since species-level identification is essential in clinical microbiology, we built a reference database and used phylogenetic placement followed by most recent common ancestor classification to look at the species distribution for Staphylococcus, Klebsiella and Enterococcus.

MAIN RESULTS: We show that selecting the accurate region of the 16S rRNA gene to sequence is analogous to carefully selecting culture conditions to distinguish closely related bacterial species. Analysis of the HMP data showed that Staphylococcus aureus was present in the nares of 36% of healthy volunteers, consistent with culture-based epidemiological data. Klebsiella pneumoniae and Enterococcus faecalis were found less frequently, but across many habitats.

CONCLUSIONS: This work demonstrates that large 16S rRNA survey studies can be used to support epidemiological goals in the context of an increasing awareness that microbes flourish and compete within a larger bacterial community. This study demonstrates how genomic techniques and information could be critically important to trace microbial evolution and implement hospital infection control.}, } @article {pmid23028285, year = {2012}, author = {Friedman, J and Alm, EJ}, title = {Inferring correlation networks from genomic survey data.}, journal = {PLoS computational biology}, volume = {8}, number = {9}, pages = {e1002687}, pmid = {23028285}, issn = {1553-7358}, mesh = {Chromosome Mapping/*methods ; Computer Simulation ; *Genetics, Population ; Genome, Bacterial/*genetics ; Humans ; Microbial Consortia/*genetics ; *Models, Genetic ; Recombination, Genetic/*genetics ; Statistics as Topic ; }, abstract = {High-throughput sequencing based techniques, such as 16S rRNA gene profiling, have the potential to elucidate the complex inner workings of natural microbial communities - be they from the world's oceans or the human gut. A key step in exploring such data is the identification of dependencies between members of these communities, which is commonly achieved by correlation analysis. However, it has been known since the days of Karl Pearson that the analysis of the type of data generated by such techniques (referred to as compositional data) can produce unreliable results since the observed data take the form of relative fractions of genes or species, rather than their absolute abundances. Using simulated and real data from the Human Microbiome Project, we show that such compositional effects can be widespread and severe: in some real data sets many of the correlations among taxa can be artifactual, and true correlations may even appear with opposite sign. Additionally, we show that community diversity is the key factor that modulates the acuteness of such compositional effects, and develop a new approach, called SparCC (available at https://bitbucket.org/yonatanf/sparcc), which is capable of estimating correlation values from compositional data. To illustrate a potential application of SparCC, we infer a rich ecological network connecting hundreds of interacting species across 18 sites on the human body. Using the SparCC network as a reference, we estimated that the standard approach yields 3 spurious species-species interactions for each true interaction and misses 60% of the true interactions in the human microbiome data, and, as predicted, most of the erroneous links are found in the samples with the lowest diversity.}, } @article {pmid23015504, year = {2012}, author = {Rogers, AB}, title = {Gastric Helicobacter spp. in animal models: pathogenesis and modulation by extragastric coinfections.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {921}, number = {}, pages = {175-188}, doi = {10.1007/978-1-62703-005-2_21}, pmid = {23015504}, issn = {1940-6029}, mesh = {Animals ; *Coinfection ; *Disease Models, Animal ; Helicobacter/*pathogenicity ; Helicobacter Infections/*complications/*microbiology ; Humans ; Stomach/*microbiology ; }, abstract = {Animal models are used to study complex host, microbial, and environmental influences associated with gastric Helicobacter infection. Evidence that gastric helicobacters are pathogenic in animals first came from ferrets. Felids, nonhuman primates, and many other species also harbor stomach helicobacters. Today, mice are preferred by most researchers for scientific investigation because of cost-efficiencies, rapid reproduction, choice of laboratory reagents, and availability of genetically engineered models. Infection with Helicobacter felis or H. pylori Sydney strain-1 in appropriate mouse strains produces disease with remarkable similarities to H. pylori in humans. Due to recent advances in genetic engineering, in vivo imaging, and system-wide genomics and proteomics, these models will become even more widespread in the future. Recently, it has been shown that extragastric infections can dramatically affect the severity of disease induced by gastric Helicobacter spp. through heterologous immunity. These models provide proof-of-principle for the "African enigma" wherein gastric cancer is underrepresented in low-lying tropical countries with concurrently high H. pylori and internal parasite prevalence. Helicobacter gastritis and carcinogenesis in mouse models may be augmented or ameliorated by other infectious agents depending on the character of the invoked immune response. Knowledge gained from the Human Microbiome Project and other investigations is certain to shed new light on the influence of extragastric bacterial, viral, fungal, and parasitic coinfections on H. pylori-associated peptic ulcer disease and gastric adenocarcinoma.}, } @article {pmid22904687, year = {2012}, author = {Gevers, D and Knight, R and Petrosino, JF and Huang, K and McGuire, AL and Birren, BW and Nelson, KE and White, O and Methé, BA and Huttenhower, C}, title = {The Human Microbiome Project: a community resource for the healthy human microbiome.}, journal = {PLoS biology}, volume = {10}, number = {8}, pages = {e1001377}, pmid = {22904687}, issn = {1545-7885}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Computational Biology ; Ecosystem ; Genes, rRNA ; *Genomics ; Health ; High-Throughput Nucleotide Sequencing ; Humans ; *Internet ; *Metagenome ; Organizations/*organization & administration ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; }, abstract = {This manuscript describes the NIH Human Microbiome Project, including a brief review of human microbiome research, a history of the project, and a comprehensive overview of the consortium's recent collection of publications analyzing the human microbiome.}, } @article {pmid22902418, year = {2012}, author = {Triggle, DJ}, title = {Nous sommes tous des bacteries: implications for medicine, pharmacology and public health.}, journal = {Biochemical pharmacology}, volume = {84}, number = {12}, pages = {1543-1550}, doi = {10.1016/j.bcp.2012.08.005}, pmid = {22902418}, issn = {1873-2968}, mesh = {*Bacteria ; Humans ; *Metagenome ; *Pharmacology ; *Public Health ; }, abstract = {As a species we humans are outnumbered by bacteria in both cell and gene count. This somewhat humbling observation is key to the increasing recognition that the long-standing symbiotic and commensal relations between Homo sapiens and bacteria are of great significance to basic human physiology and health. Knowledge of our human bacterial environment is contributing to an understanding of a variety of disorders including obesity and metabolic syndrome, cardiovascular disease, immunity, and neuronal development and behavior. The Human Microbiome Project is providing a genetic and ecological analysis and will serve as a parallel to the Human Genome Project. Exploration of the chemical space utilized by bacteria will contribute to the development of new small molecule therapeutic agents, including new antibiotics. And genetically re-engineered bacteria are proving to be of potential value as actual therapeutic entities. Our understanding of our bacterial world has the capability to transform radically our current approach to human health diverting it from an emphasis on acute treatments to living in healthy harmony with both our internal and external environments.}, } @article {pmid22850139, year = {2012}, author = {McGuire, AL and Achenbaum, LS and Whitney, SN and Slashinski, MJ and Versalovic, J and Keitel, WA and McCurdy, SA}, title = {Perspectives on human microbiome research ethics.}, journal = {Journal of empirical research on human research ethics : JERHRE}, volume = {7}, number = {3}, pages = {1-14}, pmid = {22850139}, issn = {1556-2654}, support = {R01 HG004853/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Ethics, Research ; Female ; Humans ; Information Dissemination ; Informed Consent ; Interviews as Topic ; Male ; *Metagenome ; Metagenomics/*ethics/legislation & jurisprudence ; Middle Aged ; National Institutes of Health (U.S.) ; Research Personnel ; Research Subjects ; United States ; }, abstract = {Study of ethical, legal, and social implications (ELSI) of human microbiome research has been integral to the Human Microbiome Project (HMP). This study explores core ELSI issues that arose during the first phase of the HMP from the perspective of individuals involved in the research. We conducted semi-structured in-depth interviews with investigators and NIH employees ("investigators") involved in the HMP, and with individuals recruited to participate in the HMP Healthy Cohort Study at Baylor College of Medicine ("recruits"). We report findings related to three major ELSI issues: informed consent, data sharing, and return of results. Our findings demonstrate that investigators and recruits were similarly sensitive to these issues yet generally comfortable with study design in light of current knowledge about the microbiome.}, } @article {pmid22848458, year = {2012}, author = {Fodor, AA and DeSantis, TZ and Wylie, KM and Badger, JH and Ye, Y and Hepburn, T and Hu, P and Sodergren, E and Liolios, K and Huot-Creasy, H and Birren, BW and Earl, AM}, title = {The "most wanted" taxa from the human microbiome for whole genome sequencing.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e41294}, pmid = {22848458}, issn = {1932-6203}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/*genetics ; Cohort Studies ; Female ; *Genes, Bacterial ; Genes, rRNA/*genetics ; Humans ; Male ; Metagenome/*genetics ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {The goal of the Human Microbiome Project (HMP) is to generate a comprehensive catalog of human-associated microorganisms including reference genomes representing the most common species. Toward this goal, the HMP has characterized the microbial communities at 18 body habitats in a cohort of over 200 healthy volunteers using 16S rRNA gene (16S) sequencing and has generated nearly 1,000 reference genomes from human-associated microorganisms. To determine how well current reference genome collections capture the diversity observed among the healthy microbiome and to guide isolation and future sequencing of microbiome members, we compared the HMP's 16S data sets to several reference 16S collections to create a 'most wanted' list of taxa for sequencing. Our analysis revealed that the diversity of commonly occurring taxa within the HMP cohort microbiome is relatively modest, few novel taxa are represented by these OTUs and many common taxa among HMP volunteers recur across different populations of healthy humans. Taken together, these results suggest that it should be possible to perform whole-genome sequencing on a large fraction of the human microbiome, including the 'most wanted', and that these sequences should serve to support microbiome studies across multiple cohorts. Also, in stark contrast to other taxa, the 'most wanted' organisms are poorly represented among culture collections suggesting that novel culture- and single-cell-based methods will be required to isolate these organisms for sequencing.}, } @article {pmid22841660, year = {2012}, author = {Liu, L and Chen, X and Skogerbø, G and Zhang, P and Chen, R and He, S and Huang, DW}, title = {The human microbiome: a hot spot of microbial horizontal gene transfer.}, journal = {Genomics}, volume = {100}, number = {5}, pages = {265-270}, doi = {10.1016/j.ygeno.2012.07.012}, pmid = {22841660}, issn = {1089-8646}, mesh = {*Biota ; Computational Biology ; Gene Transfer, Horizontal/*genetics ; Genes, Bacterial/*genetics ; Genomics/*methods ; Humans ; Metagenome/*genetics ; Molecular Sequence Annotation ; }, abstract = {The human body harbors numerous microbes, and here exists a close relationship between microbes and human health. The Human Microbiome Project has generated whole genome sequences of several hundred human microbes. In this study, we identified horizontal gene transfer (HGT) events in human microbes and tried to elucidate the relationships between the gene-transferring microbes. A total of 13,514 high confidence HGT genes were identified in 308 human microbes. The horizontally transferred genes were enriched for Gene Ontology terms pertaining to catalytic functions and metabolic processes. Construction of an HGT event network suggested that the human microbes could be divided into specific communities which only partly overlap their distribution in human body. Our research suggests that human microbiome may facilitate frequent horizontal gene transfer among bacteria in human body. Awareness of HGT in human microbiome may aid our understanding of the relationship between the human microbiome and human health.}, } @article {pmid22807668, year = {2012}, author = {Faust, K and Sathirapongsasuti, JF and Izard, J and Segata, N and Gevers, D and Raes, J and Huttenhower, C}, title = {Microbial co-occurrence relationships in the human microbiome.}, journal = {PLoS computational biology}, volume = {8}, number = {7}, pages = {e1002606}, pmid = {22807668}, issn = {1553-7358}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification ; *Bacterial Physiological Phenomena ; Computational Biology ; DNA, Bacterial/chemistry ; Ecosystem ; Female ; Gastrointestinal Tract/microbiology ; Genes, rRNA/genetics ; Humans ; Linear Models ; Male ; Metagenome/*physiology ; Microbial Interactions/physiology ; Nasal Cavity/microbiology ; Phylogeny ; Skin/microbiology ; Vagina/microbiology ; }, abstract = {The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles of this cohort, resulting in a global network of 3,005 significant co-occurrence and co-exclusion relationships between 197 clades occurring throughout the human microbiome. This network revealed strong niche specialization, with most microbial associations occurring within body sites and a number of accompanying inter-body site relationships. Microbial communities within the oropharynx grouped into three distinct habitats, which themselves showed no direct influence on the composition of the gut microbiota. Conversely, niches such as the vagina demonstrated little to no decomposition into region-specific interactions. Diverse mechanisms underlay individual interactions, with some such as the co-exclusion of Porphyromonaceae family members and Streptococcus in the subgingival plaque supported by known biochemical dependencies. These differences varied among broad phylogenetic groups as well, with the Bacilli and Fusobacteria, for example, both enriched for exclusion of taxa from other clades. Comparing phylogenetic versus functional similarities among bacteria, we show that dominant commensal taxa (such as Prevotellaceae and Bacteroides in the gut) often compete, while potential pathogens (e.g. Treponema and Prevotella in the dental plaque) are more likely to co-occur in complementary niches. This approach thus serves to open new opportunities for future targeted mechanistic studies of the microbial ecology of the human microbiome.}, } @article {pmid22792232, year = {2012}, author = {Markowitz, VM and Chen, IM and Chu, K and Szeto, E and Palaniappan, K and Jacob, B and Ratner, A and Liolios, K and Pagani, I and Huntemann, M and Mavromatis, K and Ivanova, NN and Kyrpides, NC}, title = {IMG/M-HMP: a metagenome comparative analysis system for the Human Microbiome Project.}, journal = {PloS one}, volume = {7}, number = {7}, pages = {e40151}, pmid = {22792232}, issn = {1932-6203}, support = {U01 HG004866/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/genetics ; *Database Management Systems ; *Databases, Genetic ; Eukaryota/genetics ; Humans ; *Internet ; Metagenome/*genetics ; User-Computer Interface ; }, abstract = {The Integrated Microbial Genomes and Metagenomes (IMG/M) resource is a data management system that supports the analysis of sequence data from microbial communities in the integrated context of all publicly available draft and complete genomes from the three domains of life as well as a large number of plasmids and viruses. IMG/M currently contains thousands of genomes and metagenome samples with billions of genes. IMG/M-HMP is an IMG/M data mart serving the US National Institutes of Health (NIH) Human Microbiome Project (HMP), focussed on HMP generated metagenome datasets, and is one of the central resources provided from the HMP Data Analysis and Coordination Center (DACC). IMG/M-HMP is available at http://www.hmpdacc-resources.org/imgm_hmp/.}, } @article {pmid22720093, year = {2012}, author = {, }, title = {Evaluation of 16S rDNA-based community profiling for human microbiome research.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e39315}, pmid = {22720093}, issn = {1932-6203}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; HHSN272200900018C/AI/NIAID NIH HHS/United States ; HHSN272200900008C/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; HHSN2722009000018C//PHS HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; HHSN272200900001C/AI/NIAID NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; 1U01HG004866/HG/NHGRI NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics ; Bayes Theorem ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {The Human Microbiome Project will establish a reference data set for analysis of the microbiome of healthy adults by surveying multiple body sites from 300 people and generating data from over 12,000 samples. To characterize these samples, the participating sequencing centers evaluated and adopted 16S rDNA community profiling protocols for ABI 3730 and 454 FLX Titanium sequencing. In the course of establishing protocols, we examined the performance and error characteristics of each technology, and the relationship of sequence error to the utility of 16S rDNA regions for classification- and OTU-based analysis of community structure. The data production protocols used for this work are those used by the participating centers to produce 16S rDNA sequence for the Human Microbiome Project. Thus, these results can be informative for interpreting the large body of clinical 16S rDNA data produced for this project.}, } @article {pmid22719832, year = {2012}, author = {Aagaard, K and Riehle, K and Ma, J and Segata, N and Mistretta, TA and Coarfa, C and Raza, S and Rosenbaum, S and Van den Veyver, I and Milosavljevic, A and Gevers, D and Huttenhower, C and Petrosino, J and Versalovic, J}, title = {A metagenomic approach to characterization of the vaginal microbiome signature in pregnancy.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e36466}, pmid = {22719832}, issn = {1932-6203}, support = {DP2120OD001500-01/OD/NIH HHS/United States ; #R01DK080558-01/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; NIHU54HG004969/HG/NHGRI NIH HHS/United States ; R01 DK080558/DK/NIDDK NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 DK083990L/DK/NIDDK NIH HHS/United States ; NIH 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Bacteria/classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Female ; Humans ; *Metagenome ; *Metagenomics ; Pregnancy ; Vagina/*microbiology ; }, abstract = {While current major national research efforts (i.e., the NIH Human Microbiome Project) will enable comprehensive metagenomic characterization of the adult human microbiota, how and when these diverse microbial communities take up residence in the host and during reproductive life are unexplored at a population level. Because microbial abundance and diversity might differ in pregnancy, we sought to generate comparative metagenomic signatures across gestational age strata. DNA was isolated from the vagina (introitus, posterior fornix, midvagina) and the V5V3 region of bacterial 16S rRNA genes were sequenced (454FLX Titanium platform). Sixty-eight samples from 24 healthy gravidae (18 to 40 confirmed weeks) were compared with 301 non-pregnant controls (60 subjects). Generated sequence data were quality filtered, taxonomically binned, normalized, and organized by phylogeny and into operational taxonomic units (OTU); principal coordinates analysis (PCoA) of the resultant beta diversity measures were used for visualization and analysis in association with sample clinical metadata. Altogether, 1.4 gigabytes of data containing >2.5 million reads (averaging 6,837 sequences/sample of 493 nt in length) were generated for computational analyses. Although gravidae were not excluded by virtue of a posterior fornix pH >4.5 at the time of screening, unique vaginal microbiome signature encompassing several specific OTUs and higher-level clades was nevertheless observed and confirmed using a combination of phylogenetic, non-phylogenetic, supervised, and unsupervised approaches. Both overall diversity and richness were reduced in pregnancy, with dominance of Lactobacillus species (L. iners crispatus, jensenii and johnsonii, and the orders Lactobacillales (and Lactobacillaceae family), Clostridiales, Bacteroidales, and Actinomycetales. This intergroup comparison using rigorous standardized sampling protocols and analytical methodologies provides robust initial evidence that the vaginal microbial 16S rRNA gene catalogue uniquely differs in pregnancy, with variance of taxa across vaginal subsite and gestational age.}, } @article {pmid22719831, year = {2012}, author = {Martin, J and Sykes, S and Young, S and Kota, K and Sanka, R and Sheth, N and Orvis, J and Sodergren, E and Wang, Z and Weinstock, GM and Mitreva, M}, title = {Optimizing read mapping to reference genomes to determine composition and species prevalence in microbial communities.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e36427}, pmid = {22719831}, issn = {1932-6203}, support = {U54HG004969/HG/NHGRI NIH HHS/United States ; NIH-NHGRI U54HG003079//PHS HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; NIH-NIAID UH3AI083263//PHS HHS/United States ; }, mesh = {Biodiversity ; Databases, Factual ; Humans ; *Metagenome ; *Metagenomics ; Phylogeny ; }, abstract = {The Human Microbiome Project (HMP) aims to characterize the microbial communities of 18 body sites from healthy individuals. To accomplish this, the HMP generated two types of shotgun data: reference shotgun sequences isolated from different anatomical sites on the human body and shotgun metagenomic sequences from the microbial communities of each site. The alignment strategy for characterizing these metagenomic communities using available reference sequence is important to the success of HMP data analysis. Six next-generation aligners were used to align a community of known composition against a database comprising reference organisms known to be present in that community. All aligners report nearly complete genome coverage (>97%) for strains with over 6X depth of coverage, however they differ in speed, memory requirement and ease of use issues such as database size limitations and supported mapping strategies. The selected aligner was tested across a range of parameters to maximize sensitivity while maintaining a low false positive rate. We found that constraining alignment length had more impact on sensitivity than does constraining similarity in all cases tested. However, when reference species were replaced with phylogenetic neighbors, similarity begins to play a larger role in detection. We also show that choosing the top hit randomly when multiple, equally strong mappings are available increases overall sensitivity at the expense of taxonomic resolution. The results of this study identified a strategy that was used to map over 3 tera-bases of microbial sequence against a database of more than 5,000 reference genomes in just over a month.}, } @article {pmid22719826, year = {2012}, author = {Wylie, KM and Truty, RM and Sharpton, TJ and Mihindukulasuriya, KA and Zhou, Y and Gao, H and Sodergren, E and Weinstock, GM and Pollard, KS}, title = {Novel bacterial taxa in the human microbiome.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e35294}, pmid = {22719826}, issn = {1932-6203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; }, mesh = {DNA, Ribosomal/genetics ; Humans ; *Metagenome ; Metagenomics ; }, abstract = {The human gut harbors thousands of bacterial taxa. A profusion of metagenomic sequence data has been generated from human stool samples in the last few years, raising the question of whether more taxa remain to be identified. We assessed metagenomic data generated by the Human Microbiome Project Consortium to determine if novel taxa remain to be discovered in stool samples from healthy individuals. To do this, we established a rigorous bioinformatics pipeline that uses sequence data from multiple platforms (Illumina GAIIX and Roche 454 FLX Titanium) and approaches (whole-genome shotgun and 16S rDNA amplicons) to validate novel taxa. We applied this approach to stool samples from 11 healthy subjects collected as part of the Human Microbiome Project. We discovered several low-abundance, novel bacterial taxa, which span three major phyla in the bacterial tree of life. We determined that these taxa are present in a larger set of Human Microbiome Project subjects and are found in two sampling sites (Houston and St. Louis). We show that the number of false-positive novel sequences (primarily chimeric sequences) would have been two orders of magnitude higher than the true number of novel taxa without validation using multiple datasets, highlighting the importance of establishing rigorous standards for the identification of novel taxa in metagenomic data. The majority of novel sequences are related to the recently discovered genus Barnesiella, further encouraging efforts to characterize the members of this genus and to study their roles in the microbial communities of the gut. A better understanding of the effects of less-abundant bacteria is important as we seek to understand the complex gut microbiome in healthy individuals and link changes in the microbiome to disease.}, } @article {pmid22719824, year = {2012}, author = {Huse, SM and Ye, Y and Zhou, Y and Fodor, AA}, title = {A core human microbiome as viewed through 16S rRNA sequence clusters.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e34242}, pmid = {22719824}, issn = {1932-6203}, support = {NIH-NHGRI U54HG004968//PHS HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; UH2 DK083993/DK/NIDDK NIH HHS/United States ; 1UH2DK083993-01/DK/NIDDK NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; NIH 1R01HG004908/HG/NHGRI NIH HHS/United States ; }, mesh = {Humans ; *Metagenome ; RNA, Ribosomal, 16S/*genetics ; Reference Values ; }, abstract = {We explore the microbiota of 18 body sites in over 200 individuals using sequences amplified V1-V3 and the V3-V5 small subunit ribosomal RNA (16S) hypervariable regions as part of the NIH Common Fund Human Microbiome Project. The body sites with the greatest number of core OTUs, defined as OTUs shared amongst 95% or more of the individuals, were the oral sites (saliva, tongue, cheek, gums, and throat) followed by the nose, stool, and skin, while the vaginal sites had the fewest number of OTUs shared across subjects. We found that commonalities between samples based on taxonomy could sometimes belie variability at the sub-genus OTU level. This was particularly apparent in the mouth where a given genus can be present in many different oral sites, but the sub-genus OTUs show very distinct site selection, and in the vaginal sites, which are consistently dominated by the Lactobacillus genus but have distinctly different sub-genus V1-V3 OTU populations across subjects. Different body sites show approximately a ten-fold difference in estimated microbial richness, with stool samples having the highest estimated richness, followed by the mouth, throat and gums, then by the skin, nasal and vaginal sites. Richness as measured by the V1-V3 primers was consistently higher than richness measured by V3-V5. We also show that when such a large cohort is analyzed at the genus level, most subjects fit the stool "enterotype" profile, but other subjects are intermediate, blurring the distinction between the enterotypes. When analyzed at the finer-scale, OTU level, there was little or no segregation into stool enterotypes, but in the vagina distinct biotypes were apparent. Finally, we note that even OTUs present in nearly every subject, or that dominate in some samples, showed orders of magnitude variation in relative abundance emphasizing the highly variable nature across individuals.}, } @article {pmid22719823, year = {2012}, author = {Li, K and Bihan, M and Yooseph, S and Methé, BA}, title = {Analyses of the microbial diversity across the human microbiome.}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e32118}, pmid = {22719823}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; #AI084844/AI/NIAID NIH HHS/United States ; }, mesh = {Biodiversity ; Humans ; *Metagenome ; }, abstract = {Analysis of human body microbial diversity is fundamental to understanding community structure, biology and ecology. The National Institutes of Health Human Microbiome Project (HMP) has provided an unprecedented opportunity to examine microbial diversity within and across body habitats and individuals through pyrosequencing-based profiling of 16 S rRNA gene sequences (16 S) from habits of the oral, skin, distal gut, and vaginal body regions from over 200 healthy individuals enabling the application of statistical techniques. In this study, two approaches were applied to elucidate the nature and extent of human microbiome diversity. First, bootstrap and parametric curve fitting techniques were evaluated to estimate the maximum number of unique taxa, S(max), and taxa discovery rate for habitats across individuals. Next, our results demonstrated that the variation of diversity within low abundant taxa across habitats and individuals was not sufficiently quantified with standard ecological diversity indices. This impact from low abundant taxa motivated us to introduce a novel rank-based diversity measure, the Tail statistic, ("τ"), based on the standard deviation of the rank abundance curve if made symmetric by reflection around the most abundant taxon. Due to τ's greater sensitivity to low abundant taxa, its application to diversity estimation of taxonomic units using taxonomic dependent and independent methods revealed a greater range of values recovered between individuals versus body habitats, and different patterns of diversity within habitats. The greatest range of τ values within and across individuals was found in stool, which also exhibited the most undiscovered taxa. Oral and skin habitats revealed variable diversity patterns, while vaginal habitats were consistently the least diverse. Collectively, these results demonstrate the importance, and motivate the introduction, of several visualization and analysis methods tuned specifically for next-generation sequence data, further revealing that low abundant taxa serve as an important reservoir of genetic diversity in the human microbiome.}, } @article {pmid22719821, year = {2012}, author = {Goll, J and Thiagarajan, M and Abubucker, S and Huttenhower, C and Yooseph, S and Methé, BA}, title = {A case study for large-scale human microbiome analysis using JCVI's metagenomics reports (METAREP).}, journal = {PloS one}, volume = {7}, number = {6}, pages = {e29044}, pmid = {22719821}, issn = {1932-6203}, support = {U54 AI084844/AI/NIAID NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; N01 AI 30071/AI/NIAID NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; N01 AI030071/AI/NIAID NIH HHS/United States ; U54-AI084844/AI/NIAID NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Cluster Analysis ; Humans ; *Metagenomics ; National Institutes of Health (U.S.) ; United States ; }, abstract = {As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code are available at http://www.jcvi.org/hmp-metarep.}, } @article {pmid22719260, year = {2012}, author = {Rho, M and Wu, YW and Tang, H and Doak, TG and Ye, Y}, title = {Diverse CRISPRs evolving in human microbiomes.}, journal = {PLoS genetics}, volume = {8}, number = {6}, pages = {e1002441}, pmid = {22719260}, issn = {1553-7404}, support = {R01 HG004908/HG/NHGRI NIH HHS/United States ; 1R01HG004908/HG/NHGRI NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/genetics/virology ; Bacteriophages/genetics ; Base Sequence ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Genome, Bacterial ; Humans ; Inverted Repeat Sequences/*genetics ; Metagenome/*genetics ; Metagenomics ; Molecular Sequence Data ; Plasmids/genetics ; Sequence Analysis, DNA ; Streptococcus/genetics/virology ; }, abstract = {CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) loci, together with cas (CRISPR-associated) genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP) enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes), we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones) are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ∼8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals. This work indicates the importance of effective identification and characterization of CRISPR loci to the study of the dynamic ecology of microbiomes.}, } @article {pmid22719234, year = {2012}, author = {Abubucker, S and Segata, N and Goll, J and Schubert, AM and Izard, J and Cantarel, BL and Rodriguez-Mueller, B and Zucker, J and Thiagarajan, M and Henrissat, B and White, O and Kelley, ST and Methé, B and Schloss, PD and Gevers, D and Mitreva, M and Huttenhower, C}, title = {Metabolic reconstruction for metagenomic data and its application to the human microbiome.}, journal = {PLoS computational biology}, volume = {8}, number = {6}, pages = {e1002358}, pmid = {22719234}, issn = {1553-7358}, support = {R01 HG005969/HG/NHGRI NIH HHS/United States ; R21 DE017106/DE/NIDCR NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; 5R01HG005975/HG/NHGRI NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; 1R01HG005969/HG/NHGRI NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; Digestive System/metabolism/microbiology ; Female ; Genetics, Microbial ; Glycosaminoglycans/metabolism ; Humans ; Hydrogen-Ion Concentration ; Metabolic Networks and Pathways/genetics ; Metabolome/genetics ; *Metagenome ; Multigene Family ; Vagina/metabolism/microbiology ; }, abstract = {Microbial communities carry out the majority of the biochemical activity on the planet, and they play integral roles in processes including metabolism and immune homeostasis in the human microbiome. Shotgun sequencing of such communities' metagenomes provides information complementary to organismal abundances from taxonomic markers, but the resulting data typically comprise short reads from hundreds of different organisms and are at best challenging to assemble comparably to single-organism genomes. Here, we describe an alternative approach to infer the functional and metabolic potential of a microbial community metagenome. We determined the gene families and pathways present or absent within a community, as well as their relative abundances, directly from short sequence reads. We validated this methodology using a collection of synthetic metagenomes, recovering the presence and abundance both of large pathways and of small functional modules with high accuracy. We subsequently applied this method, HUMAnN, to the microbial communities of 649 metagenomes drawn from seven primary body sites on 102 individuals as part of the Human Microbiome Project (HMP). This provided a means to compare functional diversity and organismal ecology in the human microbiome, and we determined a core of 24 ubiquitously present modules. Core pathways were often implemented by different enzyme families within different body sites, and 168 functional modules and 196 metabolic pathways varied in metagenomic abundance specifically to one or more niches within the microbiome. These included glycosaminoglycan degradation in the gut, as well as phosphate and amino acid transport linked to host phenotype (vaginal pH) in the posterior fornix. An implementation of our methodology is available at http://huttenhower.sph.harvard.edu/humann. This provides a means to accurately and efficiently characterize microbial metabolic pathways and functional modules directly from high-throughput sequencing reads, enabling the determination of community roles in the HMP cohort and in future metagenomic studies.}, } @article {pmid22699610, year = {2012}, author = {, }, title = {A framework for human microbiome research.}, journal = {Nature}, volume = {486}, number = {7402}, pages = {215-221}, pmid = {22699610}, issn = {1476-4687}, support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; N01HG62088/HG/NHGRI NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; RC1DE020298/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; N01AI30071/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG00485/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/*genetics ; Female ; Humans ; Male ; *Metagenome ; Metagenomics/*methods ; RNA, Ribosomal, 16S/genetics ; Reference Standards ; Statistics as Topic ; Young Adult ; }, abstract = {A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies.}, } @article {pmid22699609, year = {2012}, author = {, }, title = {Structure, function and diversity of the healthy human microbiome.}, journal = {Nature}, volume = {486}, number = {7402}, pages = {207-214}, pmid = {22699609}, issn = {1476-4687}, support = {R01HG004856/HG/NHGRI NIH HHS/United States ; R01HG004908/HG/NHGRI NIH HHS/United States ; P30DE020751/DE/NIDCR NIH HHS/United States ; R21HG005811/HG/NHGRI NIH HHS/United States ; R01HG005172/HG/NHGRI NIH HHS/United States ; UH3DK083993/DK/NIDDK NIH HHS/United States ; R01 HG005969/HG/NHGRI NIH HHS/United States ; R01HG004900/HG/NHGRI NIH HHS/United States ; UH2 DK083990/DK/NIDDK NIH HHS/United States ; N01HG62088/HG/NHGRI NIH HHS/United States ; R01 HG004857/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; U01DE016937/DE/NIDCR NIH HHS/United States ; UH2 AR057504/AR/NIAMS NIH HHS/United States ; U54HG004969/HG/NHGRI NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; U54HG003273/HG/NHGRI NIH HHS/United States ; R01HG004877/HG/NHGRI NIH HHS/United States ; R01 HG004900/HG/NHGRI NIH HHS/United States ; DP2OD001500/OD/NIH HHS/United States ; R01HG004885/HG/NHGRI NIH HHS/United States ; R01HG004872/HG/NHGRI NIH HHS/United States ; R01 HG004856/HG/NHGRI NIH HHS/United States ; R01 HG005171/HG/NHGRI NIH HHS/United States ; UH3AI083263/AI/NIAID NIH HHS/United States ; UH2 AR057506/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UH2AR057504/AR/NIAMS NIH HHS/United States ; U01HG004866/HG/NHGRI NIH HHS/United States ; U54HG003067/HG/NHGRI NIH HHS/United States ; U54 AI084844/AI/NIAID NIH HHS/United States ; UH3AR057504/AR/NIAMS NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; UH2AI083263/AI/NIAID NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; U54AI084844/AI/NIAID NIH HHS/United States ; R01 HG005975/HG/NHGRI NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; UH3 DK083993/DK/NIDDK NIH HHS/United States ; R01DE021574/DE/NIDCR NIH HHS/United States ; R01 HG004885/HG/NHGRI NIH HHS/United States ; U54 HG004968/HG/NHGRI NIH HHS/United States ; U54HG004973/HG/NHGRI NIH HHS/United States ; R01HG004857/HG/NHGRI NIH HHS/United States ; UH2 AI083263/AI/NIAID NIH HHS/United States ; R01HG005171/HG/NHGRI NIH HHS/United States ; T32AI007528/AI/NIAID NIH HHS/United States ; R01HG004906/HG/NHGRI NIH HHS/United States ; U54HG003079/HG/NHGRI NIH HHS/United States ; RC1 DE020298/DE/NIDCR NIH HHS/United States ; DP2 OD001500/OD/NIH HHS/United States ; R01 DE021574/DE/NIDCR NIH HHS/United States ; T32 GM087237/GM/NIGMS NIH HHS/United States ; R01 HG004908/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; R21 CA139193/CA/NCI NIH HHS/United States ; R01HG005975/HG/NHGRI NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21CA139193/CA/NCI NIH HHS/United States ; R21 HG005811/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01 HG004853/HG/NHGRI NIH HHS/United States ; N01AI30071/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; R01HG004853/HG/NHGRI NIH HHS/United States ; UH3 AI083263/AI/NIAID NIH HHS/United States ; UH2DK083990/DK/NIDDK NIH HHS/United States ; U54HG004968/HG/NHGRI NIH HHS/United States ; RC1DE0202098/DE/NIDCR NIH HHS/United States ; R01 HG004906/HG/NHGRI NIH HHS/United States ; R01HG005969/HG/NHGRI NIH HHS/United States ; R01 HG004877/HG/NHGRI NIH HHS/United States ; P30 DE020751/DE/NIDCR NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; UH2AR057506/AR/NIAMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/*classification/genetics ; *Biodiversity ; Ecosystem ; Female ; *Health ; Humans ; Male ; Metabolic Networks and Pathways/physiology ; *Metagenome ; Metagenomics ; Phenotype ; RNA, Ribosomal, 16S/genetics ; Young Adult ; }, abstract = {Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.}, } @article {pmid22698087, year = {2012}, author = {Segata, N and Haake, SK and Mannon, P and Lemon, KP and Waldron, L and Gevers, D and Huttenhower, C and Izard, J}, title = {Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples.}, journal = {Genome biology}, volume = {13}, number = {6}, pages = {R42}, pmid = {22698087}, issn = {1474-760X}, support = {HG004969/HG/NHGRI NIH HHS/United States ; DE020751/DE/NIDCR NIH HHS/United States ; HG005969/HG/NHGRI NIH HHS/United States ; CA139193/CA/NCI NIH HHS/United States ; DE020298/DE/NIDCR NIH HHS/United States ; DE021574/DE/NIDCR NIH HHS/United States ; }, mesh = {Actinobacteria/classification/genetics/isolation & purification ; Adolescent ; Adult ; Bacterial Typing Techniques/methods ; Bacteroidetes/classification/genetics/isolation & purification ; *Biota ; Feces/*microbiology ; Female ; Genes, rRNA ; Humans ; Male ; *Metagenome ; Mouth/*microbiology ; Palatine Tonsil/*microbiology ; Pharynx/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/analysis/genetics ; Saliva/microbiology ; Veillonellaceae/classification/genetics/isolation & purification ; Young Adult ; }, abstract = {BACKGROUND: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body's greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites.

RESULTS: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub- and supra-gingival plaques; and stool. Phyla initially identified from environmental samples were detected throughout this population, primarily TM7, SR1, and Synergistetes. Genera with pathogenic members were well-represented among this disease-free cohort. Tooth-associated communities were distinct, but not entirely dissimilar, from other oral surfaces. The Porphyromonadaceae, Veillonellaceae and Lachnospiraceae families were common to all sites, but the distributions of their genera varied significantly. Most metabolic processes were distributed widely throughout the digestive tract microbiota, with variations in metagenomic abundance between body habitats. These included shifts in sugar transporter types between the supragingival plaque, other oral surfaces, and stool; hydrogen and hydrogen sulfide production were also differentially distributed.

CONCLUSIONS: The microbiomes of ten digestive tract sites separated into four types based on composition. A core set of metabolic pathways was present across these diverse digestive tract habitats. These data provide a critical baseline for future studies investigating local and systemic diseases affecting human health.}, } @article {pmid22683238, year = {2012}, author = {Dave, M and Higgins, PD and Middha, S and Rioux, KP}, title = {The human gut microbiome: current knowledge, challenges, and future directions.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {160}, number = {4}, pages = {246-257}, doi = {10.1016/j.trsl.2012.05.003}, pmid = {22683238}, issn = {1878-1810}, mesh = {Adaptive Immunity/physiology ; Bacteria/*classification ; Computational Biology ; Gastrointestinal Tract/*microbiology ; Humans ; Immunity, Innate/physiology ; }, abstract = {The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded "The Human Microbiome Project." Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host-microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously "uncultivable" microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains.}, } @article {pmid22675588, year = {2011}, author = {Earl, AM and Desjardins, CA and Fitzgerald, MG and Arachchi, HM and Zeng, Q and Mehta, T and Griggs, A and Birren, BW and Toney, NC and Carr, J and Posey, J and Butler, WR}, title = {High quality draft genome sequence of Segniliparus rugosus CDC 945(T)= (ATCC BAA-974(T)).}, journal = {Standards in genomic sciences}, volume = {5}, number = {3}, pages = {389-397}, pmid = {22675588}, issn = {1944-3277}, support = {HHSN272200900017C/AI/NIAID NIH HHS/United States ; U54 HG004969/HG/NHGRI NIH HHS/United States ; }, abstract = {Segniliparus rugosus represents one of two species in the genus Segniliparus, the sole genus in the family Segniliparaceae. A unique and interesting feature of this family is the presence of extremely long carbon-chain length mycolic acids bound in the cell wall. S. rugosus is also a medically important species because it is an opportunistic pathogen associated with mammalian lung disease. This report represents the second species in the genus to have its genome sequenced. The 3,567,567 bp long genome with 3,516 protein-coding and 49 RNA genes is part of the NIH Roadmap for Medical Research, Human Microbiome Project.}, } @article {pmid22635997, year = {2012}, author = {Wu, YW and Rho, M and Doak, TG and Ye, Y}, title = {Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes.}, journal = {Applied and environmental microbiology}, volume = {78}, number = {15}, pages = {5288-5296}, pmid = {22635997}, issn = {1098-5336}, mesh = {Base Pairing ; Base Sequence ; Cluster Analysis ; Computational Biology/*methods ; Computer Simulation ; DNA Primers/genetics ; Humans ; Integrons/*genetics ; Metagenome/*genetics ; Molecular Sequence Data ; Phylogeny ; Polymerase Chain Reaction ; Stomatognathic Diseases/*microbiology ; Treponema/*genetics ; }, abstract = {The NIH Human Microbiome Project (HMP) has produced several hundred metagenomic data sets, allowing studies of the many functional elements in human-associated microbial communities. Here, we survey the distribution of oral spirochetes implicated in dental diseases in normal human individuals, using recombination sites associated with the chromosomal integron in Treponema genomes, taking advantage of the multiple copies of the integron recombination sites (repeats) in the genomes, and using a targeted assembly approach that we have developed. We find that integron-containing Treponema species are present in ∼80% of the normal human subjects included in the HMP. Further, we are able to de novo assemble the integron gene cassettes using our constrained assembly approach, which employs a unique application of the de Bruijn graph assembly information; most of these cassette genes were not assembled in whole-metagenome assemblies and could not be identified by mapping sequencing reads onto the known reference Treponema genomes due to the dynamic nature of integron gene cassettes. Our study significantly enriches the gene pool known to be carried by Treponema chromosomal integrons, totaling 826 (598 97% nonredundant) genes. We characterize the functions of these gene cassettes: many of these genes have unknown functions. The integron gene cassette arrays found in the human microbiome are extraordinarily dynamic, with different microbial communities sharing only a small number of common genes.}, } @article {pmid22577297, year = {2012}, author = {Liu, Z and Bensmail, H and Tan, M}, title = {Efficient feature selection and multiclass classification with integrated instance and model based learning.}, journal = {Evolutionary bioinformatics online}, volume = {8}, number = {}, pages = {197-205}, pmid = {22577297}, issn = {1176-9343}, support = {R03 CA133899/CA/NCI NIH HHS/United States ; }, abstract = {Multiclass classification and feature (variable) selections are commonly encountered in many biological and medical applications. However, extending binary classification approaches to multiclass problems is not trivial. Instance-based methods such as the K nearest neighbor (KNN) can naturally extend to multiclass problems and usually perform well with unbalanced data, but suffer from the curse of dimensionality. Their performance is degraded when applied to high dimensional data. On the other hand, model-based methods such as logistic regression require the decomposition of the multiclass problem into several binary problems with one-vs.-one or one-vs.-rest schemes. Even though they can be applied to high dimensional data with L(1) or L(p) penalized methods, such approaches can only select independent features and the features selected with different binary problems are usually different. They also produce unbalanced classification problems with one vs. the rest scheme even if the original multiclass problem is balanced.By combining instance-based and model-based learning, we propose an efficient learning method with integrated KNN and constrained logistic regression (KNNLog) for simultaneous multiclass classification and feature selection. Our proposed method simultaneously minimizes the intra-class distance and maximizes the interclass distance with fewer estimated parameters. It is very efficient for problems with small sample size and unbalanced classes, a case common in many real applications. In addition, our model-based feature selection methods can identify highly correlated features simultaneously avoiding the multiplicity problem due to multiple tests. The proposed method is evaluated with simulation and real data including one unbalanced microRNA dataset for leukemia and one multiclass metagenomic dataset from the Human Microbiome Project (HMP). It performs well with limited computational experiments.}, } @article {pmid22574119, year = {2012}, author = {Sanchez, LM and Wong, WR and Riener, RM and Schulze, CJ and Linington, RG}, title = {Examining the fish microbiome: vertebrate-derived bacteria as an environmental niche for the discovery of unique marine natural products.}, journal = {PloS one}, volume = {7}, number = {5}, pages = {e35398}, pmid = {22574119}, issn = {1932-6203}, support = {U01 TW006634/TW/FIC NIH HHS/United States ; 2R25GM05803-12/GM/NIGMS NIH HHS/United States ; TW006634/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/growth & development/*isolation & purification/*metabolism ; Biodiversity ; Biological Products/*metabolism ; Culture Techniques ; *Drug Discovery ; Fishes/*microbiology ; Intestines/microbiology ; *Metagenome ; Oceans and Seas ; Phylogeny ; }, abstract = {Historically, marine invertebrates have been a prolific source of unique natural products, with a diverse array of biological activities. Recent studies of invertebrate-associated microbial communities are revealing microorganisms as the true producers of many of these compounds. Inspired by the human microbiome project, which has highlighted the human intestine as a unique microenvironment in terms of microbial diversity, we elected to examine the bacterial communities of fish intestines (which we have termed the fish microbiome) as a new source of microbial and biosynthetic diversity for natural products discovery. To test the hypothesis that the fish microbiome contains microorganisms with unique capacity for biosynthesizing natural products, we examined six species of fish through a combination of dissection and culture-dependent evaluation of intestinal microbial communities. Using isolation media designed to enrich for marine Actinobacteria, we have found three main clades that show taxonomic divergence from known strains, several of which are previously uncultured. Extracts from these strains exhibit a wide range of activities against both gram-positive and gram-negative human pathogens, as well as several fish pathogens. Exploration of one of these extracts has identified the novel bioactive lipid sebastenoic acid as an anti-microbial agent, with activity against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecium, and Vibrio mimicus.}, } @article {pmid23908833, year = {2012}, author = {Solt, I and Cohavy, O}, title = {The great obstetrical syndromes and the human microbiome-a new frontier.}, journal = {Rambam Maimonides medical journal}, volume = {3}, number = {2}, pages = {e0009}, pmid = {23908833}, issn = {2076-9172}, abstract = {Over the last two decades, advanced molecular genetics technology has enabled analysis of complex microbial communities and the study of microbial genomics. Interest has grown in characterizing the microbiome, defined as a collective microbial community and its extensive genome, as a clue to disease mechanisms. "The Human Microbiome Project," sponsored by the NIH Common Fund, was established to characterize the pathology-associated human microbiome in nasal passages, oral cavities, skin, the gastrointestinal tract, and the urogenital compartment. In particular, characterization of urogenital microbiota may elucidate etiologies of complex obstetrical syndromes and factors in fetal development that define risk for pathology in adulthood. This article summarizes recent findings defining the microbiome associated with the female urogenital compartment in child-bearing age women. We also describe our analysis of microbiome samples from the oral, vaginal, and rectal compartments in a cohort of pregnant women. Findings present technical considerations in the characterization of microbial diversity and composition associated with gestational diabetes as a model pregnancy-associated pathology.}, } @article {pmid22237180, year = {2012}, author = {Baig, S}, title = {Reviewing personal bacteria - the human microbiome project.}, journal = {Journal of the College of Physicians and Surgeons--Pakistan : JCPSP}, volume = {22}, number = {1}, pages = {3-4}, pmid = {22237180}, issn = {1681-7168}, mesh = {Bacteria/*genetics ; Bacterial Infections/*microbiology ; *Biomedical Research ; Female ; Humans ; Male ; *Metagenome ; }, } @article {pmid22209085, year = {2012}, author = {Rath, CM and Dorrestein, PC}, title = {The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes.}, journal = {Current opinion in microbiology}, volume = {15}, number = {2}, pages = {147-154}, pmid = {22209085}, issn = {1879-0364}, support = {R01 GM094802/GM/NIGMS NIH HHS/United States ; R01 GM086283/GM/NIGMS NIH HHS/United States ; GM094802/GM/NIGMS NIH HHS/United States ; AI095125/AI/NIAID NIH HHS/United States ; R01 AI095125/AI/NIAID NIH HHS/United States ; GM086283/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*chemistry/classification/growth & development/*metabolism ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Mice ; *Microbial Interactions ; Phenotype ; }, abstract = {Microbial communities in the gut have been hypothesized to play key roles in the health of the host organism. Exploring the relationship between these populations and disease states has been a focus of the human microbiome project. However, the biological roles of the compounds produced by the gut bacteria are largely unknown. We hypothesize that these compounds act as metabolic exchange factors-mediating inter-species and intra-species interactions in the microbiome. This view is supported through this review of known bacterial metabolic exchange factors and evidence for uncharacterized metabolic exchange factors in the gut. The impact of model systems and technological developments in exploring this hypothesis are also discussed. Together, these investigations are revolutionizing our understanding of the gut microbiome-presenting the possibility of identifying new strategies for treating disease in the host.}, } @article {pmid23678462, year = {2012}, author = {Eslami, S and Barzgari, Z and Saliani, N and Saeedi, N and Barzegari, A}, title = {Annual fasting; the early calories restriction for cancer prevention.}, journal = {BioImpacts : BI}, volume = {2}, number = {4}, pages = {213-215}, pmid = {23678462}, issn = {2228-5652}, abstract = {Essentially, people's diet and nutritional status has been changed substantially worldwide and several lines of evidence suggest that these changes are to the detriment of their health. Additionally, it has been well documented that unhealthy diet especially the fast foods, untraditional foods or bad-eating-habits influence the human gut microbiome. The gut microbiota shapes immune responses during human life and affects his/her metabolomic profiles. Furthermore, many studies highlight the molecular pathways that mediate host and symbiont interactions that regulate proper immune function and prevention of cancer in the body. Intriguingly, if cancer forms in a human body due to the weakness of immune system in detriment of microbiome, the removal of cancer stem cells can be carried out through early Calories Restriction with Annual Fasting (AF) before tumor development or progress. Besides, fasting can balance the gut microbiome for enhancement of immune system against cancer formation.}, } @article {pmid23587224, year = {2012}, author = {McDonald, D and Clemente, JC and Kuczynski, J and Rideout, JR and Stombaugh, J and Wendel, D and Wilke, A and Huse, S and Hufnagle, J and Meyer, F and Knight, R and Caporaso, JG}, title = {The Biological Observation Matrix (BIOM) format or: how I learned to stop worrying and love the ome-ome.}, journal = {GigaScience}, volume = {1}, number = {1}, pages = {7}, pmid = {23587224}, issn = {2047-217X}, abstract = {BACKGROUND: We present the Biological Observation Matrix (BIOM, pronounced "biome") format: a JSON-based file format for representing arbitrary observation by sample contingency tables with associated sample and observation metadata. As the number of categories of comparative omics data types (collectively, the "ome-ome") grows rapidly, a general format to represent and archive this data will facilitate the interoperability of existing bioinformatics tools and future meta-analyses.

FINDINGS: The BIOM file format is supported by an independent open-source software project (the biom-format project), which initially contains Python objects that support the use and manipulation of BIOM data in Python programs, and is intended to be an open development effort where developers can submit implementations of these objects in other programming languages.

CONCLUSIONS: The BIOM file format and the biom-format project are steps toward reducing the "bioinformatics bottleneck" that is currently being experienced in diverse areas of biological sciences, and will help us move toward the next phase of comparative omics where basic science is translated into clinical and environmental applications. The BIOM file format is currently recognized as an Earth Microbiome Project Standard, and as a Candidate Standard by the Genomic Standards Consortium.}, } @article {pmid22194640, year = {2012}, author = {Markowitz, VM and Chen, IM and Palaniappan, K and Chu, K and Szeto, E and Grechkin, Y and Ratner, A and Jacob, B and Huang, J and Williams, P and Huntemann, M and Anderson, I and Mavromatis, K and Ivanova, NN and Kyrpides, NC}, title = {IMG: the Integrated Microbial Genomes database and comparative analysis system.}, journal = {Nucleic acids research}, volume = {40}, number = {Database issue}, pages = {D115-22}, pmid = {22194640}, issn = {1362-4962}, support = {U01-HG004866/HG/NHGRI NIH HHS/United States ; }, mesh = {*Databases, Genetic ; Eukaryota/genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Genome, Viral ; *Genomics ; Phenotype ; Plasmids/genetics ; Proteomics ; Software ; Systems Integration ; }, abstract = {The Integrated Microbial Genomes (IMG) system serves as a community resource for comparative analysis of publicly available genomes in a comprehensive integrated context. IMG integrates publicly available draft and complete genomes from all three domains of life with a large number of plasmids and viruses. IMG provides tools and viewers for analyzing and reviewing the annotations of genes and genomes in a comparative context. IMG's data content and analytical capabilities have been continuously extended through regular updates since its first release in March 2005. IMG is available at http://img.jgi.doe.gov. Companion IMG systems provide support for expert review of genome annotations (IMG/ER: http://img.jgi.doe.gov/er), teaching courses and training in microbial genome analysis (IMG/EDU: http://img.jgi.doe.gov/edu) and analysis of genomes related to the Human Microbiome Project (IMG/HMP: http://www.hmpdacc-resources.org/img_hmp).}, } @article {pmid22134646, year = {2012}, author = {McDonald, D and Price, MN and Goodrich, J and Nawrocki, EP and DeSantis, TZ and Probst, A and Andersen, GL and Knight, R and Hugenholtz, P}, title = {An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea.}, journal = {The ISME journal}, volume = {6}, number = {3}, pages = {610-618}, pmid = {22134646}, issn = {1751-7370}, support = {UH2/UH3CA140233/CA/NCI NIH HHS/United States ; U01 HG004866/HG/NHGRI NIH HHS/United States ; R01 HG004872/HG/NHGRI NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; /HHMI_/Howard Hughes Medical Institute/United States ; }, mesh = {Archaea/*classification/genetics ; Bacteria/*classification/genetics ; Classification/*methods ; *Databases, Genetic ; Metagenomics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Software ; }, abstract = {Reference phylogenies are crucial for providing a taxonomic framework for interpretation of marker gene and metagenomic surveys, which continue to reveal novel species at a remarkable rate. Greengenes is a dedicated full-length 16S rRNA gene database that provides users with a curated taxonomy based on de novo tree inference. We developed a 'taxonomy to tree' approach for transferring group names from an existing taxonomy to a tree topology, and used it to apply the Greengenes, National Center for Biotechnology Information (NCBI) and cyanoDB (Cyanobacteria only) taxonomies to a de novo tree comprising 408,315 sequences. We also incorporated explicit rank information provided by the NCBI taxonomy to group names (by prefixing rank designations) for better user orientation and classification consistency. The resulting merged taxonomy improved the classification of 75% of the sequences by one or more ranks relative to the original NCBI taxonomy with the most pronounced improvements occurring in under-classified environmental sequences. We also assessed candidate phyla (divisions) currently defined by NCBI and present recommendations for consolidation of 34 redundantly named groups. All intermediate results from the pipeline, which includes tree inference, jackknifing and transfer of a donor taxonomy to a recipient tree (tax2tree) are available for download. The improved Greengenes taxonomy should provide important infrastructure for a wide range of megasequencing projects studying ecosystems on scales ranging from our own bodies (the Human Microbiome Project) to the entire planet (the Earth Microbiome Project). The implementation of the software can be obtained from http://sourceforge.net/projects/tax2tree/.}, } @article {pmid22112388, year = {2012}, author = {Lewis, CM and Obregón-Tito, A and Tito, RY and Foster, MW and Spicer, PG}, title = {The Human Microbiome Project: lessons from human genomics.}, journal = {Trends in microbiology}, volume = {20}, number = {1}, pages = {1-4}, pmid = {22112388}, issn = {1878-4380}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; R01 HG005172/HG/NHGRI NIH HHS/United States ; R01 HG005172-01/HG/NHGRI NIH HHS/United States ; R01 GM089886-01A1/GM/NIGMS NIH HHS/United States ; }, mesh = {Genomics/*methods/trends ; Humans ; Medicine/methods/trends ; *Metagenome ; }, abstract = {The Human Microbiome Project (HMP) is following in the footsteps of the Human Genome Project (HGP), which will include exciting discoveries, but also potential disappointment and resentment over the lack of medical applications. There is a wiser path for the HMP. This path includes a greater attention to rare variation, an early commitment to an ethical inclusion of indigenous communities, and a recruitment strategy in which medical benefits are de-emphasized.}, } @article {pmid21726221, year = {2011}, author = {Peterson, SN and Snesrud, E and Schork, NJ and Bretz, WA}, title = {Dental caries pathogenicity: a genomic and metagenomic perspective.}, journal = {International dental journal}, volume = {61 Suppl 1}, number = {Suppl 1}, pages = {11-22}, pmid = {21726221}, issn = {0020-6539}, support = {R01 DE015351/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; *Biofilms ; Dental Caries/*genetics/*microbiology ; Dental Plaque/genetics/microbiology ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genomics ; Glycolysis ; Humans ; Metagenome ; Microbial Interactions ; Streptococcus mutans/genetics/metabolism ; }, abstract = {In this review we address the subject of dental caries pathogenicity from a genomic and metagenomic perspective. The application of genomic technologies is certain to yield novel insights into the relationship between the bacterial flora, dental health and disease. Three primary attributes of bacterial species are thought to have direct impact on caries development, these include: adherence on tooth surfaces (biofilm formation), acid production and acid tolerance. Attempts to define the specific aetiological agents of dental caries have proven to be elusive, supporting the notion that caries aetiology is perhaps complex and multi-faceted. The recently introduced Human Microbiome Project (HMP) that endeavors to characterise the micro-organisms living in and on the human body is likely to shed new light on these questions and improve our understanding of polymicrobial disease, microbial ecology in the oral cavity and provide new avenues for therapeutic and molecular diagnostics developments.}, } @article {pmid22018227, year = {2011}, author = {Proctor, LM}, title = {The Human Microbiome Project in 2011 and beyond.}, journal = {Cell host & microbe}, volume = {10}, number = {4}, pages = {287-291}, doi = {10.1016/j.chom.2011.10.001}, pmid = {22018227}, issn = {1934-6069}, mesh = {*Biodiversity ; Humans ; *Metagenome ; }, abstract = {The human microbiome comprises the genes and genomes of the microbiota that inhabit the body. We highlight Human Microbiome Project (HMP) resources, including 600 microbial reference genomes, 70 million 16S sequences, 700 metagenomes, and 60 million predicted genes from healthy adult microbiomes. Microbiome studies of specific diseases and future research directions are also discussed.}, } @article {pmid21772835, year = {2011}, author = {Young, VB and Kahn, SA and Schmidt, TM and Chang, EB}, title = {Studying the Enteric Microbiome in Inflammatory Bowel Diseases: Getting through the Growing Pains and Moving Forward.}, journal = {Frontiers in microbiology}, volume = {2}, number = {}, pages = {144}, pmid = {21772835}, issn = {1664-302X}, support = {UH3 DK083993/DK/NIDDK NIH HHS/United States ; }, abstract = {In this commentary, we will review some of the early efforts aimed at understanding the role of the enteric microbiota in the causality of inflammatory bowel diseases. By examining these studies and drawing on our own experiences bridging clinical gastroenterology and microbial ecology as part of the NIH-funded Human Microbiome Project (Turnbaugh et al., 2007), we hope to help define some of the "growing pains" that have hampered these initial efforts. It is our sincere hope that this discussion will help advance future efforts in this area by identifying current challenges and limitations and by suggesting strategies to overcome these obstacles.}, } @article {pmid21729521, year = {2011}, author = {Wu, KF and Zheng, GG and Ma, XT and Song, YH and Zhu, XF}, title = {[Mechanism of leukemia relapse: novel insights on old problem].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {19}, number = {3}, pages = {557-560}, pmid = {21729521}, issn = {1009-2137}, mesh = {Cell Fusion ; Humans ; Leukemia/*pathology ; Neoplasm, Residual/pathology ; Recurrence ; }, abstract = {Relapse, which puzzled several generations of hematologists, is the bottle-neck of radical treatment for leukemias. The progress of Human Microbiome Project at the beginning of 21st century suggested that human body was a super-organism constituted by the core of human cells and symbiotic microorganisms. The elucidation and characterization of endogenous retrovirus and prion protein suggested the possible effects of co-evolutional microorganisms on human health. Recently, the elucidation of the roles of tunneling nanotubes in intercellular communication and transportation suggested a novel way for cellular communication and transport of oncogenic materials. The role and significance of in vivo cell fusion have been studied in more detail. On the other hand, donor cell leukemia was reported. All of these approaches provide novel insights for studying the mechanism of leukemia relapse. Based on previous work, the authors suggest the hypothesis: there are two possible mechanisms for the relapse of leukemias: the minimal residual disease (MRD) and intercellular transportation of oncogenic materials.}, } @article {pmid21559529, year = {2011}, author = {Saulnier, DM and Santos, F and Roos, S and Mistretta, TA and Spinler, JK and Molenaar, D and Teusink, B and Versalovic, J}, title = {Exploring metabolic pathway reconstruction and genome-wide expression profiling in Lactobacillus reuteri to define functional probiotic features.}, journal = {PloS one}, volume = {6}, number = {4}, pages = {e18783}, pmid = {21559529}, issn = {1932-6203}, support = {P30 DK56338/DK/NIDDK NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacterial Adhesion ; Biofilms ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Humans ; Limosilactobacillus reuteri/*genetics ; Metabolic Networks and Pathways/genetics ; Milk, Human/microbiology ; Multigene Family ; Polysaccharides/chemistry ; Probiotics/*metabolism ; Species Specificity ; Transcriptome ; }, abstract = {The genomes of four Lactobacillus reuteri strains isolated from human breast milk and the gastrointestinal tract have been recently sequenced as part of the Human Microbiome Project. Preliminary genome comparisons suggested that these strains belong to two different clades, previously shown to differ with respect to antimicrobial production, biofilm formation, and immunomodulation. To explain possible mechanisms of survival in the host and probiosis, we completed a detailed genomic comparison of two breast milk-derived isolates representative of each group: an established probiotic strain (L. reuteri ATCC 55730) and a strain with promising probiotic features (L. reuteri ATCC PTA 6475). Transcriptomes of L. reuteri strains in different growth phases were monitored using strain-specific microarrays, and compared using a pan-metabolic model representing all known metabolic reactions present in these strains. Both strains contained candidate genes involved in the survival and persistence in the gut such as mucus-binding proteins and enzymes scavenging reactive oxygen species. A large operon predicted to encode the synthesis of an exopolysaccharide was identified in strain 55730. Both strains were predicted to produce health-promoting factors, including antimicrobial agents and vitamins (folate, vitamin B(12)). Additionally, a complete pathway for thiamine biosynthesis was predicted in strain 55730 for the first time in this species. Candidate genes responsible for immunomodulatory properties of each strain were identified by transcriptomic comparisons. The production of bioactive metabolites by human-derived probiotics may be predicted using metabolic modeling and transcriptomics. Such strategies may facilitate selection and optimization of probiotics for health promotion, disease prevention and amelioration.}, } @article {pmid21540692, year = {2011}, author = {Gregory, KE}, title = {Microbiome aspects of perinatal and neonatal health.}, journal = {The Journal of perinatal & neonatal nursing}, volume = {25}, number = {2}, pages = {158-62; quiz 163-4}, pmid = {21540692}, issn = {1550-5073}, support = {K23 NR011320/NR/NINR NIH HHS/United States ; }, mesh = {DNA, Bacterial ; Female ; Genes, Bacterial ; Gram-Negative Bacteria/genetics ; Gram-Positive Bacteria/genetics ; Humans ; *Infant Welfare ; Infant, Newborn ; Infant, Newborn, Diseases/*microbiology ; Male ; *Maternal Welfare ; Metagenome/*physiology ; Nursing Research ; Perinatal Care ; Pregnancy ; Sensitivity and Specificity ; }, abstract = {Our human cells are outnumbered 10 to 1 by bacterial cells. For this reason, the role of microorganisms, specifically bacteria, in health and disease has brought forth intense research via the Human Microbiome Project. The Human Microbiome Project is a National Institutes of Health sponsored effort to build upon the Human Genome Project in understanding human genetic and physiologic diversity. Perinatal and neonatal health represents areas of high importance for knowledge generated by the Human Microbiome Project as the microbiome is largely influenced during pregnancy, birth, and the neonatal period by nutrition, lifestyle, environmental factors of care, and the administration of medications, specifically antibiotics. As nurses have a depth of expertise in these areas, they will make a significant contribution toward better understanding the role of the microbiome in disease, and how to manipulate the microbiome to advantage patients toward health. This article describes the human microbiome and why it is important to overall health and disease. Three major unsolved problems in perinatal and neonatal health including (1) preterm birth; (2) the neonatal consequences of vaginal versus cesarean birth; and (3) neonatal gastrointestinal disease, specifically, necrotizing enterocolitis, are discussed in the context of current and future research on the human microbiome.}, } @article {pmid21524302, year = {2011}, author = {DeSantis, TZ and Keller, K and Karaoz, U and Alekseyenko, AV and Singh, NN and Brodie, EL and Pei, Z and Andersen, GL and Larsen, N}, title = {Simrank: Rapid and sensitive general-purpose k-mer search tool.}, journal = {BMC ecology}, volume = {11}, number = {}, pages = {11}, pmid = {21524302}, issn = {1472-6785}, support = {AI075410-01/AI/NIAID NIH HHS/United States ; U01-HG004866/HG/NHGRI NIH HHS/United States ; UH2/UH3CA140233/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology ; DNA ; *Databases, Bibliographic ; *Databases, Factual ; *Molecular Biology ; Proteins ; RNA ; *Software ; }, abstract = {BACKGROUND: Terabyte-scale collections of string-encoded data are expected from consortia efforts such as the Human Microbiome Project http://nihroadmap.nih.gov/hmp. Intra- and inter-project data similarity searches are enabled by rapid k-mer matching strategies. Software applications for sequence database partitioning, guide tree estimation, molecular classification and alignment acceleration have benefited from embedded k-mer searches as sub-routines. However, a rapid, general-purpose, open-source, flexible, stand-alone k-mer tool has not been available.

RESULTS: Here we present a stand-alone utility, Simrank, which allows users to rapidly identify database strings the most similar to query strings. Performance testing of Simrank and related tools against DNA, RNA, protein and human-languages found Simrank 10X to 928X faster depending on the dataset.

CONCLUSIONS: Simrank provides molecular ecologists with a high-throughput, open source choice for comparing large sequence sets to find similarity.}, } @article {pmid21304728, year = {2010}, author = {Gilbert, JA and Meyer, F and Jansson, J and Gordon, J and Pace, N and Tiedje, J and Ley, R and Fierer, N and Field, D and Kyrpides, N and Glöckner, FO and Klenk, HP and Wommack, KE and Glass, E and Docherty, K and Gallery, R and Stevens, R and Knight, R}, title = {The Earth Microbiome Project: Meeting report of the "1 EMP meeting on sample selection and acquisition" at Argonne National Laboratory October 6 2010.}, journal = {Standards in genomic sciences}, volume = {3}, number = {3}, pages = {249-253}, pmid = {21304728}, issn = {1944-3277}, abstract = {This report details the outcome the first meeting of the Earth Microbiome Project to discuss sample selection and acquisition. The meeting, held at the Argonne National Laboratory on Wednesday October 6(th) 2010, focused on discussion of how to prioritize environmental samples for sequencing and metagenomic analysis as part of the global effort of the EMP to systematically determine the functional and phylogenetic diversity of microbial communities across the world.}, } @article {pmid21304727, year = {2010}, author = {Gilbert, JA and Meyer, F and Antonopoulos, D and Balaji, P and Brown, CT and Brown, CT and Desai, N and Eisen, JA and Evers, D and Field, D and Feng, W and Huson, D and Jansson, J and Knight, R and Knight, J and Kolker, E and Konstantindis, K and Kostka, J and Kyrpides, N and Mackelprang, R and McHardy, A and Quince, C and Raes, J and Sczyrba, A and Shade, A and Stevens, R}, title = {Meeting report: the terabase metagenomics workshop and the vision of an Earth microbiome project.}, journal = {Standards in genomic sciences}, volume = {3}, number = {3}, pages = {243-248}, pmid = {21304727}, issn = {1944-3277}, abstract = {Between July 18(th) and 24(th) 2010, 26 leading microbial ecology, computation, bioinformatics and statistics researchers came together in Snowbird, Utah (USA) to discuss the challenge of how to best characterize the microbial world using next-generation sequencing technologies. The meeting was entitled "Terabase Metagenomics" and was sponsored by the Institute for Computing in Science (ICiS) summer 2010 workshop program. The aim of the workshop was to explore the fundamental questions relating to microbial ecology that could be addressed using advances in sequencing potential. Technological advances in next-generation sequencing platforms such as the Illumina HiSeq 2000 can generate in excess of 250 billion base pairs of genetic information in 8 days. Thus, the generation of a trillion base pairs of genetic information is becoming a routine matter. The main outcome from this meeting was the birth of a concept and practical approach to exploring microbial life on earth, the Earth Microbiome Project (EMP). Here we briefly describe the highlights of this meeting and provide an overview of the EMP concept and how it can be applied to exploration of the microbiome of each ecosystem on this planet.}, } @article {pmid21183674, year = {2011}, author = {Cuív, PÓ and Klaassens, ES and Durkin, AS and Harkins, DM and Foster, L and McCorrison, J and Torralba, M and Nelson, KE and Morrison, M}, title = {Draft genome sequence of Turicibacter sanguinis PC909, isolated from human feces.}, journal = {Journal of bacteriology}, volume = {193}, number = {5}, pages = {1288-1289}, pmid = {21183674}, issn = {1098-5530}, mesh = {Feces/*microbiology ; *Genome, Bacterial ; Gram-Positive Bacteria/*genetics ; Humans ; Molecular Sequence Data ; }, abstract = {While the microbiota resident in the human gut is now known to provide a range of functions relevant to host health, many of the microbial members of the community have not yet been cultured or are represented by a limited number of isolates. We describe here the draft genome sequence of Turicibacter sanguinis PC909, isolated from a pooled healthy human fecal sample as part of the Australian Human Gut Microbiome Project.}, } @article {pmid21133690, year = {2010}, author = {Alauzet, C and Marchandin, H and Lozniewski, A}, title = {New insights into Prevotella diversity and medical microbiology.}, journal = {Future microbiology}, volume = {5}, number = {11}, pages = {1695-1718}, doi = {10.2217/fmb.10.126}, pmid = {21133690}, issn = {1746-0921}, mesh = {Bacteroidaceae Infections/*microbiology ; Drug Resistance, Bacterial ; *Genetic Variation ; Humans ; *Metagenome ; Prevotella/*classification/genetics/isolation & purification/*pathogenicity ; Virulence ; }, abstract = {In light of recent studies based on cultivation-independent methods, it appears that the diversity of Prevotella in human microbiota is greater than was previously assumed from cultivation-based studies, and that the implication of these bacteria in several human diseases was unrecognized. While some Prevotella taxa were found during opportunistic infections, changes in Prevotella abundance and diversity were discovered during dysbiosis-associated diseases. As member of the microbiota, Prevotella may also be considered as a reservoir for resistance genes. Greater knowledge on Prevotella diversity, as well as new insights into its pathogenic potential and implication in dysbiosis are expected from the use of human microbe identification microarrays, from whole-genome sequence analyse, and from the NIH Human Microbiome Project data. New approaches, including molecular-based methods, could contribute to improve the diagnosis of Prevotella infections.}, } @article {pmid20924228, year = {2010}, author = {Foxman, B and Goldberg, D}, title = {Why the human microbiome project should motivate epidemiologists to learn ecology.}, journal = {Epidemiology (Cambridge, Mass.)}, volume = {21}, number = {6}, pages = {757-759}, pmid = {20924228}, issn = {1531-5487}, support = {R01 DE014899/DE/NIDCR NIH HHS/United States ; R01 HD038098/HD/NICHD NIH HHS/United States ; R01DE014899/DE/NIDCR NIH HHS/United States ; }, mesh = {*Ecology ; Epidemiology/*trends ; Humans ; *Metagenome ; Sequence Analysis, DNA ; }, } @article {pmid20807838, year = {2010}, author = {Sahota, G and Stormo, GD}, title = {Novel sequence-based method for identifying transcription factor binding sites in prokaryotic genomes.}, journal = {Bioinformatics (Oxford, England)}, volume = {26}, number = {21}, pages = {2672-2677}, pmid = {20807838}, issn = {1367-4811}, support = {T32 GM07200/GM/NIGMS NIH HHS/United States ; T32 GM008802/GM/NIGMS NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; R01 HG000249/HG/NHGRI NIH HHS/United States ; R01 HG00249/HG/NHGRI NIH HHS/United States ; }, mesh = {Binding Sites ; Computational Biology/methods ; *Genome ; *Promoter Regions, Genetic ; Sequence Analysis, DNA/*methods ; Transcription Factors/*chemistry/*metabolism ; }, abstract = {MOTIVATION: Computational techniques for microbial genomic sequence analysis are becoming increasingly important. With next-generation sequencing technology and the human microbiome project underway, current sequencing capacity is significantly greater than the speed at which organisms of interest can be studied experimentally. Most related computational work has been focused on sequence assembly, gene annotation and metabolic network reconstruction. We have developed a method that will primarily use available sequence data in order to determine prokaryotic transcription factor (TF) binding specificities.

RESULTS: Specificity determining residues (critical residues) were identified from crystal structures of DNA-protein complexes and TFs with the same critical residues were grouped into specificity classes. The putative binding regions for each class were defined as the set of promoters for each TF itself (autoregulatory) and the immediately upstream and downstream operons. MEME was used to find putative motifs within each separate class. Tests on the LacI and TetR TF families, using RegulonDB annotated sites, showed the sensitivity of prediction 86% and 80%, respectively.

AVAILABILITY: http://ural.wustl.edu/∼gsahota/HTHmotif/}, } @article {pmid20624719, year = {2010}, author = {Chen, T and Yu, WH and Izard, J and Baranova, OV and Lakshmanan, A and Dewhirst, FE}, title = {The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information.}, journal = {Database : the journal of biological databases and curation}, volume = {2010}, number = {}, pages = {baq013}, pmid = {20624719}, issn = {1758-0463}, support = {R21 DE017106-01A1/DE/NIDCR NIH HHS/United States ; DE017106/DE/NIDCR NIH HHS/United States ; R21 DE017106-02/DE/NIDCR NIH HHS/United States ; U01 DE016937/DE/NIDCR NIH HHS/United States ; R21 DE017106/DE/NIDCR NIH HHS/United States ; DE016937/DE/NIDCR NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation & purification ; Computers ; *Databases, Genetic ; Genome, Bacterial ; Humans ; Internet ; Metagenome/*genetics ; Metagenomics ; Mouth/*microbiology ; Phenotype ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Software ; }, abstract = {The human oral microbiome is the most studied human microflora, but 53% of the species have not yet been validly named and 35% remain uncultivated. The uncultivated taxa are known primarily from 16S rRNA sequence information. Sequence information tied solely to obscure isolate or clone numbers, and usually lacking accurate phylogenetic placement, is a major impediment to working with human oral microbiome data. The goal of creating the Human Oral Microbiome Database (HOMD) is to provide the scientific community with a body site-specific comprehensive database for the more than 600 prokaryote species that are present in the human oral cavity based on a curated 16S rRNA gene-based provisional naming scheme. Currently, two primary types of information are provided in HOMD--taxonomic and genomic. Named oral species and taxa identified from 16S rRNA gene sequence analysis of oral isolates and cloning studies were placed into defined 16S rRNA phylotypes and each given unique Human Oral Taxon (HOT) number. The HOT interlinks phenotypic, phylogenetic, genomic, clinical and bibliographic information for each taxon. A BLAST search tool is provided to match user 16S rRNA gene sequences to a curated, full length, 16S rRNA gene reference data set. For genomic analysis, HOMD provides comprehensive set of analysis tools and maintains frequently updated annotations for all the human oral microbial genomes that have been sequenced and publicly released. Oral bacterial genome sequences, determined as part of the Human Microbiome Project, are being added to the HOMD as they become available. We provide HOMD as a conceptual model for the presentation of microbiome data for other human body sites. Database URL: http://www.homd.org.}, } @article {pmid20471127, year = {2010}, author = {Candela, M and Maccaferri, S and Turroni, S and Carnevali, P and Brigidi, P}, title = {Functional intestinal microbiome, new frontiers in prebiotic design.}, journal = {International journal of food microbiology}, volume = {140}, number = {2-3}, pages = {93-101}, doi = {10.1016/j.ijfoodmicro.2010.04.017}, pmid = {20471127}, issn = {1879-3460}, mesh = {Animals ; Bacteria/genetics/*metabolism ; Humans ; Intestinal Mucosa/metabolism ; Intestines/*microbiology ; *Metagenome ; Prebiotics/*analysis ; }, abstract = {In this review we focus on the revision of the prebiotic concept in the context of the new metagenomic era. Functional metagenomic data provided by the Human Microbiome Project are revolutionizing the view of the symbiotic relationship between the intestinal microbiota and the human host. A deeper knowledge of the mechanisms that govern the dynamic interplay between diet, intestinal microbiota and host nutrition opens the way to better information on the prebiotic structure-function relationships, tailoring prebiotic formula into specific health attributes. On the other hand, functional genomic studies of the sourdough microbial communities allow to scan the environmental variability to identify novel metabolic traits for the biosynthesis of new potential prebiotic molecules. The integration of the functional analyses provided by the massive sequencing of bacterial genomes and metagenomes will allow the rational production of a desired prebiotic molecule with specific functional properties.}, } @article {pmid20418441, year = {2010}, author = {Pei, AY and Oberdorf, WE and Nossa, CW and Agarwal, A and Chokshi, P and Gerz, EA and Jin, Z and Lee, P and Yang, L and Poles, M and Brown, SM and Sotero, S and Desantis, T and Brodie, E and Nelson, K and Pei, Z}, title = {Diversity of 16S rRNA genes within individual prokaryotic genomes.}, journal = {Applied and environmental microbiology}, volume = {76}, number = {12}, pages = {3886-3897}, pmid = {20418441}, issn = {1098-5336}, support = {R01 AI063477/AI/NIAID NIH HHS/United States ; UH2 CA140233/CA/NCI NIH HHS/United States ; R01AI063477/AI/NIAID NIH HHS/United States ; UH2CA140233/CA/NCI NIH HHS/United States ; }, mesh = {Genes, rRNA/*genetics ; *Genome, Archaeal ; *Genome, Bacterial ; *Polymorphism, Genetic ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Analysis of intragenomic variation of 16S rRNA genes is a unique approach to examining the concept of ribosomal constraints on rRNA genes; the degree of variation is an important parameter to consider for estimation of the diversity of a complex microbiome in the recently initiated Human Microbiome Project (http://nihroadmap.nih.gov/hmp). The current GenBank database has a collection of 883 prokaryotic genomes representing 568 unique species, of which 425 species contained 2 to 15 copies of 16S rRNA genes per genome (2.22 +/- 0.81). Sequence diversity among the 16S rRNA genes in a genome was found in 235 species (from 0.06% to 20.38%; 0.55% +/- 1.46%). Compared with the 16S rRNA-based threshold for operational definition of species (1 to 1.3% diversity), the diversity was borderline (between 1% and 1.3%) in 10 species and >1.3% in 14 species. The diversified 16S rRNA genes in Haloarcula marismortui (diversity, 5.63%) and Thermoanaerobacter tengcongensis (6.70%) were highly conserved at the 2 degrees structure level, while the diversified gene in B. afzelii (20.38%) appears to be a pseudogene. The diversified genes in the remaining 21 species were also conserved, except for a truncated 16S rRNA gene in "Candidatus Protochlamydia amoebophila." Thus, this survey of intragenomic diversity of 16S rRNA genes provides strong evidence supporting the theory of ribosomal constraint. Taxonomic classification using the 16S rRNA-based operational threshold could misclassify a number of species into more than one species, leading to an overestimation of the diversity of a complex microbiome. This phenomenon is especially seen in 7 bacterial species associated with the human microbiome or diseases.}, } @article {pmid20337064, year = {2010}, author = {Xue, J and Xiao, LY and Zhou, XD}, title = {[The latest progress in studies of human oral microbiome].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {28}, number = {1}, pages = {5-8}, pmid = {20337064}, issn = {1000-1182}, mesh = {Humans ; *Metagenome ; *Microbiota ; Mouth/*microbiology ; }, abstract = {With the successful implementation of Human Genome Project, more and more scientists started to pay attention on the second genome of human body: Microbiome. This paper will briefly introduce the latest developments of the Human Microbiome Project, the human oral microbiome research, and new technologies of microbial gene research.}, } @article {pmid19968883, year = {2009}, author = {Aziz, RK}, title = {A hundred-year-old insight into the gut microbiome!.}, journal = {Gut pathogens}, volume = {1}, number = {1}, pages = {21}, pmid = {19968883}, issn = {1757-4749}, abstract = {As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions.}, } @article {pmid19819907, year = {2009}, author = {, and Peterson, J and Garges, S and Giovanni, M and McInnes, P and Wang, L and Schloss, JA and Bonazzi, V and McEwen, JE and Wetterstrand, KA and Deal, C and Baker, CC and Di Francesco, V and Howcroft, TK and Karp, RW and Lunsford, RD and Wellington, CR and Belachew, T and Wright, M and Giblin, C and David, H and Mills, M and Salomon, R and Mullins, C and Akolkar, B and Begg, L and Davis, C and Grandison, L and Humble, M and Khalsa, J and Little, AR and Peavy, H and Pontzer, C and Portnoy, M and Sayre, MH and Starke-Reed, P and Zakhari, S and Read, J and Watson, B and Guyer, M}, title = {The NIH Human Microbiome Project.}, journal = {Genome research}, volume = {19}, number = {12}, pages = {2317-2323}, pmid = {19819907}, issn = {1549-5469}, mesh = {*Bacteria/classification/genetics/isolation & purification ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Metagenome/*genetics ; Mouth/*microbiology ; National Health Programs ; *National Institutes of Health (U.S.) ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; United States ; Vagina/*microbiology ; }, abstract = {The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.}, } @article {pmid19815760, year = {2009}, author = {Chain, PS and Grafham, DV and Fulton, RS and Fitzgerald, MG and Hostetler, J and Muzny, D and Ali, J and Birren, B and Bruce, DC and Buhay, C and Cole, JR and Ding, Y and Dugan, S and Field, D and Garrity, GM and Gibbs, R and Graves, T and Han, CS and Harrison, SH and Highlander, S and Hugenholtz, P and Khouri, HM and Kodira, CD and Kolker, E and Kyrpides, NC and Lang, D and Lapidus, A and Malfatti, SA and Markowitz, V and Metha, T and Nelson, KE and Parkhill, J and Pitluck, S and Qin, X and Read, TD and Schmutz, J and Sozhamannan, S and Sterk, P and Strausberg, RL and Sutton, G and Thomson, NR and Tiedje, JM and Weinstock, G and Wollam, A and , and Detter, JC}, title = {Genomics. Genome project standards in a new era of sequencing.}, journal = {Science (New York, N.Y.)}, volume = {326}, number = {5950}, pages = {236-237}, pmid = {19815760}, issn = {1095-9203}, support = {U54 HG004968/HG/NHGRI NIH HHS/United States ; U54 HG004973/HG/NHGRI NIH HHS/United States ; }, mesh = {Computational Biology ; Databases, Nucleic Acid/*standards ; *Genome ; Genomics/*standards ; Sequence Analysis, DNA/*standards ; }, abstract = {More detailed sequence standards that keep up with revolutionary sequencing technologies will aid the research community in evaluating data.}, } @article {pmid19507517, year = {2009}, author = {Hattori, M}, title = {[Disease and metagenomics of intestinal microbiomes].}, journal = {Nihon rinsho. Japanese journal of clinical medicine}, volume = {67}, number = {6}, pages = {1214-1218}, pmid = {19507517}, issn = {0047-1852}, mesh = {Animals ; Bacteria/*genetics ; Disease/etiology ; Humans ; Intestines/*microbiology ; }, abstract = {The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, leading to maintain their homeostasis, and can be causative of various diseases such as inflammatory bowel disease and obesity. A culture-independent approach 'metagenomics' now makes it possible to comprehensively explore the genetic nature of intestinal microbiome (collective genomes of microbes), providing the mechanistic basis for the functional roles of intestinal microbiome. The International Human Microbiome Project was recently launched to further promote this newly developing field, which will provide new strategies for the maintenance of human health.}, } @article {pmid19491241, year = {2009}, author = {Turnbaugh, PJ and Gordon, JI}, title = {The core gut microbiome, energy balance and obesity.}, journal = {The Journal of physiology}, volume = {587}, number = {Pt 17}, pages = {4153-4158}, pmid = {19491241}, issn = {1469-7793}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; DK078669/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Energy Metabolism ; Humans ; Intestines/*microbiology/*physiopathology ; Metagenome/*physiology ; *Models, Biological ; Obesity/*microbiology/pathology/*physiopathology ; }, abstract = {Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.}, } @article {pmid19393196, year = {2009}, author = {Proal, AD and Albert, PJ and Marshall, T}, title = {Autoimmune disease in the era of the metagenome.}, journal = {Autoimmunity reviews}, volume = {8}, number = {8}, pages = {677-681}, doi = {10.1016/j.autrev.2009.02.016}, pmid = {19393196}, issn = {1873-0183}, mesh = {Alkanesulfonic Acids/metabolism ; Autoantibodies/immunology ; Autoimmune Diseases/genetics/metabolism/*microbiology ; Bacteria/genetics/*metabolism ; DNA, Bacterial/metabolism ; *Genomics ; Humans ; Immunity, Innate ; Metabolome/*genetics ; *Metabolomics ; Metagenome/*genetics ; }, abstract = {Studies of autoimmune disease have focused on the characteristics of the identifiable antibodies. But as our knowledge of the genes associated with the disease states expands, we understand that humans must be viewed as superorganisms in which a plethora of bacterial genomes - a metagenome - work in tandem with our own. The NIH has estimated that 90% of the cells in Homo sapiens are microbial and not human in origin. Some of these microbes create metabolites that interfere with the expression of genes associated with autoimmune disease. Thus, we must re-examine how human gene transcription is affected by the plethora of microbial metabolites. We can no longer assume that antibodies generated in autoimmune disease are created solely as autoantibodies to human DNA. Evidence is now emerging that the human microbiota accumulates during a lifetime, and a variety of persistence mechanisms are coming to light. In one model, obstruction of VDR nuclear-receptor-transcription prevents the innate immune system from making key antimicrobials, allowing the microbes to persist. Genes from these microbes must necessarily impact disease progression. Recent efforts to decrease this VDR-perverting microbiota in patients with autoimmune disease have resulted in reversal of autoimmune processes. As the NIH Human Microbiome Project continues to better characterize the human metagenome, new insights into autoimmune pathogenesis are beginning to emerge.}, } @article {pmid19340927, year = {2009}, author = {Hsiao, WW and Fraser-Liggett, CM}, title = {Human Microbiome Project--paving the way to a better understanding of ourselves and our microbes.}, journal = {Drug discovery today}, volume = {14}, number = {7-8}, pages = {331-333}, doi = {10.1016/j.drudis.2009.03.001}, pmid = {19340927}, issn = {1878-5832}, mesh = {*Disease Susceptibility ; Genome, Bacterial ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Symbiosis ; Virulence ; }, } @article {pmid19264858, year = {2009}, author = {Petrosino, JF and Highlander, S and Luna, RA and Gibbs, RA and Versalovic, J}, title = {Metagenomic pyrosequencing and microbial identification.}, journal = {Clinical chemistry}, volume = {55}, number = {5}, pages = {856-866}, pmid = {19264858}, issn = {1530-8561}, support = {U54 HG004973/HG/NHGRI NIH HHS/United States ; U54 HG003273-04S1/HG/NHGRI NIH HHS/United States ; P30 DK56338/DK/NIDDK NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; R21AT003482/AT/NCCIH NIH HHS/United States ; R01 DK065075-01A2/DK/NIDDK NIH HHS/United States ; R21 AT003482/AT/NCCIH NIH HHS/United States ; R21 AT003482-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326-01A1/AT/NCCIH NIH HHS/United States ; R01 AT004326/AT/NCCIH NIH HHS/United States ; U54 HG004973-01/HG/NHGRI NIH HHS/United States ; R01 DK065075/DK/NIDDK NIH HHS/United States ; }, mesh = {Computational Biology ; DNA, Bacterial/chemistry/genetics ; Genomics/*methods ; Humans ; *Metagenome ; RNA, Ribosomal, 16S/chemistry/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The Human Microbiome Project has ushered in a new era for human metagenomics and high-throughput next-generation sequencing strategies.

CONTENT: This review describes evolving strategies in metagenomics, with a special emphasis on the core technology of DNA pyrosequencing. The challenges of microbial identification in the context of microbial populations are discussed. The development of next-generation pyrosequencing strategies and the technical hurdles confronting these methodologies are addressed. Bioinformatics-related topics include taxonomic systems, sequence databases, sequence-alignment tools, and classifiers. DNA sequencing based on 16S rRNA genes or entire genomes is summarized with respect to potential pyrosequencing applications.

SUMMARY: Both the approach of 16S rDNA amplicon sequencing and the whole-genome sequencing approach may be useful for human metagenomics, and numerous bioinformatics tools are being deployed to tackle such vast amounts of microbiological sequence diversity. Metagenomics, or genetic studies of microbial communities, may ultimately contribute to a more comprehensive understanding of human health, disease susceptibilities, and the pathophysiology of infectious and immune-mediated diseases.}, } @article {pmid19147530, year = {2009}, author = {Hattori, M and Taylor, TD}, title = {The human intestinal microbiome: a new frontier of human biology.}, journal = {DNA research : an international journal for rapid publication of reports on genes and genomes}, volume = {16}, number = {1}, pages = {1-12}, pmid = {19147530}, issn = {1756-1663}, mesh = {Humans ; Inflammatory Bowel Diseases/genetics/microbiology ; Intestinal Mucosa/metabolism/microbiology ; Intestines/*microbiology ; *Metagenome ; Models, Biological ; }, abstract = {To analyze the vast number and variety of microorganisms inhabiting the human intestine, emerging metagenomic technologies are extremely powerful. The intestinal microbes are taxonomically complex and constitute an ecologically dynamic community (microbiota) that has long been believed to possess a strong impact on human physiology. Furthermore, they are heavily involved in the maturation and proliferation of human intestinal cells, helping to maintain their homeostasis and can be causative of various diseases, such as inflammatory bowel disease and obesity. A simplified animal model system has provided the mechanistic basis for the molecular interactions that occur at the interface between such microbes and host intestinal epithelia. Through metagenomic analysis, it is now possible to comprehensively explore the genetic nature of the intestinal microbiome, the mutually interacting system comprising the host cells and the residing microbial community. The human microbiome project was recently launched as an international collaborative research effort to further promote this newly developing field and to pave the way to a new frontier of human biology, which will provide new strategies for the maintenance of human health.}, } @article {pmid19115471, year = {2009}, author = {Mai, V and Draganov, PV}, title = {Recent advances and remaining gaps in our knowledge of associations between gut microbiota and human health.}, journal = {World journal of gastroenterology}, volume = {15}, number = {1}, pages = {81-85}, pmid = {19115471}, issn = {2219-2840}, mesh = {Animals ; Colorectal Neoplasms/etiology/microbiology ; Diabetes Mellitus/etiology/microbiology ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology ; Intestines/*microbiology ; Metagenome/*physiology ; Obesity/microbiology ; Probiotics/therapeutic use ; }, abstract = {The complex gut microbial flora harbored by individuals (microbiota) has long been proposed to contribute to intestinal health as well as disease. Pre- and probiotic products aimed at improving health by modifying microbiota composition have already become widely available and acceptance of these products appears to be on the rise. However, although required for the development of effective microbiota based interventions, our basic understanding of microbiota variation on a population level and its dynamics within individuals is still rudimentary. Powerful new parallel sequence technologies combined with other efficient molecular microbiota analysis methods now allow for comprehensive analysis of microbiota composition in large human populations. Recent findings in the field strongly suggest that microbiota contributes to the development of obesity, atopic diseases, inflammatory bowel diseases and intestinal cancers. Through the ongoing National Institutes of Health Roadmap 'Human Microbiome Project' and similar projects in other parts of the world, a large coordinated effort is currently underway to study how microbiota can impact human health. Translating findings from these studies into effective interventions that can improve health, possibly personalized based on an individuals existing microbiota, will be the task for the next decade(s).}, } @article {pmid19023400, year = {2008}, author = {Huse, SM and Dethlefsen, L and Huber, JA and Mark Welch, D and Relman, DA and Sogin, ML}, title = {Exploring microbial diversity and taxonomy using SSU rRNA hypervariable tag sequencing.}, journal = {PLoS genetics}, volume = {4}, number = {11}, pages = {e1000255}, pmid = {19023400}, issn = {1553-7404}, support = {DP1 OD000964/OD/NIH HHS/United States ; DP1 OD000964-03/OD/NIH HHS/United States ; P50 ES012742/ES/NIEHS NIH HHS/United States ; 1 P50 ES012742-01/ES/NIEHS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics ; Biodiversity ; Classification/methods ; Humans ; Metagenome/genetics ; RNA, Ribosomal/*genetics ; Sequence Analysis, DNA ; Sequence Tagged Sites ; }, abstract = {Massively parallel pyrosequencing of hypervariable regions from small subunit ribosomal RNA (SSU rRNA) genes can sample a microbial community two or three orders of magnitude more deeply per dollar and per hour than capillary sequencing of full-length SSU rRNA. As with full-length rRNA surveys, each sequence read is a tag surrogate for a single microbe. However, rather than assigning taxonomy by creating gene trees de novo that include all experimental sequences and certain reference taxa, we compare the hypervariable region tags to an extensive database of rRNA sequences and assign taxonomy based on the best match in a Global Alignment for Sequence Taxonomy (GAST) process. The resulting taxonomic census provides information on both composition and diversity of the microbial community. To determine the effectiveness of using only hypervariable region tags for assessing microbial community membership, we compared the taxonomy assigned to the V3 and V6 hypervariable regions with the taxonomy assigned to full-length SSU rRNA sequences isolated from both the human gut and a deep-sea hydrothermal vent. The hypervariable region tags and full-length rRNA sequences provided equivalent taxonomy and measures of relative abundance of microbial communities, even for tags up to 15% divergent from their nearest reference match. The greater sampling depth per dollar afforded by massively parallel pyrosequencing reveals many more members of the "rare biosphere" than does capillary sequencing of the full-length gene. In addition, tag sequencing eliminates cloning bias and the sequences are short enough to be completely sequenced in a single read, maximizing the number of organisms sampled in a run while minimizing chimera formation. This technique allows the cost-effective exploration of changes in microbial community structure, including the rare biosphere, over space and time and can be applied immediately to initiatives, such as the Human Microbiome Project.}, } @article {pmid19004758, year = {2008}, author = {Fierer, N and Hamady, M and Lauber, CL and Knight, R}, title = {The influence of sex, handedness, and washing on the diversity of hand surface bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {46}, pages = {17994-17999}, pmid = {19004758}, issn = {1091-6490}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; P01DK078669/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Functional Laterality/*physiology ; *Genetic Variation ; Hand/*microbiology ; Humans ; *Sex Characteristics ; *Skin Care ; }, abstract = {Bacteria thrive on and within the human body. One of the largest human-associated microbial habitats is the skin surface, which harbors large numbers of bacteria that can have important effects on health. We examined the palmar surfaces of the dominant and nondominant hands of 51 healthy young adult volunteers to characterize bacterial diversity on hands and to assess its variability within and between individuals. We used a novel pyrosequencing-based method that allowed us to survey hand surface bacterial communities at an unprecedented level of detail. The diversity of skin-associated bacterial communities was surprisingly high; a typical hand surface harbored >150 unique species-level bacterial phylotypes, and we identified a total of 4,742 unique phylotypes across all of the hands examined. Although there was a core set of bacterial taxa commonly found on the palm surface, we observed pronounced intra- and interpersonal variation in bacterial community composition: hands from the same individual shared only 17% of their phylotypes, with different individuals sharing only 13%. Women had significantly higher diversity than men, and community composition was significantly affected by handedness, time since last hand washing, and an individual's sex. The variation within and between individuals in microbial ecology illustrated by this study emphasizes the challenges inherent in defining what constitutes a "healthy" bacterial community; addressing these challenges will be critical for the International Human Microbiome Project.}, } @article {pmid19002248, year = {2008}, author = {Tito, RY and Macmil, S and Wiley, G and Najar, F and Cleeland, L and Qu, C and Wang, P and Romagne, F and Leonard, S and Ruiz, AJ and Reinhard, K and Roe, BA and Lewis, CM}, title = {Phylotyping and functional analysis of two ancient human microbiomes.}, journal = {PloS one}, volume = {3}, number = {11}, pages = {e3703}, pmid = {19002248}, issn = {1932-6203}, mesh = {Bacteria/classification/isolation & purification ; DNA, Bacterial/analysis ; Evolution, Molecular ; Gastrointestinal Tract/*microbiology ; Genome, Bacterial ; Geography ; Humans ; Metagenome/*genetics ; Mexico ; *Phylogeny ; }, abstract = {BACKGROUND: The Human Microbiome Project (HMP) is one of the U.S. National Institutes of Health Roadmap for Medical Research. Primary interests of the HMP include the distinctiveness of different gut microbiomes, the factors influencing microbiome diversity, and the functional redundancies of the members of human microbiotas. In this present work, we contribute to these interests by characterizing two extinct human microbiotas.

We examine two paleofecal samples originating from cave deposits in Durango Mexico and dating to approximately 1300 years ago. Contamination control is a serious issue in ancient DNA research; we use a novel approach to control contamination. After we determined that each sample originated from a different human, we generated 45 thousand shotgun DNA sequencing reads. The phylotyping and functional analysis of these reads reveals a signature consistent with the modern gut ecology. Interestingly, inter-individual variability for phenotypes but not functional pathways was observed. The two ancient samples have more similar functional profiles to each other than to a recently published profile for modern humans. This similarity could not be explained by a chance sampling of the databases.

CONCLUSIONS/SIGNIFICANCE: We conduct a phylotyping and functional analysis of ancient human microbiomes, while providing novel methods to control for DNA contamination and novel hypotheses about past microbiome biogeography. We postulate that natural selection has more of an influence on microbiome functional profiles than it does on the species represented in the microbial ecology. We propose that human microbiomes were more geographically structured during pre-Columbian times than today.}, } @article {pmid18971311, year = {2008}, author = {McGuire, AL and Colgrove, J and Whitney, SN and Diaz, CM and Bustillos, D and Versalovic, J}, title = {Ethical, legal, and social considerations in conducting the Human Microbiome Project.}, journal = {Genome research}, volume = {18}, number = {12}, pages = {1861-1864}, pmid = {18971311}, issn = {1088-9051}, support = {UH2 DK083990/DK/NIDDK NIH HHS/United States ; UH3 DK083990/DK/NIDDK NIH HHS/United States ; }, mesh = {*Bioethics ; Confidentiality ; Human Genome Project/*legislation & jurisprudence ; Humans ; Informed Consent ; Metagenome/*genetics ; Social Change ; United States ; }, } @article {pmid18842991, year = {2008}, author = {Lampe, JW}, title = {The Human Microbiome Project: getting to the guts of the matter in cancer epidemiology.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {17}, number = {10}, pages = {2523-2524}, doi = {10.1158/1055-9965.EPI-08-0792}, pmid = {18842991}, issn = {1055-9965}, mesh = {Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; *Metagenome ; National Institutes of Health (U.S.) ; Neoplasms/*epidemiology/*microbiology ; United States ; }, } @article {pmid18806222, year = {2008}, author = {Lozupone, CA and Hamady, M and Cantarel, BL and Coutinho, PM and Henrissat, B and Gordon, JI and Knight, R}, title = {The convergence of carbohydrate active gene repertoires in human gut microbes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, number = {39}, pages = {15076-15081}, pmid = {18806222}, issn = {1091-6490}, support = {P01 DK078669/DK/NIDDK NIH HHS/United States ; R01 DK030292/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; DK30292/DK/NIDDK NIH HHS/United States ; DK70977/DK/NIDDK NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; DK78669/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaea/classification/*genetics/isolation & purification ; Bacteria/classification/*genetics/isolation & purification ; Carbohydrates/biosynthesis/genetics ; Cluster Analysis ; Gene Transfer, Horizontal ; *Genes, Archaeal ; *Genes, Bacterial ; Genetic Variation ; Glycoside Hydrolases/*genetics ; Glycosyltransferases/*genetics ; Humans ; Intestines/*microbiology ; Multigene Family ; Phylogeny ; }, abstract = {The extreme variation in gene content among phylogenetically related microorganisms suggests that gene acquisition, expansion, and loss are important evolutionary forces for adaptation to new environments. Accordingly, phylogenetically disparate organisms that share a habitat may converge in gene content as they adapt to confront shared challenges. This response should be especially pronounced for functional genes that are important for survival in a particular habitat. We illustrate this principle by showing that the repertoires of two different types of carbohydrate-active enzymes, glycoside hydrolases and glycosyltransferases, have converged in bacteria and archaea that live in the human gut and that this convergence is largely due to horizontal gene transfer rather than gene family expansion. We also identify gut microbes that may have more similar dietary niches in the human gut than would be expected based on phylogeny. The techniques used to obtain these results should be broadly applicable to understanding the functional genes and evolutionary processes important for adaptation in many environments and useful for interpreting the large number of reference microbial genome sequences being generated for the International Human Microbiome Project.}, } @article {pmid18794915, year = {2008}, author = {Ley, RE and Lozupone, CA and Hamady, M and Knight, R and Gordon, JI}, title = {Worlds within worlds: evolution of the vertebrate gut microbiota.}, journal = {Nature reviews. Microbiology}, volume = {6}, number = {10}, pages = {776-788}, pmid = {18794915}, issn = {1740-1534}, support = {R37 DK030292-27/DK/NIDDK NIH HHS/United States ; T32GM065103/GM/NIGMS NIH HHS/United States ; T32 GM065103-07/GM/NIGMS NIH HHS/United States ; T32 GM142607/GM/NIGMS NIH HHS/United States ; R37 DK030292/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; R01 DK070977-04/DK/NIDDK NIH HHS/United States ; R01 DK070977/DK/NIDDK NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; *Biological Evolution ; Gastrointestinal Tract/metabolism/*microbiology ; Humans ; Metagenome/*genetics ; RNA, Ribosomal, 16S/analysis/genetics ; Vertebrates/*anatomy & histology ; }, abstract = {In this Analysis we use published 16S ribosomal RNA gene sequences to compare the bacterial assemblages that are associated with humans and other mammals, metazoa and free-living microbial communities that span a range of environments. The composition of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, and in this respect the human gut bacterial community is typical of an omnivorous primate. However, the vertebrate gut microbiota is different from free-living communities that are not associated with animal body habitats. We propose that the recently initiated international Human Microbiome Project should strive to include a broad representation of humans, as well as other mammalian and environmental samples, as comparative analyses of microbiotas and their microbiomes are a powerful way to explore the evolutionary history of the biosphere.}, } @article {pmid18714051, year = {2008}, author = {Friedrich, MJ}, title = {Microbiome project seeks to understand human body's microscopic residents.}, journal = {JAMA}, volume = {300}, number = {7}, pages = {777-778}, doi = {10.1001/jama.300.7.777}, pmid = {18714051}, issn = {1538-3598}, mesh = {*Disease Susceptibility ; Homeostasis ; Host-Pathogen Interactions ; Humans ; *Metagenome ; Microbiology ; Symbiosis ; Virulence ; }, } @article {pmid17943116, year = {2007}, author = {Turnbaugh, PJ and Ley, RE and Hamady, M and Fraser-Liggett, CM and Knight, R and Gordon, JI}, title = {The human microbiome project.}, journal = {Nature}, volume = {449}, number = {7164}, pages = {804-810}, pmid = {17943116}, issn = {1476-4687}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; P30 DK056341-06/DK/NIDDK NIH HHS/United States ; P30 DK056341-07/DK/NIDDK NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biodiversity ; Genome, Bacterial/genetics ; Genomics ; Humans ; Intestines/cytology/immunology/*microbiology ; *Metagenome/genetics/immunology ; Mice ; Sequence Analysis, DNA ; }, abstract = {A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.}, }