@article {pmid33492450, year = {2021}, author = {Grenda, A and Krawczyk, P}, title = {Cancer trigger or remedy: two faces of the human microbiome.}, journal = {Applied microbiology and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {33492450}, issn = {1432-0614}, abstract = {Currently, increasing attention cancer treatment has focused on molecularly targeted therapies and more recently on immunotherapies targeting immune checkpoints. However, even such advanced treatment may be ineffective. The reasons for this are sought, inter alia, in the human microbiome. In our intestines, there are bacteria that are beneficial to us, but pathogenic microorganisms may also be present. Microbial imbalance (dysbiosis) is now perceived as one of the gateways to cancer. However, it is feasible to use bacteria and their metabolites to restore the natural, beneficial microbiome during oncological treatment. Akkermansia mucinifila, Enterococcus hirae, or Faecalibacterium prausnitzii are bacteria that exhibit this beneficial potential. Greater benefits of therapy can be observed in cancer patients enriched in these bacterial species and treated with anti-PD-1, anti-PD-L1, or anti-CTLA-4 monoclonal antibodies. In this review, we present issues related to the role of bacteria in carcinogenesis and their therapeutic potential "supporting" modern anti-cancer therapies.Key Points• Bacteria can be directly or indirectly a cancer trigger.• Bacterial metabolites regulate the pathways associated with carcinogenesis.• Intestinal bacteria activate the immune system to fight cancer.}, }
@article {pmid33488555, year = {2020}, author = {Luo, Z and Alekseyenko, AV and Ogunrinde, E and Li, M and Li, QZ and Huang, L and Tsao, BP and Kamen, DL and Oates, JC and Li, Z and Gilkeson, GS and Jiang, W}, title = {Rigorous Plasma Microbiome Analysis Method Enables Disease Association Discovery in Clinic.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {613268}, doi = {10.3389/fmicb.2020.613268}, pmid = {33488555}, issn = {1664-302X}, abstract = {Blood microbiome is important to investigate microbial-host interactions and the effects on systemic immune perturbations. However, this effort has met with major challenges due to low microbial biomass and background artifacts. In the current study, microbial 16S DNA sequencing was applied to analyze plasma microbiome. We have developed a quality-filtering strategy to evaluate and exclude low levels of microbial sequences, potential contaminations, and artifacts from plasma microbial 16S DNA sequencing analyses. Furthermore, we have applied our technique in three cohorts, including tobacco-smokers, HIV-infected individuals, and individuals with systemic lupus erythematosus (SLE), as well as corresponding controls. More than 97% of total sequence data was removed using stringent quality-filtering strategy analyses; those removed amplicon sequence variants (ASVs) were low levels of microbial sequences, contaminations, and artifacts. The specifically enriched pathobiont bacterial ASVs have been identified in plasmas from tobacco-smokers, HIV-infected individuals, and individuals with SLE but not from control subjects. The associations between these ASVs and disease pathogenesis were demonstrated. The pathologic activities of some identified bacteria were further verified in vitro. We present a quality-filtering strategy to identify pathogenesis-associated plasma microbiome. Our approach provides a method for studying the diagnosis of subclinical microbial infection as well as for understanding the roles of microbiome-host interaction in disease pathogenesis.}, }
@article {pmid33483519, year = {2021}, author = {Simon-Soro, A and Kim, D and Li, Y and Liu, Y and Ito, T and Sims, KR and Benoit, DSW and Bittinger, K and Koo, H}, title = {Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes.}, journal = {NPJ biofilms and microbiomes}, volume = {7}, number = {1}, pages = {7}, pmid = {33483519}, issn = {2055-5008}, support = {R01DE025220//U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; R01DE018023//U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; F31DE026944//U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)/ ; }, abstract = {Drug repurposing is a feasible strategy for the development of novel therapeutic applications. However, its potential use for oral treatments and impact on host microbiota remain underexplored. Here, we assessed the influences of topical oral applications of a repurposed FDA-approved drug, thonzonium bromide, on gastrointestinal microbiomes and host tissues in a rat model of dental caries designed to reduce cross-contamination associated with coprophagy. Using this model, we recapitulated the body site microbiota that mirrored the human microbiome profile. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella without affecting the global composition of the fecal microbiome. However, disturbances in the oral-gut microbial interactions were identified using nestedness and machine learning, showing increased sharing of oral taxon Sutterella in the gut microbiota. Host-tissue analyses revealed caries reduction on teeth by thonzonium bromide without cytotoxic effects, indicating bioactivity and biocompatibility when used orally. Altogether, we demonstrate how an oral treatment using a repurposed drug causes localized microbial disturbances and therapeutic effects while promoting turnover of specific oral species in the lower gut in vivo.}, }
@article {pmid33482907, year = {2021}, author = {Loomis, KH and Wu, SK and Ernlund, A and Zudock, K and Reno, A and Blount, K and Karig, DK}, title = {A mixed community of skin microbiome representatives influences cutaneous processes more than individual members.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {22}, pmid = {33482907}, issn = {2049-2618}, support = {W911NF-14-1-0490//Army Research Laboratory/ ; }, abstract = {BACKGROUND: Skin, the largest organ of the human body by weight, hosts a diversity of microorganisms that can influence health. The microbial residents of the skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various skin disorders. Still, much remains to be discovered in terms of the host pathways influenced by skin microorganisms, as well as the higher-level skin properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point to pronounced changes in the transcriptional profiles of the skin in response to the presence of a microbial community. However, there is a need to quantify the roles of microorganisms at both the individual and community-level in healthy human skin. In this study, we utilize human skin equivalents to study the effects of individual taxa and a microbial community in a precisely controlled context. Through transcriptomics analysis, we identify key genes and pathways influenced by skin microbes, and we also characterize higher-level impacts on skin processes and properties through histological analyses.
RESULTS: The presence of a microbiome on a 3D skin tissue model led to significantly altered patterns of gene expression, influencing genes involved in the regulation of apoptosis, proliferation, and the extracellular matrix (among others). Moreover, microbiome treatment influenced the thickness of the epidermal layer, reduced the number of actively proliferating cells, and increased filaggrin expression. Many of these findings were evident upon treatment with the mixed community, but either not detected or less pronounced in treatments by single microorganisms, underscoring the impact that a diverse skin microbiome has on the host.
CONCLUSIONS: This work contributes to the understanding of how microbiome constituents individually and collectively influence human skin processes and properties. The results show that, while it is important to understand the effect of individual microbes on the host, a full community of microbes has unique and pronounced effects on the skin. Thus, in its impacts on the host, the skin microbiome is more than the sum of its parts. Video abstract.}, }
@article {pmid33476584, year = {2021}, author = {Barquero-Orias, D and Muñoz Moreno-Arrones, O and Vañó-Galván, S}, title = {Alopecia and the Microbiome: A Future Therapeutic Target?.}, journal = {Actas dermo-sifiliograficas}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ad.2020.12.005}, pmid = {33476584}, issn = {1578-2190}, abstract = {The human microbiome includes viruses, bacteria, and fungi. There is evidence that in addition to microbiome variation in different areas of the body or according to ethnicity and sex, the microbiome specific to the scalp is conditioned by such factors as humidity, protection from UV light, and pH. Although little information has yet been published about the microbiome of hair follicles and its role in the pathogenesis of diseases, interest in this area of research is emerging. Studies have shown that components of the follicular microbiome influence such disorders as androgenetic alopecia and alopecia areata. A current hypothesis is that interventions that target the microbiome may lead to innovative therapies for many diseases.}, }
@article {pmid33472859, year = {2021}, author = {Finlay, BB and Amato, KR and Azad, M and Blaser, MJ and Bosch, TCG and Chu, H and Dominguez-Bello, MG and Ehrlich, SD and Elinav, E and Geva-Zatorsky, N and Gros, P and Guillemin, K and Keck, F and Korem, T and McFall-Ngai, MJ and Melby, MK and Nichter, M and Pettersson, S and Poinar, H and Rees, T and Tropini, C and Zhao, L and Giles-Vernick, T}, title = {The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {118}, number = {6}, pages = {}, doi = {10.1073/pnas.2010217118}, pmid = {33472859}, issn = {1091-6490}, abstract = {The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.}, }
@article {pmid33468103, year = {2021}, author = {Boddy, SL and Giovannelli, I and Sassani, M and Cooper-Knock, J and Snyder, MP and Segal, E and Elinav, E and Barker, LA and Shaw, PJ and McDermott, CJ}, title = {The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS).}, journal = {BMC medicine}, volume = {19}, number = {1}, pages = {13}, pmid = {33468103}, issn = {1741-7015}, support = {1U54DE02378901//NIH Human Microbiome Project/ ; }, abstract = {BACKGROUND: Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS.
MAIN BODY: The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications.
CONCLUSION: Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.}, }
@article {pmid33453902, year = {2020}, author = {Balty, C and Guillot, A and Fradale, L and Brewee, C and Lefranc, B and Herrero, C and Sandström, C and Leprince, J and Berteau, O and Benjdia, A}, title = {Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes.}, journal = {The Journal of biological chemistry}, volume = {295}, number = {49}, pages = {16665-16677}, doi = {10.1074/jbc.RA120.015371}, pmid = {33453902}, issn = {1083-351X}, abstract = {Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether-containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC-MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.}, }
@article {pmid33459632, year = {2021}, author = {Cuñé Castellana, J}, title = {[Microbioma and lithiasis.].}, journal = {Archivos espanoles de urologia}, volume = {74}, number = {1}, pages = {157-170}, pmid = {33459632}, issn = {0004-0614}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Lithiasis ; Prebiotics ; *Probiotics ; *Urinary Tract ; }, abstract = {Human microbiome understanding and its relationship with health has represented a revolution in biomedicine, facilitated by the emergence of new molecular microbiology techniques. Lithiasic pathology has not been alien to this new approach to etiological knowledge. As a result of this research activity, it has been possible to elucidate the importance of the intestine-kidney axis, understood as the impact of the intestinal microbiota on nephrourinary health. In this regard the ability to use oxalate as an energy source by certain intestinal microorganisms has been used as a target form odulators of the intestinal microbiota in order to correcthyperoxaluria, both primary and secondary. However,the importance of the microbiome configuration, and its role in oxalocalcic lithiasis, transcends the existence of certain trophic networks. In particular, intestinal microbiome has the ability to promote tubular lesions resulting from oxidative stress caused by chronic low-grade inflammation, closely linked to the composition of the microbiota and the dialogue established with the immune system at the intestinal level. The importance of the urobiome, a stable microbia lstructure residing in the urinary tract, allowed to calibrate the importance of urinary microorganisms in lithiasic pathology, breaking with the paradigm of urine sterility in healthy conditions. Thus, recent studies suggest that the composition and structure of the urobiome have a crucial impact on infectious but also non-infectious lithiasis, since certain microorganisms can act as nucleants and promoters of the lithogenic process. Associated with the advances in the study of binomial microbiota and lithiasic pathology, new ways are opened for patient management, in terms of prevention and treatment, based on intervention on the microbiome. Future therapeutic arsenal, in addition to probiotics and prebiotics, will integrate consortia of different microbial groups and microbiota transplantation, both urinary and intestinal.}, }
@article {pmid33449153, year = {2021}, author = {Strickland, AB and Shi, M}, title = {Mechanisms of fungal dissemination.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {}, number = {}, pages = {}, pmid = {33449153}, issn = {1420-9071}, support = {AI131219/NH/NIH HHS/United States ; AI131905/NH/NIH HHS/United States ; }, abstract = {Fungal infections are an increasing threat to global public health. There are more than six million fungal species worldwide, but less than 1% are known to infect humans. Most of these fungal infections are superficial, affecting the hair, skin and nails, but some species are capable of causing life-threatening diseases. The most common of these include Cryptococcus neoformans, Aspergillus fumigatus and Candida albicans. These fungi are typically innocuous and even constitute a part of the human microbiome, but if these pathogens disseminate throughout the body, they can cause fatal infections which account for more than one million deaths worldwide each year. Thus, systemic dissemination of fungi is a critical step in the development of these deadly infections. In this review, we discuss our current understanding of how fungi disseminate from the initial infection sites to the bloodstream, how immune cells eliminate fungi from circulation and how fungi leave the blood and enter distant organs, highlighting some recent advances and offering some perspectives on future directions.}, }
@article {pmid33440171, year = {2021}, author = {Tanes, C and Bittinger, K and Gao, Y and Friedman, ES and Nessel, L and Paladhi, UR and Chau, L and Panfen, E and Fischbach, MA and Braun, J and Xavier, RJ and Clish, CB and Li, H and Bushman, FD and Lewis, JD and Wu, GD}, title = {Role of dietary fiber in the recovery of the human gut microbiome and its metabolome.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2020.12.012}, pmid = {33440171}, issn = {1934-6069}, abstract = {Gut microbiota metabolites may be important for host health, yet few studies investigate the correlation between human gut microbiome and production of fecal metabolites and their impact on the plasma metabolome. Since gut microbiota metabolites are influenced by diet, we performed a longitudinal analysis of the impact of three divergent diets, vegan, omnivore, and a synthetic enteral nutrition (EEN) diet lacking fiber, on the human gut microbiome and its metabolome, including after a microbiota depletion intervention. Omnivore and vegan, but not EEN, diets altered fecal amino acid levels by supporting the growth of Firmicutes capable of amino acid metabolism. This correlated with relative abundance of a sizable number of fecal amino acid metabolites, some not previously associated with the gut microbiota. The effect on the plasma metabolome, in contrast, were modest. The impact of diet, particularly fiber, on the human microbiome influences broad classes of metabolites that may modify health.}, }
@article {pmid33439913, year = {2021}, author = {Lee, YT and Mohd Ismail, NI and Wei, LK}, title = {Microbiome and ischemic stroke: A systematic review.}, journal = {PloS one}, volume = {16}, number = {1}, pages = {e0245038}, doi = {10.1371/journal.pone.0245038}, pmid = {33439913}, issn = {1932-6203}, abstract = {BACKGROUND: Ischemic stroke is one of the non-communicable diseases that contribute to the significant number of deaths worldwide. However, the relationship between microbiome and ischemic stroke remained unknown. Hence, the objective of this study was to perform systematic review on the relationship between human microbiome and ischemic stroke.
METHODS: A systematic review on ischemic stroke was carried out for all articles obtained from databases until 22nd October 2020. Main findings were extracted from all the eligible studies.
RESULTS: Eighteen eligible studies were included in the systematic review. These studies suggested that aging, inflammation, and different microbial compositions could contribute to ischemic stroke. Phyla Firmicutes and Bacteroidetes also appeared to manipulate post-stroke outcome. The important role of microbiota-derived short-chain fatty acids and trimethylamine N-oxide in ischemic stroke were also highlighted.
CONCLUSIONS: This is the first systematic review that investigates the relationship between microbiome and ischemic stroke. Aging and inflammation contribute to differential microbial compositions and predispose individuals to ischemic stroke.}, }
@article {pmid33436217, year = {2021}, author = {Elshahed, MS and Miron, A and Aprotosoaie, AC and Farag, MA}, title = {Pectin in diet: Interactions with the human microbiome, role in gut homeostasis, and nutrient-drug interactions.}, journal = {Carbohydrate polymers}, volume = {255}, number = {}, pages = {117388}, doi = {10.1016/j.carbpol.2020.117388}, pmid = {33436217}, issn = {1879-1344}, abstract = {Pectins are a part of daily diet as well as food additives that are indigestible polysaccharides by human enzymes, however, they can be easily degraded by gut bacteria with the production of short chain fatty acids (SCFAs). Knowledge of pectin gut homeostasis and further how pectin affect gut bacterial communities is insufficient and limited. This review focuses on providing the whole story of how pectin functions as prebiotics in the gut. Understanding the interplay between functional and immunological responses inside animal or human gut as influenced by pectin in diets is provided. The interaction between pectin and gut microbiota is presented from both sides, in terms of how pectin affects gut microbiome and or the fermentation products produced in response by gut bacteria. This knowledge can be used to define preferred dietary pectins, targeting beneficial bacteria, and favoring balanced microbiota communities in the gut to maximize pectins' health benefits.}, }
@article {pmid33436213, year = {2021}, author = {Hövels, M and Kosciow, K and Deppenmeier, U}, title = {Characterization of a novel endo-levanase from Azotobacter chroococcum DSM 2286 and its application for the production of prebiotic fructooligosaccharides.}, journal = {Carbohydrate polymers}, volume = {255}, number = {}, pages = {117384}, doi = {10.1016/j.carbpol.2020.117384}, pmid = {33436213}, issn = {1879-1344}, abstract = {Prebiotics are known for their ability to modulate the composition of the human microbiome and mediate health-promoting benefits. Endo-levanases, which hydrolyze levan into short-chain FOS, could be used for the production of levan-based prebiotics. The novel endo-levanase (LevB2286) from Azotobacter chroococcum DSM 2286, combines an exceptionally high specific activity with advantageous hydrolytic properties. Starting from levan isolated from Timothy grass, LevB2286 produced FOS ranging from DP 2 - 8. In contrast to endo-levanases described in the literature, LevB2286 formed minor amounts of fructose and levanbiose, even with greatly extended incubation. The combined activity of LevB2286 and the levansucrase LevS1417 from Gluconobacter japonicus LMG 1417 led to a one-step synthesis of levan-type FOS from sucrose. 387.4 ± 17.3 g L-1 FOS were produced within 48 h by the production strategy based on crude cell extract of recombinant Escherichia coli expressing levS1417 and levB2286 simultaneously.}, }
@article {pmid33436100, year = {2021}, author = {Silverstein, RB and Mysorekar, IU}, title = {Group therapy on in utero colonization: seeking common truths and a way forward.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {7}, pmid = {33436100}, issn = {2049-2618}, support = {R01HD091218//National Institutes for Health/ National Institute for Child Health and Development/ ; uSTAR fellowship//MARC/ ; }, abstract = {The human microbiome refers to the genetic composition of microorganisms in a particular location in the human body. Emerging evidence over the past many years suggests that the microbiome constitute drivers of human fate almost at par with our genome and epigenome. It is now well accepted after decades of disbelief that a broad understanding of human development, health, physiology, and disease requires understanding of the microbiome along with the genome and epigenome. We are learning daily of the interdependent relationships between microbiome/microbiota and immune responses, mood, cancer progression, response to therapies, aging, obesity, antibiotic usage, and overusage and much more. The next frontier in microbiome field is understanding when does this influence begin? Does the human microbiome initiate at the time of birth or are developing human fetuses already primed with microbes and their products in utero. In this commentary, we reflect on evidence gathered thus far on this question and identify the unknown common truths. We present a way forward to continue understanding our microbial colleagues and our interwoven fates.}, }
@article {pmid33435848, year = {2021}, author = {Sanders, D and Grunden, A and Dunn, RR}, title = {A review of clothing microbiology: the history of clothing and the role of microbes in textiles.}, journal = {Biology letters}, volume = {17}, number = {1}, pages = {20200700}, doi = {10.1098/rsbl.2020.0700}, pmid = {33435848}, issn = {1744-957X}, abstract = {Humans have worn clothing for thousands of years, and since its invention, clothing has evolved from its simple utilitarian function for survival to become an integral part of society. While much consideration has been given to the broad environmental impacts of the textile and laundering industries, little is known about the impact wearing clothing has had on the human microbiome, particularly that of the skin, despite our long history with clothing. This review discusses the history of clothing and the evolution of textiles, what is and is not known about microbial persistence on and degradation of various fibres, and what opportunities for the industrial and environmental application of clothing microbiology exist for the future.}, }
@article {pmid33428723, year = {2021}, author = {Laursen, MF and Bahl, MI and Licht, TR}, title = {Settlers of our inner surface - Factors shaping the gut microbiota from birth to toddlerhood.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuab001}, pmid = {33428723}, issn = {1574-6976}, abstract = {During the first three years of life, the microbial ecosystem within the human gut undergoes a process that is unlike what happens in this ecosystem at any other time of our life. This period in time is considered a highly important developmental window, where the gut microbiota is much less resilient and much more responsive to external and environmental factors than seen in the adult gut. While advanced bioinformatics and clinical correlation studies have received extensive focus within studies of the human microbiome, basic microbial growth physiology has attracted much less attention, although it plays a pivotal role to understand the developing gut microbiota during early life. In this review, we will thus take a microbial ecology perspective on the analysis of factors that influence the temporal development of the infant gut microbiota. Such factors include sources of microbes that seed the intestinal environment, physico-chemical (abiotic) conditions influencing microbial growth, and the availability of nutrients needed by the intestinal microbes.}, }
@article {pmid33428498, year = {2021}, author = {Koidl, L and Untersmayr, E}, title = {The clinical implications of the microbiome in the development of allergy diseases.}, journal = {Expert review of clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1080/1744666X.2021.1874353}, pmid = {33428498}, issn = {1744-8409}, abstract = {INTRODUCTION: A substantial number of patients worldwide is affected by allergies. Emerging evidence suggests that the individual microbial composition might contribute to the development of allergies or might even protect from allergic diseases.
AREAS COVERED: This review provides a detailed summary regarding available knowledge on the composition of a healthy human microbiome at allergy relevant body sites. It highlights factors influencing the microbiota composition. Furthermore, recent findings on the mutual interaction of the microbiota with the innate and adaptive immune system are reported. In the final part, this knowledge is combined to discuss microbial implications for food allergy, allergic asthma, allergic rhinitis and skin allergies. Literature for this review was gathered by searching PubMed and Google Scholar databases between October and December 2020.
EXPERT OPINION: Due to the highly individual composition, it is currently not possible to define the characteristics of a site-specific microbiome in health and disease. Mainly effects of bacterial communities have been investigated, while fungal or viral influences are not yet well understood. The communication between microbial communities found in different organs impact on allergy development. Thus, a personalized approach is essential to beneficially influence these complex interactions and to modulate the host specific microbiota in allergies.}, }
@article {pmid33425774, year = {2020}, author = {Campbell, PM and Humphreys, GJ and Summers, AM and Konkel, JE and Knight, CG and Augustine, T and McBain, AJ}, title = {Does the Microbiome Affect the Outcome of Renal Transplantation?.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {558644}, doi = {10.3389/fcimb.2020.558644}, pmid = {33425774}, issn = {2235-2988}, abstract = {The role of the human microbiome in health and disease is becoming increasingly apparent. Emerging evidence suggests that the microbiome is affected by solid organ transplantation. Kidney transplantation is the gold standard treatment for End-Stage Renal Disease (ESRD), the advanced stage of Chronic Kidney Disease (CKD). The question of how ESRD and transplantation affect the microbiome and vice versa includes how the microbiome is affected by increased concentrations of toxins such as urea and creatinine (which are elevated in ESRD), whether restoration of renal function following transplantation alters the composition of the microbiome, and the impact of lifelong administration of immunosuppressive drugs on the microbiome. Changes in microbiome composition and activity have been reported in ESRD and in therapeutic immunosuppression, but the effect on the outcome of transplantation is not well-understood. Here, we consider the current evidence that changes in kidney function and immunosuppression following transplantation influence the oral, gut, and urinary microbiomes in kidney transplant patients. The potential for changes in these microbiomes to lead to disease, systemic inflammation, or rejection of the organ itself is discussed, along with the possibility that restoration of kidney function might re-establish orthobiosis.}, }
@article {pmid33424043, year = {2021}, author = {Yu, L}, title = {Restoring Good Health in Elderly with Diverse Gut Microbiome and Food Intake Restriction to Combat COVID-19.}, journal = {Indian journal of microbiology}, volume = {}, number = {}, pages = {1-4}, doi = {10.1007/s12088-020-00913-3}, pmid = {33424043}, issn = {0046-8991}, abstract = {COVID-19 continues to be an ongoing global threat. The elderly with underlying health conditions like cardiovascular and lung diseases, diabetes, obesity, are the most vulnerable to this disease. Curing the pre-existing health conditions will greatly increase a person's resilience to COVID-19 and lower the death rate of the old people. Digestion and immunity form an integrated nutrition acquisition process, especially in obtaining essential amino acids and essential fatty acids from living microbial cells. A mature strong immunity coupled with gut dysbiosis in adults is the main cause of nutritional disorders like morbid obesity, diabetes mellitus, cardiovascular and pulmonary diseases. Nutrition disorders in return worsen dysbiosis. Human microbiome has an intrinsic duality. While a diverse microbiome provides a full spectrum of essential nutrients to our body, nutrition disorders fuel overgrowth of microbiota (dysbiosis) at many sites on or inside our body, and are the main causes of chronic inflammation at these sites. In the case of COVID-19, nutritional disorder impairs the immunity, causes hyperinflammation, and leads to the protracted overload of cytokines by the immune system, i.e., the cytokine storm. Autophagy induced by restrictive eating is an ideal inhibitor of microbiota overgrowth, as autophagy deprives microbiota of excessive nutrition for replication. Autophagy also attenuates inflammation. Therefore, as a precaution, the author suggests restoring good health in the elderly with the support from a diverse gut microbiome and daily regular food intake restriction, so as to lower the risk of developing into severe case even if they are infected by COVID-19.}, }
@article {pmid33422623, year = {2021}, author = {Pineider, J and Reisch, J and Harris-Tryon, T and Savory, S}, title = {Knowledge and attitude towards the human microbiome: a single-center cross-sectional survey.}, journal = {Journal of the American Academy of Dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaad.2020.12.078}, pmid = {33422623}, issn = {1097-6787}, }
@article {pmid33410935, year = {2021}, author = {Li, W and Nelson, KE}, title = {Microbial Species that Initially Colonize the Human Gut at Birth or in Early Childhood Can Stay in Human Body for Lifetime.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, pmid = {33410935}, issn = {1432-184X}, abstract = {In recent years, many studies have described the composition and function of the human microbiome at different body sites and suggested a role for the microbiome in various diseases and health conditions. Some studies, using longitudinal samples, have also suggested how the microbiome changes over time due to disease, diet, development, travel, and other environmental factors. However, to date, no study has demonstrated whether the microorganisms established at birth or in early childhood, either transmitted from parents or obtained from the environment, can stay in the human body until adult or senior age. To directly answer this question is difficult, because microbiome samples at childhood and at later adulthood for the same individual will need to be compared and the field is not old enough to have allowed for that type of sample collection. Here, using a metagenomic approach, we analyzed 1004 gut microbiome samples from senior adults (65 ± 7.8 years) from the TwinsUK cohort. Our data indicate that many species in the human gut acquired in early childhood can stay for a lifetime until senior ages. We identified the rare genomic variants (single nucleotide variation and indels) for 27 prevalent species with enough sequencing coverage for confident genomic variant identification. We found that for some species, twin pairs, including both monozygotic (MZ) and dizygotic (DZ) twins, share significantly more rare variants than unrelated subject pairs. But no significant difference is found between MZ and DZ twin pairs. These observations strongly suggest that these species acquired in early childhood remained in these persons until senior adulthood.}, }
@article {pmid33407112, year = {2021}, author = {Jing, G and Zhang, Y and Cui, W and Liu, L and Xu, J and Su, X}, title = {Meta-Apo improves accuracy of 16S-amplicon-based prediction of microbiome function.}, journal = {BMC genomics}, volume = {22}, number = {1}, pages = {9}, pmid = {33407112}, issn = {1471-2164}, support = {31771463//National Natural Science Foundation of China (CN)/ ; ZR201807060158//Natural Science Foundation of Shandong Province/ ; 2018M630807//China Postdoctoral Science Foundation/ ; 32070086//National Natural Science Foundation of China/ ; 32000389//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Due to their much lower costs in experiment and computation than metagenomic whole-genome sequencing (WGS), 16S rRNA gene amplicons have been widely used for predicting the functional profiles of microbiome, via software tools such as PICRUSt 2. However, due to the potential PCR bias and gene profile variation among phylogenetically related genomes, functional profiles predicted from 16S amplicons may deviate from WGS-derived ones, resulting in misleading results.
RESULTS: Here we present Meta-Apo, which greatly reduces or even eliminates such deviation, thus deduces much more consistent diversity patterns between the two approaches. Tests of Meta-Apo on > 5000 16S-rRNA amplicon human microbiome samples from 4 body sites showed the deviation between the two strategies is significantly reduced by using only 15 WGS-amplicon training sample pairs. Moreover, Meta-Apo enables cross-platform functional comparison between WGS and amplicon samples, thus greatly improve 16S-based microbiome diagnosis, e.g. accuracy of gingivitis diagnosis via 16S-derived functional profiles was elevated from 65 to 95% by WGS-based classification. Therefore, with the low cost of 16S-amplicon sequencing, Meta-Apo can produce a reliable, high-resolution view of microbiome function equivalent to that offered by shotgun WGS.
CONCLUSIONS: This suggests that large-scale, function-oriented microbiome sequencing projects can probably benefit from the lower cost of 16S-amplicon strategy, without sacrificing the precision in functional reconstruction that otherwise requires WGS. An optimized C++ implementation of Meta-Apo is available on GitHub (https://github.com/qibebt-bioinfo/meta-apo) under a GNU GPL license. It takes the functional profiles of a few paired WGS:16S-amplicon samples as training, and outputs the calibrated functional profiles for the much larger number of 16S-amplicon samples.}, }
@article {pmid33406974, year = {2021}, author = {Clements, TW and Tolonen, M and Ball, CG and Kirkpatrick, AW}, title = {Secondary Peritonitis and Intra-Abdominal Sepsis: An Increasingly Global Disease in Search of Better Systemic Therapies.}, journal = {Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society}, volume = {}, number = {}, pages = {1457496920984078}, doi = {10.1177/1457496920984078}, pmid = {33406974}, issn = {1799-7267}, abstract = {Secondary peritonitis and intra-abdominal sepsis are a global health problem. The life-threatening systemic insult that results from intra-abdominal sepsis has been extensively studied and remains somewhat poorly understood. While local surgical therapy for perforation of the abdominal viscera is an age-old therapy, systemic therapies to control the subsequent systemic inflammatory response are scarce. Advancements in critical care have led to improved outcomes in secondary peritonitis. The understanding of the effect of secondary peritonitis on the human microbiome is an evolving field and has yielded potential therapeutic targets. This review of secondary peritonitis discusses the history, classification, pathophysiology, diagnosis, treatment, and future directions of the management of secondary peritonitis. Ongoing clinical studies in the treatment of secondary peritonitis and the open abdomen are discussed.}, }
@article {pmid33395654, year = {2020}, author = {Kakabadze, E and Grdzelishvili, N and Sanikidze, L and Makalatia, K and Chanishvili, N}, title = {REVIVAL OF MICROBIAL THERAPEUTICS, WITH EMPHASIS ON PROBIOTIC LACTOBACILLUS (REVIEW).}, journal = {Georgian medical news}, volume = {}, number = {308}, pages = {129-134}, pmid = {33395654}, issn = {1512-0112}, abstract = {The idea to use living microorganisms for disease prevention and treatment was introduced a century ago, but yet the full potential and benefits of microbial therapeutics has not been entirely understood. In the light of developments of human microbiome studies, probiotics are gaining new momentum, where health benefit conferring by Lactobacillus are emerging as one of the novel approaches in the treatment and prophylactics of dysbiosis. The present review focuses on the origin and development of the probiotic's concept, mechanisms of action and anticipated use of probiotic Lactobacillus as well as of microbial therapeutics. The required regulatory frameworks associated with probiotic use and marketing are discussed.}, }
@article {pmid33383954, year = {2020}, author = {D'Onofrio, V and Del Chierico, F and Belci, P and Vernocchi, P and Quagliariello, A and Reddel, S and Conta, G and Mancino, MV and Fadda, M and Scigliano, MC and Morelli, R and De Francesco, A and Guagnini, F and Fassio, F and Galletti, R and Putignani, L}, title = {Effects of a Synbiotic Formula on Functional Bowel Disorders and Gut Microbiota Profile during Long-Term Home Enteral Nutrition (LTHEN): A Pilot Study.}, journal = {Nutrients}, volume = {13}, number = {1}, pages = {}, doi = {10.3390/nu13010087}, pmid = {33383954}, issn = {2072-6643}, support = {RC 201905_Genetica_Putignani//Ministry of Health, Italy/ ; -//Allergy Therapeutics Italia/ ; }, abstract = {Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients.}, }
@article {pmid33382980, year = {2020}, author = {Dohlman, AB and Arguijo Mendoza, D and Ding, S and Gao, M and Dressman, H and Iliev, ID and Lipkin, SM and Shen, X}, title = {The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2020.12.001}, pmid = {33382980}, issn = {1934-6069}, abstract = {Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types from The Cancer Genome Atlas (TCGA), revealing that species equiprevalent across sample types are predominantly contaminants, bearing unique signatures from each TCGA-designated sequencing center. Removing such species mitigated batch effects and isolated the tissue-resident microbiome, which was validated by original matched TCGA samples. Gene copies and nucleotide variants can further distinguish mixed-evidence species. We, thus, present The Cancer Microbiome Atlas (TCMA), a collection of curated, decontaminated microbial compositions of oropharyngeal, esophageal, gastrointestinal, and colorectal tissues. This led to the discovery of prognostic species and blood signatures of mucosal barrier injuries and enabled systematic matched microbe-host multi-omic analyses, which will help guide future studies of the microbiome's role in human health and disease.}, }
@article {pmid33377531, year = {2020}, author = {Fang, C and Wu, L and Zhu, C and Xie, WZ and Hu, H and Zeng, XT}, title = {A potential therapeutic strategy for prostatic disease by targeting the oral microbiome.}, journal = {Medicinal research reviews}, volume = {}, number = {}, pages = {}, doi = {10.1002/med.21778}, pmid = {33377531}, issn = {1098-1128}, support = {2019FFB03902//Nature Science Foundation of Hubei Province/ ; WJ2019H035//Health Commission of Hubei Province Scientific Research Project/ ; 2042020kf1081//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Nowadays, human microbiome research is rapidly growing and emerging evidence has witnessed the critical role that oral microbiome plays in the process of human health and disease. Oral microbial dysbiosis has been confirmed as a contributory cause for diseases in multiple body systems, ranging from the oral cavity to the gastrointestinal, endocrine, immune, cardiovascular, and even nervous system. As research progressing, oral microbiome-based diagnosis and therapy are proposed and applied, which may represent potential drug targets in systemic diseases. Recent studies have uncovered the possible association between periodontal disease and prostatic disease, suggesting new prevention and therapeutic treatment for the disease by targeting periodontal pathogens. Thus, we performed this review to first explore the association between the oral microbiome and prostatic disease, according to current knowledge based on published articles, and then mainly focus on the underlying molecular and cellular mechanisms and the potential prevention and treatment derived from these mechanistic studies.}, }
@article {pmid33372204, year = {2020}, author = {Turunen Katri, A and Kantele, A}, title = {Revisiting travellers' diarrhoea justifying antibiotic treatment: prospective study.}, journal = {Journal of travel medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/jtm/taaa237}, pmid = {33372204}, issn = {1708-8305}, abstract = {BACKGROUND: As antimicrobials increase the risk of acquiring multidrug-resistant (MDR) bacteria, unnecessary antibiotics should be avoided for travellers' diarrhoea (TD). Antibiotics are recommended in TD accompanied by fever or incapacitation (TD justifying use of antibiotics, TDjuAB). Seeking tools for reducing antibiotic use, we explored factors predisposing to TDjuAB and scrutinized antibiotic treatment among those with TDjuAB and those with diarrhoea not justifying antibiotics.
METHODS: We conducted a study among 370 prospectively recruited visitors to the tropics. Stool samples and questionnaires were collected before and after travel. Enteric pathogens were analysed by qPCR for enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC), and enteroinvasive (EIEC) E. coli/Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae, and for ETEC's toxins LT (heat-labile), STh (human heat-stable) and STp (porcine heat-stable). TD was defined by the WHO criteria and TDjuAB as diarrhoea accompanied by fever, and/or disrupting or preventing daily activities. Multivariable analysis was applied-separately for travel-related factors and pathogens-to identify risk factors for TDjuAB(+).
RESULTS: Among the 370 travellers, TD was contracted by 253 (68%), categorized as TDjuAB(+) in 93/253 (37%) and TDjuAB(-) in 160/253 (63%) of the cases. Antibiotics were used for TD by 41% in TDjuAB(+) and by 7% in the TDjuAB(-) group. Relative risk ratios (RRR) s are presented for both the TDjuAB(+) and the TDjuAB(-) groups. TDjuAB(+) was associated with long travel duration and young age. Among the 298 subjects not having taken antibiotics, increased RRRs were found e.g. for findings of Campylobacter coli/jejuni and ETEC's STh toxin.
CONCLUSIONS: The first to analyse risk factors for TDjuAB, our study presents RRRs for demographic and behavioural factors and for various pathogens. Only less than half of those in the TDjuAB(+) group took antibiotics, which demonstrates that most cases meeting the current criteria recover without antimicrobial treatment.}, }
@article {pmid33367793, year = {2020}, author = {Handa, S and Reyna, A and Wiryaman, T and Ghosh, P}, title = {Determinants of adenine-mutagenesis in diversity-generating retroelements.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaa1240}, pmid = {33367793}, issn = {1362-4962}, abstract = {Diversity-generating retroelements (DGRs) vary protein sequences to the greatest extent known in the natural world. These elements are encoded by constituents of the human microbiome and the microbial 'dark matter'. Variation occurs through adenine-mutagenesis, in which genetic information in RNA is reverse transcribed faithfully to cDNA for all template bases but adenine. We investigated the determinants of adenine-mutagenesis in the prototypical Bordetella bacteriophage DGR through an in vitro system composed of the reverse transcriptase bRT, Avd protein, and a specific RNA. We found that the catalytic efficiency for correct incorporation during reverse transcription by the bRT-Avd complex was strikingly low for all template bases, with the lowest occurring for adenine. Misincorporation across a template adenine was only somewhat lower in efficiency than correct incorporation. We found that the C6, but not the N1 or C2, purine substituent was a key determinant of adenine-mutagenesis. bRT-Avd was insensitive to the C6 amine of adenine but recognized the C6 carbonyl of guanine. We also identified two bRT amino acids predicted to nonspecifically contact incoming dNTPs, R74 and I181, as promoters of adenine-mutagenesis. Our results suggest that the overall low catalytic efficiency of bRT-Avd is intimately tied to its ability to carry out adenine-mutagenesis.}, }
@article {pmid33359433, year = {2020}, author = {Lääveri, T and Antikainen, J and Mero, S and Pakkanen, SH and Kirveskari, J and Roivainen, M and Kantele, A}, title = {Bacterial, viral and parasitic pathogens analysed by qPCR: findings from a prospective study of travellers' diarrhoea.}, journal = {Travel medicine and infectious disease}, volume = {}, number = {}, pages = {101957}, doi = {10.1016/j.tmaid.2020.101957}, pmid = {33359433}, issn = {1873-0442}, abstract = {BACKGROUND: The diagnostics of travellers' diarrhoea (TD) has been revolutionised by multiplex qPCR assays. While mostly of bacterial aetiology, viruses and parasites account for the disease among 10-20% of travellers. Despite this, prospective studies applying qPCR assays remain scarce that cover not only bacteria, such as the various diarrhoeagenic Escherichia coli (DEC), but also viral and parasitic pathogens.
METHOD: We analysed by qPCR pre- and post-travel stool samples of 146 Finnish travellers for bacterial, viral and parasitic pathogens: enteropathogenic (EPEC), enteroaggregative (EAEC), enterotoxigenic (ETEC), enterohaemorrhagic (EHEC), and enteroinvasive (EIEC) E. coli; Shigella, Campylobacter, Salmonella, Yersinia and Vibrio cholerae; norovirus G1 and G2, rotavirus, enteroviruses, and sapovirus; and Giardia lamblia, Entamoeba histolytica, and Cryptosporidium. Symptoms and medication data during travel were collected by questionnaires.
RESULTS: We detected bacterial pathogens in 102/146 samples (69.9%; EAEC, EPEC, ETEC most common), viral ones in 13 (8.9%; norovirus most common), and parasitic ones in one (0.7%; Giardia). Noroviruses were associated with severe symptoms (23.5% versus non-severe 4.9%). In the TD group, 41.7% (5/12) of those with viral pathogens (vs. 13.3%; 11/83 without) took antibiotics.
CONCLUSION: Viral pathogens, particularly noroviruses, prevail in severe TD. The symptoms of viral disease are often severe and lead to unwarranted use of antibiotics.}, }
@article {pmid33356857, year = {2020}, author = {Van Ende, M and Timmermans, B and Vanreppelen, G and Siscar-Lewin, S and Fischer, D and Wijnants, S and Romero, CL and Yazdani, S and Rogiers, O and Demuyser, L and Van Zeebroeck, G and Cen, Y and Kuchler, K and Brunke, S and Van Dijck, P}, title = {The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization.}, journal = {Virulence}, volume = {}, number = {}, pages = {}, doi = {10.1080/21505594.2020.1868825}, pmid = {33356857}, issn = {2150-5608}, abstract = {Candida glabrata is an opportunistic human fungal pathogen and is frequently present in the human microbiome. It has a high relative resistance to environmental stresses and several antifungal drugs. An important component involved in microbial stress tolerance is trehalose. In this work, we characterized the three C. glabrata trehalase enzymes Ath1, Nth1 and Nth2. Single, double and triple deletion strains were constructed and characterized both in vitro and in vivo to determine the role of these enzymes in virulence. Ath1 was found to be located in the periplasm and was essential for growth on trehalose as sole carbon source, while Nth1 on the other hand was important for oxidative stress resistance, an observation which was consistent by the lower survival rate of the NTH1 deletion strain in human macrophages. No significant phenotype was observed for Nth2. The triple deletion strain was unable to establish a stable colonization of the gastrointestinal (GI) tract in mice indicating the importance of having trehalase activity for colonization in the gut.}, }
@article {pmid33354717, year = {2020}, author = {Stewart, AG and Satlin, MJ and Schlebusch, S and Isler, B and Forde, BM and Paterson, DL and Harris, PNA}, title = {Completing the Picture - Capturing the Resistome in Antibiotic Clinical Trials.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1877}, pmid = {33354717}, issn = {1537-6591}, abstract = {Despite the accepted dogma that antibiotic use is the largest contributor to antimicrobial resistance (AMR) and human microbiome disruption, our knowledge of specific antibiotic-microbiome effects remains basic. Detection of associations between new or old antimicrobials and specific AMR burden is patchy and heterogeneous. Various microbiome analysis tools have become available that enable accurate descriptions of antibiotic effects on microbial communities in vivo over a period of time. Microbiome analysis of treatment groups in antibiotic clinical trials, powered to measure clinically meaningful endpoints would greatly assist the antibiotic development pipeline and clinician antibiotic decision making.}, }
@article {pmid33352574, year = {2020}, author = {Martins, D and Mendes, F and Schmitt, F}, title = {Microbiome: A Supportive or a Leading Actor in Lung Cancer?.}, journal = {Pathobiology : journal of immunopathology, molecular and cellular biology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1159/000511556}, pmid = {33352574}, issn = {1423-0291}, abstract = {Lung cancer is still the leading cause of cancer death worldwide. Despite the major diagnostic and therapeutic innovations, the effect on mortality has been modest and the overall survival is still poor. Better understanding of the pathology of these tumors is necessary in order to develop personalized therapeutic strategies in lung cancer patients. Human microbiome has been associated with normal physiology and function, and increasing evidence points towards a key role of the microbiome in promoting the progression of lung disease. Studies have shown that although poorly understood, lung has a distinctive microbiome that may an important role in lung cancer development and progression, and interactions between microbial populations have the potential to influence disease, suggesting that microbiome can be an emerging target in cancer therapeutics. We will review mechanisms how the lung microbiota influences carcinogenesis, focusing on the bacterial dysbiosis and inflammation. Moreover, we will discuss the link between the microbiome and cancer and the consequences induced by the immune system, as the host microbiota plays an essential role in activating and modulating the immune response. We summarize current research advances in the lung microbiome and demonstrate the potential to exploit microbiome as a mechanism to prevent carcinogenesis and modulate therapeutic strategy, suggesting microbiome as a valuable approach in lung cancer patients.}, }
@article {pmid33350604, year = {2020}, author = {Tranberg, A and Klarin, B and Johansson, J and Påhlman, LI}, title = {Efficacy of Lactiplantibacillus plantarum 299 and 299v against nosocomial oropharyngeal pathogens in vitro and as an oral prophylactic treatment in a randomized, controlled clinical trial.}, journal = {MicrobiologyOpen}, volume = {}, number = {}, pages = {e1151}, doi = {10.1002/mbo3.1151}, pmid = {33350604}, issn = {2045-8827}, support = {Doktorand-2019-0144//Region Skåne/ ; Doktorand-2020-0459//Region Skåne/ ; }, abstract = {BACKGROUND: Disturbance in the oropharyngeal microbiota is common in hospitalized patients and contributes to the development of nosocomial pneumonia. Lactiplantibacillus plantarum 299 and 299v (Lp299 and Lp299v) are probiotic bacteria with beneficial effects on the human microbiome.
AIM: To investigate how Lp299 and Lp299v affect the growth of nosocomial oropharyngeal pathogens in vitro and to evaluate the efficacy in vivo when these probiotics are administered prophylactically in hospitalized patients.
METHODS: The in vitro effect of Lp299 and Lp299v on nosocomial respiratory tract pathogens was evaluated using two methods, the co-culture and agar overlay. In the clinical study, patients were randomized to orally receive either probiotics or placebo twice daily during their hospital stay. Oropharyngeal swabs were analyzed at inclusion and every fourth day throughout hospitalization.
FINDINGS: All tested pathogens were completely inhibited by both Lp299 and Lp299v using the agar-overlay method. In the co-culture experiment, Lp299 and Lp299v significantly (p < 0.05) reduced the growth of all pathogens except for Enterococcus faecalis co-incubated with Lp299. In the clinical study, daily oral treatment with Lp299 and Lp299v did not influence the development of disturbed oropharyngeal microbiota or nosocomial infection. Proton pump inhibitors, antibiotics, and steroid treatment were identified as risk factors for developing disturbed oropharyngeal microbiota.
CONCLUSIONS: Lp299 and Lp299v inhibited pathogen growth in vitro but did not affect the oropharyngeal microbiota in vivo. The ClinicalTrials.gov Identifier for this study is NCT02303301.}, }
@article {pmid33350360, year = {2020}, author = {Holster, S and Repsilber, D and Geng, D and Hyötyläinen, T and Salonen, A and Lindqvist, CM and Rajan, SK and de Vos, WM and Brummer, RJ and König, J}, title = {Correlations between microbiota and metabolites after faecal microbiota transfer in irritable bowel syndrome.}, journal = {Beneficial microbes}, volume = {}, number = {}, pages = {1-14}, doi = {10.3920/BM2020.0010}, pmid = {33350360}, issn = {1876-2891}, abstract = {Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.}, }
@article {pmid33343536, year = {2020}, author = {Yin, X and Altman, T and Rutherford, E and West, KA and Wu, Y and Choi, J and Beck, PL and Kaplan, GG and Dabbagh, K and DeSantis, TZ and Iwai, S}, title = {A Comparative Evaluation of Tools to Predict Metabolite Profiles From Microbiome Sequencing Data.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {595910}, pmid = {33343536}, issn = {1664-302X}, support = {R44 DA043954/DA/NIDA NIH HHS/United States ; }, abstract = {Metabolomic analyses of human gut microbiome samples can unveil the metabolic potential of host tissues and the numerous microorganisms they support, concurrently. As such, metabolomic information bears immense potential to improve disease diagnosis and therapeutic drug discovery. Unfortunately, as cohort sizes increase, comprehensive metabolomic profiling becomes costly and logistically difficult to perform at a large scale. To address these difficulties, we tested the feasibility of predicting the metabolites of a microbial community based solely on microbiome sequencing data. Paired microbiome sequencing (16S rRNA gene amplicons, shotgun metagenomics, and metatranscriptomics) and metabolome (mass spectrometry and nuclear magnetic resonance spectroscopy) datasets were collected from six independent studies spanning multiple diseases. We used these datasets to evaluate two reference-based gene-to-metabolite prediction pipelines and a machine-learning (ML) based metabolic profile prediction approach. With the pre-trained model on over 900 microbiome-metabolome paired samples, the ML approach yielded the most accurate predictions (i.e., highest F1 scores) of metabolite occurrences in the human gut and outperformed reference-based pipelines in predicting differential metabolites between case and control subjects. Our findings demonstrate the possibility of predicting metabolites from microbiome sequencing data, while highlighting certain limitations in detecting differential metabolites, and provide a framework to evaluate metabolite prediction pipelines, which will ultimately facilitate future investigations on microbial metabolites and human health.}, }
@article {pmid33343520, year = {2020}, author = {Aho, EL and Ogle, JM and Finck, AM}, title = {The Human Microbiome as a Focus of Antibiotic Discovery: Neisseria mucosa Displays Activity Against Neisseria gonorrhoeae.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {577762}, pmid = {33343520}, issn = {1664-302X}, support = {/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Neisseria gonorrhoeae infections are a serious global health problem. This organism has developed disturbing levels of antibiotic resistance, resulting in the need for new approaches to prevent and treat gonorrhea. The genus Neisseria also includes several members of the human microbiome that live in close association with an array of microbial partners in a variety of niches. We designed an undergraduate antibiotic discovery project to examine a panel of nonpathogenic Neisseria species for their ability to produce antimicrobial secondary metabolites. Five strains belonging to the N. mucosa species group displayed activity against other Neisseria in delayed antagonism assays; three of these were active against N. gonorrhoeae. The antimicrobial compound secreted by N. mucosa NRL 9300 remained active in the presence of catalase, trypsin, and HEPES buffer, and effectively inhibited a DNA uptake mutant of N. gonorrhoeae. Antimicrobial activity was also retained in an ethyl acetate extract of plate grown N. mucosa NRL 9300. These data suggest N. mucosa produces an antimicrobial secondary metabolite that is distinct from previously described antigonococcal agents. This work also serves as a demonstration project that could easily be adapted to studying other members of the human microbiome in undergraduate settings. We offer the perspective that both introductory and more advanced course-based and apprentice-style antibiotic discovery projects focused on the microbiome have the potential to enrich undergraduate curricula and we describe transferrable techniques and strategies to facilitate project design.}, }
@article {pmid33339331, year = {2020}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Żaczek, M and Borysowski, J and Górski, A}, title = {The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33339331}, issn = {2076-2607}, support = {.//This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences./ ; }, abstract = {The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.}, }
@article {pmid33338541, year = {2020}, author = {Xu, CJ and Gruzieva, O and Qi, C and Esplugues, A and Gehring, U and Bergström, A and Mason, D and Chatzi, L and Porta, D and Lodrup Carlsen, KC and Baïz, N and Madore, AM and Alenius, H and van Rijkom, B and Jankipersadsing, SA and van der Vlies, P and Kull, I and van Hage, M and Bustamante, M and Lertxundi, A and Torrent, M and Santorelli, G and Fantini, MP and Hovland, V and Pesce, G and , and Fyhrquist, N and Laatikainen, T and Nawijn, MC and Li, Y and Wijmenga, C and Netea, MG and Bousquet, J and Anto, JM and Laprise, C and Haahtela, T and Annesi-Maesano, I and Carlsen, KH and Gori, D and Kogevinas, M and Wright, J and Söderhäll, C and Vonk, JM and Sunyer, J and Melén, E and Koppelman, GH}, title = {Shared DNA methylation signatures in childhood allergy: the MeDALL study.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2020.11.044}, pmid = {33338541}, issn = {1097-6825}, abstract = {BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into shared or unique etiology of asthma, rhinitis and eczema.
OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy.
METHODS: Within the European Mechanisms of the Development of ALLergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation using a cross-sectional design. Allergy is defined as having symptoms from at least one allergic disease (asthma/rhinitis/eczema) and positive serum specific IgE to common aeroallergens. The discovery study included 219 cases and 417 controls at age 4 and 228 cases and 593 controls at age 8 from three birth cohorts, with replication analyses in 325 cases and 1,111 controls. We performed additional analyses on 21 replicated sites in 785 cases and 2,124 controls by allergic symptoms only from eight cohorts, three not previously included in analyses.
RESULTS: We identified 80 differentially methylated CpG sites (CpGs) which showed 1-3% methylation difference in the discovery phase, of which 21, including five novel CpGs, passed genome-wide significance after meta-analysis. All 21 CpGs were also significantly differentially methylated with allergic symptoms, and shared between asthma, rhinitis and eczema. The 21 CpGs mapped to relevant genes, including ACOT7, LMAN3 and CLDN23. All 21 CpGs were differently methylated in asthma in isolated eosinophils, and ten were replicated in respiratory epithelium.
CONCLUSION: Reduced whole blood DNA methylation at 21 CpGs was significantly associated with childhood allergy. The findings provide novel insights into the shared molecular mechanisms underlying asthma, rhinitis and eczema.}, }
@article {pmid33329475, year = {2020}, author = {Piñar, G and Sclocchi, MC and Pinzari, F and Colaizzi, P and Graf, A and Sebastiani, ML and Sterflinger, K}, title = {The Microbiome of Leonardo da Vinci's Drawings: A Bio-Archive of Their History.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {593401}, pmid = {33329475}, issn = {1664-302X}, abstract = {Seven emblematic Leonardo da Vinci's drawings were investigated through third generation sequencing technology (Nanopore). In addition, SEM analyses were carried out to acquire photographic documentation and to infer the nature of the micro-objects removed from the surface of the drawings. The Nanopore generated microbiomes can be used as a "bio-archive" of the drawings, offering a kind of fingerprint for current and future biological comparisons. This information might help to create a biological catalog of the drawings (cataloging), a microbiome-fingerprint for each single analyzed drawing, as a reference dataset for future studies (monitoring) and last but not least a bio-archive of the history of each single object (added value). Results showed a relatively high contamination with human DNA and a surprising dominance of bacteria over fungi. However, it was possible to identify typical bacteria of the human microbiome, which are mere contaminants introduced by handling of the drawings as well as other microorganisms that seem to have been introduced through vectors, such as insects and their droppings, visible through the SEM analyses. All drawings showed very specific bio-archives, but a core microbiome of bacteria and fungi that are repeatedly found in this type of material as true degraders were identified, such as members of the phyla Proteobacteria, Actinobacteria, and Firmicutes among bacteria, and fungi belonging to the classes Sordariomycetes and Eurotiomycetes. In addition, some similarities were observed that could be influenced by their geographical location (Rome or Turin), indicating the influence of this factor and denoting the importance of environmental and storage conditions on the specific microbiomes.}, }
@article {pmid33328144, year = {2020}, author = {Kolmeder, CA and de Vos, WM}, title = {Roadmap to functional characterization of the human intestinal microbiota in its interaction with the host.}, journal = {Journal of pharmaceutical and biomedical analysis}, volume = {}, number = {}, pages = {113751}, doi = {10.1016/j.jpba.2020.113751}, pmid = {33328144}, issn = {1873-264X}, abstract = {It is known for more than 100 years that the intestinal microbes are important for the host's health and the last decade this is being intensely studied with a focus on the mechanistic aspects. Among the fundamental functions of the intestinal microbiome are the priming of the immune system, the production of essential vitamins and the energy harvest from foods. By now, several dozens of diseases, both intestinal and non-intestinal related, have been associated with the intestinal microbiome. Initially, this was based on the description of the composition between groups of different health status or treatment arms based on phylogenetic approaches based on the 16S rRNA gene sequences. This way of analysis has mostly moved to the analysis of all the genes or transcripts of the microbiome i.e. metagenomics and meta-transcriptomics. Differences are regularly found but these have to be taken with caution as we still do not know what the majority of genes of the intestinal microbiome are capable of doing. To circumvent this caveat researchers are studying the proteins and the metabolites of the microbiome and the host via metaproteomics and metabolomics approaches. However, also here the complexity is high and only a fraction of signals obtained with high throughput instruments can be identified and assigned to a known protein or molecule. Therefore, modern microbiome research needs advancement of existing and development of new analytical techniques. The usage of model systems like intestinal organoids where samples can be taken and processed rapidly as well as microfluidics systems may help. This review aims to elucidate what we know about the functionality of the human intestinal microbiome, what technologies are advancing this knowledge, and what innovations are still required to further evolve this actively developing field.}, }
@article {pmid33325062, year = {2020}, author = {Sidorina, A and Catesini, G and Levi Mortera, S and Marzano, V and Putignani, L and Boenzi, S and Taurisano, R and Garibaldi, M and Deodato, F and Dionisi-Vici, C}, title = {Combined proteomic and lipidomic studies in Pompe disease allow a better disease mechanism understanding.}, journal = {Journal of inherited metabolic disease}, volume = {}, number = {}, pages = {}, doi = {10.1002/jimd.12344}, pmid = {33325062}, issn = {1573-2665}, abstract = {Pompe disease (PD) is caused by deficiency of the enzyme acid α-glucosidase resulting in glycogen accumulation in lysosomes. Clinical symptoms include skeletal myopathy, respiratory failure, and cardiac hypertrophy. We studied plasma proteomic and lipidomic profiles in 12 PD patients compared to age-matched controls. The proteomic profiles were analyzed by nLC-MS/MS SWATH method. Wide-targeted lipidomic analysis was performed by LC-IMS/MS, allowing to quantify >1100 lipid species, spanning 13 classes. Significant differences were found for 16 proteins, with four showing the most relevant changes (GPLD1, PON1, LDHB, PKM). Lipidomic analysis showed elevated levels of three phosphatidylcholines and of the free fatty acid 22:4, and reduced levels of six lysophosphatidylcholines. Up-regulated glycolytic enzymes (LDHB and PKM) are involved in autophagy and glycogen metabolism, while down-regulated PON1 and GPLD1 combined with lipidomic data indicate an abnormal phospholipid metabolism. Reduced GPLD1 and dysregulation of lipids with acyl-chains characteristic of GPI-anchor structure suggest the potential involvement of GPI-anchor system in PD. Results of proteomic analysis displayed the involvement of multiple cellular functions affecting inflammatory, immune and antioxidant responses, autophagy, Ca2+ -homeostasis, and cell adhesion. The combined multi-omic approach revealed new biosignatures in PD, providing novel insights in disease pathophysiology with potential future clinical application.}, }
@article {pmid33324573, year = {2020}, author = {van Tilburg Bernardes, E and Gutierrez, MW and Arrieta, MC}, title = {The Fungal Microbiome and Asthma.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {583418}, pmid = {33324573}, issn = {2235-2988}, abstract = {Asthma is a group of inflammatory conditions that compromises the airways of a continuously increasing number of people around the globe. Its complex etiology comprises both genetic and environmental aspects, with the intestinal and lung microbiomes emerging as newly implicated factors that can drive and aggravate asthma. Longitudinal infant cohort studies combined with mechanistic studies in animal models have identified microbial signatures causally associated with subsequent asthma risk. The recent inclusion of fungi in human microbiome surveys has revealed that microbiome signatures associated with asthma risk are not limited to bacteria, and that fungi are also implicated in asthma development in susceptible individuals. In this review, we examine the unique properties of human-associated and environmental fungi, which confer them the ability to influence immune development and allergic responses. The important contribution of fungi to asthma development and exacerbations prompts for their inclusion in current and future asthma studies in humans and animal models.}, }
@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}, 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 = {UL1 TR001102/TR/NCATS NIH HHS/United States ; DE022586/DE/NIDCR NIH HHS/United States ; DGE1745303//National Science Foundation/ ; }, 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 {pmid33321195, year = {2020}, author = {Kantele, A and Lääveri, T and Kareinen, L and Pakkanen, SH and Blomgren, K and Mero, S and Patjas, A and Virtanen, J and Uusitalo, R and Lappalainen, M and Järvinen, A and Kurkela, S and Jääskeläinen, AJ and Vapalahti, O and Sironen, T}, title = {SARS-CoV-2 infections among healthcare workers at Helsinki University Hospital, Finland, spring 2020: Serosurvey, symptoms and risk factors.}, journal = {Travel medicine and infectious disease}, volume = {39}, number = {}, pages = {101949}, doi = {10.1016/j.tmaid.2020.101949}, pmid = {33321195}, issn = {1873-0442}, abstract = {BACKGROUND: Exposure, risks and immunity of healthcare workers (HCWs), a vital resource during the SARS-CoV-2 pandemic, warrant special attention.
METHODS: HCWs at Helsinki University Hospital, Finland, filled in questionnaires and provided serum samples for SARS-CoV-2-specific antibody screening by Euroimmun IgG assay in March-April 2020. Positive/equivocal findings were confirmed by Abbott and microneutralization tests. Positivity by two of the three assays or RT-PCR indicated a Covid-19 case (CoV+).
RESULTS: The rate of CoV(+) was 3.3% (36/1095) and seropositivity 3.0% (33/1095). CoV(+) was associated with contact with a known Covid-19 case, and working on a Covid-19-dedicated ward or one with cases among staff. The rate in the Covid-19-dedicated ICU was negligible. Smoking and age <55 years were associated with decreased risk. CoV(+) was strongly associated with ageusia, anosmia, myalgia, fatigue, fever, and chest pressure. Seropositivity was recorded for 89.3% of those with prior documented RT-PCR-positivity and 2.4% of those RT-PCR-negative. The rate of previously unidentified cases was 0.7% (8/1067) and asymptomatic ones 0% (0/36).
CONCLUSION: Undiagnosed and asymptomatic cases among HCWs proved rare. An increased risk was associated with Covid-19-dedicated wards. Particularly high rates were seen for wards with liberal HCW-HCW contacts, highlighting the importance of social distancing also among HCWs.}, }
@article {pmid33311550, year = {2020}, author = {Aluthge, ND and Tom, WA and Bartenslager, AC and Burkey, TE and Miller, PS and Heath, KD and Kreikemeier-Bower, C and Kittana, H and Schmaltz, RJ and Ramer-Tait, AE and Fernando, SC}, title = {Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {760}, pmid = {33311550}, issn = {2399-3642}, support = {2018-67015-27496//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; 2018-68003-27545//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; }, abstract = {The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.}, }
@article {pmid33307384, year = {2020}, 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}, 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 {pmid33307241, year = {2020}, author = {Tsonis, O and Gkrozou, F and Paschopoulos, M}, title = {Microbiome affecting reproductive outcome in ARTs.}, journal = {Journal of gynecology obstetrics and human reproduction}, volume = {50}, number = {3}, pages = {102036}, doi = {10.1016/j.jogoh.2020.102036}, pmid = {33307241}, issn = {2468-7847}, abstract = {Current scientific evidence reveals the importance of the human microbiome in health and disease. The presence of microbiota within the male and female reproductive tract has been well-documented and present theories imply that a possible disruption of their concentrations may have adverse effects on reproductive health and reproductive outcomes. Altered endometrial and vaginal microbiome could potential affect the reproductive outcome in infertile couples undergoing assisted reproductive techniques. Analysis of seminal fluids could also facilitate a prompt and appropriate approach in cases of abnormal male reproductive microflora. Essential knowledge on this subject could provide fertility experts better understanding with regards to unexplained fertility, increasing the success rates of ARTs. In this review, we summarise the current knowledge on the microbiota of the male and female reproductive tract and its impact on the success rates of ARTs in infertile couples.}, }
@article {pmid33307114, year = {2020}, author = {Rocks, T and West, M and Hockey, M and Aslam, H and Lane, M and Loughman, A and Jacka, FN and Ruusunen, A}, title = {Possible use of fermented foods in rehabilitation of anorexia nervosa: the gut microbiota as a modulator.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {110201}, doi = {10.1016/j.pnpbp.2020.110201}, pmid = {33307114}, issn = {1878-4216}, abstract = {Anorexia nervosa is a serious psychiatric disorder with high morbidity and mortality rate. Evidence for the optimal psychopharmacological approach to managing the disorder remains limited, with nutritional treatment, focused on weight restoration through the consumption of high energy diet, regarded as one of the fundamental steps in treatment. The human gut microbiome is increasingly recognised for its proposed role in gastrointestinal, metabolic, immune and mental health, all of which may be compromised in individuals with anorexia nervosa. Dietary intake plays an important role in shaping gut microbiota composition, whilst the use of fermented foods, foods with potential psychobiotic properties that deliver live bacteria, bacterial metabolites, prebiotics and energy, have been discussed to a lesser extent. However, fermented foods are of increasing interest due to their potential capacity to affect gut microbiota composition, provide beneficial bacterial metabolites, and confer beneficial outcomes to host health. This review provides an overview of the role of the gut microbiota in relation to the disease pathology in anorexia nervosa and especially focuses on the therapeutic potential of fermented foods, proposed here as a recommended addition to the current nutritional treatment protocols warranting further investigation.}, }
@article {pmid33305317, year = {2020}, 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 = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaa996}, pmid = {33305317}, issn = {1362-4962}, 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 {pmid33304855, year = {2020}, author = {Vural, M and Gilbert, B and Üstün, I and Caglar, S and Finckh, A}, title = {Mini-Review: Human Microbiome and Rheumatic Diseases.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {491160}, pmid = {33304855}, issn = {2235-2988}, abstract = {Rheumatoid arthritis and spondyloarthropathy are the most common inflammatory rheumatic diseases. As the human microbiome is involved in the immune homeostasis, it has the potential to be a key factor in the development of autoimmune diseases and rheumatic diseases. In this article, we review the role of various human microbiota on the pathogenesis of rheumatic diseases, focusing on spondylarthritis and rheumatoid arthritis.}, }
@article {pmid33304658, year = {2020}, author = {Koffert, J and Lahti, L and Nylund, L and Salminen, S and Hannukainen, JC and Salminen, P and de Vos, WM and Nuutila, P}, title = {Partial restoration of normal intestinal microbiota in morbidly obese women six months after bariatric surgery.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e10442}, pmid = {33304658}, issn = {2167-8359}, abstract = {We studied the impact of bariatric surgery on the intestinal microbiota of morbidly obese study subjects. A total of 13 morbidly obese women (five of which had type 2 diabetes) and 14 healthy age- and gender-matched controls were recruited and the microbiota composition of fecal samples were determined by using a phylogenetic microarray. Sampling of the patients took place just one month before and 6 months after the operation. Within six months after bariatric surgery, the obese subjects had lost on average a quarter of their weight whereas four of the five of the diabetic subjects were in remission. Bariatric surgery was associated with an increased microbial community richness and Bacteroidetes/Firmicutes ratio. In addition, we observed an increased relative abundance of facultative anaerobes, such as Streptococcus spp., and a reduction in specific butyrate-producing Firmicutes. The observed postoperative alterations in intestinal microbiota reflect adaptation to the changing conditions in the gastrointestinal tract, such as energy restriction and the inability to process fiber-rich foods after bariatric surgery.}, }
@article {pmid33301266, year = {2020}, author = {}, title = {Correction to "Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions".}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {63}, number = {6}, pages = {E609}, doi = {10.1503/cjs.024120}, pmid = {33301266}, issn = {1488-2310}, }
@article {pmid33300552, year = {2020}, author = {Ventin-Holmberg, R and Eberl, A and Saqib, S and Korpela, K and Virtanen, S and Sipponen, T and Salonen, A and Saavalainen, P and Nissilä, E}, title = {Bacterial and fungal profiles as markers of infliximab drug response in inflammatory bowel disease.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa252}, pmid = {33300552}, issn = {1876-4479}, abstract = {BACKGROUND: Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are globally increasing chronic gastro-intestinal inflammatory disorders associating with altered gut microbiota. Infliximab (IFX), a TNF-alpha blocker, is used to treat IBD patients successfully though one third of the patients do not respond to therapy. No reliable biomarkers are available for prediction of IFX response.
AIMS: Our aim was to investigate the faecal bacterial and fungal communities during IFX therapy and find predictors for IFX treatment response in IBD patients.
METHODS: 72 IBD patients (25 CD and 47 UC) started IFX therapy and were followed for one year or until IFX treatment was discontinued. Amplicon sequencing approach targeting the bacterial 16S rRNA gene and fungal ITS 1 region separately was used to determine the microbiota profiles in faecal samples collected before IFX therapy, two, six, twelve weeks and one year after initiation of therapy. The response to IFX was evaluated by colonoscopy and clinically at twelve weeks after initiation.
RESULTS: Both the faecal bacterial and fungal profiles differed significantly between response groups before start of IFX treatment. Non-responders had lower abundances of short chain fatty acid producers, particularly of the class Clostridia and higher abundances of pro-inflammatory bacteria and fungi, such as the genus Candida, compared to responders. This was further indicated by bacterial taxa predicting the response in both CD and UC patients (area under curve > 0.8).
CONCLUSIONS: Faecal bacterial and fungal microbiota composition could provide a predictive tool to estimate IFX response in IBD patients.}, }
@article {pmid33299088, year = {2020}, author = {Malard, F and Dore, J and Gaugler, B and Mohty, M}, title = {Introduction to host microbiome symbiosis in health and disease.}, journal = {Mucosal immunology}, volume = {}, number = {}, pages = {}, pmid = {33299088}, issn = {1935-3456}, abstract = {Humans share a core intestinal microbiome and yet human microbiome differs by genes, species, enterotypes (ecology), and gene count (microbial diversity). Achievement of microbiota metagenomic analysis has revealed that the microbiome gene count is a key stratifier of health in several immune disorders and clinical conditions. We review here the progress of the metagenomic pipeline analysis, and how this has allowed us to define the host-microbe symbiosis associated with a healthy status. The link between host-microbe symbiosis disruption, the so-called dysbiosis and chronic diseases or iatrogenic conditions is highlighted. Finally, opportunities to use microbiota modulation, with specific nutrients and/or live microbes, as a target for personalized nutrition and therapy for the maintenance, preservation, or restoration of host-microbe symbiosis are discussed.}, }
@article {pmid33298912, year = {2020}, author = {Daisley, BA and Chanyi, RM and Abdur-Rashid, K and Al, KF and Gibbons, S and Chmiel, JA and Wilcox, H and Reid, G and Anderson, A and Dewar, M and Nair, SM and Chin, J and Burton, JP}, title = {Author Correction: Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6394}, doi = {10.1038/s41467-020-20410-x}, pmid = {33298912}, issn = {2041-1723}, }
@article {pmid33297188, year = {2021}, author = {Harpaz, D and Veltman, B and Sadeh, Y and Marks, RS and Bernstein, N and Eltzov, E}, title = {The effect of cannabis toxicity on a model microbiome bacterium epitomized by a panel of bioluminescent E. coli.}, journal = {Chemosphere}, volume = {263}, number = {}, pages = {128241}, doi = {10.1016/j.chemosphere.2020.128241}, pmid = {33297188}, issn = {1879-1298}, mesh = {*Cannabis/toxicity ; Dronabinol/toxicity ; Escherichia coli/genetics ; Humans ; *Microbiota ; Plant Extracts ; }, abstract = {The world acceptance of medical cannabis slowly widens. Cannabinoids are known as the main therapeutic active compounds in the cannabis plant, yet their bioactive physiological effects are still unknown. In this study, the mode of action of nine selected cannabinoids was examined using a bioluminescent bacterial panel, as well as the extracts of six different cannabis varieties and cannabinoids standards artificial mixtures. The bacterial panel was composed of genetically modified E. coli bacteria that is commonly found in the gut microbiome, to which a lux operon was added to various stress promoters. The panel was exposed to the cannabinoids in order to identify bacterial defense mechanism, via the aforementioned specific stress types response. This enables the understanding of the toxicity mode of action of cannabinoids. From all the tested cannabinoids, only delta-9-tetrahydrocannabinol (THC) and delta-9-tetrahydrocannabinolic acid A (THCA) produced a genotoxic effect, while the other tested cannabinoids, demonstrated cytotoxic or oxidative damages. Unlike pure cannabinoids, cannabis plant extracts exhibited mostly genotoxicity, with minor cytotoxicity or oxidative stress responses. Moreover, cannabinoids standards artificial mixtures produced a different response patterns compared to their individual effects, which may be due to additional synergistic or antagonistic reactions between the mixed chemicals on the bacterial panel. The results showed that despite the lack of cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC) in the artificial solution mimicking the CN6 cannabis variety, a similar response pattern to the cannabinoids standards mixture was obtained. This work contributes to the understanding of such correlations and may provide a realistic view of cannabinoid effects on the human microbiome.}, }
@article {pmid33291949, year = {2020}, author = {Chen, CX and Carpenter, JS and Murphy, T and Brooks, P and Fortenberry, JD}, title = {Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study.}, journal = {Biological research for nursing}, volume = {}, number = {}, pages = {1099800420979606}, doi = {10.1177/1099800420979606}, pmid = {33291949}, issn = {1552-4175}, abstract = {Human microbiome research provides rich opportunities to elucidate factors influencing health, uncover novel biomarkers, and expand disease treatment options. A well-conducted microbiome study depends not only on a rigorous design but also on successfully engaging participants in collecting quality samples. In this paper, we aim to describe (1) strategies our team used to engage adolescents and young adults in vaginal and gut microbiome sample self-collection and (2) their effectiveness. In our prospective, longitudinal, feasibility study of 20 female adolescents and young adults, research participants self-collected vaginal and gut microbiome samples at home. Using a participatory and iterative process, we developed strategies to engage participants in sample self-collection, including (1) providing clear instructions to ensure comprehension and buy-in, (2) providing a user-friendly take-home package, (3) minimizing disgust/embarrassment associated with sample collection, and (4) follow-up communications to facilitate sample collections and return. With these strategies, we achieved 100% participant retention and 100% sample return rates. All samples (n = 80, 100%) were usable for downstream 16s rRNA gene sequencing and analysis. All participants rated the study procedures as acceptable, and qualitative data showed that strategies were well received by participants. This study suggests that carefully planning and implementing strategies to engage participants in sample self-collection can result in high degrees of participant compliance, sample quality, and participant satisfaction in microbiome research.}, }
@article {pmid33290720, year = {2020}, author = {Durrant, MG and Bhatt, AS}, title = {Automated Prediction and Annotation of Small Open Reading Frames in Microbial Genomes.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2020.11.002}, pmid = {33290720}, issn = {1934-6069}, 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 {pmid33283070, year = {2020}, author = {Banerjee, S and Suter, MA and Aagaard, KM}, title = {Interactions between Environmental Exposures and the Microbiome: Implications for Fetal Programming.}, journal = {Current opinion in endocrine and metabolic research}, volume = {13}, number = {}, pages = {39-48}, pmid = {33283070}, issn = {2451-9650}, support = {R00 HD075858/HD/NICHD NIH HHS/United States ; R01 HD091731/HD/NICHD NIH HHS/United States ; P42 ES027725/ES/NIEHS NIH HHS/United States ; R21 ES029462/ES/NIEHS NIH HHS/United States ; R01 DK089201/DK/NIDDK NIH HHS/United States ; R24 DK090964/DK/NIDDK NIH HHS/United States ; P50 MD015496/MD/NIMHD NIH HHS/United States ; }, abstract = {Decades of population-based health outcomes data highlight the importance of understanding how environmental exposures in pregnancy affect maternal and neonatal outcomes. Animal model research and epidemiological studies have revealed that such exposures are able to alter fetal programming through stable changes in the epigenome, including altered DNA methylation patterns and histone modifications in the developing fetus and infant. It is similarly known that while microbes can biotransform environmental chemicals via conjugation and de-conjugation, specific exposures can also alter the community profile and function of the human microbiome. In this review, we consider how alterations to the maternal and or fetal/infant microbiome through environmental exposures could directly and indirectly alter fetal programming. We highlight two specific environmental exposures, cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs), and outline their effects on the developing fetus and the perinatal (maternal and fetal/infant) microbiome. We further consider how chemical exposures in the setting of natural disasters may be of particular importance to environmental health.}, }
@article {pmid33281770, year = {2020}, author = {Hiippala, K and Barreto, G and Burrello, C and Diaz-Basabe, A and Suutarinen, M and Kainulainen, V and Bowers, JR and Lemmer, D and Engelthaler, DM and Eklund, KK and Facciotti, F and Satokari, R}, title = {Novel Odoribacter splanchnicus Strain and Its Outer Membrane Vesicles Exert Immunoregulatory Effects in vitro.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {575455}, pmid = {33281770}, issn = {1664-302X}, abstract = {Odoribacter splanchnicus, belonging to the order Bacteroidales, is a common, short-chain fatty acid producing member of the human intestinal microbiota. A decreased abundance of Odoribacter has been linked to different microbiota-associated diseases, such as non-alcoholic fatty liver disease, cystic fibrosis and inflammatory bowel disease (IBD). The type strain of O. splanchnicus has been genome-sequenced, but otherwise very little is known about this anaerobic bacterium. The species surfaces in many microbiota studies and, consequently, comprehension on its interactions with the host is needed. In this study, we isolated a novel strain of O. splanchnicus from a healthy fecal donor, identified it by genome sequencing and addressed its adhesive, epithelium reinforcing and immunoregulatory properties. Our results show that O. splanchnicus strain 57 is non-adherent to enterocytes or mucus, does not reinforce nor compromise Caco-2 monolayer integrity and most likely harbors penta-acylated, less endotoxic lipid A as part of its lipopolysaccharide (LPS) structure based on the lack of gene lpxM and in vitro results on low-level NF-κB activity. The studies by transmission electron microscopy revealed that O. splanchnicus produces outer membrane vesicles (OMV). O. splanchnicus cells, culture supernatant i.e., spent medium or OMVs did not induce interleukin-8 (IL-8) response in HT-29 enterocyte cells suggesting a very low proinflammatory capacity. On the contrary, the treatment of HT-29 cells with O. splanchnicus cells, spent medium or OMVs prior to exposure to Escherichia coli LPS elicited a significant decrease in IL-8 production as compared to E. coli LPS treatment alone. Moreover, O. splanchnicus spent supernatant induced IL-10 production by immune cells, suggesting anti-inflammatory activity. Our in vitro findings indicate that O. splanchnicus and its effector molecules transported in OMVs could potentially exert anti-inflammatory action in the gut epithelium. Taken together, O. splanchnicus seems to be a commensal with a primarily beneficial interaction with the host.}, }
@article {pmid33278908, year = {2020}, author = {Kirkpatrick, AW and Hamilton, DR and McKee, JL and MacDonald, B and Pelosi, P and Ball, CG and Roberts, D and McBeth, PB and Cocolini, F and Ansaloni, L and Peireira, B and Sugrue, M and Campbell, MR and Kimball, EJ and Malbrain, MLNG and Roberts, D}, title = {Do we have the guts to go? The abdominal compartment, intra-abdominal hypertension, the human microbiome and exploration class space missions.}, journal = {Canadian journal of surgery. Journal canadien de chirurgie}, volume = {63}, number = {6}, pages = {E581-E593}, pmid = {33278908}, issn = {1488-2310}, abstract = {Humans are destined to explore space, yet critical illness and injury may be catastrophically limiting for extraterrestrial travel. Humans are superorganisms living in symbiosis with their microbiomes, whose genetic diversity dwarfs that of humans. Symbiosis is critical and imbalances are associated with disease, occurring within hours of serious illness and injury. There are many characteristics of space flight that negatively influence the microbiome, especially deep space itself, with its increased radiation and absence of gravity. Prolonged weightlessness causes many physiologic changes that are detrimental; some resemble aging and will adversely affect the ability to tolerate critical illness or injury and subsequent treatment. Critical illness-induced intra-abdominal hypertension (IAH) may induce malperfusion of both the viscera and microbiome, with potentially catastrophic effects. Evidence from animal models confirms profound IAH effects on the gut, namely ischemia and disruption of barrier function, mechanistically linking IAH to resultant organ dysfunction. Therefore, a pathologic dysbiome, space-induced immune dysfunction and a diminished cardiorespiratory reserve with exacerbated susceptibility to IAH, imply that a space-deconditioned astronaut will be vulnerable to IAH-induced gut malperfusion. This sets the stage for severe gut ischemia and massive biomediator generation in an astronaut with reduced cardiorespiratory/immunological capacity. Fortunately, experiments in weightless analogue environments suggest that IAH may be ameliorated by conformational abdominal wall changes and a resetting of thoracoabdominal mechanics. Thus, review of the interactions of physiologic changes with prolonged weightlessness and IAH is required to identify appropriate questions for planning exploration class space surgical care.}, }
@article {pmid33277504, year = {2020}, author = {Tian, L and Wang, XW and Wu, AK and Fan, Y and Friedman, J and Dahlin, A and Waldor, MK and Weinstock, GM and Weiss, ST and Liu, YY}, title = {Deciphering functional redundancy in the human microbiome.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6217}, pmid = {33277504}, issn = {2041-1723}, support = {UH3 OD023268/OD/NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved - implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network - a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient's pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience.}, }
@article {pmid33274243, year = {2020}, author = {Kasperkiewicz, K and Świerzko, AS and Przybyła, M and Szemraj, J and Barski, J and Skurnik, M and Kałużyński, A and Cedzyński, M}, title = {The Role of Yersinia enterocolitica O:3 Lipopolysaccharide in Collagen-Induced Arthritis.}, journal = {Journal of immunology research}, volume = {2020}, number = {}, pages = {7439506}, pmid = {33274243}, issn = {2314-7156}, abstract = {Yersinia enterocolitica O:3 is mentioned among the most common arthritogenic pathogens. Bacterial components (including lipopolysaccharide (LPS)) may persist in the joint after eradication of infection. Having an adjuvant activity, LPS may enhance production of anticollagen antibodies, involved in the pathogenesis of rheumatoid arthritis. Furthermore, its ability to activate complement contributes to the inflammation. The aim of this work was to investigate whether Yersinia LPS (coinjected with collagen) is associated with arthritis progression or other pathological effects and to elucidate the mechanism of this association. It was demonstrated that murine mannose-binding lectin C (MBL-C) recognizes the inner core heptoses of the Rd1 chemotype LPS of Yersinia. In addition, the Rd1 LPS activates the MBL-associated serine protease 1 (MASP-1) stronger than the S and Ra chemotype LPS and comparable to Klebsiella pneumoniae O:3 LPS. However, in contrast to the latter, Yersinia Rd1 LPS was associated neither with the adjuvancity nor with the enhancement of pathological changes in animal paws/impairment of motility. On the other hand, it seemed to be more hepatotoxic when compared with the other tested endotoxins, while the enlargement of inguinal lymph nodes and drop in hepatic MBL-C expression (at the mRNA level) were independent of LPS chemotype. Our data did not suggest no greater impact Y. enterocolitica O:3 on the development or severity of arthropathy related to anticollagen antibody-induced arthritis in mice, although its interaction with MBL-C and subsequent complement activation may contribute to some adverse effects.}, }
@article {pmid33272203, year = {2020}, author = {Zhang, Q and Dao, T}, title = {A distance based multisample test for high-dimensional compositional data with applications to the human microbiome.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 9}, pages = {205}, pmid = {33272203}, issn = {1471-2105}, mesh = {Aged ; Bayes Theorem ; Computer Simulation ; Humans ; Metagenomics ; *Microbiota ; Middle Aged ; Numerical Analysis, Computer-Assisted ; }, abstract = {BACKGROUND: Compositional data refer to the data that lie on a simplex, which are common in many scientific domains such as genomics, geology and economics. As the components in a composition must sum to one, traditional tests based on unconstrained data become inappropriate, and new statistical methods are needed to analyze this special type of data.
RESULTS: In this paper, we consider a general problem of testing for the compositional difference between K populations. Motivated by microbiome and metagenomics studies, where the data are often over-dispersed and high-dimensional, we formulate a well-posed hypothesis from a Bayesian point of view and suggest a nonparametric test based on inter-point distance to evaluate statistical significance. Unlike most existing tests for compositional data, our method does not rely on any data transformation, sparsity assumption or regularity conditions on the covariance matrix, but directly analyzes the compositions. Simulated data and two real data sets on the human microbiome are used to illustrate the promise of our method.
CONCLUSIONS: Our simulation studies and real data applications demonstrate that the proposed test is more sensitive to the compositional difference than the mean-based method, especially when the data are over-dispersed or zero-inflated. The proposed test is easy to implement and computationally efficient, facilitating its application to large-scale datasets.}, }
@article {pmid33269394, year = {2020}, author = {Marco, ML and Hill, C and Hutkins, R and Slavin, J and Tancredi, DJ and Merenstein, D and Sanders, ME}, title = {Should There Be a Recommended Daily Intake of Microbes?.}, journal = {The Journal of nutrition}, volume = {150}, number = {12}, pages = {3061-3067}, pmid = {33269394}, issn = {1541-6100}, abstract = {The collective findings from human microbiome research, randomized controlled trials on specific microbes (i.e., probiotics), and associative studies of fermented dairy consumption provide evidence for the beneficial effects of the regular consumption of safe live microbes. To test the hypothesis that the inclusion of safe, live microbes in the diet supports and improves health, we propose assessment of the types and evidentiary quality of the data available on microbe intake, including the assembly and evaluation of evidence available from dietary databases. Such an analysis would help to identify gaps in the evidence needed to test this hypothesis, which can then be used to formulate and direct initiatives focused on prospective and randomized controlled trials on live microbe consumption. Outcomes will establish whether or not the evidence exists, or can be generated, to support the establishment of dietary recommendations for live microbes.}, }
@article {pmid33268781, year = {2020}, author = {Lin, H and Peddada, SD}, title = {Analysis of microbial compositions: a review of normalization and differential abundance analysis.}, journal = {NPJ biofilms and microbiomes}, volume = {6}, number = {1}, pages = {60}, pmid = {33268781}, issn = {2055-5008}, abstract = {Increasingly, researchers are discovering associations between microbiome and a wide range of human diseases such as obesity, inflammatory bowel diseases, HIV, and so on. The first step towards microbiome wide association studies is the characterization of the composition of human microbiome under different conditions. Determination of differentially abundant microbes between two or more environments, known as differential abundance (DA) analysis, is a challenging and an important problem that has received considerable interest during the past decade. It is well documented in the literature that the observed microbiome data (OTU/SV table) are relative abundances with an excess of zeros. Since relative abundances sum to a constant, these data are necessarily compositional. In this article we review some recent methods for DA analysis and describe their strengths and weaknesses.}, }
@article {pmid33264344, year = {2020}, author = {Park, IH and Lee, JS and Park, JH and Kang, SH and Hong, SM and Park, IS and Yoon, JH and Hong, SJ}, title = {Comparison of the human microbiome in adults and children with chronic rhinosinusitis.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0242770}, pmid = {33264344}, issn = {1932-6203}, abstract = {We hypothesized that differences in the microbiome could be a cause of the substantial differences in the symptoms of and treatment options for adult and pediatric patients with chronic rhinosinusitis (CRS). First, we characterized the differences in the nasal microbiomes of pediatric and adult CRS patients. Swabs were obtained from 19 patients with chronic rhinosinusitis (9 children and 10 adults). The bacterial 16S rRNA gene was pyrosequenced to compare the microbiota of the middle meatus. No significant differences were found in species richness and alpha-diversity indices between the two groups. However, in the comparison of diversity between groups using the unweighted pair group method with arithmetic mean (UPGMA) clustering of microbiome taxonomic profiles, we observed a relatively clear separation between the adult and pediatric groups. Actinobacteria had a significantly higher relative abundance in the adult group than in the pediatric group at the phylum level. At the genus level, Corynebacterium showed significantly higher relative abundance in the adult group than in the pediatric group. This is a comparative study between the microbiomes of adult and pediatric CRS patients. We expect this study to be the first step in understanding the pathogenesis of CRS in adults and children using microbiome analysis.}, }
@article {pmid33264062, year = {2020}, author = {Lamousé-Smith, E and Kelly, D and De Cremoux, I}, title = {Designing bugs as drugs: exploiting the gut microbiome.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00381.2019}, pmid = {33264062}, issn = {1522-1547}, abstract = {The extensive investigation of the human microbiome and the accumulating evidence regarding its critical relationship to human health and disease has advanced recognition of its potential as the next frontier of drug development. The rapid development of technologies, directed at understanding the compositional and functional dynamics of the human microbiome, and the ability to mine for novel therapeutic targets and biomarkers is leading innovative efforts to develop microbe-derived drugs that can prevent and treat autoimmune, metabolic, and infectious diseases. Increasingly academics, biotechs, investors, and large pharmaceutical companies are partnering to collectively advance various therapeutic modalities ranging from live bacteria to small molecules. We review the leading platforms in current development focusing on live microbial consortia, engineered microbes, and microbial-derived metabolites. We will also touch on how the field is addressing and challenging the traditional definitions of pharmacokinetics and pharmacodynamics, dosing, toxicity, and safety in order to advance the development of these novel and cutting-edge therapeutics into the clinic.}, }
@article {pmid33263886, year = {2020}, author = {Federici, S and Suez, J and Elinav, E}, title = {Our Microbiome: On the Challenges, Promises, and Hype.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {539-557}, doi = {10.1007/978-3-030-51849-3_20}, pmid = {33263886}, issn = {0080-1844}, abstract = {The microbiome field is increasingly raising interest among scientists, clinicians, biopharmaceutical entities, and the general public. Technological advances from the past two decades have enabled the rapid expansion of our ability to characterize the human microbiome in depth, highlighting its previously underappreciated role in contributing to multifactorial diseases including those with unknown etiology. Consequently, there is growing evidence that the microbiome could be utilized in medical diagnosis and patient stratification. Moreover, multiple gut microbes and their metabolic products may be bioactive, thereby serving as future potential microbiome-targeting or -associated therapeutics. Such therapies could include new generation probiotics, prebiotics, fecal microbiota transplantations, postbiotics, and dietary modulators. However, microbiome research has also been associated with significant limitations, technical and conceptual challenges, and, at times, "over-hyped" expectations that microbiome research will produce quick solutions to chronic and mechanistically complex human disorders. Herein, we summarize these challenges and also discuss some of the realistic promises associated with microbiome research and its applicability into clinical application.}, }
@article {pmid33262241, year = {2020}, author = {, }, title = {Coordinating and Assisting Research at the SARS-CoV-2/Microbiome Nexus.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33262241}, issn = {2379-5077}, abstract = {Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. To meet these needs, the MCC will provide a platform to coordinate clinical and environmental research, assist with practical obstacles, and help communicate the connections between the microbiome and COVID-19. We ask that microbiome researchers join us in these efforts to address the ongoing pandemic.}, }
@article {pmid33258596, year = {2020}, author = {Gray, HK and Arora-Williams, KK and Young, C and Bouwer, E and Davis, MF and Preheim, SP}, title = {Contribution of Time, Taxonomy, and Selective Antimicrobials to Antibiotic and Multidrug Resistance in Wastewater Bacteria.}, journal = {Environmental science & technology}, volume = {54}, number = {24}, pages = {15946-15957}, doi = {10.1021/acs.est.0c03803}, pmid = {33258596}, issn = {1520-5851}, abstract = {The use of nontherapeutic broad-spectrum antimicrobial agents triclosan (TCS) and benzalkonium chloride (BC) can contribute to bacterial resistance to clinically relevant antibiotics. Antimicrobial-resistant bacteria within wastewater may reflect the resistance burden within the human microbiome, as antibiotics and pathogens in wastewater can track with clinically relevant parameters during perturbations to the community. In this study, we monitored culturable and resistant wastewater bacteria and cross-resistance to clinically relevant antibiotics to gauge the impact of each antimicrobial and identify factors influencing cross-resistance profiles. Bacteria resistant to TCS and BC were isolated from wastewater influent over 21 months, and cross-resistance, taxonomy, and monthly changes were characterized under both antimicrobial selection regimes. Cross-resistance profiles from each antimicrobial differed within and between taxa. BC-isolated bacteria had a significantly higher prevalence of resistance to "last-resort antibiotic" colistin, while isolates resistant to TCS exhibited higher rates of multidrug resistance. Prevalence of culturable TCS-resistant bacteria decreased over time following Food and Drug Administration (FDA) TCS bans. Cross-resistance patterns varied according to sampling date, including among the most clinically important antibiotics. Correlations between strain-specific resistance profiles were largely influenced by taxonomy, with some variations associated with sampling date. The results reveal that time, taxonomy, and selection by TCS and BC impact features of cross-resistance patterns among diverse wastewater microorganisms, which could reflect the variety of factors influencing resistance patterns relevant to a community microbiome.}, }
@article {pmid33255779, year = {2020}, author = {Ricci, V and Carcione, D and Messina, S and Colombo, GI and D'Alessandra, Y}, title = {Circulating 16S RNA in Biofluids: Extracellular Vesicles as Mirrors of Human Microbiome?.}, journal = {International journal of molecular sciences}, volume = {21}, number = {23}, pages = {}, pmid = {33255779}, issn = {1422-0067}, support = {5‰ 2015//Ministero della Salute/ ; }, abstract = {The human body is inhabited by around 1013 microbes composing a multicomplex system, termed microbiota, which is strongly involved in the regulation and maintenance of homeostasis. Perturbations in microbiota composition can lead to dysbiosis, which has been associated with several human pathologies. The gold-standard method to explore microbial composition is next-generation sequencing, which involves the analysis of 16S rRNA, an indicator of the presence of specific microorganisms and the principal tool used in bacterial taxonomic classification. Indeed, the development of 16S RNA sequencing allows us to explore microbial composition in several environments and human body districts and fluids, since it has been detected in "germ-free" environments such as blood, plasma, and urine of diseased and healthy subjects. Recently, prokaryotes showed to generate extracellular vesicles, which are known to be responsible for shuttling different intracellular components such as proteins and nucleic acids (including 16S molecules) by protecting their cargo from degradation. These vesicles can be found in several human biofluids and can be exploited as tools for bacterial detection and identification. In this review, we examine the complex link between circulating 16S RNA molecules and bacteria-derived vesicles.}, }
@article {pmid33254225, year = {2020}, author = {Pacifici, R}, title = {Role of Gut Microbiota in the Skeletal Response to PTH.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1210/clinem/dgaa895}, pmid = {33254225}, issn = {1945-7197}, abstract = {Exposed surfaces of mammals are colonized with 100 trillion indigenous bacteria, fungi and viruses, creating a diverse ecosystem known as the human microbiome. The gut microbiome is the richest microbiome and is now known to regulate postnatal skeletal development and the activity of the major endocrine regulators of bone. Parathyroid hormone (PTH) is one of the bone-regulating hormone that requires elements of the gut microbiome to exert both its bone catabolic and its bone anabolic effects. How the gut microbiome regulates the skeletal response to PTH is object of intense research. Involved mechanism include absorption and diffusion of bacterial metabolites such as short-chain fatty acids, and trafficking of immune cells from the gut to the bone marrow. This review will focus on how the gut microbiome communicates and regulates bone marrow cells in order to modulate the skeletal effects of PTH.}, }
@article {pmid33253350, year = {2020}, author = {Hassan, R and Allali, I and Agamah, FE and Elsheikh, SSM and Thomford, NE and Dandara, C and Chimusa, ER}, title = {Drug response in association with pharmacogenomics and pharmacomicrobiomics: towards a better personalized medicine.}, journal = {Briefings in bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1093/bib/bbaa292}, pmid = {33253350}, issn = {1477-4054}, abstract = {Researchers have long been presented with the challenge imposed by the role of genetic heterogeneity in drug response. For many years, Pharmacogenomics and pharmacomicrobiomics has been investigating the influence of an individual's genetic background to drug response and disposition. More recently, the human gut microbiome has proven to play a crucial role in the way patients respond to different therapeutic drugs and it has been shown that by understanding the composition of the human microbiome, we can improve the drug efficacy and effectively identify drug targets. However, our knowledge on the effect of host genetics on specific gut microbes related to variation in drug metabolizing enzymes, the drug remains limited and therefore limits the application of joint host-microbiome genome-wide association studies. In this paper, we provide a historical overview of the complex interactions between the host, human microbiome and drugs. While discussing applications, challenges and opportunities of these studies, we draw attention to the critical need for inclusion of diverse populations and the development of an innovative and combined pharmacogenomics and pharmacomicrobiomics approach, that may provide an important basis in personalized medicine.}, }
@article {pmid33245146, year = {2020}, author = {Hernandez, CJ}, title = {Musculoskeletal microbiology: The utility of the microbiome in orthopedics.}, journal = {Journal of orthopaedic research : official publication of the Orthopaedic Research Society}, volume = {}, number = {}, pages = {}, doi = {10.1002/jor.24927}, pmid = {33245146}, issn = {1554-527X}, support = {R21AR0671534/AR/NIAMS NIH HHS/United States ; R21AR068061/AR/NIAMS NIH HHS/United States ; R21AR073454/AR/NIAMS NIH HHS/United States ; R56AG067997/AG/NIA NIH HHS/United States ; }, abstract = {The past 15 years have witnessed a renaissance in the study of the microbes that colonize the human body. The vast majority of the human microbiome resides within the gut. Alterations to the gut microbiome have been associated with the pathogenesis and progression of wide-ranging diseases throughout the body-including atherosclerosis, depression, and obesity. Our understanding of the effects of the gut microbiome on the musculoskeletal system remains in its infancy, but preclinical work has demonstrated an effect of the gut microbiome on the success of orthopedic surgical procedures, osteoporosis, osteoarthritis, and muscle mass. In this perspective I review preclinical findings demonstrating that an impaired presurgical gut microbiome can increase the likelihood of developing periprosthetic joint infection and how alterations in the gut microbiome can reduce bone strength by impairing bone tissue material properties. In addition to discussing these examples, I review the hypothesis that many chronic non-communicable diseases have become more prevalent in modern industrialized societies as a result of changes in the composition of the gut microbiome resulting from changes in environment/lifestyle (diet, sanitation, antibiotic use). The most burdensome musculoskeletal disorders are chronic and non-communicable and may therefore be related to generational shifts in the composition of the gut microbiome, a possibility I illustrate by reviewing changes in the prevalence of osteoarthritis over the last century. Microbiome-based therapeutics are potentially innocuous, inexpensive, and have the potential to be effective with only occasional use, making them attractive for addressing the needs of chronic and/or slowly progressing musculoskeletal disorders.}, }
@article {pmid33245088, year = {2020}, author = {Prihoda, D and Maritz, JM and Klempir, O and Dzamba, D and Woelk, CH and Hazuda, DJ and Bitton, DA and Hannigan, GD}, title = {The application potential of machine learning and genomics for understanding natural product diversity, chemistry, and therapeutic translatability.}, journal = {Natural product reports}, volume = {}, number = {}, pages = {}, doi = {10.1039/d0np00055h}, pmid = {33245088}, issn = {1460-4752}, abstract = {Covering: up to the end of 2020.The machine learning field can be defined as the study and application of algorithms that perform classification and prediction tasks through pattern recognition instead of explicitly defined rules. Among other areas, machine learning has excelled in natural language processing. As such methods have excelled at understanding written languages (e.g. English), they are also being applied to biological problems to better understand the "genomic language". In this review we focus on recent advances in applying machine learning to natural products and genomics, and how those advances are improving our understanding of natural product biology, chemistry, and drug discovery. We discuss machine learning applications in genome mining (identifying biosynthetic signatures in genomic data), predictions of what structures will be created from those genomic signatures, and the types of activity we might expect from those molecules. We further explore the application of these approaches to data derived from complex microbiomes, with a focus on the human microbiome. We also review challenges in leveraging machine learning approaches in the field, and how the availability of other "omics" data layers provides value. Finally, we provide insights into the challenges associated with interpreting machine learning models and the underlying biology and promises of applying machine learning to natural product drug discovery. We believe that the application of machine learning methods to natural product research is poised to accelerate the identification of new molecular entities that may be used to treat a variety of disease indications.}, }
@article {pmid33236419, year = {2020}, author = {Montecchiani, V and Fanos, V}, title = {Human microbiome and allergy.}, journal = {Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology}, volume = {31 Suppl 26}, number = {}, pages = {5-7}, doi = {10.1111/pai.13360}, pmid = {33236419}, issn = {1399-3038}, abstract = {Human microbiome contributes to critical functions that impact health and disease. It influences the development of the immune system, and the pathogenesis of immunological disorders included allergy. While it is easy to understand how airway microbiome, influencing local inflammation and immune activity, could contribute to shaping asthma phenotype, it is not so obvious to understand the influence by the gut microbiome, but there is growing evidence about it. The increase of allergic disorders in western countries led to investigate the role environment is playing and how it may change our microbiome and immune system, with the hope of finding new preventive approaches for allergy.}, }
@article {pmid33236315, year = {2020}, author = {Hasan, A and Hasan, LK and Schnabl, B and Greytak, M and Yadlapati, R}, title = {Microbiome of the Aerodigestive Tract in Health and Esophageal Disease.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06720-6}, pmid = {33236315}, issn = {1573-2568}, support = {120515/DK/NIDDK NIH HHS/United States ; }, abstract = {The diverse human gut microbiome is comprised of approximately 40 trillion microorganisms representing up to 1000 different bacterial species. The human microbiome plays a critical role in gut epithelial health and disease susceptibility. While the interaction between gut microbiome and gastrointestinal pathology is increasingly understood, less is known about the interaction between the microbiome and the aerodigestive tract. This review of the microbiome of the aerodigestive tract in health, and alterations in microbiome across esophageal pathologies highlights important findings and areas for future research. First, microbiome profiles are distinct along the aerodigestive tract, spanning the oral cavity to the stomach. In patients with reflux-related disease such as gastro-esophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma, investigators have observed an overall increase in gram negative bacteria in the esophageal microbiome compared to healthy individuals. However, whether differences in microbiome promote disease development, or if these shifts are a consequence of disease remains unknown. Interestingly, use of proton pump inhibitor therapy is also associated with shifts in the microbiome, with distinct shifts and patterns along the aerodigestive tract. The relationship between the human gut microbiome and esophageal pathology is a ripe area for investigation, and further understanding of these pathways may promote development of novel targets in prevention and therapy for esophageal diseases.}, }
@article {pmid33232449, year = {2020}, author = {Lyles, JK and Oli, M}, title = {The student-centered classroom: the new gut feeling.}, journal = {FEMS microbiology letters}, volume = {367}, number = {22}, pages = {}, pmid = {33232449}, issn = {1574-6968}, abstract = {A student-centered, interactive course-based undergraduate research experience (CURE) was implemented in a microbiology course in order to provide an authentic research experience and to stimulate student interest and improve understanding of fermentation, probiotics, the human microbiome and related topics. Students were immersed in the scientific process as they used fundamental techniques to investigate the probiotic composition of a fermented milk beverage, kefir-an unknown question with no predetermined outcomes. In order to assess the benefits and effect of this learning experience on the students, pre- and post-study surveys were administered using Qualtrics. Post-study, 93% of participants agreed that fermented foods are beneficial to human health (compared to 52% pre-study), and notably, 100% of participants indicated that they plan to apply this material in both their personal and professional lives and would suggest consuming probiotics or fermented products to alleviate gastrointestinal issues. As evidenced by demographic data, this CURE is suitable for implementation at both large and small institutions with diverse student populations. Collectively, these data indicate that this collaborative, discovery-based learning experience is a powerful educational tool, encouraging students to make real-life connections between microbiology, medicine and their own health.}, }
@article {pmid33227982, year = {2020}, author = {Vernocchi, P and Gili, T and Conte, F and Del Chierico, F and Conta, G and Miccheli, A and Botticelli, A and Paci, P and Caldarelli, G and Nuti, M and Marchetti, P and Putignani, L}, title = {Network Analysis of Gut Microbiome and Metabolome to Discover Microbiota-Linked Biomarkers in Patients Affected by Non-Small Cell Lung Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33227982}, issn = {1422-0067}, abstract = {Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as Akkermansia muciniphila, Rikenellaceae, Bacteroides, Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.}, }
@article {pmid33227623, year = {2020}, author = {Araujo, DV and Watson, GA and Oliva, M and Heirali, A and Coburn, B and Spreafico, A and Siu, LL}, title = {Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics.}, journal = {Cancer treatment reviews}, volume = {92}, number = {}, pages = {102125}, doi = {10.1016/j.ctrv.2020.102125}, pmid = {33227623}, issn = {1532-1967}, abstract = {The human microbiome comprising microorganisms, their collective genomes and metabolic products has gained tremendous research interest in oncology, as multiple cohorts and case studies have demonstrated discernible interpatient differences in this ecosystem based on clinical variables including disease type, stage, diet, antibiotic usage, cancer treatments, therapeutic responses and toxicities. The modulation of the gut microbiome is the subject of many ongoing preclinical and clinical investigations, through the manipulation of diet, as well as the use of prebiotics, probiotics, specific antibiotics, fecal microbial transplantation, microbial consortia and stool substitutes. Standardization and quality control are needed to maximize the information being generated in this growing field, ranging from technical assays to measure microbiome composition, to methodological aspects in the analysis and reporting of results. Proof-of-mechanism and proof-of-concept clinical trials with appropriate controls are needed to confirm or refute the feasibility, safety and ultimately the clinical utility of human microbiome modulation in cancer patients.}, }
@article {pmid33227575, year = {2020}, author = {McKenzie, ND and Hong, H and Ahmad, S and Holloway, RW}, title = {The gut microbiome and cancer immunotherapeutics: A review of emerging data and implications for future gynecologic cancer research.}, journal = {Critical reviews in oncology/hematology}, volume = {157}, number = {}, pages = {103165}, doi = {10.1016/j.critrevonc.2020.103165}, pmid = {33227575}, issn = {1879-0461}, abstract = {Investigation of the gynecologic tract microbial milieu has revealed potential new biomarkers. Simultaneously, immunotherapeutics are establishing their place in the treatment of gynecologic malignancies. The interplay between the microbiome, the tumor micro-environment and response to therapy is a burgeoning area of interest. There is evidence to support that microbes, through their genetic make-up, gene products, and metabolites affect human physiology, metabolism, immunity, disease susceptibility, response to pharmacotherapy, and the severity of disease-related side effects. Specifically, the richness and diversity of the gut microbiome appears to affect carcinogenesis, response to immunotherapy, and modulate severity of immune-mediated adverse effects. These effects have best been described in other tumor types and these have shown compelling results. This review summarizes the current understanding and scope of the interplay between the human microbiome, host factors, cancer, and response to treatments. These findings support further exploring whether these associations exist for gynecologic malignancies.}, }
@article {pmid33226693, year = {2021}, author = {Teles, F and Wang, Y and Hajishengallis, G and Hasturk, H and Marchesan, JT}, title = {Impact of systemic factors in shaping the periodontal microbiome.}, journal = {Periodontology 2000}, volume = {85}, number = {1}, pages = {126-160}, doi = {10.1111/prd.12356}, pmid = {33226693}, issn = {1600-0757}, abstract = {Since 2010, next-generation sequencing platforms have laid the foundation to an exciting phase of discovery in oral microbiology as it relates to oral and systemic health and disease. Next-generation sequencing has allowed large-scale oral microbial surveys, based on informative marker genes, such as 16S ribosomal RNA, community gene inventories (metagenomics), and functional analyses (metatranscriptomics), to be undertaken. More specifically, the availability of next-generation sequencing has also paved the way for studying, in greater depth and breadth, the effect of systemic factors on the periodontal microbiome. It was natural to investigate systemic diseases, such as diabetes, in such studies, along with systemic conditions or states, , pregnancy, menopause, stress, rheumatoid arthritis, and systemic lupus erythematosus. In addition, in recent years, the relevance of systemic "variables" (ie, factors that are not necessarily diseases or conditions, but may modulate the periodontal microbiome) has been explored in detail. These include ethnicity and genetics. In the present manuscript, we describe and elaborate on the new and confirmatory findings unveiled by next-generation sequencing as it pertains to systemic factors that may shape the periodontal microbiome. We also explore the systemic and mechanistic basis for such modulation and highlight the importance of those relationships in the management and treatment of patients.}, }
@article {pmid33226688, year = {2021}, author = {Duran-Pinedo, AE}, title = {Metatranscriptomic analyses of the oral microbiome.}, journal = {Periodontology 2000}, volume = {85}, number = {1}, pages = {28-45}, doi = {10.1111/prd.12350}, pmid = {33226688}, issn = {1600-0757}, support = {/DE/NIDCR NIH HHS/United States ; 2R01DE021553/NH/NIH HHS/United States ; /DE/NIDCR NIH HHS/United States ; 2R01DE021553/NH/NIH HHS/United States ; }, abstract = {Although the composition of the oral human microbiome is now well studied, regulation of genes within oral microbial communities remains mostly uncharacterized. Current concepts of periodontal disease and caries highlight the importance of oral biofilms and their role as etiological agents of those diseases. Currently, there is increased interest in exploring and characterizing changes in the composition and gene-expression profiles of oral microbial communities. These efforts aim to identify changes in functional activities that could explain the transition from health to disease and the reason for the chronicity of those infections. It is now clear that the functions of distinct species within the subgingival microbiota are intimately intertwined with the rest of the microbial community. This point highlights the relevance of examining the expression profile of specific species within the subgingival microbiota in the case of periodontal disease or caries lesions, in the context of the other members of the biofilm in vivo. Metatranscriptomic analysis of the oral community is the starting point for identifying environmental signals that modulate the shift in metabolism of the community from commensal to dysbiotic. These studies give a snapshot of the expression patterns of microbial communities and also allow us to determine triggers to diseases. For example, in the case of caries, studies have unveiled a potential new pathway of sugar metabolism, namely the use of sorbitol as an additional source of carbon by Streptococcus mutans; and in the case of periodontal disease, high levels of extracellular potassium could be a signal of disease. Longitudinal studies are needed to identify the real markers of the initial stages of caries and periodontal disease. More information on the gene-expression profiles of the host, along with the patterns from the microbiome, will lead to a clearer understanding of the modulation of health and disease. This review presents a summary of these initial studies, which have opened the door to a new understanding of the dynamics of the oral community during the dysbiotic process in the oral cavity.}, }
@article {pmid33221926, year = {2020}, author = {Kasmanas, JC and Bartholomäus, A and Corrêa, FB and Tal, T and Jehmlich, N and Herberth, G and von Bergen, M and Stadler, PF and Carvalho, ACPLF and Nunes da Rocha, U}, title = {HumanMetagenomeDB: a public repository of curated and standardized metadata for human metagenomes.}, journal = {Nucleic acids research}, volume = {}, number = {}, pages = {}, doi = {10.1093/nar/gkaa1031}, pmid = {33221926}, issn = {1362-4962}, abstract = {Metagenomics became a standard strategy to comprehend the functional potential of microbial communities, including the human microbiome. Currently, the number of metagenomes in public repositories is increasing exponentially. The Sequence Read Archive (SRA) and the MG-RAST are the two main repositories for metagenomic data. These databases allow scientists to reanalyze samples and explore new hypotheses. However, mining samples from them can be a limiting factor, since the metadata available in these repositories is often misannotated, misleading, and decentralized, creating an overly complex environment for sample reanalysis. The main goal of the HumanMetagenomeDB is to simplify the identification and use of public human metagenomes of interest. HumanMetagenomeDB version 1.0 contains metadata of 69 822 metagenomes. We standardized 203 attributes, based on standardized ontologies, describing host characteristics (e.g. sex, age and body mass index), diagnosis information (e.g. cancer, Crohn's disease and Parkinson), location (e.g. country, longitude and latitude), sampling site (e.g. gut, lung and skin) and sequencing attributes (e.g. sequencing platform, average length and sequence quality). Further, HumanMetagenomeDB version 1.0 metagenomes encompass 58 countries, 9 main sample sites (i.e. body parts), 58 diagnoses and multiple ages, ranging from just born to 91 years old. The HumanMetagenomeDB is publicly available at https://webapp.ufz.de/hmgdb/.}, }
@article {pmid33217332, year = {2020}, author = {Münch, PC and Franzosa, EA and Stecher, B and McHardy, AC and Huttenhower, C}, title = {Identification of Natural CRISPR Systems and Targets in the Human Microbiome.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2020.10.010}, pmid = {33217332}, issn = {1934-6069}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; }, abstract = {Many bacteria resist invasive DNA by incorporating sequences into CRISPR loci, which enable sequence-specific degradation. CRISPR systems have been well studied from isolate genomes, but culture-independent metagenomics provide a new window into their diversity. We profiled CRISPR loci and cas genes in the body-wide human microbiome using 2,355 metagenomes, yielding functional and taxonomic profiles for 2.9 million spacers by aligning the spacer content to each sample's metagenome and corresponding gene families. Spacer and repeat profiles agree qualitatively with those from isolate genomes but expand their diversity by approximately 13-fold, with the highest spacer load present in the oral microbiome. The taxonomy of spacer sequences parallels that of their source community, with functional targets enriched for viral elements. When coupled with cas gene systems, CRISPR-Cas subtypes are highly site and taxon specific. Our analysis provides a comprehensive collection of natural CRISPR-cas loci and targets in the human microbiome.}, }
@article {pmid33211665, year = {2020}, author = {Kim, SA and Kang, N and Park, T}, title = {Hierarchical structured Component Analysis for Microbiome Data Using Taxonomy Assignments.}, journal = {IEEE/ACM transactions on computational biology and bioinformatics}, volume = {PP}, number = {}, pages = {}, doi = {10.1109/TCBB.2020.3039326}, pmid = {33211665}, issn = {1557-9964}, abstract = {The advent of high-throughput sequencing technology has enabled us to study the associations between human microbiome and diseases. The DNA sequences of microbiome samples are clustered as operational taxonomic units (OTUs) according to their similarity. The OTU table is used to measure correlations between OTUs and disease status and find key microbes for prediction of the disease status. Various statistical methods have been proposed for such microbiome data analysis. However, none of these methods reflects the hierarchy of taxonomy information. Here, we propose a hierarchical structural component model for microbiome data (HisCoM-microb) using taxonomy information as well as OTU table data. The proposed HisCoM-microb consists of two layers: one for OTUs and the other for taxa at the higher taxonomy level. Then we calculate simultaneously coefficient estimates of OTUs and taxa of the two layers inserted in the hierarchical model. Through this analysis, we can infer the association between taxa or OTUs and disease status, considering the impact of taxonomic structure on disease status. Both simulation study and real microbiome data analysis show that HisCoM-microb can successfully reveal the relations between each taxon and disease status and identify the key OTUs of the disease at the same time.}, }
@article {pmid33208514, year = {2020}, author = {Hugerth, LW and Pereira, M and Zha, Y and Seifert, M and Kaldhusdal, V and Boulund, F and Krog, MC and Bashir, Z and Hamsten, M and Fransson, E and Svarre-Nielsen, H and Schuppe-Koistinen, I and Engstrand, L}, title = {Assessment of In Vitro and In Silico Protocols for Sequence-Based Characterization of the Human Vaginal Microbiome.}, journal = {mSphere}, volume = {5}, number = {6}, pages = {}, pmid = {33208514}, issn = {2379-5042}, abstract = {The vaginal microbiome has been connected to a wide range of health outcomes. This has led to a thriving research environment but also to the use of conflicting methodologies to study its microbial composition. Here, we systematically assessed best practices for the sequencing-based characterization of the human vaginal microbiome. As far as 16S rRNA gene sequencing is concerned, the V1-V3 region performed best in silico, but limitations of current sequencing technologies meant that the V3-V4 region performed equally well. Both approaches presented very good agreement with qPCR quantification of key taxa, provided that an appropriate bioinformatic pipeline was used. Shotgun metagenomic sequencing presents an interesting alternative to 16S rRNA gene amplification and sequencing but requires deeper sequencing and more bioinformatic expertise and infrastructure. We assessed different tools for the removal of host reads and the taxonomic annotation of metagenomic reads, including a new, easy-to-build and -use reference database of vaginal taxa. This curated database performed as well as the best-performing previously published strategies. Despite the many advantages of shotgun sequencing, none of the shotgun approaches assessed here agreed with the qPCR data as well as the 16S rRNA gene sequencing.IMPORTANCE The vaginal microbiome has been connected to various aspects of host health, including susceptibility to sexually transmitted infections as well as gynecological cancers and pregnancy outcomes. This has led to a thriving research environment but also to conflicting available methodologies, including many studies that do not report their molecular biological and bioinformatic methods in sufficient detail to be considered reproducible. This can lead to conflicting messages and delay progress from descriptive to intervention studies. By systematically assessing best practices for the characterization of the human vaginal microbiome, this study will enable past studies to be assessed more critically and assist future studies in the selection of appropriate methods for their specific research questions.}, }
@article {pmid33207573, year = {2020}, author = {Tsai, JC and Casteneda, G and Lee, A and Dereschuk, K and Li, WT and Chakladar, J and Lombardi, AF and Ongkeko, WM and Chang, EY}, title = {Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.}, journal = {International journal of molecular sciences}, volume = {21}, number = {22}, pages = {}, pmid = {33207573}, issn = {1422-0067}, support = {I01RX002604//U.S. Department of Veterans Affairs/ ; R21AR073496/NH/NIH HHS/United States ; I01 CX001388/CX/CSRD VA/United States ; R01AR075825/NH/NIH HHS/United States ; I01CX001388//U.S. Department of Veterans Affairs/ ; I01 RX002604/RX/RRD VA/United States ; R21 AR073496/AR/NIAMS NIH HHS/United States ; R01 AR075825/AR/NIAMS NIH HHS/United States ; }, abstract = {Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.}, }
@article {pmid33205871, year = {2020}, author = {Perttu, L and Jonna, J and Anna, H and Eero, M and Markku, H and Jari, P and Jari, K and Veli-Jukka, A and Jyrki, T and Reetta, S and Perttu, A}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required? Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {11-12}, pages = {1754-1755}, doi = {10.1111/apt.16122}, pmid = {33205871}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid33205072, year = {2020}, author = {Al, KF and Denstedt, JD and Daisley, BA and Bjazevic, J and Welk, BK and Pautler, SE and Gloor, GB and Reid, G and Razvi, H and Burton, JP}, title = {Ureteral Stent Microbiota Is Associated with Patient Comorbidities but Not Antibiotic Exposure.}, journal = {Cell reports. Medicine}, volume = {1}, number = {6}, pages = {100094}, pmid = {33205072}, issn = {2666-3791}, abstract = {Ureteral stents are commonly used to prevent urinary obstruction but can become colonized by bacteria and encrusted, leading to clinical complications. Despite recent discovery and characterization of the healthy urinary microbiota, stent-associated bacteria and their impact on encrustation are largely underexplored. We profile the microbiota of patients with typical short-term stents, as well as over 30 atypical cases (all with paired mid-stream urine) from 241 patients. Indwelling time, age, and various patient comorbidities correlate with alterations to the stent microbiota composition, whereas antibiotic exposure, urinary tract infection (UTI), and stent placement method do not. The stent microbiota most likely originates from adhesion of resident urinary microbes but subsequently diverges to a distinct, reproducible population, thereby negating the urine as a biomarker for stent encrustation or microbiota. Urological practice should reconsider standalone prophylactic antibiotics in favor of tailored therapies based on patient comorbidities in efforts to minimize bacterial burden, encrustation, and complications of ureteral stents.}, }
@article {pmid33203758, year = {2020}, author = {Patin, NV and Peña-Gonzalez, A and Hatt, JK and Moe, C and Kirby, A and Konstantinidis, KT}, title = {The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study.}, journal = {mBio}, volume = {11}, number = {6}, pages = {}, pmid = {33203758}, issn = {2150-7511}, support = {K01 AI103544/AI/NIAID NIH HHS/United States ; }, abstract = {Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes.IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.}, }
@article {pmid33203357, year = {2020}, author = {Ma, Y and Zhao, J and Ma, Y}, title = {MHSNMF: multi-view hessian regularization based symmetric nonnegative matrix factorization for microbiome data analysis.}, journal = {BMC bioinformatics}, volume = {21}, number = {Suppl 6}, pages = {234}, pmid = {33203357}, issn = {1471-2105}, abstract = {BACKGROUND: With the rapid development of high-throughput technique, multiple heterogeneous omics data have been accumulated vastly (e.g., genomics, proteomics and metabolomics data). Integrating information from multiple sources or views is challenging to obtain a profound insight into the complicated relations among micro-organisms, nutrients and host environment. In this paper we propose a multi-view Hessian regularization based symmetric nonnegative matrix factorization algorithm (MHSNMF) for clustering heterogeneous microbiome data. Compared with many existing approaches, the advantages of MHSNMF lie in: (1) MHSNMF combines multiple Hessian regularization to leverage the high-order information from the same cohort of instances with multiple representations; (2) MHSNMF utilities the advantages of SNMF and naturally handles the complex relationship among microbiome samples; (3) uses the consensus matrix obtained by MHSNMF, we also design a novel approach to predict the classification of new microbiome samples.
RESULTS: We conduct extensive experiments on two real-word datasets (Three-source dataset and Human Microbiome Plan dataset), the experimental results show that the proposed MHSNMF algorithm outperforms other baseline and state-of-the-art methods. Compared with other methods, MHSNMF achieves the best performance (accuracy: 95.28%, normalized mutual information: 91.79%) on microbiome data. It suggests the potential application of MHSNMF in microbiome data analysis.
CONCLUSIONS: Results show that the proposed MHSNMF algorithm can effectively combine the phylogenetic, transporter, and metabolic profiles into a unified paradigm to analyze the relationships among different microbiome samples. Furthermore, the proposed prediction method based on MHSNMF has been shown to be effective in judging the types of new microbiome samples.}, }
@article {pmid33198235, year = {2020}, author = {van Soest, APM and Hermes, GDA and Berendsen, AAM and van de Rest, O and Zoetendal, EG and Fuentes, S and Santoro, A and Franceschi, C and de Groot, LCPGM and de Vos, WM}, title = {Associations between Pro- and Anti-Inflammatory Gastro-Intestinal Microbiota, Diet, and Cognitive Functioning in Dutch Healthy Older Adults: The NU-AGE Study.}, journal = {Nutrients}, volume = {12}, number = {11}, pages = {}, pmid = {33198235}, issn = {2072-6643}, support = {266486//Seventh Framework Programme/ ; 818368//Horizon 2020 Framework Programme/ ; n/a//Spinoza award of The Netherlands Organization for Scientific Research 2008/ ; }, abstract = {Dietary modulation of the gastro-intestinal microbiota is a potential target in improving healthy ageing and age-related functional outcomes, including cognitive decline. We explored the association between diet, gastro-intestinal microbiota and cognition in Dutch healthy older adults of the 'New dietary strategies addressing the specific needs of the elderly population for healthy aging in Europe' (NU-AGE) study. The microbiota profile of 452 fecal samples from 226 subjects was determined using a 16S ribosomal RNA gene-targeted microarray. Dietary intake was assessed by 7-day food records. Cognitive functioning was measured with an extensive cognitive test battery. We observed a dietary and microbial pro- to anti-inflammatory gradient associated with diets richer in animal- or plant-based foods. Fresh fruits, nuts, seeds and peanuts, red and processed meat and grain products were most strongly associated to microbiota composition. Plant-rich diets containing fresh fruits, nuts, seeds and peanuts were positively correlated with alpha-diversity, various taxa from the Bacteroidetes phylum and anti-inflammatory species, including those related to Faecalibacterium prausnitzii and Eubacterium rectale and E. biforme. Animal product-rich diets associated with pro-inflammatory species, including those related to Ruminococcus gnavus and Collinsella spp.. Cognition was neither associated with microbiota composition nor alpha-diversity. In conclusion, diets richer in animal- and plant-based foods were related to a pro- and anti-inflammatory microbial profile, while cognition was associated with neither.}, }
@article {pmid33198059, year = {2020}, author = {Krishnamoorthy, M and Lenehan, JG and Burton, JP and Maleki Vareki, S}, title = {Immunomodulation in Pancreatic Cancer.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33198059}, issn = {2072-6694}, support = {N/A//London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants./ ; }, abstract = {Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.}, }
@article {pmid33197547, year = {2020}, author = {Collins, SL and Walsh, JP and Renaud, JB and McMillan, A and Rulisa, S and Miller, JD and Reid, G and Sumarah, MW}, title = {Improved methods for biomarker analysis of the big five mycotoxins enables reliable exposure characterization in a population of childbearing age women in Rwanda.}, journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association}, volume = {}, number = {}, pages = {111854}, doi = {10.1016/j.fct.2020.111854}, pmid = {33197547}, issn = {1873-6351}, abstract = {Of the five agriculturally important mycotoxins, AFB1, FB1, DON, ZEA and OTA, a well-characterized biomarker of exposure in blood is only available for aflatoxin. Working with a population of 139 women of childbearing age in Rwanda, we undertook a comprehensive assessment of their dietary mycotoxin exposure. Using high-resolution LC-MS/MS with stable isotope dilution analysis, the albumin-aflatoxin adduct was quantitated in plasma. Similarly, AFM1, AFB1, AFG1, FB1 and B2, OTA, zearalenone, α-zearalenol, deoxynivalenol, deoxynivalenol-15-glucuronide and deoxynivalenol-3-glucuronide were quantitated in urine. AFB1-Lys was detected in plasma from 81% of the women, indicative of exposures 1-2 orders of magnitude above current guidance. Zearalenone and/or α-zearalenol were detected in the urine of 61% of the women, the majority of whom had estimated exposures 2-5 times the PMTDI, with one third more than an order of magnitude above. Urinary deoxynivalenol or the two glucuronide conjugates were found in 77% of the participants. Of these, 60% were below the PMTDI, 28% were twice and 12% were >10x the PMTDI. Fumonisin B1 (30%) and ochratoxin A (71%) were also detected in urine. Exposures observed in these Rwandan women raise serious food safety concerns and highlight the need for authorities to help manage multiple mycotoxins in their diet.}, }
@article {pmid33193429, year = {2020}, author = {Irfan, M and Delgado, RZR and Frias-Lopez, J}, title = {The Oral Microbiome and Cancer.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {591088}, pmid = {33193429}, issn = {1664-3224}, abstract = {There is mounting evidence that members of the human microbiome are highly associated with a wide variety of cancer types. Among oral cancers, oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied, and it is the most common malignancy of the head and neck worldwide. However, there is a void regarding the role that the oral microbiome may play in OSCC. Previous studies have not consistently found a characteristic oral microbiome composition associated with OSCC. Although a direct causality has not been proven, individual members of the oral microbiome are capable of promoting various tumorigenic functions related to cancer development. Two prominent oral pathogens, Porphyromonas gingivalis, and Fusobacterium nucleatum can promote tumor progression in mice. P. gingivalis infection has been associated with oro-digestive cancer, increased oral cancer invasion, and proliferation of oral cancer stem cells. The microbiome can influence the evolution of the disease by directly interacting with the human body and significantly altering the response and toxicity to various forms of cancer therapy. Recent studies have shown an association of certain phylogenetic groups with the immunotherapy treatment outcomes of certain tumors. On the other side of the coin, recently it has been a resurgence in interest on the potential use of bacteria to cure cancer. These kinds of treatments were used in the late nineteenth and early twentieth centuries as the first line of defense against cancer in some hospitals but later displaced by other types of treatments such as radiotherapy. Currently, organisms such as Salmonella typhimurium and Clostridium spp. have been used for targeted strategies as potential vectors to treat cancer. In this review, we briefly summarize our current knowledge of the role of the oral microbiome, focusing on its bacterial fraction, in cancer in general and in OSCC more precisely, and a brief description of the potential use of bacteria to target tumors.}, }
@article {pmid33193202, year = {2020}, author = {Petrie, KL}, title = {There're CRISPRs in My Yogurt: A Discovery-Based CURE at the Intersection of Industrial Food Production and the Human Microbiome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {578737}, pmid = {33193202}, issn = {1664-302X}, abstract = {Support for undergraduate laboratory education based on a CURE (Course-based Undergraduate Research Experience) model is more widespread than ever. By giving students the opportunity to conduct genuine research in laboratory courses they are required to take, CUREs can expose more students to scientific practice and have the potential to make science more inclusive, especially when research topics have direct impact on students' lives. Here, I present a new microbiology CURE module where students explore the real-world intersection between industrial food production and the human microbiome. In this module, students sequence CRISPR arrays in the genomes of lactic acid bacteria they isolate from yogurt. Natural CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) act as the bacterial immune system. When a bacterial cell survives viral infection, it can incorporate a bit of that virus's DNA into its own genome, and produce small RNA guides that surveil the cell, ready to deploy virus-destroying enzymes if matching DNA from a fresh viral infection is detected. This viral immunity is of particular interest in the fermentation industry, since viral infection can destroy stocks of starter cultures and batches of product. Commercial producers of lactic acid bacteria for yogurt production often endeavor to produce strains with large CRISPR arrays and robust immunities. With this context, students are given the task of cataloging the viral immunities found in both commercial and traditionally produced yogurt, and exploring their potential impact on human health. Wet-lab practices (strain isolation, PCR, and Sanger sequencing) are combined with bioinformatic and literature sleuthing to identify the viruses to which bacteria are immune and explore whether consumption of these strains could impact human health via interactions with the human microbiome. Here, a detailed implementation of the module is presented with guides for educators and students.}, }
@article {pmid33188000, year = {2020}, author = {Coe, GL and Pinkham, NV and Celis, AI and Johnson, C and DuBois, JL and Walk, ST}, title = {Dynamic gut microbiome changes to low-iron challenge.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/AEM.02307-20}, pmid = {33188000}, issn = {1098-5336}, abstract = {Iron is an essential micronutrient for life. In mammals, dietary iron is primarily absorbed in the small intestine. Currently, the impacts of dietary iron on the taxonomic structure and function of the gut microbiome and reciprocal effects on the animal host are not well understood. Here, we establish a mouse model of low-iron challenge in which intestinal biomarkers and reduced fecal iron reveal iron stress while serum iron and mouse behavioral markers indicate maintenance of iron homeostasis. We show that the diversity of the gut microbiome in conventional C57BL/6 mice changes dramatically during two-weeks on a low-iron diet. We also show the effects of a low-iron diet on microbiome diversity are long-lasting and not easily recovered when iron is returned to the diet. Finally, after optimizing taxon association methods, we show that some bacteria are unable to fully recover after the low-iron challenge and appear to be extirpated from the gut entirely. In particular, OTUs from the Prevotellaceae and Porphyromonadaceae families and Bacteroidales order are highly sensitive to low-iron conditions, while other seemingly insensitive OTUs recover. These results provide new insights into the iron requirements of gut microbiome members and add to the growing understanding of mammalian iron cycling.IMPORTANCE All cells need iron. Both too much iron and too little lead to diseases and unwanted outcomes. Although the impact of dietary iron on human cells and tissues has been well studied, there is currently a lack of understanding about how different levels of iron influence the abundant and diverse members of the human microbiome. This study develops a well-characterized mouse model for studying low-iron levels and identifies key groups of bacteria that are most affected. We found that the microbiome undergoes large changes when iron is removed from the diet but that many individual bacteria are able to rebound when iron levels are changed by to normal. That said, a select few members, referred to as "iron-sensitive" bacteria seem to be lost. This study begins to identify individual members of the mammalian microbiome most affected by changes in dietary iron levels.}, }
@article {pmid33182444, year = {2020}, author = {A James, S and Phillips, S and Telatin, A and Baker, D and Ansorge, R and Clarke, P and J Hall, L and R Carding, S}, title = {Preterm Infants Harbour a Rapidly Changing Mycobiota That Includes Candida Pathobionts.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, pmid = {33182444}, issn = {2309-608X}, support = {BB/J004529/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R012490//BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/F/000PR10353, BBS/E/F/000PR10355 and BBS/E/F/000PR10356/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; 100974/C/13/Z/WT_/Wellcome Trust/United Kingdom ; }, abstract = {Fungi and the mycobiome are a fundamental part of the human microbiome that contributes to human health and development. Despite this, relatively little is known about the mycobiome of the preterm infant gut. Here, we have characterised faecal fungal communities present in 11 premature infants born with differing degrees of prematurity and mapped how the mycobiome develops during early infancy. Using an ITS1 sequencing-based approach, the preterm infant gut mycobiome was found to be often dominated by a single species, typically a yeast. Candida was the most abundant genus, with the pathobionts C.albicans and C.parapsilosis highly prevalent and persistent in these infants. Gestational maturity at birth affected the distribution and abundance of these Candida, with hospital-associated C.parapsilosis more prevalent and abundant in infants born at less than 31 weeks. Fungal diversity was lowest at 6 months, but increased with age and change of diet, with food-associated Saccharomycescerevisiae most abundant in infants post weaning. This study provides a first insight into the fungal communities present within the preterm infant gut, identifying distinctive features including the prominence of pathobiont species, and the influence age and environmental factors play in shaping the development of the mycobiome.}, }
@article {pmid33178777, year = {2020}, author = {Nicolaro, M and Portal, DE and Shinder, B and Patel, HV and Singer, EA}, title = {The human microbiome and genitourinary malignancies.}, journal = {Annals of translational medicine}, volume = {8}, number = {19}, pages = {1245}, pmid = {33178777}, issn = {2305-5839}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; }, abstract = {The human microbiome contains a vast network of understudied organisms that have an intimate role in our health and wellness. These microbiomes differ greatly between individuals, creating what may be thought of as a unique and dynamic microbial signature. Microbes have been shown to have various roles in metabolism, local and systemic inflammation, as well as immunity. Recent findings have confirmed the importance of both the gut and urinary microbiomes in genitourinary malignancies. Numerous studies have identified differences in microbial signatures between healthy patients and those with urologic malignancies. The microbiomes have been shown to contain microbes that may contribute to the etiology of disease state as well as yield information in regard to a person's health and their responsiveness to certain drugs such as immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Less well understood are the effects of antibiotics on oncologic outcomes in such treatment courses. This review will explore our current understanding and advancements in the field of microbiome research and discuss its intimate association with genitourinary diseases including bladder cancer, prostate cancer, and kidney cancer. With a better understanding of the association between the microbiome and genitourinary malignancy, further investigation may produce reliable predictors of disease, prognostic indicators as well as therapeutic targets.}, }
@article {pmid33178428, year = {2020}, author = {Sikakana, P and Roberts, RA}, title = {A decade of toxicological trends: what the papers say.}, journal = {Toxicology research}, volume = {9}, number = {5}, pages = {676-682}, pmid = {33178428}, issn = {2045-452X}, abstract = {Here we look at popular trends and concepts in toxicology over the decade 2009-2019. The top 10 concepts included methodological approaches such as zebrafish and genomics as well as broader concepts such as personalized medicine and adverse outcome pathways. The total number and rank order for each of the top 10 were tracked year by year via PubMed with >9500 papers contributing to the analysis. The data revealed a slow upward trend in the number of papers across all the concepts from 260 in 2009 to >1700 in 2019. Zebrafish, genomics and personalized medicine remained in the top four slots since 2009 with zebrafish dominating the rankings over the entire decade. Genomics was a strong second until 2013 when it was displaced first by the microbiome in 2014 and secondly by personalized medicine in 2015. Other notable trends were the ascendancy of the microbiome and adverse outcome pathways and the descendancy of hormesis and the 3Rs (replacement, reduction and refinement of animals in testing). The observation that the top four slots have been static over the past 4 years suggests that new ideas are introduced and increase in popularity until they find their place in scientific culture. This may suggest that relatively new concepts such as artificial intelligence and microphysiological systems have yet to find their steady state in the rankings. Similarly, as a relatively new player in toxicology, the full impact of the human microbiome on drug efficacy and safety remains to be seen.}, }
@article {pmid33177184, year = {2020}, author = {Stokholm, J and Thorsen, J and Blaser, MJ and Rasmussen, MA and Hjelmsø, M and Shah, S and Christensen, ED and Chawes, BL and Bønnelykke, K and Brix, S and Mortensen, MS and Brejnrod, A and Vestergaard, G and Trivedi, U and Sørensen, SJ and Bisgaard, H}, title = {Delivery mode and gut microbial changes correlate with an increased risk of childhood asthma.}, journal = {Science translational medicine}, volume = {12}, number = {569}, pages = {}, doi = {10.1126/scitranslmed.aax9929}, pmid = {33177184}, issn = {1946-6242}, abstract = {There have been reports of associations between cesarean section delivery and the risk of childhood asthma, potentially mediated through changes in the gut microbiota. We followed 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort prospectively from birth. We examined the effects of cesarean section delivery on gut microbial composition by 16S rRNA gene amplicon sequencing during the first year of life. We then explored whether gut microbial perturbations due to delivery mode were associated with a risk of developing asthma in the first 6 years of life. Delivery by cesarean section was accompanied by marked changes in gut microbiota composition at one week and one month of age, but by one year of age only minor differences persisted compared to vaginal delivery. Increased asthma risk was found in children born by cesarean section only if their gut microbiota composition at 1 year of age still retained a cesarean section microbial signature, suggesting that appropriate maturation of the gut microbiota could mitigate against the increased asthma risk associated with gut microbial changes due to cesarean section delivery.}, }
@article {pmid33176111, year = {2020}, author = {Hadrup, N and Aimonen, K and Ilves, M and Lindberg, H and Atluri, R and Sahlgren, NM and Jacobsen, NR and Barfod, KK and Berthing, T and Lawlor, A and Norppa, H and Wolff, H and Jensen, KA and Hougaard, KS and Alenius, H and Catalan, J and Vogel, U}, title = {Pulmonary toxicity of synthetic amorphous silica - effects of porosity and copper oxide doping.}, journal = {Nanotoxicology}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/17435390.2020.1842932}, pmid = {33176111}, issn = {1743-5404}, abstract = {Materials can be modified for improved functionality. Our aim was to test whether pulmonary toxicity of silica nanomaterials is increased by the introduction of: a) porosity; and b) surface doping with CuO; and whether c) these modifications act synergistically. Mice were exposed by intratracheal instillation and for some doses also oropharyngeal aspiration to: 1) solid silica 100 nm; 2) porous silica 100 nm; 3) porous silica 100 nm with CuO doping; 4) solid silica 300 nm; 5) porous silica 300 nm; 6) solid silica 300 nm with CuO doping; 7) porous silica 300 nm with CuO doping; 8) CuO nanoparticles 9.8 nm; or 9) carbon black Printex 90 as benchmark. Based on a pilot study, dose levels were between 0.5 and 162 µg/mouse (0.2 and 8.1 mg/kg bw). Endpoints included pulmonary inflammation (neutrophil numbers in bronchoalveolar fluid), acute phase response, histopathology, and genotoxicity assessed by the comet assay, micronucleus test, and the gamma-H2AX assay. The porous silica materials induced greater pulmonary inflammation than their solid counterparts. A similar pattern was seen for acute phase response induction and histologic changes. This could be explained by a higher specific surface area per mass unit for the most toxic particles. CuO doping further increased the acute phase response normalized according to the deposited surface area. We identified no consistent evidence of synergism between surface area and CuO doping. In conclusion, porosity and CuO doping each increased the toxicity of silica nanomaterials and there was no indication of synergy when the modifications co-occurred.}, }
@article {pmid33172400, year = {2020}, author = {Brandt, K and Barrangou, R}, title = {Adaptive response to iterative passages of five Lactobacillus species in simulated vaginal fluid.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {339}, pmid = {33172400}, issn = {1471-2180}, abstract = {BACKGROUND: Microbiome and metagenomic studies have given rise to a new understanding of microbial colonization of various human tissues and their ability to impact our health. One human microbiome growing in notoriety, the vaginal microbiome, stands out given its importance for women's health, and is peculiar in terms of its relative bacterial composition, including its simplicity and typical domination by a small number of Lactobacillus species. The loss of Lactobacillus dominance is associated with disorders such as bacterial vaginosis, and efforts are now underway to understand the ability of Lactobacillus species to colonize the vaginal tract and adapt to this dynamic and acidic environment. Here, we investigate how various Lactobacillus species often isolated from the vaginal and intestinal cavities genomically and transcriptionally respond to iterative growth in simulated vaginal fluid.
RESULTS: We determined the genomes and transcriptomes of L. acidophilus, L. crispatus, L. fermentum, L. gasseri, and L. jensenii and compared profiles after 50, 100, 500, and 1000 generations of iterative passages in synthetic vaginal fluid. In general, we identified relatively few genetic changes consisting of single nucleotide polymorphisms, with higher counts occurring more frequently in non-vaginal isolated species. Transcriptional profiles were more impacted over time and tended to be more extensive for species that typically do not dominate the vaginal tract, reflecting a more extensive need to adapt to a less familiar environment.
CONCLUSIONS: This study provides insights into how vaginal and non-vaginal Lactobacillus species respond and adapt to a simulated vaginal environment. Overall, trends indicate high genomic stability for all species involved, with more variability in the transcriptome especially for non-dominant species of the vaginal tract.}, }
@article {pmid33167080, year = {2020}, author = {Lane, MM and Davis, JA and Beattie, S and Gómez-Donoso, C and Loughman, A and O'Neil, A and Jacka, F and Berk, M and Page, R and Marx, W and Rocks, T}, title = {Ultraprocessed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies.}, journal = {Obesity reviews : an official journal of the International Association for the Study of Obesity}, volume = {}, number = {}, pages = {}, doi = {10.1111/obr.13146}, pmid = {33167080}, issn = {1467-789X}, support = {//Princess Alexandra Research Foundation/ ; //Cobram Estate Pty. Ltd/ ; //La Trobe University/ ; //Cancer Council Queensland/ ; //Multiple Sclerosis Research Australia/ ; //Alfred Deakin Postdoctoral Research Fellowship/ ; //Global Age/ ; //City of Greater Geelong/ ; //Parkdale College/ ; //Central West Gippsland Primary Care Partnership/ ; //West Gippsland Healthcare Group/ ; //Barwon Health/ ; //Primary Health Networks/ ; /HH/HHS/United States ; //Australian Disease Management Association/ ; //Black Dog Institute/ ; //Academy of Nutrition and Dietetics/ ; //The Royal Australian and New Zealand College of Psychiatrists/ ; //Nutrition Society of Australia/ ; //Dietitians Association of Australia/ ; //University of Southern Queensland/ ; //Bond University/ ; //Oxford University Press/ ; //Australian Postgraduate Awards/ ; //University of the Sunshine Coast/ ; //Harry Windsor Foundation/ ; //Avant/ ; //Beyond Blue/ ; //Medical Research Futures Fund/ ; //Medical Benefits Fund/ ; //Stanley Medical Research Foundation/ ; //Cancer Council of Victoria/ ; //Simons Autism Foundation/ ; //Cooperative Research Centre/ ; 1156072//Senior Principal Research Fellowship/ ; 1059660//Senior Principal Research Fellowship/ ; //Metagenics/ ; //Angelini Farmaceutica/ ; //Network Nutrition/ ; //Pfizer/ ; //Servier/ ; //Janssen Cilag/ ; //Sanofi-Synthelabo/ ; //Eli Lilly Australia/ ; //Ian Potter Foundation/ ; //Geelong Medical Research Foundation/ ; //Australian Rotary Health/ ; //Brain and Behaviour Research Institute/ ; //Novartis/ ; //Woolworths Limited/ ; //Meat and Livestock Australia/ ; //Sanofi/ ; //Australian Research Council/ ; //Wilson Foundation/ ; (#101160//Heart Foundation Australia/ ; //Fonds de la Recherche Scientifique (FNRS)/ ; //Falk Foundation/ ; //Australian and New Zealand College of Anaesthetists/ ; //European Society of Neurogastroenterology/ ; //International Human Microbiome Congress/ ; //Epilepsy Society of Australia/ ; //American Epilepsy Society/ ; //University of Technology Sydney/ ; //Sydney University/ ; //The Jack Brockhoff Foundation/ ; //National Institutes of Health (NIH)/ ; //Australian Academy of Science/ ; //National Health and Medical Research Council (NHMRC)/ ; //Deakin University/ ; //RMIT University/ ; //University of Melbourne/ ; //University of New South Wales/ ; FI18/00073//Carlos III Health Institute/ ; //Australian Government Research Training Program Scholarship/ ; //Deakin University Scholarship/ ; //Be Fit Foods/ ; //A2 Milk Company/ ; //Wilson Foundation/ ; //Fernwood Foundation/ ; }, abstract = {This systematic review and meta-analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and mortality. Forty-three observational studies were included (N = 891,723): 21 cross-sectional, 19 prospective, two case-control and one conducted both a prospective and cross-sectional analysis. Meta-analysis demonstrated consumption of ultraprocessed food was associated with increased risk of overweight (odds ratio: 1.36; 95% confidence interval [CI], 1.23-1.51; P < 0.001), obesity (odds ratio: 1.51; 95% CI, 1.34-1.70; P < 0.001), abdominal obesity (odds ratio: 1.49; 95% CI, 1.34-1.66; P < 0.0001), all-cause mortality (hazard ratio: 1.28; 95% CI, 1.11-1.48; P = 0.001), metabolic syndrome (odds ratio: 1.81; 95% CI, 1.12-2.93; P = 0.015) and depression in adults (hazard ratio: 1.22; 95% CI, 1.16-1.28, P < 0.001) as well as wheezing (odds ratio: 1.40; 95% CI, 1.27-1.55; P < 0.001) but not asthma in adolescents (odds ratio: 1.20; 95% CI, 0.99-1.46; P = 0.065). In addition, consumption of ultraprocessed food was associated with cardiometabolic diseases, frailty, irritable bowel syndrome, functional dyspepsia and cancer (breast and overall) in adults while also being associated with metabolic syndrome in adolescents and dyslipidaemia in children. Although links between ultraprocessed food consumption and some intermediate risk factors in adults were also highlighted, further studies are required to more clearly define associations in children and adolescents. STUDY REGISTRATION: Prospero ID: CRD42020176752.}, }
@article {pmid33166356, year = {2020}, author = {Zhang, X and Guo, B and Yi, N}, title = {Zero-Inflated gaussian mixed models for analyzing longitudinal microbiome data.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0242073}, pmid = {33166356}, issn = {1932-6203}, abstract = {MOTIVATION: The human microbiome is variable and dynamic in nature. Longitudinal studies could explain the mechanisms in maintaining the microbiome in health or causing dysbiosis in disease. However, it remains challenging to properly analyze the longitudinal microbiome data from either 16S rRNA or metagenome shotgun sequencing studies, output as proportions or counts. Most microbiome data are sparse, requiring statistical models to handle zero-inflation. Moreover, longitudinal design induces correlation among the samples and thus further complicates the analysis and interpretation of the microbiome data.
RESULTS: In this article, we propose zero-inflated Gaussian mixed models (ZIGMMs) to analyze longitudinal microbiome data. ZIGMMs is a robust and flexible method which can be applicable for longitudinal microbiome proportion data or count data generated with either 16S rRNA or shotgun sequencing technologies. It can include various types of fixed effects and random effects and account for various within-subject correlation structures, and can effectively handle zero-inflation. We developed an efficient Expectation-Maximization (EM) algorithm to fit the ZIGMMs by taking advantage of the standard procedure for fitting linear mixed models. We demonstrate the computational efficiency of our EM algorithm by comparing with two other zero-inflated methods. We show that ZIGMMs outperform the previously used linear mixed models (LMMs), negative binomial mixed models (NBMMs) and zero-inflated Beta regression mixed model (ZIBR) in detecting associated effects in longitudinal microbiome data through extensive simulations. We also apply our method to two public longitudinal microbiome datasets and compare with LMMs and NBMMs in detecting dynamic effects of associated taxa.}, }
@article {pmid33163830, year = {2020}, author = {Witjes, JJ and Smits, LP and Pekmez, CT and Prodan, A and Meijnikman, AS and Troelstra, MA and Bouter, KEC and Herrema, H and Levin, E and Holleboom, AG and Winkelmeijer, M and Beuers, UH and van Lienden, K and Aron-Wisnewky, J and Mannisto, V and Bergman, JJ and Runge, JH and Nederveen, AJ and Dragsted, LO and Konstanti, P and Zoetendal, EG and de Vos, W and Verheij, J and Groen, AK and Nieuwdorp, M}, title = {Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1578-1590}, pmid = {33163830}, issn = {2471-254X}, abstract = {The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.}, }
@article {pmid33158018, year = {2020}, author = {Zizzari, IG and Filippo, AD and Scirocchi, F and Di Pietro, FR and Rahimi, H and Ugolini, A and Scagnoli, S and Vernocchi, P and Del Chierico, F and Putignani, L and Rughetti, A and Marchetti, P and Nuti, M and Botticelli, A and Napoletano, C}, title = {Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients.}, journal = {Journal of personalized medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33158018}, issn = {2075-4426}, support = {IG grant 2015 n°17432//Associazione Italiana per la Ricerca sul Cancro/ ; RM118164277B5F2A//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; RM1181643132016E//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, abstract = {Patients with non-small cell lung cancer (NSCLC) have been shown to benefit from the introduction of anti-PD1 treatment. However, not all patients experience tumor regression and durable response. The identification of a string of markers that are direct or indirect indicators of the immune system fitness is needed to choose optimal therapeutic schedules in the management of NSCLC patients. We analyzed 34 immuno-related molecules (14 soluble immune checkpoints, 17 cytokines/chemokines, 3 adhesion molecules) released in the serum of 22 NSCLC patients under Nivolumab treatment and the gut metabolomic profile at baseline. These parameters were correlated with performance status (PS) and/or response to treatment. Nivolumab affected the release of soluble immune checkpoints (sICs). Patients with a better clinical outcome and with an optimal PS (PS = 0) showed a decreased level of PD1 and maintained low levels of several sICs at first clinical evaluation. Low levels of PDL1, PDL2, Tim3, CD137 and BTLA4 were also correlated with a long response to treatment. Moreover, responding patients showed a high proportion of eubiosis-associated gut metabolites. In this exploratory study, we propose a combination of immunological and clinical parameters (sICs, PS and gut metabolites) for the identification of patients more suitable for Nivolumab treatment. This string of parameters validated in a network analysis on a larger cohort of patients could help oncologists to improve their decision-making in an NSCLC setting.}, }
@article {pmid33155101, year = {2020}, author = {Torralba, MG and Aleti, G and Li, W and Moncera, KJ and Lin, YH and Yu, Y and Masternak, MM and Golusinski, W and Golusinski, P and Lamperska, K and Edlund, A and Freire, M and Nelson, KE}, title = {Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-020-01596-5}, pmid = {33155101}, issn = {1432-184X}, support = {R00 DE023584/DE/NIDCR NIH HHS/United States ; }, abstract = {The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.}, }
@article {pmid33151137, year = {2020}, author = {Keller, JJ and Ooijevaar, RE and Hvas, CL and Terveer, EM and Lieberknecht, SC and Högenauer, C and Arkkila, P and Sokol, H and Gridnyev, O and Mégraud, F and Kump, PK and Nakov, R and Goldenberg, SD and Satokari, R and Tkatch, S and Sanguinetti, M and Cammarota, G and Dorofeev, A and Gubska, O and Ianiro, G and Mattila, E and Arasaradnam, RP and Sarin, SK and Sood, A and Putignani, L and Alric, L and Baunwall, SM and Kupcinskas, J and Link, A and Goorhuis, AG and Verspaget, HW and Ponsioen, C and Hold, GL and Tilg, H and Kassam, Z and Kuijper, EJ and Gasbarrini, A and Mulder, CJ and Williams, HR and Vehreschild, MJ}, title = {A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {2050640620967898}, doi = {10.1177/2050640620967898}, pmid = {33151137}, issn = {2050-6414}, abstract = {BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.
OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.
METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.
RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.
CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.}, }
@article {pmid33144313, year = {2020}, author = {Manus, MB and Kuthyar, S and Perroni-Marañón, AG and Núñez-de la Mora, A and Amato, KR}, title = {Infant Skin Bacterial Communities Vary by Skin Site and Infant Age across Populations in Mexico and the United States.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33144313}, issn = {2379-5077}, abstract = {Daily practices put humans in close contact with the surrounding environment, and differences in these practices have an impact on human physiology, development, and health. There is mounting evidence that the microbiome represents an interface that mediates interactions between the human body and the environment. In particular, the skin microbiome serves as the primary interface with the external environment and aids in host immune function by contributing as the first line of defense against pathogens. Despite these important connections, we have only a basic understanding of how the skin microbiome is first established, or which environmental factors contribute to its development. To this end, this study compared the skin bacterial communities of infants (n = 47) living in four populations in Mexico and the United States that span the socioeconomic gradient, where we predicted that variation in physical and social environments would shape the infant skin microbiome. Results of 16S rRNA bacterial gene sequencing on 119 samples (armpit, hand, and forehead) showed that infant skin bacterial diversity and composition are shaped by population-level factors, including those related to socioeconomic status and household composition, and vary by skin site and infant age. Differences in infant-environment interactions, including with other people, appear to vary across the populations, likely influencing infant microbial exposures and, in turn, the composition of infant skin bacterial communities. These findings suggest that variation in microbial exposures stemming from the local environment in infancy can impact the establishment of the skin microbiome across body sites, with implications for developmental and health outcomes.IMPORTANCE This study contributes to the sparse literature on the infant skin microbiome in general, and the virtually nonexistent literature on the infant skin microbiome in a field setting. While microbiome research often addresses patterns at a national scale, this study addresses the influence of population-level factors, such as maternal socioeconomic status and contact with caregivers, on infant skin bacterial communities. This approach strengthens our understanding of how local variables influence the infant skin microbiome, and paves the way for additional studies to combine biological sample collection with questionnaires to adequately capture how specific behaviors dictate infant microbial exposures. Work in this realm has implications for infant care and health, as well as for investigating how the microbial communities of different body sites develop over time, with applications to specific health outcomes associated with the skin microbiome (e.g., immune system development or atopic dermatitis).}, }
@article {pmid33139482, year = {2020}, author = {North, OI and Davidson, AR}, title = {Phage proteins required for tail fiber assembly also bind specifically to the surface of host bacterial strains.}, journal = {Journal of bacteriology}, volume = {}, number = {}, pages = {}, doi = {10.1128/JB.00406-20}, pmid = {33139482}, issn = {1098-5530}, abstract = {To initiate their life cycle, phages must specifically bind to the surface of their bacterial hosts. Long-tailed phages often interact with the cell surface using fibers, which are elongated intertwined trimeric structures. The folding and assembly of these complex structures generally requires the activity of an intra- or intermolecular chaperone protein. Tail fiber assembly (Tfa) proteins are a very large family of proteins that serve as chaperones for fiber folding in a wide variety of phages infecting diverse species. A recent structural study showed that the Tfa protein from E. coli phage Mu (TfaMu) mediates fiber folding and stays bound to the distal tip of the fiber, becoming a component of the mature phage particle. This finding revealed the potential for TfaMu to also play a role in cell surface binding. To address this issue, here we have shown that TfaMu binds to lipopolysaccharide (LPS), the cell surface receptor of phage Mu with a similar strength as the fiber itself. Furthermore, we have found that TfaMu and the Tfa protein from E. coli phage P2 bind LPS with distinct specificities that mirror the host specificity of these two phages. By comparing the sequences of these two proteins, which are 93% identical, we identified a single residue that is responsible for their distinct LPS-binding behaviours. Although we have not yet found conditions under which Tfa proteins influence host range, the potential for such a role is now evident as we have demonstrated their ability to bind LPS in a strain-specific manner.Importance With the growing interest in using phages to combat antibiotic-resistant infections or manipulate the human microbiome, establishing approaches for the modification of phage host range has become an important research topic. Tfa proteins are a large family of proteins known previously to function as chaperones for the folding of phage fibers, which are crucial determinants of host range for long-tailed phages. Here we reveal that some Tfa proteins are bi-functional with the additional activity of binding to LPS, the surface binding receptor for many phages. This discovery opens up new potential avenues for altering phage host range through engineering of the surface binding specificity of Tfa proteins.}, }
@article {pmid33134291, year = {2020}, author = {Rooney, CM and Mankia, K and Emery, P}, title = {The Role of the Microbiome in Driving RA-Related Autoimmunity.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {538130}, pmid = {33134291}, issn = {2296-634X}, support = {22294/VAC_/Versus Arthritis/United Kingdom ; }, abstract = {Once referred to as "normal commensal flora" the human microbiome plays an integral role between health and disease. The host mucosal surface replete with a multitude of immune cells is a vast arena constantly sensing and responding to antigen presentation and microbial by-products. It is this key role that may allow the microbiome to prime or protect the host from autoimmune disease. Rheumatoid arthritis (RA) is a chronic, disabling inflammatory condition characterized by a complex multifactorial etiology. The presence of certain genetic markers has been proven to increase susceptibility to RA however it does not guarantee disease development. Given low concordance rates demonstrated in monozygotic twin studies there is a clear implication for the involvement of external players in RA pathogenesis. Since the historical description of rheumatoid factor, numerous additional autoantibodies have been described in the sera of RA patients. The presence of anti-cyclic citrullinated protein antibody is now a standard test, and is associated with a more severe disease course. Interestingly these antibodies are detectable in patient's sera long before the clinical signs of RA occur. The production of autoantibodies is driven by the lack of tolerance of the immune system, and how tolerance is broken is a crucial question for understanding RA development. Here we review current literature on the role of the microbiome in RA development including periodontal, gut and lung mucosa, with particular focus on proposed mechanisms of host microbiome interactions. We discuss the use of Mendelian randomization to assign causality to the microbiome and present considerations for future studies.}, }
@article {pmid33131263, year = {2020}, author = {Pietro Merli, and Lorenza Putignani, and Annalisa Ruggeri, and Federica Del Chierico, and Livia Gargiullo, and Federica Galaverna, and Stefania Gaspari, and Daria Pagliara, and Alessandra Russo, and Stefania Pane, and Luisa Strocchio, and Mattia Algeri, and Francesca Rea, and Erminia Francesca Romeo, and Paola Bernaschi, and Andrea Onetti Muda, and Bruno Dallapiccola, and Franco Locatelli, }, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {105}, number = {11}, pages = {2686-2690}, pmid = {33131263}, issn = {1592-8721}, }
@article {pmid33125887, year = {2020}, author = {Spencer, SP and Sonnenburg, JL}, title = {When Gut Microbiota Creep into Fat, the Fat Creeps Back.}, journal = {Cell}, volume = {183}, number = {3}, pages = {589-591}, doi = {10.1016/j.cell.2020.10.008}, pmid = {33125887}, issn = {1097-4172}, abstract = {Ha and colleagues describe a previously unappreciated diversity of microbes in the mesenteric adipose tissue (MAT) surrounding the GI tract. Viable bacteria that are mislocalized from the gut microbiota and metabolically adapted to the MAT contribute to the "creeping fat" of Crohn's disease.}, }
@article {pmid33123104, year = {2020}, author = {Saladié, M and Caparrós-Martín, JA and Agudelo-Romero, P and Wark, PAB and Stick, SM and O'Gara, F}, title = {Microbiomic Analysis on Low Abundant Respiratory Biomass Samples; Improved Recovery of Microbial DNA From Bronchoalveolar Lavage Fluid.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {572504}, pmid = {33123104}, issn = {1664-302X}, abstract = {In recent years the study of the commensal microbiota is driving a remarkable paradigm shift in our understanding of human physiology. However, intrinsic technical difficulties associated with investigating the Microbiomics of some body niches are hampering the development of new knowledge. This is particularly the case when investigating the functional role played by the human microbiota in modulating the physiology of key organ systems. A major hurdle in investigating specific Microbiome communities is linked to low bacterial density and susceptibility to bias caused by environmental contamination. To prevent such inaccuracies due to background processing noise, harmonized tools for Microbiomic and bioinformatics practices have been recommended globally. The fact that the impact of this undesirable variability is negatively correlated with the DNA concentration in the sample highlights the necessity to improve existing DNA isolation protocols. In this report, we developed and tested a protocol to more efficiently recover bacterial DNA from low volumes of bronchoalveolar lavage fluid obtained from infants and adults. We have compared the efficiency of the described method with that of a commercially available kit for microbiome analysis in body fluids. We show that this new methodological approach performs better in terms of extraction efficiency. As opposed to commercial kits, the DNA extracts obtained with this new protocol were clearly distinguishable from the negative extraction controls in terms of 16S copy number and Microbiome community profiles. Altogether, we described a cost-efficient protocol that can facilitate microbiome research in low-biomass human niches.}, }
@article {pmid33120253, year = {2020}, author = {Chowdhury, S and Fong, SS}, title = {Leveraging genome-scale metabolic models for human health applications.}, journal = {Current opinion in biotechnology}, volume = {66}, number = {}, pages = {267-276}, doi = {10.1016/j.copbio.2020.08.017}, pmid = {33120253}, issn = {1879-0429}, abstract = {Genome-scale metabolic modeling is a scalable and extensible computational method for analyzing and predicting biological function. With the ongoing improvements in computational methods and experimental capabilities, genome-scale metabolic models (GEMs) are demonstrating utility in addressing human health applications. The initial areas of highest impact are likely to be health applications where disease states involve metabolic changes. In this review, we focus on recent application of GEMs to studying cancer and the human microbiome by describing the enabling methodologies and outcomes of these studies. We conclude with proposing some areas of research that are likely to arise as a result of recent methodological advances.}, }
@article {pmid33119023, year = {2020}, author = {Schwarz, M and Murphy, EJ and Foley, AM and Woods, DF and Castilla, IA and Reen, FJ and Collins, SG and O'Gara, F and Maguire, AR}, title = {Exploring the synthetic potential of a marine transaminase including discrimination at a remote stereocentre.}, journal = {Organic & biomolecular chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1039/d0ob01848a}, pmid = {33119023}, issn = {1477-0539}, abstract = {The marine transaminase, P-ω-TA, can be employed for the transamination from 1-aminotetralins and 1-aminoindanes with differentiation of stereochemistry at both the site of reaction and at a remote stereocentre resulting in formation of ketone products with up to 93% ee. While 4-substituents are tolerated on the tetralin core, the presence of 3- or 8-substituents is not tolerated by the transaminase. In general P-ω-TA shows capacity for remote diastereoselectivity, although both the stereoselectivity and efficiency are dependent on the specific substrate structure. Optimum efficiency and selectivity are seen with 4-haloaryl-1-aminotetralins and 3-haloaryl-1-aminoindanes, which may be associated with the marine origin of this enzyme.}, }
@article {pmid33117737, year = {2020}, author = {Amado, PPP and Kawamoto, D and Albuquerque-Souza, E and Franco, DC and Saraiva, L and Casarin, RCV and Horliana, ACRT and Mayer, MPA}, title = {Oral and Fecal Microbiome in Molar-Incisor Pattern Periodontitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {583761}, pmid = {33117737}, issn = {2235-2988}, abstract = {In order to improve our understanding on the microbial complexity associated with Grade C/molar-incisor pattern periodontitis (GC/MIP), we surveyed the oral and fecal microbiomes of GC/MIP and compared to non-affected individuals (Control). Seven Afro-descendants with GC/MIP and seven age/race/gender-matched controls were evaluated. Biofilms from supra/subgingival sites (OB) and feces were collected and submitted to 16S rRNA sequencing. Aggregatibacter actinomycetemcomitans (Aa) JP2 clone genotyping and salivary nitrite levels were determined. Supragingival biofilm of GC/MIP presented greater abundance of opportunistic bacteria. Selenomonas was increased in subgingival healthy sites of GC/MIP compared to Control. Synergistetes and Spirochaetae were more abundant whereas Actinobacteria was reduced in OB of GC/MIP compared to controls. Aa abundance was 50 times higher in periodontal sites with PD≥ 4 mm of GC/MIP than in controls. GC/MIP oral microbiome was characterized by a reduction in commensals such as Kingella, Granulicatella, Haemophilus, Bergeyella, and Streptococcus and enrichment in periodontopathogens, especially Aa and sulfate reducing Deltaproteobacteria. The oral microbiome of the Aa JP2-like+ patient was phylogenetically distant from other GC/MIP individuals. GC/MIP presented a higher abundance of sulfidogenic bacteria in the feces, such as Desulfovibrio fairfieldensis, Erysipelothrix tonsillarum, and Peptostreptococcus anaerobius than controls. These preliminary data show that the dysbiosis of the microbiome in Afro-descendants with GC/MIP was not restricted to affected sites, but was also observed in supragingival and subgingival healthy sites, as well as in the feces. The understanding on differences of the microbiome between healthy and GC/MIP patients will help in developing strategies to improve and monitor periodontal treatment.}, }
@article {pmid33117362, year = {2020}, author = {Yegorov, S and Babenko, D and Kozhakhmetov, S and Akhmaltdinova, L and Kadyrova, I and Nurgozhina, A and Nurgaziyev, M and Good, SV and Hortelano, GH and Yermekbayeva, B and Kushugulova, A}, title = {Psoriasis Is Associated With Elevated Gut IL-1α and Intestinal Microbiome Alterations.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {571319}, pmid = {33117362}, issn = {1664-3224}, abstract = {Background: Psoriasis is a chronic inflammatory condition that predominantly affects the skin and is associated with extracutaneous disorders, such as inflammatory bowel disease and arthritis. Changes in gut immunology and microbiota are important drivers of proinflammatory disorders and could play a role in the pathogenesis of psoriasis. Therefore, we explored whether psoriasis in a Central Asian cohort is associated with alterations in select immunological markers and/or microbiota of the gut.
Methods: We undertook a case-control study of stool samples collected from outpatients, aged 30-45 years, of a dermatology clinic in Kazakhstan presenting with plaque, guttate, or palmoplantar psoriasis (n = 20), and age-sex matched subjects without psoriasis (n = 20). Stool supernatant was subjected to multiplex ELISA to assess the concentration of 47 cytokines and immunoglobulins and to 16S rRNA gene sequencing to characterize microbial diversity in both psoriasis participants and controls.
Results: The psoriasis group tended to have higher concentrations of most analytes in stool (29/47 = 61.7%) and gut IL-1α was significantly elevated (4.19-fold, p = 0.007) compared to controls. Levels of gut IL-1α in the psoriasis participants remained significantly unaltered up to 3 months after the first sampling (p = 0.430). Psoriasis was associated with alterations in gut Firmicutes, including elevated Faecalibacterium and decreased Oscillibacter and Roseburia abundance, but no association was observed between gut microbial diversity or Firmicutes/Bacteroidetes ratios and disease status.
Conclusions: Psoriasis may be associated with gut inflammation and dysbiosis. Studies are warranted to explore the use of gut microbiome-focused therapies in the management of psoriasis in this under-studied population.}, }
@article {pmid33114761, year = {2020}, author = {Haange, SB and Groeger, N and Froment, J and Rausch, T and Burkhardt, W and Gonnermann, S and Braune, A and Blaut, M and von Bergen, M and Rolle-Kampczyk, U}, title = {Multiplexed Quantitative Assessment of the Fate of Taurine and Sulfoquinovose in the Intestinal Microbiome.}, journal = {Metabolites}, volume = {10}, number = {11}, pages = {}, pmid = {33114761}, issn = {2218-1989}, support = {BR 2269/5-1//Deutsche Forschungsgemeinschaft/ ; BL 257/13-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {(1) Introduction: Sulfonates, which can be diet- or host-derived, are a class of compounds detected in the gut, are involved in host-microbiome interactions and have several health effects. Our aim was to develop a method to quantify five of the sulfonates in the intestine and apply it in a simplified human microbiome model. These were taurine, its metabolic precursor cysteate and one of its degradation products isethionate, as well as sulfoquinovose and one of its most relevant degradation products 2,3-dihydroxy-1-propanesulfonate. (2) Methods: An extraction and sample preparation method was developed, without the need for derivatization. To detect and quantify the extracted sulfonates, a multiplexed LC-MS/MS-MRM method was established. (3) Results: The accuracy and precision of the method were within GLP-accepted parameters (www.ema.europa.eu). To apply this method in a pilot study, we spiked either taurine or sulfoquinovose into an in vitro simplified human microbiota model with and without Bilophila wadsworthia, a known sulfonate utilizer. The results revealed that only the culture with B. wadsworthia was able to degrade taurine, with isethionate as an intermediate. After spiking the communities with sulfoquinovose, the results revealed that the simplified human microbiome model was able to degrade sulfoquinovose to 2,3-dihydroxypropane-1-sulfonate, which was probably catalyzed by Escherichia coli. In the community with B. wadsworthia, the 2,3-dihydroxypropane-1-sulfonate produced was further degraded by B. wadsworthia to sulfide. (4) Conclusions: We successfully developed a method for sulfonate quantification and applied it in a first pilot study.}, }
@article {pmid33113343, year = {2020}, author = {Hayes, W and Sahu, S}, title = {The Human Microbiome: History and Future.}, journal = {Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques}, volume = {23}, number = {}, pages = {404-411}, doi = {10.18433/jpps31525}, pmid = {33113343}, issn = {1482-1826}, abstract = {The microbiome plays an important role in human health and disease. Our current understanding of the human microbiome is limited. A significant amount of progress has been made in this area of research in the last two decades. The human microbiome plays an important role in host metabolism and physiology. Recent studies suggest a critical relationship between the human microbiome and host metabolism. The interactions between the microbiome and host metabolism affect human health and disease. However, this review of the literature indicates that more studies are required using new technologies to have a greater understanding of the role the human microbiome plays in human health and disease.}, }
@article {pmid33109750, year = {2020}, author = {Brinkac, LM and Rahman, N and Chua, LL and Thomas, S}, title = {Biomimetic Gut Model Systems for Development of Targeted Microbial Solutions for Enhancing Warfighter Health and Performance.}, journal = {mSystems}, volume = {5}, number = {5}, pages = {}, pmid = {33109750}, issn = {2379-5077}, abstract = {The human gut microbiome plays a vital role in both health and disease states and as a mediator of cognitive and physical performance. Despite major advances in our understanding of the role of gut microbes in host physiology, mechanisms underlying human-microbiome dynamics have yet to be fully elucidated. This knowledge gap represents a major hurdle to the development of targeted gut microbiome solutions influencing human health and performance outcomes. The microbiome as it relates to warfighter health and performance is of interest to the Department of Defense (DoD) with the development of interventions impacting gut microbiome resiliency among its top research priorities. While technological advancements are enabling the development of experimental model systems that facilitate mechanistic insights underpinning human health, disease, and performance, translatability to human outcomes is still questionable. This review discusses some of the drivers influencing the DoD's interest in the warfighter gut microbiome and describes current in vitro gut model systems supporting direct microbial-host interactions.}, }
@article {pmid33099885, year = {2020}, author = {Marco, ML}, title = {Defining how microorganisms benefit human health.}, journal = {Microbial biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-7915.13685}, pmid = {33099885}, issn = {1751-7915}, abstract = {An appreciation for how microorganisms can benefit human health has grown over the past century. The future of this research will be to identify the specific microbial enzymatic pathways and molecules necessary for health promotion. Some of these 'beneficial factors' are already known for probiotics and species in the human microbiome, however, precise descriptions of the mechanistic details for their effects remain to be discovered. The need for this research is elevated by the potential use of microorganisms for preventing and treating the non-communicable diseases which are now the leading causes of death worldwide.}, }
@article {pmid33096717, year = {2020}, author = {Kiljunen, S}, title = {Editorial for the Special Issue: "Phage Therapy: A Biological Approach to Treatment of Bacterial Infections".}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33096717}, issn = {2079-6382}, abstract = {The emergence of antibiotic-resistant bacteria presents a major challenge in terms of increased morbidity, mortality, and healthcare costs [...].}, }
@article {pmid33092203, year = {2020}, author = {Yang, D and Xu, W}, title = {Clustering on Human Microbiome Sequencing Data: A Distance-Based Unsupervised Learning Model.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {33092203}, issn = {2076-2607}, support = {145546/CAPMC/CIHR/Canada ; RGPIN20170667//Natural Sciences and Engineering Research Council of Canada/ ; CCCGEMIII//Crohn's and Colitis Canada/ ; 2019-2022//Edwin S.H. Leong Scholarship/ ; }, abstract = {Modeling and analyzing human microbiome allows the assessment of the microbial community and its impacts on human health. Microbiome composition can be quantified using 16S rRNA technology into sequencing data, which are usually skewed and heavy-tailed with excess zeros. Clustering methods are useful in personalized medicine by identifying subgroups for patients stratification. However, there is currently a lack of standardized clustering method for the complex microbiome sequencing data. We propose a clustering algorithm with a specific beta diversity measure that can address the presence-absence bias encountered for sparse count data and effectively measure the sample distances for sample stratification. Our distance measure used for clustering is derived from a parametric based mixture model producing sample-specific distributions conditional on the observed operational taxonomic unit (OTU) counts and estimated mixture weights. The method can provide accurate estimates of the true zero proportions and thus construct a precise beta diversity measure. Extensive simulation studies have been conducted and suggest that the proposed method achieves substantial clustering improvement compared with some widely used distance measures when a large proportion of zeros is presented. The proposed algorithm was implemented to a human gut microbiome study on Parkinson's diseases to identify distinct microbiome states with biological interpretations.}, }
@article {pmid33085540, year = {2020}, author = {Del Chierico, F and Grassini, P and Quagliariello, A and Torti, M and Russo, A and Reddel, S and Stocchi, F}, title = {The impact of intestinal microbiota on weight loss in Parkinson's disease patients: a pilot study.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1393-1404}, doi = {10.2217/fmb-2019-0336}, pmid = {33085540}, issn = {1746-0921}, abstract = {Background: There is increasing evidence of the association between microbiome dysfunction and Parkinson's disease (PD). Moreover, some PD patients suffer from unintentional weight loss (WL) which may precede the motor manifestations of the disease. Materials & methods: Gut microbiota profiling by 16S rRNA gene sequencing was performed in PD patients with an unintended WL, in steady weight patients (non-WL [NWL]) and in matched normal subjects. KEGG functional predictions were carried out. Results: Microbiota profiles revealed a dissimilarity between WL and NWL. Moreover, WL pathways were characterized by fatty acid biosynthesis, while NWL by inflammation pathways. Conclusion: The gut microbiota could participate in weight alteration observed in PD by the presence of bacteria involved in weight gain and inflammation, or conversely by bacteria implicated in energy expenditure.}, }
@article {pmid33085024, year = {2020}, author = {Deschamps, C and Fournier, E and Uriot, O and Lajoie, F and Verdier, C and Comtet-Marre, S and Thomas, M and Kapel, N and Cherbuy, C and Alric, M and Almeida, M and Etienne-Mesmin, L and Blanquet-Diot, S}, title = {Comparative methods for fecal sample storage to preserve gut microbial structure and function in an in vitro model of the human colon.}, journal = {Applied microbiology and biotechnology}, volume = {104}, number = {23}, pages = {10233-10247}, doi = {10.1007/s00253-020-10959-4}, pmid = {33085024}, issn = {1432-0614}, abstract = {In vitro gut models, such as the mucosal artificial colon (M-ARCOL), provide timely and cost-efficient alternatives to in vivo assays allowing mechanistic studies to better understand the role of human microbiome in health and disease. Using such models inoculated with human fecal samples may require a critical step of stool storage. The effects of preservation methods on microbial structure and function in in vitro gut models have been poorly investigated. This study aimed to assess the impact of three commonly used preserving methods, compared with fresh fecal samples used as a control, on the kinetics of lumen and mucus-associated microbiota colonization in the M-ARCOL model. Feces from two healthy donors were frozen 48 h at - 80 °C with or without cryoprotectant (10% glycerol) or lyophilized with maltodextrin and trehalose prior to inoculation of four parallel bioreactors (e.g., fresh stool, raw stool stored at - 80 °C, stool stored at - 80 °C with glycerol and lyophilized stool). Microbiota composition and diversity (qPCR and 16S metabarcoding) as well as metabolic activity (gases and short chain fatty acids) were monitored throughout the fermentation process (9 days). All the preservative treatments allowed the maintaining inside the M-ARCOL of a complex and functional microbiota, but considering stabilization time of microbial profiles and activities (and not technical constraints associated with the supply of frozen material), our results highlighted 48 h freezing at - 80 °C without cryoprotectant as the most efficient method. These results will help scientists to determine the most accurate method for fecal storage prior to inoculation of in vitro gut microbiome models. KEY POINTS: • In vitro ARCOL model reproduces luminal and mucosal human microbiome. • Short-term storage of fecal sample influences microbial stabilization and activity. • 48 h freezing at - 80°C: most efficient method to preserve microbial ecosystem. • Scientific and technical requirements: influencers of preservation method.}, }
@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 = {EY029266/NH/NIH HHS/United States ; }, 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 {pmid33075154, year = {2020}, author = {Wenger, K and Pendleton, C and Xie, XJ and Caplan, DJ and Drake, D and Marchini, L}, title = {Factors associated with the counts of selected oral microorganisms in nursing home residents.}, journal = {Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry}, volume = {}, number = {}, pages = {}, doi = {10.1111/scd.12530}, pmid = {33075154}, issn = {1754-4505}, support = {/TR/NCATS NIH HHS/United States ; #U54TR001356/NH/NIH HHS/United States ; //Delta Dental of Iowa Foundation/ ; }, abstract = {PURPOSE/AIM: To analyze potential factors associated with levels of selected oral pathogens, as well as total aerobic bacterial species, among nursing home residents.
MATERIALS AND METHODS: Nursing home residents were divided into three groups (G1 included people with teeth but no dentures, G2 included people with teeth and dentures, and G3 included people with no teeth and with dentures). All participants had microbiological samples collected from their oral cavity and dentures. Counts of total aerobic bacterial species, Porphyromonas gingivalis, Fusobacterium nucleatum, Actinomyces viscosus, Aggregatibacter actinomycetemcomitans, and Candida albicans were compared among groups using the Wilcoxon rank sum test. A multivariate analysis was also performed to control other available covariates.
RESULTS: Bivariate analysis revealed significant differences among the groups, and multivariate analysis showed that sex, the presence of natural teeth, denture wearing, oral hygiene indices, and systemic health conditions were associated with bacterial and Candida albicans log counts.
CONCLUSIONS: Presence of natural teeth and denture wearing, as well as oral hygiene, sex and systemic health conditions were associated with bacterial and Candida albicans log counts among nursing home residents.}, }
@article {pmid33073043, year = {2020}, author = {De Souza, ALPB}, title = {Finding the hot spot: identifying immune sensitive gastrointestinal tumors.}, journal = {Translational gastroenterology and hepatology}, volume = {5}, number = {}, pages = {48}, pmid = {33073043}, issn = {2415-1289}, abstract = {Although researchers have been trying to harness the immune system for over 100 years, the advent of immune checkpoint blockers (ICB) marks an era of significant clinical outcomes in various metastatic solid tumors, characterized by complete and durable responses. ICBs are monoclonal antibodies that target either of a pair of transmembrane molecules in tumors or T-cells involved in immune evasion. Currently 2 ICBs targeting the checkpoint program death 1 (PD-1), nivolumab and pembrolizumab, and one cytotoxic lymphocyte antigen-4 (CTLA-4) inhibitor (ipilimumab) are approved in gastrointestinal malignancies. We review herein the current evidence on predictive biomarkers for ICB response in gastrointestinal tumors. A review of literature based on the National Cancer Institute list of FDA-approved drugs for neoplasms and FDA-approved therapies at the FDA website was performed. An initial literature review was based on the American Association for Clinical Research meeting 2019, the American Society of Clinical Oncology meeting 2019 and the European Society of Medical Oncology 2019 proceedings. A systematic search of PubMed was performed involving MeSH browser terms such as biomarkers, immunotherapy, gastrointestinal diseases and neoplasms. When appropriate, American and British terms were used in the search. The most relevant predictor of response to ICBs is microsatellite instability (MSI) and the data is strongest for colorectal cancer. At least 3 prospective trials show evidence of PD-L1 as a predictive biomarker for ICB response in gastroesophageal malignancies. At least one prospective trial has described tumor mutational burden high (TMB-H), independent of MSI, as predictive of response in anal and biliary tract carcinomas. DNA Polymerase Epsilon (POLE) or delta (POL-D) mutations have been implicated in a subset of MSS colorectal cancer with TMB-H but this biomarker requires prospective validation. There is evolving data based on retrospective observations that gene alterations predicting acquired resistance and hyper-progression. Ongoing clinical research is assessing the role of the human microbiome and RNA-editing complex mutations as predictive biomarkers of response to ICBs. MSI has the strongest predictive power among current biomarkers for ICB response in gastrointestinal cancers. Data continue to accumulate from ongoing clinical trials and new biomarkers are emerging from pre-clinical studies, suggesting that drug combinations targeting pathways complimentary to the PD-1/PD-L1 axis inhibition will define a robust field of clinical research.}, }
@article {pmid33072872, year = {2020}, author = {Flores Bueso, Y and Walker, SP and Tangney, M}, title = {Characterization of FFPE-induced bacterial DNA damage and development of a repair method.}, journal = {Biology methods & protocols}, volume = {5}, number = {1}, pages = {bpaa015}, pmid = {33072872}, issn = {2396-8923}, abstract = {Formalin-fixed, paraffin-embedded (FFPE) specimens have huge potential as source material in the field of human microbiome research. However, the effects of FFPE processing on bacterial DNA remain uncharacterized. Any effects are relevant for microbiome studies, where DNA template is often minimal and sequences studied are not limited to one genome. As such, we aimed to both characterize this FFPE-induced bacterial DNA damage and develop strategies to reduce and repair this damage. Our analyses indicate that bacterial FFPE DNA is highly fragmented, a poor template for PCR, crosslinked and bears sequence artefacts derived predominantly from oxidative DNA damage. Two strategies to reduce this damage were devised - an optimized decrosslinking procedure reducing sequence artefacts generated by high-temperature incubation, and secondly, an in vitro reconstitution of the base excision repair pathway. As evidenced by whole genome sequencing, treatment with these strategies significantly increased fragment length, reduced the appearance of sequence artefacts and improved the sequencing readability of bacterial and mammalian FFPE DNA. This study provides a new understanding of the condition of bacterial DNA in FFPE specimens and how this impacts downstream analyses, in addition to a strategy to improve the sequencing quality of bacterial and possibly mammalian FFPE DNA.}, }
@article {pmid33072766, year = {2020}, author = {Kirichenko, TV and Markina, YV and Sukhorukov, VN and Khotina, VA and Wu, WK and Orekhov, AN}, title = {A Novel Insight at Atherogenesis: The Role of Microbiome.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {586189}, pmid = {33072766}, issn = {2296-634X}, abstract = {There is an important task of current medicine to identify mechanisms and new markers of subclinical atherosclerosis in order to develop early targets for the diagnosis and treatment of this disease, since it causes such widespread diseases as myocardial infarction, stroke, sudden death, and other common reasons of disability and mortality in developed countries. In recent years, studies of the human microbiome in different fields of medicine have become increasingly popular; there is evidence from numerous studies of the significant contribution of microbiome in different steps of atherogenesis. This review attempted to determine the current status of the databases PubMed and Scopus (until May, 2020) to highlight current ideas on the potential role of microbiome and its metabolites in atherosclerosis development, its mechanisms of action in lipids metabolism, endothelial dysfunction, inflammatory pathways, and mitochondrial dysfunction. Results of clinical studies elucidating the relationship of microbiome with subclinical atherosclerosis and cardiovascular disease considered in this article demonstrate strong association of microbiome composition and its metabolites with atherosclerosis and cardiovascular disease. Data on microbiome impact in atherogenesis open a wide perspective to develop new diagnostic and therapeutic approaches, but further comprehensive studies are necessary.}, }
@article {pmid33067429, year = {2020}, author = {Rackaityte, E and Lynch, SV}, title = {The human microbiome in the 21st century.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5256}, pmid = {33067429}, issn = {2041-1723}, support = {F31 AI136336/AI/NIAID NIH HHS/United States ; UM1 AI114271/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation & purification/metabolism ; Biodiversity ; Humans ; Mice ; *Microbiota ; }, }
@article {pmid33066814, year = {2020}, author = {Castañeda, S and Muñoz, M and Villamizar, X and Hernández, PC and Vásquez, LR and Tito, RY and Ramírez, JD}, title = {Microbiota characterization in Blastocystis-colonized and Blastocystis-free school-age children from Colombia.}, journal = {Parasites & vectors}, volume = {13}, number = {1}, pages = {521}, pmid = {33066814}, issn = {1756-3305}, abstract = {BACKGROUND: Blastocystis is a protist that lives in the intestinal tract of a variety of hosts, including humans. It is still unclear how Blastocystis causes disease, which presents an ongoing challenge for researchers. Despite the controversial findings on the association between Blastocystis and clinical digestive manifestations, there is currently no consensus as to whether this protozoan actually behaves as a pathogen in humans. Furthermore, the relationship between Blastocystis and the intestinal microbiota composition is not yet clear. For that reason, the aim of this study was to identify if colonization by Blastocystis is related to changes in the diversity and relative abundance of bacterial communities, compared with those of Blastocystis-free individuals in a group of Colombian children.
METHODS: We took stool samples from 57 school-aged children attending a daycare institution in Popayán (Southwest Colombia). Whole DNA was extracted and examined by 16S-rRNA amplicon-based sequencing. Blastocystis was detected by real time PCR and other intestinal parasites were detected by microscopy. We evaluated if Blastocystis was associated with host variables and the diversity and abundance of microbial communities.
RESULTS: The composition of the intestinal bacterial community was not significantly different between Blastocystis-free and Blastocystis-colonized children. Despite this, we observed a higher microbial richness in the intestines of children colonized by Blastocystis, which could, therefore, be considered a benefit to intestinal health. The phylum Firmicutes was the predominant taxonomic unit in both groups analyzed. In Blastocystis-free individuals, there was a higher proportion of Bacteroidetes; similarly, in children colonized by Blastocystis, there was a higher relative abundance of the phylum Proteobacteria; however, no statistically significant differences were found between the comparison groups.
CONCLUSIONS: The presence of Blastocystis showed a decrease in Bacteroides, and an increase in the relative abundance of the genus Faecalibacterium. It was also evident that the presence of Blastocystis was unrelated to dysbiosis at the intestinal level; on the contrary, its presence did not show statistically differences in the intestinal microbiota composition. Nevertheless, we believe that Blastocystis plays a role in the ecology of the intestinal microbiota through its interaction with other microbial components.}, }
@article {pmid33062112, year = {2020}, author = {Tan, HY and Toh, YC}, title = {What can microfluidics do for human microbiome research?.}, journal = {Biomicrofluidics}, volume = {14}, number = {5}, pages = {051303}, pmid = {33062112}, issn = {1932-1058}, abstract = {Dysregulation of the human microbiome has been linked to various disease states, which has galvanized the efforts to modulate human health through microbiomes. Currently, human microbiome research is going through several phases to identify the constituent components of the microbiome, associate microbiome changes with physiological and pathological states, understand causative relationships, and finally translate this knowledge into therapeutics and diagnostics. The convergence of microfluidic technologies with molecular and cell profiling, microbiology, and tissue engineering can potentially be applied to these different phases of microbiome research to overcome the existing challenges faced by conventional approaches. The goal of this paper is to discuss and highlight the opportunities of applying different microfluidic technologies to specific areas of microbiome research as well as unique challenges that microfluidics must overcome when working with microbiome-relevant biological materials, e.g., micro-organisms, host tissues, and fluids. We will discuss the applicability of integrated microfluidic systems for processing biological samples for genomic sequencing analyses. For functional analysis of the microbiota, we will cover state-of-the-art microfluidic devices for microbiota cultivation and functional measurements. Finally, we highlight the use of organs-on-chips to model various microbiome-host tissue interactions. We envision that microfluidic technologies may hold great promise in advancing the knowledge on the interplay between microbiome and human health, as well as its eventual translation into microbiome-based diagnostics and therapeutics.}, }
@article {pmid33054163, year = {2020}, author = {Eller, CH and Raines, RT}, title = {Antimicrobial Synergy of a Ribonuclease and a Peptide Secreted by Human Cells.}, journal = {ACS infectious diseases}, volume = {6}, number = {11}, pages = {3083-3088}, pmid = {33054163}, issn = {2373-8227}, support = {R01 CA073808/CA/NCI NIH HHS/United States ; S10 OD018202/OD/NIH HHS/United States ; }, abstract = {LL-37 is a secretory peptide that has antimicrobial activity. Ribonuclease 1 (RNase 1) is a secretory enzyme that is not cytotoxic. We find that human LL-37 and human RNase 1 can act synergistically to kill Gram-negative bacterial cells. In the presence of nontoxic concentrations of LL-37, RNase 1 is toxic to Escherichia coli cells at picomolar levels. Using wild-type RNase 1 and an inactive variant labeled with a fluorophore, we observe the adherence of RNase 1 to E. coli cells and its cellular entry in the presence of LL-37. These data suggest a natural means of modulating the human microbiome via the cooperation of an endogenous peptide (37 residues) and small enzyme (128 residues).}, }
@article {pmid33052545, year = {2020}, author = {Haak, BW and Westendorp, WF and van Engelen, TSR and Brands, X and Brouwer, MC and Vermeij, JD and Hugenholtz, F and Verhoeven, A and Derks, RJ and Giera, M and Nederkoorn, PJ and de Vos, WM and van de Beek, D and Wiersinga, WJ}, title = {Disruptions of Anaerobic Gut Bacteria Are Associated with Stroke and Post-stroke Infection: a Prospective Case-Control Study.}, journal = {Translational stroke research}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12975-020-00863-4}, pmid = {33052545}, issn = {1868-601X}, support = {171002302//ZonMw (NL)/ ; 016116358//ZonMw (NL)/ ; 91716475//ZonMw (NL)/ ; 2009B095//Hartstichting (NL)/ ; ERC Starting Grant//H2020 European Research Council ()/ ; Spinoza Grant//ZonMw/ ; }, abstract = {In recent years, preclinical studies have illustrated the potential role of intestinal bacterial composition in the risk of stroke and post-stroke infections. The results of these studies suggest that bacteria capable of producing volatile metabolites, including trimethylamine-N-oxide (TMAO) and butyrate, play opposing, yet important roles in the cascade of events leading to stroke. However, no large-scale studies have been undertaken to determine the abundance of these bacterial communities in stroke patients and to assess the impact of disrupted compositions of the intestinal microbiota on patient outcomes. In this prospective case-control study, rectal swabs from 349 ischemic and hemorrhagic stroke patients (median age, 71 years; IQR: 67-75) were collected within 24 h of hospital admission. Samples were subjected to 16S rRNA amplicon sequencing and subsequently compared with samples obtained from 51 outpatient age- and sex-matched controls (median age, 72 years; IQR, 62-80) with similar cardiovascular risk profiles but without active signs of stroke. Plasma protein biomarkers were analyzed using a combination of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Alpha and beta diversity analyses revealed higher disruption of intestinal communities during ischemic and hemorrhagic stroke compared with non-stroke matched control subjects. Additionally, we observed an enrichment of bacteria implicated in TMAO production and a loss of butyrate-producing bacteria. Stroke patients displayed two-fold lower plasma levels of TMAO than controls (median 1.97 vs 4.03 μM, Wilcoxon p < 0.0001). Finally, lower abundance of butyrate-producing bacteria within 24 h of hospital admission was an independent predictor of enhanced risk of post-stroke infection (odds ratio 0.77, p = 0.005), but not of mortality or functional patient outcome. In conclusion, aberrations in trimethylamine- and butyrate-producing gut bacteria are associated with stroke and stroke-associated infections.}, }
@article {pmid33047342, year = {2020}, author = {Reichhardt, MP and Messing, M and Andersson, S and Kolho, KL and Meri, S}, title = {Intestinal SALSA/dmbt1 levels are decreased in prematurely born infants.}, journal = {Scandinavian journal of immunology}, volume = {}, number = {}, pages = {e12987}, doi = {10.1111/sji.12987}, pmid = {33047342}, issn = {1365-3083}, support = {TYH2018313//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; TYH2019311//Helsingin ja Uudenmaan Sairaanhoitopiiri/ ; 292393//Academy of Finland/ ; //Sigrid Juséliuksen Säätiö/ ; //Pediatic Research Foundation/ ; }, abstract = {The first months of life represent a crucial time period for an infant. Alongside establishing the early microbiome, the mucosal immunological homeostasis is being developed. Both processes may be perturbed in prematurely born infants. The glycoprotein SALSA plays a role in mucosal inflammation and microbial clearance. It is one of the most abundant molecules on the intestinal mucosal surfaces in early life. SALSA binds to many types of microbes and host defence molecules like IgA, C1q and collectin molecules. We here describe the development in faecal SALSA levels during the first three months of life. During these 90 days, the median SALSA level in full-term babies decreased from 1100 μg/mL (range 49-17 000 μg/mL) to 450 μg/mL (range 33-1000 μg/mL). Lower levels of SALSA were observed in prematurely born infants in the same time period. Our novel observation thus indicates an impact of prematurity on an important component of the infant intestinal immune system. Changes in SALSA in early life may have an effect on the early establishment of the human microbiome.}, }
@article {pmid33045987, year = {2020}, author = {Kenney, T and Gao, J and Gu, H}, title = {Application of OU processes to modelling temporal dynamics of the human microbiome, and calculating optimal sampling schemes.}, journal = {BMC bioinformatics}, volume = {21}, number = {1}, pages = {450}, pmid = {33045987}, issn = {1471-2105}, support = {RGPIN/4945-2014//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2017-05108//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Healthy Volunteers ; Humans ; Kinetics ; *Microbiota ; *Models, Biological ; Stochastic Processes ; }, abstract = {BACKGROUND: The vast majority of microbiome research so far has focused on the structure of the microbiome at a single time-point. There have been several studies that measure the microbiome from a particular environment over time. A few models have been developed by extending time series models to accomodate specific features in microbiome data to address questions of stability and interactions of the microbime time series. Most research has observed the stability and mean reversion for some microbiomes. However, little has been done to study the mean reversion rates of these stable microbes and how sampling frequencies are related to such conclusions. In this paper, we begin to rectify this situation. We analyse two widely studied microbial time series data sets on four healthy individuals. We choose to study healthy individuals because we are interested in the baseline temporal dynamics of the microbiome.
RESULTS: For this analysis, we focus on the temporal dynamics of individual genera, absorbing all interactions in a stochastic term. We use a simple stochastic differential equation model to assess the following three questions. (1) Does the microbiome exhibit temporal continuity? (2) Does the microbiome have a stable state? (3) To better understand the temporal dynamics, how frequently should data be sampled in future studies? We find that a simple Ornstein-Uhlenbeck model which incorporates both temporal continuity and reversion to a stable state fits the data for almost every genus better than a Brownian motion model that contains only temporal continuity. The Ornstein-Uhlenbeck model also fits the data better than modelling separate time points as independent. Under the Ornstein-Uhlenbeck model, we calculate the variance of the estimated mean reversion rate (the speed with which each genus returns to its stable state). Based on this calculation, we are able to determine the optimal sample schemes for studying temporal dynamics.
CONCLUSIONS: There is evidence of temporal continuity for most genera; there is clear evidence of a stable state; and the optimal sampling frequency for studying temporal dynamics is in the range of one sample every 0.8-3.2 days.}, }
@article {pmid33042984, year = {2020}, author = {Gao, H and Sun, T and Yang, F and Yuan, J and Yang, M and Kang, W and Tang, D and Zhang, J and Feng, Q}, title = {The Pathogenic Effects of Fusobacterium nucleatum on the Proliferation, Osteogenic Differentiation, and Transcriptome of Osteoblasts.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {807}, pmid = {33042984}, issn = {2296-634X}, abstract = {As one of the most common oral diseases, periodontitis is closely correlated with tooth loss in middle-aged and elderly people. Fusobacterium nucleatum (F. nucleatum) contributes to periodontitis, but the evidence in alveolar bone loss is still unclear. In this study, cytological experiments and transcriptome analyses were performed to characterize the biological process abnormalities and the molecular changes of F. nucleatum-stimulated osteoblasts. F. nucleatum could inhibit cell proliferation, promote cell apoptosis, and elevate pro-inflammatory cytokine production of osteoblasts, and it also inhibited osteoblast differentiation and mineralized nodule formation and decreased the expression of osteogenetic genes and proteins. Whole-transcriptome analyses identified a total of 235 transcripts that were differentially expressed in all six time points, most of which were inflammation-related genes. The genes, Ccl2, Ccl20, Csf1, Cx3cl1, Cxcl1, Cxcl3, Il6, Birc3, Map3k8, Nos2, Nfkb2, Tnfrsf1b, and Vcam1, played core roles in a PPI network, and interacted closely with other ones in the infection. In addition, 133 osteogenesis-related differential expression genes (DEGs) were time-serially dynamically changed in a short time-series expression miner (STEM) analysis, which were enriched in multiple cancer-related pathways. The core dynamic DEGs (Mnda, Cyp1b1, Comp, Phex, Mmp3, Tnfrsf1b, Fbln5, and Nfkb2) had been reported to be closely related to the development and metastasis in tumor and cancer progress. This study is the first to evaluate the long-term interaction of F. nucleatum on osteoblasts, which might increase the risk of cell carcinogenesis of normal osteoblasts, and provides new insight into the pathogenesis of bacterial-induced bone destruction.}, }
@article {pmid33036309, year = {2020}, author = {Vernocchi, P and Marini, F and Capuani, G and Tomassini, A and Conta, G and Del Chierico, F and Malattia, C and De Benedetti, F and Martini, A and Dallapiccola, B and van Dijkhuizen, EHP and Miccheli, A and Putignani, L}, title = {Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {33036309}, issn = {2076-2607}, abstract = {Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.}, }
@article {pmid33031136, year = {2020}, author = {Shi, HL and Lan, YH and Hu, ZC and Yan, ZN and Liu, ZZ and Kadier, X and Ma, L and Yu, JY and Liu, J}, title = {Microecology research: a new target for the prevention of asthma.}, journal = {Chinese medical journal}, volume = {133}, number = {22}, pages = {2712-2720}, pmid = {33031136}, issn = {2542-5641}, abstract = {The incidence and prevalence of asthma have increased remarkably in recent years. There are lots of factors contributing to the occurrence and development of asthma. With the improvement of sequencing technology, it has been found that the microbiome plays an important role in the formation of asthma in early life. The roles of the microbial environment and human microbiome in the occurrence and development of asthma have attracted more and more attention. The environmental microbiome influences the occurrence of asthma by shaping the human microbiome. The specific mechanism may be related to the immune regulation of Toll-like receptors and T cells (special Tregs). Intestinal microbiome is formed and changed by regulating diet and lifestyle in early life, which may affect the development and maturation of the pulmonary immune system through the intestinal-pulmonary axis. It is well-recognized that both environmental microbiomes and human microbiomes can influence the onset of asthma. This review aims to summarize the recent advances in the research of microbiome, its relationship with asthma, and the possible mechanism of the microbiome in the occurrence and development of asthma. The research of the microbial environment and human microbiome may provide a new target for the prevention of asthma in children who have high-risk factors to allergy. However, further study of "when and how" to regulate microbiome is still needed.}, }
@article {pmid33025908, year = {2020}, author = {Kozik, AJ}, title = {mSphere of Influence: Frameshift-a Vision for Human Microbiome Research.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33025908}, issn = {2379-5042}, mesh = {Female ; Humans ; *Microbiota ; }, abstract = {Ariangela J. Kozik studies the respiratory microbiome as it relates to asthma. In this mSphere of Influence article, she reflects on how two papers, "Time's up to adopt a biopsychosocial model to address racial and ethnic disparities in asthma outcomes" (E. C. Matsui, A. S. Adamson, and R. D. Peng, Allergy Clin Immunol 143:2024-2025, 2019, https://doi.org/10.1016/j.jaci.2019.03.015) and "Health disparities and the microbiome" (K. Findley, D. R. Williams, E. A. Grice, and V. L. Bonham, Trends Microbiol 24:847-850, 2016, https://doi.org/10.1016/j.tim.2016.08.001), shape her approach to human microbiome research.}, }
@article {pmid33019595, year = {2020}, author = {Santacroce, L and Charitos, IA and Ballini, A and Inchingolo, F and Luperto, P and De Nitto, E and Topi, S}, title = {The Human Respiratory System and its Microbiome at a Glimpse.}, journal = {Biology}, volume = {9}, number = {10}, pages = {}, pmid = {33019595}, issn = {2079-7737}, abstract = {The recent COVID-19 pandemic promoted efforts to better understand the organization of the respiratory microbiome and its evolution from birth to adulthood and how it interacts with external pathogens and the host immune system. This review aims to deepen understanding of the essential physiological functions of the resident microbiome of the respiratory system on human health and diseases. First, the general characteristics of the normal microbiota in the different anatomical sites of the airways have been reported in relation to some factors such as the effect of age, diet and others on its composition and stability. Second, we analyze in detail the functions and composition and the correct functionality of the microbiome in the light of current knowledge. Several studies suggest the importance of preserving the micro-ecosystem of commensal, symbiotic and pathogenic microbes of the respiratory system, and, more recently, its relationship with the intestinal microbiome, and how it also leads to the maintenance of human health, has become better understood.}, }
@article {pmid33014929, year = {2020}, author = {Durack, J and Christophersen, CT}, title = {Human Respiratory and Gut Microbiomes-Do They Really Contribute to Respiratory Health?.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {528}, pmid = {33014929}, issn = {2296-2360}, abstract = {Human gastrointestinal and respiratory tracts are colonized by diverse polymicrobial communities shortly after birth, which are continuously molded by environmental exposure. The development of the resident microbiota in early life is a critical factor in the maturation of a healthy immune system. Disturbances to the intricate relationship between environmental exposure and maturation of the infant microbiome have been increasingly identified as a potential contributor to a range of childhood diseases. This review details recent evidence that implicates the contribution of gut and airway microbiome to pediatric respiratory health.}, }
@article {pmid33012230, year = {2020}, author = {Jacobson, DK and Honap, TP and Monroe, C and Lund, J and Houk, BA and Novotny, AC and Robin, C and Marini, E and Lewis, CM}, title = {Functional diversity of microbial ecologies estimated from ancient human coprolites and dental calculus.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1812}, pages = {20190586}, pmid = {33012230}, issn = {1471-2970}, support = {R01 GM089886/GM/NIGMS NIH HHS/United States ; }, abstract = {Human microbiome studies are increasingly incorporating macroecological approaches, such as community assembly, network analysis and functional redundancy to more fully characterize the microbiome. Such analyses have not been applied to ancient human microbiomes, preventing insights into human microbiome evolution. We address this issue by analysing published ancient microbiome datasets: coprolites from Rio Zape (n = 7; 700 CE Mexico) and historic dental calculus (n = 44; 1770-1855 CE, UK), as well as two novel dental calculus datasets: Maya (n = 7; 170 BCE-885 CE, Belize) and Nuragic Sardinians (n = 11; 1400-850 BCE, Italy). Periodontitis-associated bacteria (Treponema denticola, Fusobacterium nucleatum and Eubacterium saphenum) were identified as keystone taxa in the dental calculus datasets. Coprolite keystone taxa included known short-chain fatty acid producers (Eubacterium biforme, Phascolarctobacterium succinatutens) and potentially disease-associated bacteria (Escherichia, Brachyspira). Overlap in ecological profiles between ancient and modern microbiomes was indicated by similarity in functional response diversity profiles between contemporary hunter-gatherers and ancient coprolites, as well as parallels between ancient Maya, historic UK, and modern Spanish dental calculus; however, the ancient Nuragic dental calculus shows a distinct ecological structure. We detected key ecological signatures from ancient microbiome data, paving the way to expand understanding of human microbiome evolution. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.}, }
@article {pmid33012224, year = {2020}, author = {Schnorr, SL}, title = {The soil in our microbial DNA informs about environmental interfaces across host and subsistence modalities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1812}, pages = {20190577}, pmid = {33012224}, issn = {1471-2970}, abstract = {In this study, I use microbiome datasets from global soil samples and diverse hosts to learn whether soil microbial taxa are found in host microbiomes, and whether these observations fit the narrative that environmental interaction influences human microbiomes. A major motivation for conducting host-associated microbiome research is to contribute towards understanding how the environment may influence host physiology. The microbial molecular network is considered a key vector by which environmental traits may be transmitted to the host. Research on human evolution seeks evidence that can inform about the living experiences of human ancestors. This objective is substantially enhanced by recent work on ancient biomolecules from preserved microbial tissues, such as dental calculus, faecal sediments and whole coprolites. A challenge yet is to distinguish authentic biomolecules from environmental contaminants deposited contemporaneously, primarily from soil. However, we do not have sound expectations about the soil microbial elements arriving to host-associated microbiomes in a modern context. One assumption in human microbiome research is that proximity to the natural environment should affect biodiversity or impart genetic elements. I present evidence supporting the assumption that environmental soil taxa are found among host-associated gut taxa, which can recapitulate the surrounding host habitat ecotype. Soil taxa found in gut microbiomes relate to a set of universal 'core' taxa for all soil ecotypes, demonstrating that widespread host organisms may experience a consistent pattern of external environmental cues, perhaps critical for development. Observed differentiation of soil feature diversity, abundance and composition among human communities, great apes and invertebrate hosts also indicates that lifestyle patterns are inferable from an environmental signal that is retrievable from gut microbiome amplicon data. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.}, }
@article {pmid33007632, year = {2020}, author = {Wan, X and Hendrix, H and Skurnik, M and Lavigne, R}, title = {Phage-based target discovery and its exploitation towards novel antibacterial molecules.}, journal = {Current opinion in biotechnology}, volume = {68}, number = {}, pages = {1-7}, doi = {10.1016/j.copbio.2020.08.015}, pmid = {33007632}, issn = {1879-0429}, abstract = {The deeply intertwined evolutionary history between bacteriophages and bacteria has endowed phages with highly specific mechanisms to hijack bacterial cell metabolism for their propagation. Here, we present a comprehensive, phage-driven strategy to reveal novel antibacterial targets by the exploitation of phage-bacteria interactions. This strategy will enable the design of small molecules, which mimic the inhibitory phage proteins, and allow the subsequent hit-to-lead development of these antimicrobial compounds. This proposed small molecule approach is distinct from phage therapy and phage enzyme-based antimicrobials and may produce a more sustainable generation of new antibiotics that exploit novel bacterial targets and act in a pathogen-specific manner.}, }
@article {pmid33007464, year = {2021}, author = {Bhar, S and Edelmann, MJ and Jones, MK}, title = {Characterization and proteomic analysis of outer membrane vesicles from a commensal microbe, Enterobacter cloacae.}, journal = {Journal of proteomics}, volume = {231}, number = {}, pages = {103994}, doi = {10.1016/j.jprot.2020.103994}, pmid = {33007464}, issn = {1876-7737}, abstract = {Outer membrane vesicles (OMVs) are membrane-enclosed spherical entities released by gram-negative bacteria and are important for bacterial survival under stress conditions. There have been numerous studies on OMVs released by gram-negative pathogenic bacteria, but an understanding of the functions and characteristics of the OMVs produced by commensal microbes is still lacking. Enterobacter cloacae is a gram-negative commensal bacterium present in the human gut microbiome, but this organism can also function as an opportunistic pathogen. Understanding the OMV-mediated communication route between bacteria-bacteria or bacteria-host is essential for the determination of the biological functions of the commensal bacterium in the gut and delineating between benign and virulent characteristics. In this study, we have described a proteome of E. cloacae OMVs, which are membrane vesicles in a size range of 20-300 nm. Proteomic analysis showed the presence of membrane-bound proteins, including transporters, receptors, signaling molecules, and protein channels. The physical and proteomic analyses also indicate this bacterium uses two mechanisms for OMV production. This study is one of the few existing descriptions of the proteomic profile of OMVs generated by a commensal Proteobacteria, and the first report of OMVs produced by E. cloacae. SIGNIFICANCE: This study prioritizes the importance of understanding the vesicular proteome of the human commensal bacterium, Enterobacter cloacae. We demonstrate for the first time that the gram-negative bacterium E. cloacae ATCC 13047 produces outer membrane vesicles (OMVs). The proteomic analysis showed enrichment of membrane-bound proteins in these vesicles. Understanding the cargo proteins of OMVs will help in exploring the physiological and functional role of these vesicles in the human microbiome and how they assist in the conversion of a bacterium from commensal to pathogen under certain conditions. While EM images reveal vesicles budding from the bacterial surface, the presence of cytoplasmic proteins and genomic DNA within the OMVs indicate that explosive cell lysis is an additional mechanism of biogenesis for these OMVs along with outer membrane blebbing. This research encourages future work on characterizing membrane vesicles produced by commensal bacterial and investigating their role in cell to cell communication.}, }
@article {pmid33007342, year = {2020}, author = {Rajeev, R and Prathiviraj, R and Kiran, GS and Selvin, J}, title = {Zoonotic evolution and implications of microbiome in viral transmission and infection.}, journal = {Virus research}, volume = {290}, number = {}, pages = {198175}, doi = {10.1016/j.virusres.2020.198175}, pmid = {33007342}, issn = {1872-7492}, mesh = {Animals ; *Biological Evolution ; COVID-19/transmission/virology ; Chiroptera/virology ; Coronaviridae/classification/*genetics/physiology ; Coronaviridae Infections/*transmission/virology ; Genome, Viral/genetics ; Humans ; *Microbiota ; Phylogeny ; SARS-CoV-2/classification/genetics/physiology ; Zoonoses/*transmission/virology ; }, abstract = {The outbreak and spread of new strains of coronavirus (SARS-CoV-2) remain a global threat with increasing cases in affected countries. The evolutionary tree of SARS-CoV-2 revealed that Porcine Reproductive and Respiratory Syndrome virus 2, which belongs to the Beta arterivirus genus from the Arteriviridae family is possibly the most ancient ancestral origin of SARS-CoV-2 and other Coronaviridae. This review focuses on phylogenomic distribution and evolutionary lineage of zoonotic viral cross-species transmission of the Coronaviridae family and the implications of bat microbiome in zoonotic viral transmission and infection. The review also casts light on the role of the human microbiome in predicting and controlling viral infections. The significance of microbiome-mediated interventions in the treatment of viral infections is also discussed. Finally, the importance of synthetic viruses in the study of viral evolution and transmission is highlighted.}, }
@article {pmid33007265, year = {2020}, author = {Korpela, K and Helve, O and Kolho, KL and Saisto, T and Skogberg, K and Dikareva, E and Stefanovic, V and Salonen, A and Andersson, S and de Vos, WM}, title = {Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.}, journal = {Cell}, volume = {183}, number = {2}, pages = {324-334.e5}, doi = {10.1016/j.cell.2020.08.047}, pmid = {33007265}, issn = {1097-4172}, abstract = {Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.}, }
@article {pmid33001550, year = {2020}, author = {Shetty, SA and Boeren, S and Bui, TPN and Smidt, H and de Vos, WM}, title = {Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics.}, journal = {Environmental microbiology}, volume = {22}, number = {11}, pages = {4863-4875}, pmid = {33001550}, issn = {1462-2920}, support = {024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; NRGWI.obrug.2018.005//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {The d- and l-forms of lactate are important fermentation metabolites produced by intestinal bacteria but are found to negatively affect mucosal barrier function and human health. Both enantiomers of lactate can be converted with acetate into the presumed beneficial butyrate by a phylogenetically related group of anaerobes, including Anaerobutyricum and Anaerostipes spp. This is a low energy yielding process with a partially unknown pathway in Anaerobutyricum and Anaerostipes spp. and hence, we sought to address this via a comparative genomics, proteomics and physiology approach. We compared growth of Anaerobutyricum soehngenii on lactate with that on sucrose and sorbitol. Comparative proteomics revealed complete pathway of butyrate formation from sucrose, sorbitol and lactate. Notably, a gene cluster, lctABCDEF was abundantly expressed when grown on lactate. This gene cluster encodes a lactate dehydrogenase (lctD), electron transport proteins A and B (lctCB), nickel-dependent racemase (lctE), lactate permease (lctF) and short-chain acyl-CoA dehydrogenase (lctG). Investigation of available genomes of intestinal bacteria revealed this new gene cluster to be highly conserved in only Anaerobutyricum and Anaerostipes spp. Present study demonstrates that A. soehngenii and several related Anaerobutyricum and Anaerostipes spp. are highly adapted for a lifestyle involving lactate plus acetate utilization in the human intestinal tract.}, }
@article {pmid33001460, year = {2020}, author = {Ottman, N and Barrientos-Somarribas, M and Fyhrquist, N and Alexander, H and Wisgrill, L and Olah, P and Tsoka, S and Greco, D and Levi-Schaffer, F and Soumelis, V and Schröder, JM and Kere, J and Nestle, FO and Barker, J and Ranki, A and Lauerma, A and Homey, B and Andersson, B and Alenius, H}, title = {Microbial and transcriptional differences elucidate atopic dermatitis heterogeneity across skin sites.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.14606}, pmid = {33001460}, issn = {1398-9995}, support = {821511//IMI2/ ; //Knut och Alice Wallenbergs Stiftelse/ ; 261366//FP7 Health/ ; }, abstract = {It is well established that different sites in healthy human skin are colonized by distinct microbial communities due to different physiological conditions. However, few studies have explored microbial heterogeneity between skin sites in diseased skin, such as atopic dermatitis (AD) lesions. To address this issue, we carried out deep analysis of the microbiome and transcriptome in the skin of a large cohort of AD patients and healthy volunteers, comparing two physiologically different sites: upper back and posterior thigh. Microbiome samples and biopsies were obtained from both lesional and nonlesional skin to identify changes related to the disease process. Transcriptome analysis revealed distinct disease-related gene expression profiles depending on anatomical location, with keratinization dominating the transcriptomic signatures in posterior thigh, and lipid metabolism in the upper back. Moreover, we show that relative abundance of Staphylococcus aureus is associated with disease severity in the posterior thigh, but not in the upper back. Our results suggest that AD may select for similar microbes in different anatomical locations-an "AD-like microbiome," but distinct microbial dynamics can still be observed when comparing posterior thigh to upper back. This study highlights the importance of considering the variability across skin sites when studying the development of skin inflammation.}, }
@article {pmid32999084, year = {2020}, author = {Johnson, MDL}, title = {mSphere Highlights Black In Microbiology Week.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32999084}, issn = {2379-5042}, mesh = {African Continental Ancestry Group/*genetics ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/epidemiology ; *Genetic Determinism ; Humans ; Microbiology ; Microbiota ; Pandemics ; Pneumonia, Viral/epidemiology ; Racism/*prevention & control ; SARS-CoV-2 ; }, abstract = {The inaugural Black In Microbiology Week (#BlackInMicro) is 28 September 2020 through 4 October 2020. Its mission is to "showcase the presence and accomplishments of Black microbiologists from around the globe, connect Black microbiologists with one another and foster a sense of community among them, and provide a forum for the discussion of racial disparities in microbiology and its subfields." Participation in this event will happen primarily over Twitter through the hashtag #BlackInMicro and over Zoom through registration on the website https://blackinmicrobiology.org/ An additional mission of Black In Microbiology Week is to amplify black scientists. Today, mSphere does this by presenting two mSphere of Influence commentaries from Black In Microbiology co-lead organizers Ariangela J. Kozik ("mSphere of Influence: frameshift-a vision for human microbiome research" [mSphere 5:e00944-20, 2020, https://doi.org/10.1128/mSphere.00944-20]) and Kishana Taylor ("mSphere of Influence: that's racist-COVID-19, biological determinism, and the limits of hypotheses" [mSphere 5:e00945-20, 2020, https://doi.org/10.1128/mSphere.00945-20]).}, }
@article {pmid32998695, year = {2020}, author = {Soverini, M and Rampelli, S and Turroni, S and Brigidi, P and Biagi, E and Candela, M}, title = {Do the human gut metagenomic species possess the minimal set of core functionalities necessary for life?.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {678}, pmid = {32998695}, issn = {1471-2164}, abstract = {BACKGROUND: Advances in bioinformatics recently allowed for the recovery of 'metagenomes assembled genomes' from human microbiome studies carried on with shotgun sequencing techniques. Such approach is used as a mean to discover new unclassified metagenomic species, putative biological entities having distinct metabolic traits.
RESULTS: In the present analysis we compare 400 genomes from isolates available on NCBI database and 10,000 human gut metagenomic species, screening all of them for the presence of a minimal set of core functionalities necessary, but not sufficient, for life. As a result, the metagenome-assembled genomes resulted systematically depleted in genes encoding for essential functions apparently needed to support autonomous bacterial life.
CONCLUSIONS: The relevant degree of lacking core functionalities that we observed in metagenome-assembled genomes raises some concerns about the effective completeness of metagenome-assembled genomes, suggesting caution in extrapolating biological information about their metabolic propensity and ecology in a complex environment like the human gastrointestinal tract.}, }
@article {pmid32995898, year = {2020}, author = {Lang, S and Brandau, S and Marchesi, JR and Jablonska, J and Thurnher, D and Mattheis, S and Buer, J and Hussain, T}, title = {[The microbiome in head and neck tumors-initial findings and outlook].}, journal = {HNO}, volume = {68}, number = {12}, pages = {905-910}, pmid = {32995898}, issn = {1433-0458}, mesh = {*Head and Neck Neoplasms ; Humans ; *Microbiota ; }, abstract = {Technical progress in molecular biology has allowed for a more detailed analysis of the composition of the human microbiome in recent years. Inter- and intraindividual differences in microbiome composition have been demonstrated, which in part correlate with the occurrence of certain diseases. For some of the so-called oncomicrobes, a direct relationship between their effect on the host organism and carcinogenesis has been demonstrated, predominantly for gastrointestinal cancers. Initial results for head and neck cancer show inter- and intraindividual differences in the local microbiota of the tumor environment, with certain bacterial strains over- or underrepresented. Our results confirm these findings, e.g., by showing a relative abundance of fusobacteria in tumor tissue while streptococci were relatively reduced. Currently available results show a high degree of inter- and intraindividual variation, thus requiring larger patient cohorts for functional analyses.}, }
@article {pmid32994293, year = {2020}, author = {Schmidt, V and Enav, H and Spector, TD and Youngblut, ND and Ley, RE}, title = {Strain-Level Analysis of Bifidobacterium spp. from Gut Microbiomes of Adults with Differing Lactase Persistence Genotypes.}, journal = {mSystems}, volume = {5}, number = {5}, pages = {}, pmid = {32994293}, issn = {2379-5077}, support = {/WT_/Wellcome Trust/United Kingdom ; R01 DK093595/DK/NIDDK NIH HHS/United States ; }, abstract = {One of the strongest associations between human genetics and the gut microbiome is a greater relative abundance of Bifidobacterium in adults with lactase gene (LCT) single nucleotide polymorphisms (SNPs) associated with lactase nonpersistence (GG genotypes), versus lactase persistence (AA/AG genotypes). To gain a finer-grained phylogenetic resolution of this association, we interrogated 1,680 16S rRNA libraries and 245 metagenomes from gut microbiomes of adults with various lactase persistence genotypes. We further employed a novel genome-capture-based enrichment of Bifidobacterium DNA from a subset of these metagenomes, including monozygotic (MZ) twin pairs, each sampled 2 or 3 times. B. adolescentis and B. longum were the most abundant Bifidobacterium species regardless of host LCT genotype. LCT genotypes could not be discriminated based on relative abundances of Bifidobacterium species or Bifidobacterium community structure. Three distinct metagenomic analysis methods of Bifidobacterium-enriched DNA revealed intraindividual temporal stability of B. longum, B. adolescentis, and B. bifidum strains against the background of a changeable microbiome. Two of our three methods also observed greater strain sharing within MZ twin pairs than within unrelated individuals for B. adolescentis, while no method revealed an effect of host LCT genotype on Bifidobacterium strain composition. Our results support a "rising tide lifts all boats" model for the dominant bifidobacteria in the adult gut: their higher abundance in lactase-nonpersistent than in lactase-persistent individuals results from an expansion at the genus level. Bifidobacterium species are known to be transmitted from mother to child and stable within individuals in infancy and childhood: our results extend this stability into adulthood.IMPORTANCE When humans domesticated animals, some adapted genetically to digest milk into adulthood (lactase persistence). The gut microbiomes of people with lactase-persistent genotypes (AA or AG) differ from those with lactase-nonpersistent genotypes (GG) by containing fewer bacteria belonging to the bifidobacteria, a group which contains beneficial species. Here, we asked if the gut microbiomes of adults with GG and AA/AG genotypes differ in the species of bifidobacteria present. In particular, we used a novel technique which allowed us to compare bifidobacteria in adults at the strain level, without the traditional need for culturing. Our results show that the GG genotype enhances the abundance of bifidobacteria regardless of species. We also noted that a person's specific strains are recoverable several years later, and twins can share the same ones. Given that bifidobacteria are inherited from mother to child, strain stability over time in adulthood suggests long-term, multigenerational inheritance.}, }
@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}, 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 {pmid32993020, year = {2020}, author = {Ternák, G and Berényi, K and Sümegi, A and Szenczi, Á and Fodor, B and Németh, B and Kiss, I}, title = {Antibiotic Consumption Patterns in European Countries May Be Associated with the Incidence of Major Carcinomas.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {32993020}, issn = {2079-6382}, abstract = {The possible role of the altered intestinal microbiome in the development of malignancies has been raised recently in several publications. Among external factors, antibiotics are considered to be the most important agent capable of producing dysbiosis in the gut flora, either temporally or permanently. The human microbiome has several beneficial effects in terms of maintaining appropriate human health, but its alteration has been implicated in the development of many illnesses. Our basic aim was to explore a possible relationship between the consumption of different antibiotic classes and the incidence of the most common cancer types (male, female) in European countries. A database of the average, yearly antibiotic consumption (1997-2018) has been developed and the consumption figures were compared to the eight, most frequent cancer incidence calculated for 2018 in 30 European countries. Pearson correlation has indicated different degrees of positive (supportive) and negative (inhibitor) significant associations between antibiotic consumption figures and cancer prevalence. It has been observed that certain antibiotic classes with positive correlation probably augment the incidence of certain cancer types, while others, with negative correlation, may show some inhibitory effect. The relatively higher or lower consumption pattern of different classes of antibiotics could be related to certain cancer prevalence figures in different European countries. Our results indicated that countries with relatively high consumption of narrow-spectrum penicillin (J01CE, J01CF) and tetracycline (J01A), like certain Scandinavian countries, showed a higher incidence of female colorectal cancer, female lung cancer, melanoma, breast, prostate and uterus corpus cancer. Countries with relatively higher consumption of broad-spectrum penicillin (J01CA, J01CR) and some broad-spectrum antibiotics (J01D, J01F, J01M), like Greece, Hungary, Slovakia, France, etc. showed a higher incidence rate of male lung cancer and male bladder cancer. The higher incidence rate of different cancer types showed association with the higher consumption of antibiotics with "augmenting" properties and with less consumption of antibiotics with "inhibitory" properties.}, }
@article {pmid32992653, year = {2020}, author = {Quagliariello, A and Del Chierico, F and Reddel, S and Russo, A and Onetti Muda, A and D'Argenio, P and Angelino, G and Romeo, EF and Dall'Oglio, L and De Angelis, P and Putignani, L and All The Other Fmt Opbg Committee Collaborators, }, title = {Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {32992653}, issn = {2076-2607}, support = {201702P003961//Ministero della Salute/ ; 201802G004314//MINISTERO DELLA SALUTE/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.}, }
@article {pmid32991841, year = {2020}, author = {Ha, CWY and Martin, A and Sepich-Poore, GD and Shi, B and Wang, Y and Gouin, K and Humphrey, G and Sanders, K and Ratnayake, Y and Chan, KSL and Hendrick, G and Caldera, JR and Arias, C and Moskowitz, JE and Ho Sui, SJ and Yang, S and Underhill, D and Brady, MJ and Knott, S and Kaihara, K and Steinbaugh, MJ and Li, H and McGovern, DPB and Knight, R and Fleshner, P and Devkota, S}, title = {Translocation of Viable Gut Microbiota to Mesenteric Adipose Drives Formation of Creeping Fat in Humans.}, journal = {Cell}, volume = {183}, number = {3}, pages = {666-683.e17}, doi = {10.1016/j.cell.2020.09.009}, pmid = {32991841}, issn = {1097-4172}, support = {F30 CA243480/CA/NCI NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; R01 DK123446/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; }, abstract = {A mysterious feature of Crohn's disease (CD) is the extra-intestinal manifestation of "creeping fat" (CrF), defined as expansion of mesenteric adipose tissue around the inflamed and fibrotic intestine. In the current study, we explore whether microbial translocation in CD serves as a central cue for CrF development. We discovered a subset of mucosal-associated gut bacteria that consistently translocated and remained viable in CrF in CD ileal surgical resections, and identified Clostridium innocuum as a signature of this consortium with strain variation between mucosal and adipose isolates, suggesting preference for lipid-rich environments. Single-cell RNA sequencing characterized CrF as both pro-fibrotic and pro-adipogenic with a rich milieu of activated immune cells responding to microbial stimuli, which we confirm in gnotobiotic mice colonized with C. innocuum. Ex vivo validation of expression patterns suggests C. innocuum stimulates tissue remodeling via M2 macrophages, leading to an adipose tissue barrier that serves to prevent systemic dissemination of bacteria.}, }
@article {pmid32988391, year = {2020}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {82}, pmid = {32988391}, issn = {1756-994X}, support = {TL1 TR002344/TR/NCATS NIH HHS/United States ; 1U1CI000033 301/CC/CDC HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; }, abstract = {The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.}, }
@article {pmid32984078, year = {2020}, author = {Marazzato, M and Zicari, AM and Aleandri, M and Conte, AL and Longhi, C and Vitanza, L and Bolognino, V and Zagaglia, C and De Castro, G and Brindisi, G and Schiavi, L and De Vittori, V and Reddel, S and Quagliariello, A and Del Chierico, F and Putignani, L and Duse, M and Palamara, AT and Conte, MP}, title = {16S Metagenomics Reveals Dysbiosis of Nasal Core Microbiota in Children With Chronic Nasal Inflammation: Role of Adenoid Hypertrophy and Allergic Rhinitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {458}, pmid = {32984078}, issn = {2235-2988}, abstract = {Allergic rhinitis (AR) and adenoid hypertrophy (AH) are, in children, the main cause of partial or complete upper airway obstruction and reduction in airflow. However, limited data exist about the impact of the increased resistance to airflow, on the nasal microbial composition of children with AR end AH. Allergic rhinitis (AR) as well as adenoid hypertrophy (AH), represent extremely common pathologies in this population. Their known inflammatory obstruction is amplified when both pathologies coexist. In our study, the microbiota of anterior nares of 75 pediatric subjects with AR, AH or both conditions, was explored by 16S rRNA-based metagenomic approach. Our data show for the first time, that in children, the inflammatory state is associated to similar changes in the microbiota composition of AR and AH subjects respect to the healthy condition. Together with such alterations, we observed a reduced variability in the between-subject biodiversity on the other hand, these same alterations resulted amplified by the nasal obstruction that could constitute a secondary risk factor for dysbiosis. Significant differences in the relative abundance of specific microbial groups were found between diseased phenotypes and the controls. Most of these taxa belonged to a stable and quantitatively dominating component of the nasal microbiota and showed marked potentials in discriminating the controls from diseased subjects. A pauperization of the nasal microbial network was observed in diseased status in respect to the number of involved taxa and connectivity. Finally, while stable co-occurrence relationships were observed within both control- and diseases-associated microbial groups, only negative correlations were present between them, suggesting that microbial subgroups potentially act as maintainer of the eubiosis state in the nasal ecosystem. In the nasal ecosystem, inflammation-associated shifts seem to impact the more intimate component of the microbiota rather than representing the mere loss of microbial diversity. The discriminatory potential showed by differentially abundant taxa provide a starting point for future research with the potential to improve patient outcomes. Overall, our results underline the association of AH and AR with the impairment of the microbial interplay leading to unbalanced ecosystems.}, }
@article {pmid32981293, year = {2020}, author = {Son, JW and Shoaie, S and Lee, S}, title = {Systems Biology: A Multi-Omics Integration Approach to Metabolism and the Microbiome.}, journal = {Endocrinology and metabolism (Seoul, Korea)}, volume = {35}, number = {3}, pages = {507-514}, pmid = {32981293}, issn = {2093-5978}, support = {EP/S001301/1//Engineering and Physical Sciences Research Council/International ; //Biotechnology Biological Sciences Research Council/International ; BCMC19LH03//Institute of Clinical Medicine Research of Bucheon St. Mary's Hospital/International ; //Catholic Medical Center Research Foundation/International ; }, abstract = {The complex and dynamic nature of human physiology, as exemplified by metabolism, has often been overlooked due to the lack of quantitative and systems approaches. Recently, systems biology approaches have pushed the boundaries of our current understanding of complex biochemical, physiological, and environmental interactions, enabling proactive medicine in the near future. From this perspective, we review how state-of-the-art computational modelling of human metabolism, i.e., genome-scale metabolic modelling, could be used to identify the metabolic footprints of diseases, to guide the design of personalized treatments, and to estimate the microbiome contributions to host metabolism. These state-of-the-art models can serve as a scaffold for integrating multi-omics data, thereby enabling the identification of signatures of dysregulated metabolism by systems approaches. For example, increased plasma mannose levels due to decreased uptake in the liver have been identified as a potential biomarker of early insulin resistance by multi-omics approaches. In addition, we also review the emerging axis of human physiology and the human microbiome, discussing its contribution to host metabolism and quantitative approaches to study its variations in individuals.}, }
@article {pmid32978472, year = {2020}, author = {Daisley, BA and Pitek, AP and Chmiel, JA and Gibbons, S and Chernyshova, AM and Al, KF and Faragalla, KM and Burton, JP and Thompson, GJ and Reid, G}, title = {Lactobacillus spp. attenuate antibiotic-induced immune and microbiota dysregulation in honey bees.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {534}, pmid = {32978472}, issn = {2399-3642}, support = {RGPIN-2014-05188//Gouvernement du Canada | National Research Council Canada (Conseil national de recherches Canada)/ ; CGSD-519379-2018//Gouvernement du Canada | National Research Council Canada (Conseil national de recherches Canada)/ ; ND2017-3164//Ontario Ministry of Agriculture, Food and Rural Affairs (Ministère de l'Agriculture, de l'Alimentation et des Affaires rurales)/ ; ND2017-3164//Ontario Ministry of Agriculture, Food and Rural Affairs (Ministère de l'Agriculture, de l'Alimentation et des Affaires rurales)/ ; }, abstract = {Widespread antibiotic usage in apiculture contributes substantially to the global dissemination of antimicrobial resistance and has the potential to negatively influence bacterial symbionts of honey bees (Apis mellifera). Here, we show that routine antibiotic administration with oxytetracycline selectively increased tetB (efflux pump resistance gene) abundance in the gut microbiota of adult workers while concurrently depleting several key symbionts known to regulate immune function and nutrient metabolism such as Frischella perrera and Lactobacillus Firm-5 strains. These microbial changes were functionally characterized by decreased capped brood counts (marker of hive nutritional status and productivity) and reduced antimicrobial capacity of adult hemolymph (indicator of immune competence). Importantly, combination therapy with three immunostimulatory Lactobacillus strains could mitigate antibiotic-associated microbiota dysbiosis and immune deficits in adult workers, as well as maximize the intended benefit of oxytetracycline by suppressing larval pathogen loads to near-undetectable levels. We conclude that microbial-based therapeutics may offer a simple but effective solution to reduce honey bee disease burden, environmental xenobiotic exposure, and spread of antimicrobial resistance.}, }
@article {pmid32976571, year = {2020}, 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 = {}, number = {}, pages = {}, doi = {10.1093/aje/kwaa204}, pmid = {32976571}, issn = {1476-6256}, 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 (2df-test) or additionally on squares and cross-product of mean distances (5df-test). We compared the power of 2df- and 5df-tests to the microbiome regression-based kernel association test (MiRKAT). In simulations, MiRKAT had moderately greater power than the 2df-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 2df-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 5df-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 comparable power to MiRKAT (and to permutational multivariate analysis of variance), but more simulations and applications are needed to confirm this.}, }
@article {pmid32975912, year = {2020}, author = {Kim, GH and Rosiana, S and Kirienko, NV and Shapiro, RS}, title = {A Simple Nematode Infection Model for Studying Candida albicans Pathogenesis.}, journal = {Current protocols in microbiology}, volume = {59}, number = {1}, pages = {e114}, doi = {10.1002/cpmc.114}, pmid = {32975912}, issn = {1934-8533}, support = {//Canadian Institutes for Health Research/ ; }, abstract = {Candida albicans is an opportunistic fungal pathogen and a model organism to study fungal pathogenesis. It exists as a harmless commensal organism and member of the healthy human microbiome, but can cause life-threatening mucosal and systemic infections. A model host to study C. albicans infection and pathogenesis is the nematode Caenorhabditis elegans. C. elegans is frequently used as a model host to study microbial-host interactions because it can be infected by many human pathogens and there are also close morphological resemblances between the intestinal cells of C. elegans and mammals, where C. albicans infections can occur. This article outlines a detailed methodology for exploiting C. elegans as a host to study C. albicans infection, including a C. elegans egg preparation protocol and an agar-based C. elegans killing protocol to monitor fungal virulence. These protocols can additionally be used to study C. albicans genetic mutants in order to further our understanding of the genes involved in pathogenesis and virulence in C. albicans and the mechanisms of host-microbe interactions. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Preparation of Caenorhabditis elegans eggs Support Protocol 1: Freezing and recovering Caenorhabditis elegans Support Protocol 2: Making superfood agar and OP50 plates Basic Protocol 2: Caenorhabditis elegans/Candida albicans agar killing assay Support Protocol 3: Constructing a worm pick.}, }
@article {pmid32974330, year = {2020}, author = {Rasinkangas, P and Tytgat, HLP and Ritari, J and Reunanen, J and Salminen, S and Palva, A and Douillard, FP and de Vos, WM}, title = {Characterization of Highly Mucus-Adherent Non-GMO Derivatives of Lacticaseibacillus rhamnosus GG.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {1024}, pmid = {32974330}, issn = {2296-4185}, abstract = {Lacticaseibacillus rhamnosus GG is one of the best studied lactic acid bacteria in the context of probiotic effects. L. rhamnosus GG has been shown to prevent diarrhea in children and adults and has been implicated to have mitigating or preventive effects in several disorders connected to microbiota dysbiosis. The probiotic effects are largely attributed to its adhesive heterotrimeric sortase-dependent pili, encoded by the spaCBA-srtC1 gene cluster. Indeed, the strain-specific SpaCBA pili have been shown to contribute to adherence, biofilm formation and host signaling. In this work we set out to generate non-GMO derivatives of L. rhamnosus GG that adhere stronger to mucus compared to the wild-type strain using chemical mutagenesis. We selected 13 derivatives that showed an increased mucus-adherent phenotype. Deep shotgun resequencing of the strains enabled division of the strains into three classes, two of which revealed SNPs (single nucleotide polymorphisms) in the spaA and spaC genes encoding the shaft and tip adhesive pilins, respectively. Strikingly, the other class derivatives demonstrated less clear genotype - phenotype relationships, illustrating that pili biogenesis and structure is also affected by other processes. Further characterization of the different classes of derivatives was performed by PacBio SMRT sequencing and RNAseq analysis, which resulted in the identification of molecular candidates driving pilin biosynthesis and functionality. In conclusion, we report on the generation and characterization of three classes of strongly adherent L. rhamnosus GG derivatives that show an increase in adhesion to mucus. These are of special interest as they provide a window on processes and genes driving piliation and its control in L. rhamnosus GG and offer a variety of non-GMO derivatives of this key probiotic strain that are applicable in food products.}, }
@article {pmid32973149, year = {2020}, author = {Daisley, BA and Chanyi, RM and Abdur-Rashid, K and Al, KF and Gibbons, S and Chmiel, JA and Wilcox, H and Reid, G and Anderson, A and Dewar, M and Nair, SM and Chin, J and Burton, JP}, title = {Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4822}, pmid = {32973149}, issn = {2041-1723}, mesh = {Abiraterone Acetate/metabolism/*pharmacology/therapeutic use ; Akkermansia ; Androgen Antagonists/pharmacology ; Androgens/metabolism ; Bacteria/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Male ; Prostatic Neoplasms/*drug therapy ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; RNA, Ribosomal, 16S/genetics ; Verrucomicrobia/*drug effects/genetics/metabolism ; Vitamin K 2/metabolism/pharmacology ; }, abstract = {Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.}, }
@article {pmid32972973, year = {2020}, author = {Balty, C and Guillot, A and Fradale, L and Brewee, C and Lefranc, B and Herrero, C and Sandström, C and Leprince, J and Berteau, O and Benjdia, A}, title = {Biosynthesis of the sactipeptide Ruminococcin C by the human microbiome: Mechanistic insights into thioether bond formation by radical SAM enzymes.}, journal = {The Journal of biological chemistry}, volume = {295}, number = {49}, pages = {16665-16677}, doi = {10.1074/jbc.RA120.015371}, pmid = {32972973}, issn = {1083-351X}, abstract = {Despite its major importance in human health, the metabolic potential of the human gut microbiota is still poorly understood. We have recently shown that biosynthesis of Ruminococcin C (RumC), a novel ribosomally synthesized and posttranslationally modified peptide (RiPP) produced by the commensal bacterium Ruminococcus gnavus, requires two radical SAM enzymes (RumMC1 and RumMC2) catalyzing the formation of four Cα-thioether bridges. These bridges, which are essential for RumC's antibiotic properties against human pathogens such as Clostridium perfringens, define two hairpin domains giving this sactipeptide (sulfur-to-α-carbon thioether-containing peptide) an unusual architecture among natural products. We report here the biochemical and spectroscopic characterizations of RumMC2. EPR spectroscopy and mutagenesis data support that RumMC2 is a member of the large family of SPASM domain radical SAM enzymes characterized by the presence of three [4Fe-4S] clusters. We also demonstrate that this enzyme initiates its reaction by Cα H-atom abstraction and is able to catalyze the formation of nonnatural thioether bonds in engineered peptide substrates. Unexpectedly, our data support the formation of a ketoimine rather than an α,β-dehydro-amino acid intermediate during Cα-thioether bridge LC-MS/MS fragmentation. Finally, we explored the roles of the leader peptide and of the RiPP precursor peptide recognition element, present in myriad RiPP-modifying enzymes. Collectively, our data support a more complex role for the peptide recognition element and the core peptide for the installation of posttranslational modifications in RiPPs than previously anticipated and suggest a possible reaction intermediate for thioether bond formation.}, }
@article {pmid32971377, year = {2020}, author = {AlShahrani, I and Hosmani, J and AlShahrani, A and Togoo, RA and Syed, S and Yassin, SM and Chandramoorthy, HC and Devaraj, A}, title = {High altitude as a possible factor for dysbiosis of salivary microbiome in orthodontic patients.}, journal = {Archives of oral biology}, volume = {119}, number = {}, pages = {104917}, doi = {10.1016/j.archoralbio.2020.104917}, pmid = {32971377}, issn = {1879-1506}, abstract = {BACKGROUND: External stressors such as high altitude and low oxygen are known to affect the human microbiome, and in light of the increased occurrence of dental caries and periodontitis in orthodontic patients, the effect of high altitude and the altered oral environment in orthodontic patients on the oral salivary microbiome was researched.
MATERIALS & METHODS: 31 orthodontic patients from high altitude, Aseer region and 25 orthodontic patients, residing at sea level, as controls were included. DNA isolation was done from the saliva collected from the study participants. V3 area of 16s RNA was targeted by universal primers through PCR to decipher the salivary microbiome in both the groups.
RESULTS: A total of 11 genera belonging to 4 phyla of bacteria were identified in both groups. The most abundant microbiome at the phylum level was: Firmicutes, Bacteroidetes Proteobacteria, and Cyanobacteria. The salivary microbiome was more diverse in sea level controls compared to that of the orthodontic patients at high altitude wherein the presence of only two main phyla: Firmicutes and Proteobacteria were seen. The controls revealed Firmicutes, Proteobacteria, Bacteroidetes and Cyanobacteria.
CONCLUSIONS: The findings of the study suggest that the biodiversity of the salivary microbiome is severely perturbed under the cumulative influences of high altitude and presence of fixed orthodontic appliance. Under these circumstances, a strict and meticulous oral hygiene regimen should be recommended and followed to avoid harmful effects on the periodontal tissues.}, }
@article {pmid32967314, year = {2020}, author = {Kim, B and Cho, EJ and Yoon, JH and Kim, SS and Cheong, JY and Cho, SW and Park, T}, title = {Pathway-Based Integrative Analysis of Metabolome and Microbiome Data from Hepatocellular Carcinoma and Liver Cirrhosis Patients.}, journal = {Cancers}, volume = {12}, number = {9}, pages = {}, pmid = {32967314}, issn = {2072-6694}, support = {HI16C2037//Ministry of Health and Welfare/ ; 2013M3A9C4078158//National Research Foundation of Korea/ ; }, abstract = {Aberrations of the human microbiome are associated with diverse liver diseases, including hepatocellular carcinoma (HCC). Even if we can associate specific microbes with particular diseases, it is difficult to know mechanistically how the microbe contributes to the pathophysiology. Here, we sought to reveal the functional potential of the HCC-associated microbiome with the human metabolome which is known to play a role in connecting host phenotype to microbiome function. To utilize both microbiome and metabolomic data sets, we propose an innovative, pathway-based analysis, Hierarchical structural Component Model for pathway analysis of Microbiome and Metabolome (HisCoM-MnM), for integrating microbiome and metabolomic data. In particular, we used pathway information to integrate these two omics data sets, thus providing insight into biological interactions between different biological layers, with regard to the host's phenotype. The application of HisCoM-MnM to data sets from 103 and 97 patients with HCC and liver cirrhosis (LC), respectively, showed that this approach could identify HCC-related pathways related to cancer metabolic reprogramming, in addition to the significant metabolome and metagenome that make up those pathways.}, }
@article {pmid32964353, year = {2020}, author = {Morar, N and Skorburg, JA}, title = {Why We Never Eat Alone: The Overlooked Role of Microbes and Partners in Obesity Debates in Bioethics.}, journal = {Journal of bioethical inquiry}, volume = {17}, number = {3}, pages = {435-448}, doi = {10.1007/s11673-020-10047-2}, pmid = {32964353}, issn = {1176-7529}, abstract = {Debates about obesity in bioethics tend to unfold in predictable epicycles between individual choices and behaviours (e.g., restraint, diet, exercise) and the oppressive socio-economic structures constraining them (e.g., food deserts, advertising). Here, we argue that recent work from two cutting-edge research programmes in microbiology and social psychology can advance this conceptual stalemate in the literature. We begin in section 1 by discussing two promising lines of obesity research involving the human microbiome and relationship partners. Then, in section 2, we show how this research has made viable novel strategies for fighting obesity, including microbial therapies and dyad-level interventions. Finally, in section 3, we consider objections to our account and conclude by arguing that attention to the most immediate features of our biological and social environment offers a middle ground solution, while also raising important new issues for bioethicists.}, }
@article {pmid32961592, year = {2020}, author = {Sainz, T and Delgado, J and Mendez-Echevarría, A and Santiago, B and Lopez-Varela, E and Aguilera-Alonso, D and Saavedra-Lozano, J and Rodríguez-Fernández, R and Holguín, Á and Navarro, ML and Muñoz-Fernández, MÁ and Rivero-Calle, I and Solana, MJ and López-Herce, J and Calvo, C}, title = {The clinical relevance of the microbiome when managing paediatric infectious diseases-Narrative review.}, journal = {Acta paediatrica (Oslo, Norway : 1992)}, volume = {}, number = {}, pages = {}, doi = {10.1111/apa.15578}, pmid = {32961592}, issn = {1651-2227}, support = {PI17/01283//Instituto de Salud Carlos III/ ; JR16/00021//Instituto de Salud Carlos III/ ; JR16/00036//Instituto de Salud Carlos III/ ; CM18/00100//Instituto de Salud Carlos III/ ; PEJ2018-003755-P//Ministerio de Economía y Competitividad/ ; }, abstract = {In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge.
AIMS: This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children.
METHODS: We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome-related knowledge for translation to clinical practice.
RESULTS AND CONCLUSION: The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so-called microbiome thinking into our routine clinical practice.}, }
@article {pmid32958790, year = {2020}, author = {Sun, X and Li, M and Xia, L and Fang, Z and Yu, S and Gao, J and Feng, Q and Yang, P}, title = {Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {15363}, pmid = {32958790}, issn = {2045-2322}, mesh = {Adult ; Bacteroidetes/genetics ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Female ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Metformin/*therapeutic use ; Microbiota/*genetics ; Middle Aged ; Periodontitis/*microbiology ; Prevotella/genetics ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; }, abstract = {We aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of Prevotella copri, Alloprevotella rava, and Ralstonia pickettii, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of Prevotella copri, Alloprevotella rava, Ralstonia pickettii, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.}, }
@article {pmid32958525, year = {2020}, author = {Pinto, D and Trink, A and Sorbellini, E and Giuliani, G and Rinaldi, F}, title = {'Omics' approaches for studying the microbiome in Alopecia areata.}, journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research}, volume = {68}, number = {7}, pages = {1292-1294}, pmid = {32958525}, issn = {1708-8267}, abstract = {Nowadays, the involvement of the microbiome in human health and many human diseases, including that strictly related to the scalphas been brought to the light. Indeed, more recently, authors highlighted the presence of a significant microbial shift both in nonscarring (Androgenetic alopecia and Alopecia areata) and scarring Alopecias. The advent of novel technologies together with the effort of many scientists in the microbiome field could provide in the nearest future a clearest framework about the strict relationship between human healthiness and symbiotic microorganism resident on different ecosystem of our body. In this view, the use of Omics approaches has to be considered as no longer negligible when studying the microbiome implication in human health and disease.}, }
@article {pmid32958509, year = {2020}, author = {Ormseth, MJ and Wu, Q and Zhao, S and Allen, RM and Solus, J and Sheng, Q and Guo, Y and Ye, F and Ramirez-Solano, M and Bridges, SL and Curtis, JR and Vickers, K and Stein, CM}, title = {Circulating microbial small RNAs are altered in patients with rheumatoid arthritis.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {12}, pages = {1557-1564}, pmid = {32958509}, issn = {1468-2060}, support = {IK2 CX001269/CX/CSRD VA/United States ; P60 AR056116/AR/NIAMS NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/*blood/*microbiology/pathology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; RNA, Bacterial/*blood/drug effects ; RNA, Fungal/*blood/drug effects ; RNA, Small Untranslated/*blood/drug effects ; }, abstract = {OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs).
METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05.
RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment.
CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.}, }
@article {pmid32939371, year = {2020}, author = {Belkova, N and Klimenko, E and Vilson, N and Sambialova, A and Markova, D and Igumnov, I and Suturina, L}, title = {Metagenome datasets from women with polycystic ovary syndrome from Irkutsk, Eastern Siberia, Russia.}, journal = {Data in brief}, volume = {32}, number = {}, pages = {106137}, pmid = {32939371}, issn = {2352-3409}, abstract = {For the metagenomic characterization of potential taxonomic and functional diversity of microorganisms associated with polycystic ovary syndrome (PCOS) in women, we surveyed five women with PCOS and collected samples of feces, saliva, and serum. After quality processing, we have obtained from 915,594 to 3,880,379 reads; these 16,693 sequences had ribosomal RNA genes, 2,091,990 sequences contained predicted proteins with known functions, and 3,750,261 sequences had predicted proteins with unknown functions. Host DNA accounted for ca. 0.03% and less in datasets of fecal samples, from 1.41 to 24.94% in saliva samples; the remaining sequences were attributed to archaeal, bacterial, or viral DNA. In serum, from 38.18 to 75.77% were characterized as fragments of the human genome, but the remaining sequences were unidentified. Among microbes, a total of one archaeal and eight bacterial phyla were revealed. Viral DNA was detected in several fecal and one saliva sample and was classified as C2likevirus, Flavivirus, and Streptococcus bacteriophage. The metagenome sequence data were deposited at NCBI SRA as BioProject No. PRJNA625611.}, }
@article {pmid32939014, year = {2020}, author = {Yang, J and Moon, HE and Park, HW and McDowell, A and Shin, TS and Jee, YK and Kym, S and Paek, SH and Kim, YK}, title = {Brain tumor diagnostic model and dietary effect based on extracellular vesicle microbiome data in serum.}, journal = {Experimental & molecular medicine}, volume = {52}, number = {9}, pages = {1602-1613}, doi = {10.1038/s12276-020-00501-x}, pmid = {32939014}, issn = {2092-6413}, support = {NRF-2016M3A9B6901516//National Research Foundation of Korea (NRF)/ ; NRF-2020M3A9G80220292//National Research Foundation of Korea (NRF)/ ; 10050154//Ministry of Trade, Industry and Energy (Ministry of Trade, Industry and Energy, Korea)/ ; }, abstract = {The human microbiome has been recently associated with human health and disease. Brain tumors (BTs) are a particularly difficult condition to directly link to the microbiome, as microorganisms cannot generally cross the blood-brain barrier (BBB). However, some nanosized extracellular vesicles (EVs) released from microorganisms can cross the BBB and enter the brain. Therefore, we conducted metagenomic analysis of microbial EVs in both serum (152 BT patients and 198 healthy controls (HC)) and brain tissue (5 BT patients and 5 HC) samples based on the V3-V4 regions of 16S rDNA. We then developed diagnostic models through logistic regression and machine learning algorithms using serum EV metagenomic data to assess the ability of various dietary supplements to reduce BT risk in vivo. Models incorporating the stepwise method and the linear discriminant analysis effect size (LEfSe) method yielded 12 and 29 significant genera as potential biomarkers, respectively. Models using the selected biomarkers yielded areas under the curves (AUCs) >0.93, and the model using machine learning resulted in an AUC of 0.99. In addition, Dialister and [Eubacterium] rectale were significantly lower in both blood and tissue samples of BT patients than in those of HCs. In vivo tests showed that BT risk was decreased through the addition of sorghum, brown rice oil, and garlic but conversely increased by the addition of bellflower and pear. In conclusion, serum EV metagenomics shows promise as a rich data source for highly accurate detection of BT risk, and several foods have potential for mitigating BT risk.}, }
@article {pmid32938697, year = {2020}, author = {Domingues, CPF and Rebelo, JS and Dionisio, F and Botelho, A and Nogueira, T}, title = {The Social Distancing Imposed To Contain COVID-19 Can Affect Our Microbiome: a Double-Edged Sword in Human Health.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32938697}, issn = {2379-5042}, mesh = {Betacoronavirus ; *Biodiversity ; COVID-19 ; Coronavirus Infections/mortality/*prevention & control ; Dysbiosis/microbiology ; Humans ; *Microbiota ; Pandemics/*prevention & control ; Pneumonia, Viral/mortality/*prevention & control ; *Psychological Distance ; SARS-CoV-2 ; Social Networking ; }, abstract = {Hygienic measures imposed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and contain COVID-19 have proven effective in controlling the pandemic. In this article, we argue that these measures could impact the human microbiome in two different and disparate ways, acting as a double-edged sword in human health. New lines of research have shown that the diversity of human intestinal and oropharyngeal microbiomes can shape pulmonary viral infection progression. Here, we suggest that the disruption in microbial sharing, as it is associated with dysbiosis (loss of bacterial diversity associated with an imbalance of the microbiota with deleterious consequences for the host), may worsen the prognosis of COVID-19 disease. In addition, social detachment can also decrease the rate of transmission of antibiotic-resistant bacteria. Therefore, it seems crucial to perform new studies combining the pandemic control of COVID-19 with the diversity of the human microbiome.}, }
@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 {pmid32934239, year = {2020}, author = {Gupta, VK and Kim, M and Bakshi, U and Cunningham, KY and Davis, JM and Lazaridis, KN and Nelson, H and Chia, N and Sung, J}, title = {A predictive index for health status using species-level gut microbiome profiling.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4635}, pmid = {32934239}, issn = {2041-1723}, mesh = {Bacteria/classification/genetics/*isolation & purification ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Health Status ; Humans ; Metagenome ; Microbiota ; }, abstract = {Providing insight into one's health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. GMHI is formulated upon 50 microbial species associated with healthy gut ecosystems. These species are identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different nonhealthy conditions, i.e., disease or abnormal bodyweight. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of disease presence (or absence) compared to α-diversity indices. Validation on 679 samples from 9 additional studies results in a balanced accuracy of 73.7% in distinguishing healthy from non-healthy groups. Our findings suggest that gut taxonomic signatures can predict health status, and highlight how data sharing efforts can provide broadly applicable discoveries.}, }
@article {pmid32928475, year = {2020}, author = {Blanchet, L and Vitale, R and van Vorstenbosch, R and Stavropoulos, G and Pender, J and Jonkers, D and Schooten, FV and Smolinska, A}, title = {Constructing bi-plots for random forest: Tutorial.}, journal = {Analytica chimica acta}, volume = {1131}, number = {}, pages = {146-155}, doi = {10.1016/j.aca.2020.06.043}, pmid = {32928475}, issn = {1873-4324}, abstract = {Current technological developments have allowed for a significant increase and availability of data. Consequently, this has opened enormous opportunities for the machine learning and data science field, translating into the development of new algorithms in a wide range of applications in medical, biomedical, daily-life, and national security areas. Ensemble techniques are among the pillars of the machine learning field, and they can be defined as approaches in which multiple, complex, independent/uncorrelated, predictive models are subsequently combined by either averaging or voting to yield a higher model performance. Random forest (RF), a popular ensemble method, has been successfully applied in various domains due to its ability to build predictive models with high certainty and little necessity of model optimization. RF provides both a predictive model and an estimation of the variable importance. However, the estimation of the variable importance is based on thousands of trees, and therefore, it does not specify which variable is important for which sample group. The present study demonstrates an approach based on the pseudo-sample principle that allows for construction of bi-plots (i.e. spin plots) associated with RF models. The pseudo-sample principle for RF. is explained and demonstrated by using two simulated datasets, and three different types of real data, which include political sciences, food chemistry and the human microbiome data. The pseudo-sample bi-plots, associated with RF and its unsupervised version, allow for a versatile visualization of multivariate models, and the variable importance and the relation among them.}, }
@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 ; }, 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 {pmid32916129, year = {2020}, author = {Mars, RAT and Yang, Y and Ward, T and Houtti, M and Priya, S and Lekatz, HR and Tang, X and Sun, Z and Kalari, KR and Korem, T and Bhattarai, Y and Zheng, T and Bar, N and Frost, G and Johnson, AJ and van Treuren, W and Han, S and Ordog, T and Grover, M and Sonnenburg, J and D'Amato, M and Camilleri, M and Elinav, E and Segal, E and Blekhman, R and Farrugia, G and Swann, JR and Knights, D and Kashyap, PC}, title = {Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome.}, journal = {Cell}, volume = {182}, number = {6}, pages = {1460-1473.e17}, doi = {10.1016/j.cell.2020.08.007}, pmid = {32916129}, issn = {1097-4172}, abstract = {The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.}, }
@article {pmid32915102, year = {2020}, author = {Taddese, R and Garza, DR and Ruiter, LN and de Jonge, MI and Belzer, C and Aalvink, S and Nagtegaal, ID and Dutilh, BE and Boleij, A}, title = {Growth rate alterations of human colorectal cancer cells by 157 gut bacteria.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-20}, pmid = {32915102}, issn = {1949-0984}, abstract = {Several bacteria in the human gut microbiome have been associated with colorectal cancer (CRC) by high-throughput screens. In some cases, molecular mechanisms have been elucidated that drive tumorigenesis, including bacterial membrane proteins or secreted molecules that interact with the human cancer cells. For most gut bacteria, however, it remains unknown if they enhance or inhibit cancer cell growth. Here, we screened bacteria-free supernatants (secretomes) and inactivated cells of over 150 cultured bacterial strains for their effects on cell growth. We observed family-level and strain-level effects that often differed between bacterial cells and secretomes, suggesting that different molecular mechanisms are at play. Secretomes of Bacteroidaceae, Enterobacteriaceae, and Erysipelotrichaceae bacteria enhanced cell growth, while most Fusobacteriaceae cells and secretomes inhibited growth, contrasting prior findings. In some bacteria, the presence of specific functional genes was associated with cell growth rates, including the virulence genes TcdA, TcdB in Clostridiales and FadA in Fusobacteriaceae, which both inhibited growth. Bacteroidaceae cells that enhanced growth were enriched for genes of the cobalamin synthesis pathway, while Fusobacteriaceae cells that inhibit growth were enriched for genes of the ethanolamine utilization pathway. Together, our results reveal how different gut bacteria have wide-ranging effects on cell growth, contribute a better understanding of the effects of the gut microbiome on host cells, and provide a valuable resource for identifying candidate target genes for potential microbiome-based diagnostics and treatment strategies.}, }
@article {pmid32914503, year = {2020}, author = {Koponen, A and Pan, G and Kivelä, AM and Ralko, A and Taskinen, JH and Arora, A and Kosonen, R and Kari, OK and Ndika, J and Ikonen, E and Cho, W and Yan, D and Olkkonen, VM}, title = {ORP2, a cholesterol transporter, regulates angiogenic signaling in endothelial cells.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {11}, pages = {14671-14694}, doi = {10.1096/fj.202000202R}, pmid = {32914503}, issn = {1530-6860}, support = {285223//Academy of Finland (Suomen Akatemia)/ ; 322647//Academy of Finland (Suomen Akatemia)/ ; 282192//Academy of Finland (Suomen Akatemia)/ ; 307415//Academy of Finland (Suomen Akatemia)/ ; //The Sigrid Juselius Foundation/ ; //The Magnus Ehrnrooth Foundation/ ; //The Finnish Foundation for Cardiovascular Research/ ; //The Emil Aaltonen Foundation/ ; //The Ida Montin Foundation/ ; R35GM122530//The National Institutes of Health/ ; 8170438//NSFC, China/ ; 91439122//NSFC, China/ ; //The Leducq Foundation for Cardiovascular Research./ ; }, abstract = {Oxysterol-binding protein-related protein 2 (ORP2), a cholesterol-PI(4,5)P2 countercurrent transporter, was recently identified as a novel regulator of plasma membrane (PM) cholesterol and PI(4,5)P2 content in HeLa cells. Here, we investigate the role of ORP2 in endothelial cell (EC) cholesterol and PI(4,5)P2 distribution, angiogenic signaling, and angiogenesis. We show that ORP2 knock-down modifies the distribution of cholesterol accessible to a D4H probe, between late endosomes and the PM. Depletion of ORP2 from ECs inhibits their angiogenic tube formation capacity, alters the gene expression of angiogenic signaling pathways such as VEGFR2, Akt, mTOR, eNOS, and Notch, and reduces EC migration, proliferation, and cell viability. We show that ORP2 regulates the integrity of VEGFR2 at the PM in a cholesterol-dependent manner, the depletion of ORP2 resulting in proteolytic cleavage by matrix metalloproteinases, and reduced activity of VEGFR2 and its downstream signaling. We demonstrate that ORP2 depletion increases the PM PI(4,5)P2 coincident with altered F-actin morphology, and reduces both VEGFR2 and cholesterol in buoyant raft membranes. Moreover, ORP2 knock-down suppresses the expression of the lipid raft-associated proteins VE-cadherin and caveolin-1. Analysis of the retinal microvasculature in ORP2 knock-out mice generated during this study demonstrates the subtle alterations of morphology characterized by reduced vessel length and increased density of tip cells and perpendicular sprouts. Gene expression changes in the retina suggest disturbance of sterol homeostasis, downregulation of VE-cadherin, and a putative disturbance of Notch signaling. Our data identifies ORP2 as a novel regulator of EC cholesterol and PI(4,5)P2 homeostasis and cholesterol-dependent angiogenic signaling.}, }
@article {pmid32912857, year = {2020}, author = {Feng, Q and Lan, X and Ji, X and Li, M and Liu, S and Xiong, J and Yu, Y and Liu, Z and Xu, Z and He, L and Chen, Y and Dong, H and Chen, P and Chen, B and He, K and Li, Y}, title = {Time series analysis of microbiome and metabolome at multiple body sites in steady long-term isolation confinement.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2020-320666}, pmid = {32912857}, issn = {1468-3288}, }
@article {pmid32908210, year = {2020}, author = {Sharma, A and Im, SH}, title = {Special issue on the human microbiome: from symbiosis to therapy.}, journal = {Experimental & molecular medicine}, volume = {52}, number = {9}, pages = {1361-1363}, doi = {10.1038/s12276-020-00488-5}, pmid = {32908210}, issn = {2092-6413}, }
@article {pmid32907948, year = {2020}, author = {Al, KF and Daisley, BA and Chanyi, RM and Bjazevic, J and Razvi, H and Reid, G and Burton, JP}, title = {Oxalate-Degrading Bacillus subtilis Mitigates Urolithiasis in a Drosophila melanogaster Model.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {32907948}, issn = {2379-5042}, abstract = {Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a high-throughput screening platform for evaluation of the therapeutic potential of oxalate-degrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients.IMPORTANCE Kidney stone disease is a morbid condition that is increasing in prevalence, with few nonsurgical treatment options. The majority of stones are composed of calcium oxalate. Unlike humans, some microbes can break down oxalate, suggesting that microbial therapeutics may provide a novel treatment for kidney stone patients. This study demonstrated that Bacillus subtilis 168 (BS168) decreased stone burden, improved health, and complemented the microbiota in a Drosophila melanogaster urolithiasis model, while not exacerbating calcium oxalate aggregation or adhesion to renal cells in vitro These results identify this bacterium as a candidate for ameliorating stone formation; given that other strains of B. subtilis are components of fermented foods and are used as probiotics for digestive health, strain 168 warrants testing in humans. With the severe burden that recurrent kidney stone disease imposes on patients and the health care system, this microbial therapeutic approach could provide an inexpensive therapeutic adjunct.}, }
@article {pmid32901266, year = {2020}, author = {Giangaspero, A and Barlaam, A and Pane, S and Marchili, MR and Onetti Muda, A and Putignani, L and Hall, MJR}, title = {Accidental Nasal Myiasis Caused by Megaselia rufipes (Diptera: Phoridae) in a Child.}, journal = {Journal of medical entomology}, volume = {}, number = {}, pages = {}, doi = {10.1093/jme/tjaa184}, pmid = {32901266}, issn = {1938-2928}, abstract = {A case of a nasal myiasis in a 3-yr-old Italian girl who was referred to Bambino Gesù Hospital in Rome, Italy, is reported. Larvae discharged with the nasal mucus were microscopically identified as Megaselia spp.; DNA barcoding analysis showed that they belonged to the 'scuttle fly' species Megaselia rufipes (Meigen). Based on the patient's history, she became infected when she played outside. This is the first report of myiasis in humans due to M. rufipes (Diptera: Phoridae).}, }
@article {pmid32901128, year = {2020}, author = {Federici, S and Nobs, SP and Elinav, E}, title = {Phages and their potential to modulate the microbiome and immunity.}, journal = {Cellular & molecular immunology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41423-020-00532-4}, pmid = {32901128}, issn = {2042-0226}, abstract = {Bacteriophages (hence termed phages) are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection. However, the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades, limiting their therapeutic application. While many phages and their functional repertoires remain unknown, the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria. Furthermore, the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation. Importantly, the narrow host range, immense antibacterial repertoire, and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic, commensal and pathobiont members of the microbiome, thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiome-associated diseases. In this review, we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics. We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.}, }
@article {pmid32898133, year = {2020}, author = {Chen, B and Xu, W}, title = {Generalized estimating equation modeling on correlated microbiome sequencing data with longitudinal measures.}, journal = {PLoS computational biology}, volume = {16}, number = {9}, pages = {e1008108}, pmid = {32898133}, issn = {1553-7358}, mesh = {Computational Biology/*methods ; *DNA, Bacterial/classification/genetics ; Databases, Genetic ; Gastrointestinal Microbiome/*genetics ; Humans ; *Models, Statistical ; Sequence Analysis, DNA/*methods ; }, abstract = {Existing models for assessing microbiome sequencing such as operational taxonomic units (OTUs) can only test predictors' effects on OTUs. There is limited work on how to estimate the correlations between multiple OTUs and incorporate such relationship into models to evaluate longitudinal OTU measures. We propose a novel approach to estimate OTU correlations based on their taxonomic structure, and apply such correlation structure in Generalized Estimating Equations (GEE) models to estimate both predictors' effects and OTU correlations. We develop a two-part Microbiome Taxonomic Longitudinal Correlation (MTLC) model for multivariate zero-inflated OTU outcomes based on the GEE framework. In addition, longitudinal and other types of repeated OTU measures are integrated in the MTLC model. Extensive simulations have been conducted to evaluate the performance of the MTLC method. Compared with the existing methods, the MTLC method shows robust and consistent estimation, and improved statistical power for testing predictors' effects. Lastly we demonstrate our proposed method by implementing it into a real human microbiome study to evaluate the obesity on twins.}, }
@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}, doi = {10.1002/cncr.33161}, pmid = {32888342}, issn = {1097-0142}, support = {//Betty B. Marcus Chair in Cancer Prevention/ ; R01DE022891/DE/NIDCR NIH HHS/United States ; R21DE026837/DE/NIDCR NIH HHS/United States ; RP160693//Cancer Prevention and Research Institute of Texas/ ; RP170259//Cancer Prevention and Research Institute of Texas/ ; 1R01CA131324/CA/NCI NIH HHS/United States ; CA016672/CA/NCI NIH HHS/United States ; P50CA140388/CA/NCI NIH HHS/United States ; R01DE022891/DE/NIDCR NIH HHS/United States ; R21DE026837/DE/NIDCR NIH HHS/United States ; 1R01CA131324/CA/NCI NIH HHS/United States ; CA016672/CA/NCI NIH HHS/United States ; P50CA140388/CA/NCI NIH HHS/United States ; }, 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 {pmid32887714, year = {2020}, author = {García, MG and Pérez-Cárceles, MD and Osuna, E and Legaz, I}, title = {Impact of the Human Microbiome in Forensic Sciences: a Systematic Review.}, journal = {Applied and environmental microbiology}, volume = {86}, number = {22}, pages = {}, pmid = {32887714}, issn = {1098-5336}, mesh = {Bacteria/classification/*isolation & purification ; *Bacterial Physiological Phenomena ; *Forensic Sciences ; Humans ; *Microbiota ; }, abstract = {Numerous studies relate differences in microbial communities to human health and disease; however, little is known about microbial changes that occur postmortem or the possible applications of microbiome analysis in the field of forensic science. The aim of this review was to study the microbiome and its applications in forensic sciences and to determine the main lines of investigation that are emerging, as well as its possible contributions to the forensic field. A systematic review of the human microbiome in relation to forensic science was carried out by following PRISMA guidelines. This study sheds light on the role of microbiome research in the postmortem interval during the process of decomposition, identifying death caused by drowning or sudden death, locating the geographical location of death, establishing a connection between the human microbiome and personal items, sexual contact, and the identification of individuals. Actinomycetaceae, Bacteroidaceae, Alcaligenaceae, and Bacilli play an important role in determining the postmortem interval. Aeromonas can be used to determine the cause of death, and Corynebacterium or Helicobacter pylori can be used to ascertain personal identity or geographical location. Several studies point to a promising future for microbiome analysis in the different fields of forensic science, opening up an important new area of research.}, }
@article {pmid32885090, year = {2020}, author = {Suojanen, LU and Ahola, AJ and Kupila, S and Korpela, R and Pietiläinen, KH}, title = {Effectiveness of a web-based real-life weight management program: Study design, methods, and participants' baseline characteristics.}, journal = {Contemporary clinical trials communications}, volume = {19}, number = {}, pages = {100638}, pmid = {32885090}, issn = {2451-8654}, abstract = {Obesity is an important public health concern with limited effective treatment options. Internet-based technologies offer a cost-effective means to treat obesity. However, most of the online programs have been of short duration, have focused on a limited number of treatment modalities, and have not utilized the potential of coaching as part of the intervention. In this paper, we present the design, methods and participants' baseline characteristics in a real-life internet-based weight management program. Healthy Weight Coaching (HWC) is a 12-month web-based intervention for the management of obesity. The program is based on the Acceptance and Commitment Therapy and includes themes important for weight loss, including diet, physical activity, psychological factors, and sleep. In addition to the automated, interactive program, a personal coach is allocated to each participant. The participants are nationally enrolled through referrals from primary care, occupational health, hospitals, and private health care units. Adult individuals with BMI ≥25 kg/m2 without severe complications are included. On a weekly basis, participants submit their weight logs, training sessions, and lifestyle targets to the internet portal and are scheduled to have online discussions with their coaches 26 times over the course of a year. Questionnaires on lifestyle, diet, physical activity, psychological factors, sleep, and quality of life are completed at baseline, 3, 6, 9, and 12 months, and thereafter yearly until 5 years. Additionally, log data on the use of the service and discussions with the coach are collected. The main outcome is weight change from baseline to 12 months. Recruitment to the HWC is ongoing. Baseline data of the participants recruited between Oct 2016 and Mar 2019 (n = 1189) are provided. This research will bring insight into how internet-based technologies can be implemented in the virtual management of obesity.
Trial registration: The trial is registered at clinicaltrials.cov (Clinical Trials Identifier NCT04019249).}, }
@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 {pmid32882798, year = {2020}, author = {Jiang, Q and Kainulainen, V and Stamatova, I and Janket, SJ and Meurman, JH and Korpela, R}, title = {Mouthwash Effects on LGG-Integrated Experimental Oral Biofilms.}, journal = {Dentistry journal}, volume = {8}, number = {3}, pages = {}, pmid = {32882798}, issn = {2304-6767}, support = {201206310016//China Scholarship Council/ ; 285632//Academy of Finland/ ; }, abstract = {In order to investigate the effects of mouthwashes on oral biofilms with probiotics, we compared in biofilms the susceptibility to mouthwashes of probiotic Lactobacillus rhamnosus GG (LGG) and oral pathogens Streptococcus mutans, Streptococcus sanguinis, and Candida albicans. We also evaluated these pathogens' susceptibility to the mouthwashes and their recovery after mouthwash-rinsing in biofilms with/without LGG. First, 1-day-/3-day-old LGG-integrated multi-species biofilms were exposed for 1 min to mouthwashes containing chlorhexidine, essential oils, or amine fluoride/stannous fluoride. Cells were plate-counted and relative survival rates (RSRs) of LGG and pathogens calculated. Second, 1-day-/3-day-old multispecies biofilms with and without LGG were exposed for 1 min to mouthwashes; cells were plate-counted and the pathogens' RSRs were calculated. Third, 1-day-old biofilms were treated for 1 min with mouthwashes. Cells were plate-counted immediately and after 2-day cultivation. Recovery rates of pathogens were calculated and compared between biofilms with/without LGG. Live/Dead® staining served for structural analyses. Our results showed that RSRs of LGG were insignificantly smaller than those of pathogens in both 1-day and 3-day biofilms. No significant differences appeared in pathogens' RSRs and recovery rates after treatment between biofilms with/without LGG. To conclude, biofilm LGG was susceptible to the mouthwashes; but biofilm LGG altered neither the mouthwash effects on oral pathogens nor affected their recovery.}, }
@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 {pmid32878769, year = {2020}, author = {Halley, A and Leonetti, A and Gregori, A and Tiseo, M and Deng, DM and Giovannetti, E and Peters, GJ}, title = {The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer.}, journal = {Anticancer research}, volume = {40}, number = {9}, pages = {4807-4818}, doi = {10.21873/anticanres.14484}, pmid = {32878769}, issn = {1791-7530}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/therapeutic use ; Bacteria/drug effects/isolation & purification ; Carcinoma, Non-Small-Cell Lung/immunology/*microbiology/pathology/*therapy ; Humans ; Immunomodulation ; Lung Neoplasms/immunology/*microbiology/pathology/*therapy ; Microbiota/drug effects/*physiology ; Treatment Outcome ; }, abstract = {The microbiome is extremely important for human health; more recently its role in the context of cancer became clear. Microbial effects range from enhancing cancer immunity and cancer therapy efficacy, to promoting cancer progression and inhibiting treatment efficacy. These broad implications led researchers to investigate these specific interactions, as well as how modification of the microbiome can improve cancer survival and treatment efficacy. While these interactions are better established for cancers such as gastric cancer, they are far less understood in others. As non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases, and is among the top causes of cancer deaths worldwide, understanding the mechanisms by which the microbiome may impact progression and treatment is crucial to improve patient survival and treatment response. A literature review was conducted to reveal the crosslink between human microbiome and lung cancer. This includes immune priming, induction of pro- or anti-tumor response, and the local effects of intra-tumoral microbiota. Overall, this is a complex multifactorial relationship, and there are broad implications as to how this knowledge can improve cancer treatment. Solutions include manipulation of the microbiome using probiotics, bacterial vaccines and antibiotics. Bacteria biomarkers may also be used as a diagnostic tool.}, }
@article {pmid32872562, year = {2020}, author = {Ristori, MV and Mortera, SL and Marzano, V and Guerrera, S and Vernocchi, P and Ianiro, G and Gardini, S and Torre, G and Valeri, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Proteomics and Metabolomics Approaches towards a Functional Insight onto AUTISM Spectrum Disorders: Phenotype Stratification and Biomarker Discovery.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32872562}, issn = {1422-0067}, abstract = {Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by behavioral alterations and currently affect about 1% of children. Significant genetic factors and mechanisms underline the causation of ASD. Indeed, many affected individuals are diagnosed with chromosomal abnormalities, submicroscopic deletions or duplications, single-gene disorders or variants. However, a range of metabolic abnormalities has been highlighted in many patients, by identifying biofluid metabolome and proteome profiles potentially usable as ASD biomarkers. Indeed, next-generation sequencing and other omics platforms, including proteomics and metabolomics, have uncovered early age disease biomarkers which may lead to novel diagnostic tools and treatment targets that may vary from patient to patient depending on the specific genomic and other omics findings. The progressive identification of new proteins and metabolites acting as biomarker candidates, combined with patient genetic and clinical data and environmental factors, including microbiota, would bring us towards advanced clinical decision support systems (CDSSs) assisted by machine learning models for advanced ASD-personalized medicine. Herein, we will discuss novel computational solutions to evaluate new proteome and metabolome ASD biomarker candidates, in terms of their recurrence in the reviewed literature and laboratory medicine feasibility. Moreover, the way to exploit CDSS, performed by artificial intelligence, is presented as an effective tool to integrate omics data to electronic health/medical records (EHR/EMR), hopefully acting as added value in the near future for the clinical management of ASD.}, }
@article {pmid32872386, year = {2020}, author = {Neckovic, A and A H van Oorschot, R and Szkuta, B and Durdle, A}, title = {Challenges in Human Skin Microbial Profiling for Forensic Science: A Review.}, journal = {Genes}, volume = {11}, number = {9}, pages = {}, pmid = {32872386}, issn = {2073-4425}, abstract = {The human microbiome is comprised of the microbes that live on and within an individual, as well as immediately surrounding them. Microbial profiling may have forensic utility in the identification or association of individuals with criminal activities, using microbial signatures derived from a personal microbiome. This review highlights some important aspects of recent studies, many of which have revealed issues involving the effect of contamination of microbial samples from both technical and environmental sources and their impacts on microbiome research and the potential forensic applications of microbial profiling. It is imperative that these challenges be discussed and evaluated within a forensic context to better understand the future directions and potential applications of microbial profiling for human identification. It is necessary that the limitations identified be resolved prior to the adoption of microbial profiling, or, at a minimum, acknowledged by those applying this new approach.}, }
@article {pmid32868914, year = {2020}, author = {Martino, C and Shenhav, L and Marotz, CA and Armstrong, G and McDonald, D and Vázquez-Baeza, Y and Morton, JT and Jiang, L and Dominguez-Bello, MG and Swafford, AD and Halperin, E and Knight, R}, title = {Context-aware dimensionality reduction deconvolutes gut microbial community dynamics.}, journal = {Nature biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41587-020-0660-7}, pmid = {32868914}, issn = {1546-1696}, support = {5R25GM112625//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1F31DE028478-01//U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)/ ; HG010505//U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI)/ ; 1P30DK120515//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 5UL1TR001881//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1DP1AT010885//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; R01 HL140976/HL/NHLBI NIH HHS/United States ; 20175015//Janssen Pharmaceuticals (Janssen Pharmaceuticals, Inc.)/ ; 1R56MD013312//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1R01MH115979//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; 1705197//NSF | Directorate for Computer & Information Science & Engineering | Division of Information and Intelligent Systems (Information & Intelligent Systems)/ ; }, abstract = {The translational power of human microbiome studies is limited by high interindividual variation. We describe a dimensionality reduction tool, compositional tensor factorization (CTF), that incorporates information from the same host across multiple samples to reveal patterns driving differences in microbial composition across phenotypes. CTF identifies robust patterns in sparse compositional datasets, allowing for the detection of microbial changes associated with specific phenotypes that are reproducible across datasets.}, }
@article {pmid32868839, year = {2020}, author = {Kostopoulos, I and Elzinga, J and Ottman, N and Klievink, JT and Blijenberg, B and Aalvink, S and Boeren, S and Mank, M and Knol, J and de Vos, WM and Belzer, C}, title = {Akkermansia muciniphila uses human milk oligosaccharides to thrive in the early life conditions in vitro.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {14330}, pmid = {32868839}, issn = {2045-2322}, abstract = {Akkermansia muciniphila is a well-studied anaerobic bacterium specialized in mucus degradation and associated with human health. Because of the structural resemblance of mucus glycans and free human milk oligosaccharides (HMOs), we studied the ability of A. muciniphila to utilize human milk oligosaccharides. We found that A. muciniphila was able to grow on human milk and degrade HMOs. Analyses of the proteome of A. muciniphila indicated that key-glycan degrading enzymes were expressed when the bacterium was grown on human milk. Our results display the functionality of the key-glycan degrading enzymes (α-L-fucosidases, β-galactosidases, exo-α-sialidases and β-acetylhexosaminidases) to degrade the HMO-structures 2'-FL, LNT, lactose, and LNT2. The hydrolysation of the host-derived glycan structures allows A. muciniphila to promote syntrophy with other beneficial bacteria, contributing in that way to a microbial ecological network in the gut. Thus, the capacity of A. muciniphila to utilize human milk will enable its survival in the early life intestine and colonization of the mucosal layer in early life, warranting later life mucosal and metabolic health.}, }
@article {pmid32865840, year = {2020}, author = {Ruokolainen, L and Fyhrquist, N and Laatikainen, T and Auvinen, P and Fortino, V and Scala, G and Jousilahti, P and Karisola, P and Vendelin, J and Karkman, A and Markelova, O and Mäkelä, MJ and Lehtimäki, S and Ndika, J and Ottman, N and Paalanen, L and Paulin, L and Vartiainen, E and von Hertzen, L and Greco, D and Haahtela, T and Alenius, H}, title = {Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence.}, journal = {Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology}, volume = {50}, number = {10}, pages = {1148-1158}, doi = {10.1111/cea.13728}, pmid = {32865840}, issn = {1365-2222}, support = {//Helsinki University Hospital/ ; //European Union's Seventh Framework Programme (MeDALL)/ ; //Sigrid Juselius Foundation/ ; //Academy of Finland/ ; //Jane and Aatos Erkko Foundation/ ; /ERC_/European Research Council/International ; }, abstract = {BACKGROUND: After the Second World War, the population living in the Karelian region was strictly divided by the "iron curtain" between Finland and Russia. This resulted in different lifestyle, standard of living, and exposure to the environment. Allergic manifestations and sensitization to common allergens have been much more common on the Finnish compared to the Russian side.
OBJECTIVE: The remarkable allergy disparity in the Finnish and Russian Karelia calls for immunological explanations.
METHODS: Young people, aged 15-20 years, in the Finnish (n = 69) and Russian (n = 75) Karelia were studied. The impact of genetic variation on the phenotype was studied by a genome-wide association analysis. Differences in gene expression (transcriptome) were explored from the blood mononuclear cells (PBMC) and related to skin and nasal epithelium microbiota and sensitization.
RESULTS: The genotype differences between the Finnish and Russian populations did not explain the allergy gap. The network of gene expression and skin and nasal microbiota was richer and more diverse in the Russian subjects. When the function of 261 differentially expressed genes was explored, innate immunity pathways were suppressed among Russians compared to Finns. Differences in the gene expression paralleled the microbiota disparity. High Acinetobacter abundance in Russians correlated with suppression of innate immune response. High-total IgE was associated with enhanced anti-viral response in the Finnish but not in the Russian subjects.
Young populations living in the Finnish and Russian Karelia show marked differences in genome-wide gene expression and host contrasting skin and nasal epithelium microbiota. The rich gene-microbe network in Russians seems to result in a better-balanced innate immunity and associates with low allergy prevalence.}, }
@article {pmid32864214, year = {2020}, author = {Miossec, MJ and Valenzuela, SL and Pérez-Losada, M and Johnson, WE and Crandall, KA and Castro-Nallar, E}, title = {Evaluation of computational methods for human microbiome analysis using simulated data.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9688}, pmid = {32864214}, issn = {2167-8359}, abstract = {Background: Our understanding of the composition, function, and health implications of human microbiota has been advanced by high-throughput sequencing and the development of new genomic analyses. However, trade-offs among alternative strategies for the acquisition and analysis of sequence data remain understudied.
Methods: We assessed eight popular taxonomic profiling pipelines; MetaPhlAn2, metaMix, PathoScope 2.0, Sigma, Kraken, ConStrains, Centrifuge and Taxator-tk, against a battery of metagenomic datasets simulated from real data. The metagenomic datasets were modeled on 426 complete or permanent draft genomes stored in the Human Oral Microbiome Database and were designed to simulate various experimental conditions, both in the design of a putative experiment; read length (75-1,000 bp reads), sequence depth (100K-10M), and in metagenomic composition; number of species present (10, 100, 426), species distribution. The sensitivity and specificity of each of the pipelines under various scenarios were measured. We also estimated the relative root mean square error and average relative error to assess the abundance estimates produced by different methods. Additional datasets were generated for five of the pipelines to simulate the presence within a metagenome of an unreferenced species, closely related to other referenced species. Additional datasets were also generated in order to measure computational time on datasets of ever-increasing sequencing depth (up to 6 × 107).
Results: Testing of eight pipelines against 144 simulated metagenomic datasets initially produced 1,104 discrete results. Pipelines using a marker gene strategy; MetaPhlAn2 and ConStrains, were overall less sensitive, than other pipelines; with the notable exception of Taxator-tk. This difference in sensitivity was largely made up in terms of runtime, significantly lower than more sensitive pipelines that rely on whole-genome alignments such as PathoScope2.0. However, pipelines that used strategies to speed-up alignment between genomic references and metagenomic reads, such as kmerization, were able to combine both high sensitivity and low run time, as is the case with Kraken and Centrifuge. Absent species genomes in the database mostly led to assignment of reads to the most closely related species available in all pipelines. Our results therefore suggest that taxonomic profilers that use kmerization have largely superseded those that use gene markers, coupling low run times with high sensitivity and specificity. Taxonomic profilers using more time-consuming read reassignment, such as PathoScope 2.0, provided the most sensitive profiles under common metagenomic sequencing scenarios. All the results described and discussed in this paper can be visualized using the dedicated R Shiny application (https://github.com/microgenomics/HumanMicrobiomeAnalysis). All of our datasets, pipelines and results are made available through the GitHub repository for future benchmarking.}, }
@article {pmid32862522, year = {2020}, author = {Fidel, PL and Moyes, D and Samaranayake, L and Hagensee, ME}, title = {Interplay between oral immunity in HIV and the microbiome.}, journal = {Oral diseases}, volume = {26 Suppl 1}, number = {}, pages = {59-68}, pmid = {32862522}, issn = {1601-0825}, support = {R01 DE022815/DE/NIDCR NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; }, mesh = {*HIV Infections/drug therapy/microbiology ; Humans ; India ; *Microbiota ; *Mouth Diseases/microbiology/virology ; }, abstract = {This Basic Science Workshop addressed the oral microbiome. At the 7th World Workshop on Oral Health & Disease in HIV/AIDS in India in 2014, some aspects of the human microbiome were discussed, and research questions formulated. Since that time, there have been major advances in technology, which have stimulated a number of publications on many aspects of the human microbiome, including the oral cavity. This workshop aimed to summarize current understanding of the "normal" microbiome of the oral cavity compared to that during HIV infection, and how oral immune factors and other clinical variables alter or control the oral microbiome. An important question is whether successful treatment with anti-retroviral therapy, which leads to a significant drop in viral loads and immune reconstitution, is associated with any change or recovery of the oral microbiome. Additionally, the workshop addressed the issue of which parameters are most appropriate/correct to evaluate the oral microbiome and how clinically relevant are shifts/changes in the oral microbiome. The workshop evaluated current knowledge in five research areas related to five basic questions and identified further topics where further research is required.}, }
@article {pmid32853680, year = {2020}, author = {Bilen, M}, title = {Strategies and advancements in human microbiome description and the importance of culturomics.}, journal = {Microbial pathogenesis}, volume = {149}, number = {}, pages = {104460}, doi = {10.1016/j.micpath.2020.104460}, pmid = {32853680}, issn = {1096-1208}, abstract = {The human microbiota gained a big interest among the scientific community with numerous studies being performed to better understand its role in health and diseases. Even with all the success achieved in studying the bacterial populations at the different body sites and its interaction among each other and with the host, some links remain missing and might have therapeutic benefits. In this review, we summarize the main means used for bacterial identification, human microbiota description and the role of culturomics in leading the way towards the development of new bacterio-therapeutic approaches.}, }
@article {pmid32852821, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {5}, pages = {925-926}, doi = {10.1111/apt.15942}, pmid = {32852821}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, }
@article {pmid32852581, year = {2020}, author = {Griffiths, JC and De Vries, J and McBurney, MI and Wopereis, S and Serttas, S and Marsman, DS}, title = {Measuring health promotion: translating science into policy.}, journal = {European journal of nutrition}, volume = {59}, number = {Suppl 2}, pages = {11-23}, pmid = {32852581}, issn = {1436-6215}, abstract = {Commonly, it is the end of life when our health is deteriorating, that many will make drastic lifestyle changes to improve their quality of life. However, it is increasingly recognized that bringing good health-promoting behaviors into practice as early in life as possible has the most significant impact across the maximal healthspan. The WHO has brought clarity to health promotion over the last fifteen years, always centering on language relating to a process of enabling people to increase control over, and to improve, their physical, mental and social health. A good healthspan is not just freedom from morbidity and mortality, it is that joie de vivre ("joy of living") that should accompany every day of our lifespan. Therefore, health promotion includes not only the health sector, but also needs individual commitment to achieve that target of a healthspan aligned with the lifespan. This paper explores health promotion and health literacy, and how to design appropriate nutritional studies to characterize contributors to a positive health outcome, the role the human microbiome plays in promoting health and addressing and alleviating morbidity and diseases, and finally how to characterize phenotypic flexibility and a physiologic resilience that we must maintain as our structural and functional systems are bombarded with the insults and perturbations of life.}, }
@article {pmid32851161, year = {2020}, author = {Khazaei, T and Williams, RL and Bogatyrev, SR and Doyle, JC and Henry, CS and Ismagilov, RF}, title = {Metabolic multistability and hysteresis in a model aerobe-anaerobe microbiome community.}, journal = {Science advances}, volume = {6}, number = {33}, pages = {eaba0353}, pmid = {32851161}, issn = {2375-2548}, abstract = {Major changes in the microbiome are associated with health and disease. Some microbiome states persist despite seemingly unfavorable conditions, such as the proliferation of aerobe-anaerobe communities in oxygen-exposed environments in wound infections or small intestinal bacterial overgrowth. Mechanisms underlying transitions into and persistence of these states remain unclear. Using two microbial taxa relevant to the human microbiome, we combine genome-scale mathematical modeling, bioreactor experiments, transcriptomics, and dynamical systems theory to show that multistability and hysteresis (MSH) is a mechanism describing the shift from an aerobe-dominated state to a resilient, paradoxically persistent aerobe-anaerobe state. We examine the impact of changing oxygen and nutrient regimes and identify changes in metabolism and gene expression that lead to MSH and associated multi-stable states. In such systems, conceptual causation-correlation connections break and MSH must be used for analysis. Using MSH to analyze microbiome dynamics will improve our conceptual understanding of stability of microbiome states and transitions between states.}, }
@article {pmid32850496, year = {2020}, author = {Wagner Mackenzie, B and West, AG and Waite, DW and Lux, CA and Douglas, RG and Taylor, MW and Biswas, K}, title = {A Novel Description of the Human Sinus Archaeome During Health and Chronic Rhinosinusitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {398}, pmid = {32850496}, issn = {2235-2988}, abstract = {Human microbiome studies remain focused on bacteria, as they comprise the dominant component of the microbiota. Recent advances in sequencing technology and optimization of amplicon sequencing protocols have allowed the description of other members of the microbiome, including eukaryotes (fungi) and, most recently, archaea. There are no known human-associated archaeal pathogens. Their diversity and contribution to health and chronic respiratory diseases, such as chronic rhinosinusitis (CRS), are unknown. Patients with CRS suffer from long-term sinus infections, and while the microbiota is hypothesized to play a role in its pathogenesis, the exact mechanism is poorly understood. In this cross-sectional study, we applied a recently optimized protocol to describe the prevalence, diversity and abundance of archaea in swab samples from the middle meatus of 60 individuals with and without CRS. A nested PCR approach was used to amplify the archaeal 16S rRNA gene for sequencing, and bacterial and archaeal load (also based on 16S rRNA genes) were estimated using Droplet Digital™ PCR (ddPCR). A total of 16 archaeal amplicon sequence variants (ASVs) from the phyla Euryarchaeota and Thaumarchaeota were identified. Archaeal ASVs were detected in 7/60 individuals, independent of disease state, whereas bacterial ASVs were detected in 60/60. Bacteria were also significantly more abundant than archaea. The ddPCR method was more sensitive than amplicon sequencing at detecting archaeal DNA in samples. Phylogenetic trees were constructed to visualize the evolutionary relationships between archaeal ASVs, isolates and clones. ASVs were placed into phylogenetic clades containing an apparent paucity of human-associated reference sequences, revealing how little studied the human archaeome is. This is the largest study to date to examine the human respiratory-associated archaeome, and provides the first insights into the prevalence, diversity and abundance of archaea in the human sinuses.}, }
@article {pmid32845143, year = {2020}, author = {Bushin, LB and Covington, BC and Rued, BE and Federle, MJ and Seyedsayamdost, MR}, title = {Discovery and Biosynthesis of Streptosactin, a Sactipeptide with an Alternative Topology Encoded by Commensal Bacteria in the Human Microbiome.}, journal = {Journal of the American Chemical Society}, volume = {142}, number = {38}, pages = {16265-16275}, doi = {10.1021/jacs.0c05546}, pmid = {32845143}, issn = {1520-5126}, abstract = {Mammalian microbiomes encode thousands of biosynthetic gene clusters (BGCs) and represent a new frontier in natural product research. We recently found an abundance of quorum sensing-regulated BGCs in mammalian microbiome streptococci that code for ribosomally synthesized and post-translationally modified peptides (RiPPs) and contain one or more radical S-adenosylmethionine (RaS) enzymes, a versatile superfamily known to catalyze some of the most unusual reactions in biology. In the current work, we target a widespread group of streptococcal RiPP BGCs and elucidate both the reaction carried out by its encoded RaS enzyme and identify its peptide natural product, which we name streptosactin. Streptosactin is the first sactipeptide identified from Streptococcus spp.; it contains two sequential four amino acid sactionine macrocycles, an unusual topology for this compound family. Bioactivity assays reveal potent but narrow-spectrum activity against the producing strain and its closest relatives that carry the same BGC, suggesting streptosactin may be a long-suspected fratricidal agent of Streptococcus thermophilus. Our results highlight mammalian streptococci as a rich source of unusual enzymatic chemistries and bioactive natural products.}, }
@article {pmid32843932, year = {2020}, author = {Li, WZ and Stirling, K and Yang, JJ and Zhang, L}, title = {Gut microbiota and diabetes: From correlation to causality and mechanism.}, journal = {World journal of diabetes}, volume = {11}, number = {7}, pages = {293-308}, pmid = {32843932}, issn = {1948-9358}, abstract = {In this review, we summarize the recent microbiome studies related to diabetes disease and discuss the key findings that show the early emerging potential causal roles for diabetes. On a global scale, diabetes causes a significant negative impact to the health status of human populations. This review covers type 1 diabetes and type 2 diabetes. We examine promising studies which lead to a better understanding of the potential mechanism of microbiota in diabetes diseases. It appears that the human oral and gut microbiota are deeply interdigitated with diabetes. It is that simple. Recent studies of the human microbiome are capturing the attention of scientists and healthcare practitioners worldwide by focusing on the interplay of gut microbiome and diabetes. These studies focus on the role and the potential impact of intestinal microflora in diabetes. We paint a clear picture of how strongly microbes are linked and associated, both positively and negatively, with the fundamental and essential parts of diabetes in humans. The microflora seems to have an endless capacity to impact and transform diabetes. We conclude that there is clear and growing evidence of a close relationship between the microbiota and diabetes and this is worthy of future investments and research efforts.}, }
@article {pmid32842596, year = {2020}, author = {Jalanka, J and Cheng, J and Hiippala, K and Ritari, J and Salojärvi, J and Ruuska, T and Kalliomäki, M and Satokari, R}, title = {Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32842596}, issn = {1422-0067}, support = {323156//Academy of Finland/ ; 316338//Academy of Finland/ ; Senior Research Fellow//Sigrid Juséliuksen Säätiö/ ; A three-year grant//Helsingin Yliopisto/ ; 160048//Lastentautien Tutkimussäätiö/ ; EVO 13004//Varsinais-Suomen Sairaanhoitopiiri/ ; }, abstract = {Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.}, }
@article {pmid32841200, year = {2020}, author = {Nurgaziyev, M and Sergazy, S and Chulenbayeva, L and Nurgozhina, A and Gulyayev, A and Kozhakhmetov, S and Kartbayeva, G and Kushugulova, A}, title = {THE EFFECTS OF ANTIBIOTICS ON THE GUT MICROBIOME AND THE IMMUNE SYSTEM (Review).}, journal = {Georgian medical news}, volume = {}, number = {303}, pages = {167-173}, pmid = {32841200}, issn = {1512-0112}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; Drug Resistance, Microbial/drug effects ; *Gastrointestinal Microbiome ; Humans ; Immune System/drug effects ; *Microbiota ; }, abstract = {Antibiotic resistance and its impact on human microbiome remains a global public health concern. Studies have shown that treatment with antibiotics leads to dramatic changes in composition and function of gut microbiome. This review focuses on the association between antibiotics use and its impact on gut microbiome of adults and children, gut microbiota metabolic interactions and presents the current understanding of the link between human gut microbiome and immune system.}, }
@article {pmid32834004, year = {2020}, author = {Dong, M and Li, L and Chen, M and Kusalik, A and Xu, W}, title = {Predictive analysis methods for human microbiome data with application to Parkinson's disease.}, journal = {PloS one}, volume = {15}, number = {8}, pages = {e0237779}, pmid = {32834004}, issn = {1932-6203}, mesh = {Adult ; Age Factors ; Aged ; Aged, 80 and over ; Bacteria/*classification/genetics/isolation & purification ; Cohort Studies ; Computer Simulation ; DNA, Bacterial/isolation & purification ; *Data Interpretation, Statistical ; Datasets as Topic ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; *Models, Biological ; Parkinson Disease/*diagnosis/microbiology ; Predictive Value of Tests ; Prognosis ; RNA, Ribosomal, 16S/genetics ; Sex Factors ; }, abstract = {Microbiome data consists of operational taxonomic unit (OTU) counts characterized by zero-inflation, over-dispersion, and grouping structure among samples. Currently, statistical testing methods are commonly performed to identify OTUs that are associated with a phenotype. The limitations of statistical testing methods include that the validity of p-values/q-values depend sensitively on the correctness of models and that the statistical significance does not necessarily imply predictivity. Predictive analysis using methods such as LASSO is an alternative approach for identifying associated OTUs and for measuring the predictability of the phenotype variable with OTUs and other covariate variables. We investigate three strategies of performing predictive analysis: (1) LASSO: fitting a LASSO multinomial logistic regression model to all OTU counts with specific transformation; (2) screening+GLM: screening OTUs with q-values returned by fitting a GLMM to each OTU, then fitting a GLM model using a subset of selected OTUs; (3) screening+LASSO: fitting a LASSO to a subset of OTUs selected with GLMM. We have conducted empirical studies using three simulation datasets generated using Dirichlet-multinomial models and a real gut microbiome data related to Parkinson's disease to investigate the performance of the three strategies for predictive analysis. Our simulation studies show that the predictive performance of LASSO with appropriate variable transformation works remarkably well on zero-inflated data. Our results of real data analysis show that Parkinson's disease can be predicted based on selected OTUs after the binary transformation, age, and sex with high accuracy (Error Rate = 0.199, AUC = 0.872, AUPRC = 0.912). These results provide strong evidences of the relationship between Parkinson's disease and the gut microbiome.}, }
@article {pmid32833508, year = {2020}, author = {Kurian, SM and Gordon, S and Barrick, B and Dadlani, MN and Fanelli, B and Cornell, JB and Head, SR and Marsh, CL and Case, J}, title = {Feasibility and Comparison Study of Fecal Sample Collection Methods in Healthy Volunteers and Solid Organ Transplant Recipients Using 16S rRNA and Metagenomics Approaches.}, journal = {Biopreservation and biobanking}, volume = {18}, number = {5}, pages = {425-440}, doi = {10.1089/bio.2020.0032}, pmid = {32833508}, issn = {1947-5543}, abstract = {The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold" standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.}, }
@article {pmid32825532, year = {2020}, author = {Nava Lara, RA and Beltrán, JA and Brizuela, CA and Del Rio, G}, title = {Relevant Features of Polypharmacologic Human-Target Antimicrobials Discovered by Machine-Learning Techniques.}, journal = {Pharmaceuticals (Basel, Switzerland)}, volume = {13}, number = {9}, pages = {}, pmid = {32825532}, issn = {1424-8247}, support = {CB252316//Consejo Nacional de Ciencia y Tecnología/ ; IN208817//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, abstract = {Polypharmacologic human-targeted antimicrobials (polyHAM) are potentially useful in the treatment of complex human diseases where the microbiome is important (e.g., diabetes, hypertension). We previously reported a machine-learning approach to identify polyHAM from FDA-approved human targeted drugs using a heterologous approach (training with peptides and non-peptide compounds). Here we discover that polyHAM are more likely to be found among antimicrobials displaying a broad-spectrum antibiotic activity and that topological, but not chemical features, are most informative to classify this activity. A heterologous machine-learning approach was trained with broad-spectrum antimicrobials and tested with human metabolites; these metabolites were labeled as antimicrobials or non-antimicrobials based on a naïve text-mining approach. Human metabolites are not commonly recognized as antimicrobials yet circulate in the human body where microbes are found and our heterologous model was able to classify those with antimicrobial activity. These results provide the basis to develop applications aimed to design human diets that purposely alter metabolic compounds proportions as a way to control human microbiome.}, }
@article {pmid32822862, year = {2020}, author = {Sharma, AK}, title = {Special Issue: Mining human microbiome bringing newer paradigms to anticancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.08.008}, pmid = {32822862}, issn = {1096-3650}, }
@article {pmid32821643, year = {2020}, author = {Cafiero, C and Re, A and Pisconti, S and Trombetti, M and Perri, M and Colosimo, M and D'Amato, G and Gallelli, L and Cannataro, R and Molinario, C and Fazio, A and Caroleo, MC and Cione, E}, title = {Dysbiosis in intestinal microbiome linked to fecal blood determined by direct hybridization.}, journal = {3 Biotech}, volume = {10}, number = {8}, pages = {358}, pmid = {32821643}, issn = {2190-572X}, abstract = {The important physiological and pathophysiological roles of intestinal human microbiome (HMB) in human health have been emerging, owing to the access to molecular biology techniques. Herein we evaluated, for the first time, the intestinal HMB through direct hybridization approach using n-counter flex DX technology which bypasses the amplification procedure currently applied by other technologies to study the human microbiome. To this purpose, a clinical study was carried out on fecal samples, recruiting both healthy volunteers (N-FOB) and subjects positive for occult blood (P-FOB). A relevant custom panel of 79 16S rRNA target gene was engineered and 32 of them displayed a variation between the two clusters of subjects. Our findings revealed that bacteria belonging to Proteobacteria have higher distribution in P-FOB describing dysbiosis. Similarly, Bacteroidetes and Firmicutes phylum display high distribution in P-FOB. Of interest, the presence of Clostridium difficile that belongs to Firmicutes phylum displayed about 70% of low presence in N-FOB compared to P-FOB subjects. Only one bacterium belonging to the Actinobacteria phylum, the Bifidobacterium bifidum, was present.}, }
@article {pmid32817490, year = {2020}, author = {Britton, GJ and Contijoch, EJ and Spindler, MP and Aggarwala, V and Dogan, B and Bongers, G and San Mateo, L and Baltus, A and Das, A and Gevers, D and Borody, TJ and Kaakoush, NO and Kamm, MA and Mitchell, H and Paramsothy, S and Clemente, JC and Colombel, JF and Simpson, KW and Dubinsky, MC and Grinspan, A and Faith, JJ}, title = {Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {35}, pages = {21536-21545}, pmid = {32817490}, issn = {1091-6490}, support = {R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Colitis/prevention & control ; Colon/microbiology ; Crohn Disease/metabolism/microbiology ; Cytokines/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/*immunology ; T-Lymphocytes, Regulatory/*immunology/microbiology ; Th17 Cells/*immunology/microbiology ; }, abstract = {The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt+ regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.}, }
@article {pmid32816985, year = {2020}, author = {Lamont, EI and Hendrickson, EL and McLean, JS and He, X and Bor, B}, title = {Complete Genome Sequence of Strain BB001, a Novel Epibiont Bacterium from the Candidate Phylum Saccharibacteria (TM7).}, journal = {Microbiology resource announcements}, volume = {9}, number = {34}, pages = {}, pmid = {32816985}, issn = {2576-098X}, support = {F32 DE025548/DE/NIDCR NIH HHS/United States ; K99 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; R00 DE027719/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; }, abstract = {Strain BB001 is cultivated from the human oral cavity on its basibiont bacterial host Actinomyces sp. It is an ultrasmall bacterium with a reduced genome that grows obligately on its bacterial host. BB001 is the first member of human microbiome taxon 957.}, }
@article {pmid32816830, year = {2020}, author = {Yan, R and Murphy, M and Genoni, A and Marlow, E and Dunican, IC and Lo, J and Andrew, L and Devine, A and Christophersen, CT}, title = {Does Fibre-fix provided to people with irritable bowel syndrome who are consuming a low FODMAP diet improve their gut health, gut microbiome, sleep and mental health? A double-blinded, randomised controlled trial.}, journal = {BMJ open gastroenterology}, volume = {7}, number = {1}, pages = {}, pmid = {32816830}, issn = {2054-4774}, abstract = {INTRODUCTION: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) is an effective way to reduce gut symptoms in people with irritable bowel syndrome (IBS). This diet reduces the intake of fermentable fibres, leading to changes of the gut microbiota and insufficient fermentation in the large bowel, resulting in reduced production of short-chain fatty acids (SCFAs), such as butyrate, which has unfavourable implications for gut health, sleep and mental health. This study will examine the effect of Fibre-fix, a supplement containing a mix of dietary fibres, on the human gut microbiome composition, fermentative capacity, sleep, quality of life (QOL) and mental health of people with IBS who consume a low FODMAP diet (LFD).
METHODS AND ANALYSIS: A randomised, double-blind, placebo-controlled, study design is proposed to examine whether Fibre-fix added to an existing LFD may help modulate gastrointestinal function, improve markers of sleep, mental health and promote QOL in patients with IBS. Participants will provide stool and blood samples, daily bowel symptoms diaries and 3-day diet records. Additionally, they will complete validated questionnaires relating to FODMAP intake, sleep, mental health and QOL before and after a 3-week intervention. Gut health will be assessed via faecal microbiome composition, faecal pH and SCFA levels. Alteration of sleep will be recorded using an actigraphy device worn by all participants over the whole study. Multivariate analysis will be used to examine the gut microbiome and repeated measures Analysis of variance (ANOVA) will be used for dependent variables from questionnaires related to bowel symptoms, stool type, sleep, mental health and QOL to assess the differences between intervention and control groups after adjustment for confounding variables.
ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committee of Edith Cowan University (2019-00619-YAN). Results will be disseminated in peer-review journal publications, and conference presentations. Participants will be provided with a summary of findings once the study is completed. If Fibre-fix is shown to result in favourable changes in gut microbial composition, SCFA production, sleep and mental well-being without exacerbating symptoms, this will provide additional dietary management options for those with IBS following an LFD.
TRIAL REGISTRATION NUMBER: ACTRN12620000032954.}, }
@article {pmid32814564, year = {2020}, author = {Vidanaarachchi, R and Shaw, M and Tang, SL and Halgamuge, S}, title = {IMPARO: inferring microbial interactions through parameter optimisation.}, journal = {BMC molecular and cell biology}, volume = {21}, number = {Suppl 1}, pages = {34}, pmid = {32814564}, issn = {2661-8850}, abstract = {BACKGROUND: Microbial Interaction Networks (MINs) provide important information for understanding bacterial communities. MINs can be inferred by examining microbial abundance profiles. Abundance profiles are often interpreted with the Lotka Volterra model in research. However existing research fails to consider a biologically meaningful underlying mathematical model for MINs or to address the possibility of multiple solutions.
RESULTS: In this paper we present IMPARO, a method for inferring microbial interactions through parameter optimisation. We use biologically meaningful models for both the abundance profile, as well as the MIN. We show how multiple MINs could be inferred with similar reconstructed abundance profile accuracy, and argue that a unique solution is not always satisfactory. Using our method, we successfully inferred clear interactions in the gut microbiome which have been previously observed in in-vitro experiments.
CONCLUSIONS: IMPARO was used to successfully infer microbial interactions in human microbiome samples as well as in a varied set of simulated data. The work also highlights the importance of considering multiple solutions for MINs.}, }
@article {pmid32806740, year = {2020}, author = {Kari, OK and Tavakoli, S and Parkkila, P and Baan, S and Savolainen, R and Ruoslahti, T and Johansson, NG and Ndika, J and Alenius, H and Viitala, T and Urtti, A and Lajunen, T}, title = {Light-Activated Liposomes Coated with Hyaluronic Acid as a Potential Drug Delivery System.}, journal = {Pharmaceutics}, volume = {12}, number = {8}, pages = {}, pmid = {32806740}, issn = {1999-4923}, support = {311122//Academy of Finland/ ; 317336//Academy of Finland/ ; 4208/31/2015//Business Finland/ ; 676137//Horizon 2020/ ; 9-8214-9//Orionin Tutkimussäätiö/ ; 0//Phospholipid Research Center/ ; 0//Emil Aaltosen Säätiö/ ; 0//Instrumentariumin Tiedesäätiö/ ; 0//Mary och Georg C. Ehrnrooths Stiftelse/ ; 0//Evald ja Hilda Nissin Säätiö/ ; 0//Inkeri and Mauri Vänskä Foundation/ ; 0//Paulon Säätiö/ ; 0//Päivikki ja Sakari Sohlbergin Säätiö/ ; }, abstract = {Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA-lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.}, }
@article {pmid32806589, year = {2020}, author = {Sun, Y and Kong, L and Wu, G and Cao, B and Pang, X and Deng, Z and Dedon, PC and Zhang, C and You, D}, title = {DNA Phosphorothioate Modifications Are Widely Distributed in the Human Microbiome.}, journal = {Biomolecules}, volume = {10}, number = {8}, pages = {}, pmid = {32806589}, issn = {2218-273X}, support = {31630002//National Natural Science Foundation of China/ ; }, abstract = {The DNA phosphorothioate (PT) modification existing in many prokaryotes, including bacterial pathogens and commensals, confers multiple characteristics, including restricting gene transfer, influencing the global transcriptional response, and reducing fitness during exposure to chemical mediators of inflammation. While PT-containing bacteria have been investigated in a variety of environments, they have not been studied in the human microbiome. Here, we investigated the distribution of PT-harboring strains and verified their existence in the human microbiome. We found over 2000 PT gene-containing strains distributed in different body sites, especially in the gastrointestinal tract. PT-modifying genes are preferentially distributed within several genera, including Pseudomonas, Clostridioides, and Escherichia, with phylogenic diversities. We also assessed the PT modification patterns and found six new PT-linked dinucleotides (CpsG, CpsT, ApsG, TpsG, GpsC, ApsT) in human fecal DNA. To further investigate the PT in the human gut microbiome, we analyzed the abundance of PT-modifying genes and quantified the PT-linked dinucleotides in the fecal DNA. These results confirmed that human microbiome is a rich reservoir for PT-containing microbes and contains a wide variety of PT modification patterns.}, }
@article {pmid32801832, year = {2020}, author = {Lichota, A and Gwozdzinski, K and Szewczyk, EM}, title = {Microbial Modulation of Coagulation Disorders in Venous Thromboembolism.}, journal = {Journal of inflammation research}, volume = {13}, number = {}, pages = {387-400}, pmid = {32801832}, issn = {1178-7031}, abstract = {Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third leading cause of cardiovascular death in the world. Important risk factors of thrombosis include bed restraint, surgery, major trauma, long journeys, inflammation, pregnancy, and oral contraceptives, previous venous thromboembolism, cancer, and bacterial infections. Sepsis increases the risk of blood clot formation 2-20 times. In this review, we discussed various mechanisms related to the role of bacteria in venous thrombosis also taking into consideration the role of the human microbiome. Many known bacteria, such as Helicobacter pylori, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, causing infections may increase the risk of thrombotic complications through platelet activation or may lead to an inflammatory reaction involving the fibrinolytic system. Additionally, the bacteria participate in the production of factors causing or increasing the risk of cardiovascular diseases. An example can be trimethylamine N-oxide (TMAO) but also uremic toxins (indoxyl sulfate), short-chain fatty acids (SCFA) phytoestrogens, and bile acids. Finally, we presented the involvement of many bacteria in the development of venous thromboembolism and other cardiovascular diseases.}, }
@article {pmid32797272, year = {2020}, author = {Bayar, E and Bennett, PR and Chan, D and Sykes, L and MacIntyre, DA}, title = {The pregnancy microbiome and preterm birth.}, journal = {Seminars in immunopathology}, volume = {42}, number = {4}, pages = {487-499}, pmid = {32797272}, issn = {1863-2300}, support = {EPRC//March of Dimes Foundation/ ; }, abstract = {Preterm birth is a global health concern and continues to contribute to substantial neonatal morbidity and mortality despite advances in obstetric and neonatal care. The underlying aetiology is multi-factorial and remains incompletely understood. In this review, the complex interplay between the vaginal microbiome in pregnancy and its association with preterm birth is discussed in depth. Advances in the study of bacteriology and an improved understanding of the human microbiome have seen an improved awareness of the vaginal microbiota in both health and in disease.}, }
@article {pmid32794312, year = {2020}, author = {Farahani, L and Tharakan, T and Yap, T and Ramsay, JW and Jayasena, CN and Minhas, S}, title = {The semen microbiome and its impact on sperm function and male fertility: A systematic review and meta-analysis.}, journal = {Andrology}, volume = {}, number = {}, pages = {}, doi = {10.1111/andr.12886}, pmid = {32794312}, issn = {2047-2927}, abstract = {BACKGROUND: Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting.
MATERIALS AND METHODS: A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction.
RESULTS: The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology.
DISCUSSION AND CONCLUSIONS: Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.}, }
@article {pmid32793130, year = {2020}, author = {Moran, GP and Al-Hebshi, N}, title = {Editorial: The Human Microbiome and Cancer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1514}, pmid = {32793130}, issn = {1664-302X}, }
@article {pmid32791981, year = {2020}, author = {Yan, Y and Nguyen, LH and Franzosa, EA and Huttenhower, C}, title = {Strain-level epidemiology of microbial communities and the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {71}, pmid = {32791981}, issn = {1756-994X}, support = {C10674/A27140//Cancer Research UK Grand Challenge Initiative/International ; R24DK110499//NIH NIDDK/International ; }, abstract = {The biological importance and varied metabolic capabilities of specific microbial strains have long been established in the scientific community. Strains have, in the past, been largely defined and characterized based on microbial isolates. However, the emergence of new technologies and techniques has enabled assessments of their ecology and phenotypes within microbial communities and the human microbiome. While it is now more obvious how pathogenic strain variants are detrimental to human health, the consequences of subtle genetic variation in the microbiome have only recently been exposed. Here, we review the operational definitions of strains (e.g., genetic and structural variants) as they can now be identified from microbial communities using different high-throughput, often culture-independent techniques. We summarize the distribution and diversity of strains across the human body and their emerging links to health maintenance, disease risk and progression, and biochemical responses to perturbations, such as diet or drugs. We list methods for identifying, quantifying, and tracking strains, utilizing high-throughput sequencing along with other molecular and "culturomics" technologies. Finally, we discuss implications of population studies in bridging experimental gaps and leading to a better understanding of the health effects of strains in the human microbiome.}, }
@article {pmid32791626, year = {2020}, author = {Wang, L and Chen, F and Yang, L and Li, J}, title = {[Role of nasal microbiome in chronic sinusitis].}, journal = {Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery}, volume = {34}, number = {5}, pages = {474-477}, doi = {10.13201/j.issn.2096-7993.2020.05.023}, pmid = {32791626}, issn = {2096-7993}, mesh = {Biofilms ; Chronic Disease ; Humans ; *Microbiota ; Nasal Mucosa ; *Rhinitis ; *Sinusitis ; Superantigens ; }, abstract = {Chronic sinusitis is a common disease in otolaryngology head and neck surgery, but the pathogenesis is unknown. For a long time, we have used fungi, bacterial biofilms, superantigens, and low host immunity as the cause of chronic sinusitis. With the rapid development of molecular biology technology, especially the advancement of DNA sequencing technology, people's research on human microbiome is deeper. We gradually realize the role of bacterial community in chronic sinusitis. This review will describe the role of bacteria in chronic sinusitis from three aspects: the composition of nasal bacterial community, the relationship between bacterial community and inflammatory phenotype, and the role between bacteria-host interaction.}, }
@article {pmid32791127, year = {2020}, author = {McCracken, BA and Nathalia Garcia, M}, title = {Phylum Synergistetes in the oral cavity: A possible contributor to periodontal disease.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102250}, doi = {10.1016/j.anaerobe.2020.102250}, pmid = {32791127}, issn = {1095-8274}, abstract = {Microbial contributions to periodontal disease have been under renewed scrutiny with the advent of newer technologies to identify their presence and gene expression at the molecular level. Members of the phylum Synergistetes are some of the more recent bacteria to be associated with periodontal disease. Bacteria classified in this phylum can be found in a wide variety of habitats including both inside and outside of a mammalian host. Members of this phylum have been identified as part of the human microbiome. Indeed, many of the identified phylotypes have yet to be cultivated. Here we consider contributions of three named and formally described species to the oral microbial community and to pathogenesis of periodontal disease.}, }
@article {pmid32789110, year = {2020}, author = {Kim, YY and Joh, JS and Lee, JY}, title = {Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential.}, journal = {Asia Pacific allergy}, volume = {10}, number = {3}, pages = {e25}, pmid = {32789110}, issn = {2233-8276}, abstract = {There are rising evidences of the human microbiome as a potentially influential player that is actively engaged in shaping the pathogenetic processes and other unresolved issues both in asthma and other chronic respiratory diseases, particularly of the airways. The biological components such as microbiome in inhaled air can induce immune dysfunction and inflammation, leading to inflammatory pulmonary disorders such as asthma and chronic obstructive pulmonary disease (COPD). Microbe-derived extracellular vesicles (EVs) with biologically active information or functions can reprogram their respective target cells and EV may have a role for the development of asthma and COPD. To evaluate the role of microbe-derived EV in the pathogenesis of asthma and COPD and its role in diagnosis, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement method was used for the study. An electronic search was performed using PubMed, PubMed Central, and Embase up to 2020. EVs serve as an intercellular transporter of miRNAs for cell-to-cell communication in the lungs. Bacteria-derived EVs have distinctive characteristics in the lungs of patients with asthma and COPD compared to healthy controls. Furthermore, bacterial EV IgG antibody titers in serum were significantly higher in patients with asthma and COPD than in healthy controls, suggesting that antibacterial EV antibodies titers can be used as a diagnostic tool for lung disease. Taken together, microbial EVs and miRNAs have important roles in the pathogenesis of asthma and COPD and they can provide novel diagnostic biomarkers for asthma and COPD.}, }
@article {pmid32786473, year = {2020}, author = {Jiang, X and Liu, S and Zhang, Y and Ji, Y and Sohail, A and Cao, C and Wang, P and Xiao, H}, title = {Free-Flow Isoelectric Focusing for Comprehensive Separation and Analysis of Human Salivary Microbiome for Lung Cancer.}, journal = {Analytical chemistry}, volume = {92}, number = {17}, pages = {12017-12025}, doi = {10.1021/acs.analchem.0c02627}, pmid = {32786473}, issn = {1520-6882}, abstract = {Human microbiome contains billions of microorganisms that play important roles in the biological system and different diseases. Due to its complexity, conventional culture-independent technology may underestimate the value of low-abundance bacteria, which calls for a highly efficient method for its enrichment and comprehensive analysis. In this study, we developed a recycling free-flow isoelectric focusing (RFFIEF) method-based electrophoresis method to separate salivary microbiome. First, we used Escherichia coli (DH5α) as a model for RFFIEF method development, which was focused in a narrow pH range (0.38 pH unit). The recovery rate was 80.81% with 5.85% relative standard deviation (n = 5). The optimized method was then adopted to separate the human salivary microbiome into 32 fractions, followed by 16S rRNA gene sequencing and metaproteomics analysis. After RFFIEF fractionation, we identified 508 bacterial genera, which increased by 225% on average (n = 3) when compared to the results before fractionation. We further compared the compositional change of microbiome in the saliva of lung cancer group (n = 22) and control group (n = 21) through RFFIEF. Quantitative results demonstrated that six bacterial genera were upregulated dramatically in the lung cancer group, while two genera were downregulated. Through qPCR verification in an independent sample set (n = 48), we confirmed that genus Granulicatella was significantly upregulated in the lung cancer group, whereas Pseudomonas was remarkably downregulated (p < 0.001). RFFIEF is an efficient and reproducible technology to fractionate the microbiome for its comprehensive analysis, which can be further applied to the in-depth study of the complex microbiomes and contribute to the discovery of disease-associated bacteria.}, }
@article {pmid32782301, year = {2020}, author = {Chen, L and Collij, V and Jaeger, M and van den Munckhof, ICL and Vich Vila, A and Kurilshikov, A and Gacesa, R and Sinha, T and Oosting, M and Joosten, LAB and Rutten, JHW and Riksen, NP and Xavier, RJ and Kuipers, F and Wijmenga, C and Zhernakova, A and Netea, MG and Weersma, RK and Fu, J}, title = {Gut microbial co-abundance networks show specificity in inflammatory bowel disease and obesity.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4018}, pmid = {32782301}, issn = {2041-1723}, mesh = {Adult ; Bacteria/growth & development/isolation & purification/metabolism ; Cohort Studies ; Dysbiosis/metabolism/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Host Specificity ; Humans ; Inflammatory Bowel Diseases/metabolism/*microbiology ; Male ; Metabolic Networks and Pathways ; *Microbial Consortia ; Middle Aged ; Obesity/metabolism/*microbiology ; }, abstract = {The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.}, }
@article {pmid32780794, year = {2020}, author = {Crimarco, A and Springfield, S and Petlura, C and Streaty, T and Cunanan, K and Lee, J and Fielding-Singh, P and Carter, MM and Topf, MA and Wastyk, HC and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT).}, journal = {The American journal of clinical nutrition}, volume = {112}, number = {5}, pages = {1188-1199}, pmid = {32780794}, issn = {1938-3207}, support = {T32 HL007034/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Cardiovascular Diseases/*prevention & control ; Cattle ; Chickens ; Cross-Over Studies ; *Diet, Vegetarian ; Exercise ; Female ; Humans ; Male ; *Meat ; Methylamines/*metabolism ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: Despite the rising popularity of plant-based alternative meats, there is limited evidence of the health effects of these products.
OBJECTIVES: We aimed to compare the effect of consuming plant-based alternative meat (Plant) as opposed to animal meat (Animal) on health factors. The primary outcome was fasting serum trimethylamine-N-oxide (TMAO). Secondary outcomes included fasting insulin-like growth factor 1, lipids, glucose, insulin, blood pressure, and weight.
METHODS: SWAP-MEAT (The Study With Appetizing Plantfood-Meat Eating Alternatives Trial) was a single-site, randomized crossover trial with no washout period. Participants received Plant and Animal products, dietary counseling, lab assessments, microbiome assessments (16S), and anthropometric measurements. Participants were instructed to consume ≥2 servings/d of Plant compared with Animal for 8 wk each, while keeping all other foods and beverages as similar as possible between the 2 phases.
RESULTS: The 36 participants who provided complete data for both crossover phases included 67% women, were 69% Caucasian, had a mean ± SD age 50 ± 14 y, and BMI 28 ± 5 kg/m2. Mean ± SD servings per day were not different by intervention sequence: 2.5 ± 0.6 compared with 2.6 ± 0.7 for Plant and Animal, respectively (P = 0.76). Mean ± SEM TMAO concentrations were significantly lower overall for Plant (2.7 ± 0.3) than for Animal (4.7 ± 0.9) (P = 0.012), but a significant order effect was observed (P = 0.023). TMAO concentrations were significantly lower for Plant among the n = 18 who received Plant second (2.9 ± 0.4 compared with 6.4 ± 1.5, Plant compared with Animal, P = 0.007), but not for the n = 18 who received Plant first (2.5 ± 0.4 compared with 3.0 ± 0.6, Plant compared with Animal, P = 0.23). Exploratory analyses of the microbiome failed to reveal possible responder compared with nonresponder factors. Mean ± SEM LDL-cholesterol concentrations (109.9 ± 4.5 compared with 120.7 ± 4.5 mg/dL, P = 0.002) and weight (78.7 ± 3.0 compared with 79.6 ± 3.0 kg, P < 0.001) were lower during the Plant phase.
CONCLUSIONS: Among generally healthy adults, contrasting Plant with Animal intake, while keeping all other dietary components similar, the Plant products improved several cardiovascular disease risk factors, including TMAO; there were no adverse effects on risk factors from the Plant products.This trial was registered at clinicaltrials.gov as NCT03718988.}, }
@article {pmid32778754, year = {2020}, author = {Cairns, J and Jokela, R and Becks, L and Mustonen, V and Hiltunen, T}, title = {Repeatable ecological dynamics govern the response of experimental communities to antibiotic pulse perturbation.}, journal = {Nature ecology & evolution}, volume = {4}, number = {10}, pages = {1385-1394}, doi = {10.1038/s41559-020-1272-9}, pmid = {32778754}, issn = {2397-334X}, mesh = {*Anti-Bacterial Agents ; Bacteria/genetics ; Metagenome ; *Microbiota ; Residence Characteristics ; }, abstract = {In an era of pervasive anthropogenic ecological disturbances, there is a pressing need to understand the factors that constitute community response and resilience. A detailed understanding of disturbance response needs to go beyond associations and incorporate features of disturbances, species traits, rapid evolution and dispersal. Multispecies microbial communities that experience antibiotic perturbation represent a key system with important medical dimensions. However, previous microbiome studies on this theme have relied on high-throughput sequencing data from uncultured species without the ability to explicitly account for the role of species traits and immigration. Here, we serially passage a 34-species defined bacterial community through different levels of pulse antibiotic disturbance, manipulating the presence or absence of species immigration. To understand the ecological community response measured using amplicon sequencing, we combine initial trait data measured for each species separately and metagenome sequencing data revealing adaptive mutations during the experiment. We found that the ecological community response was highly repeatable within the experimental treatments, which could be attributed in part to key species traits (antibiotic susceptibility and growth rate). Increasing antibiotic levels were also coupled with an increasing probability of species extinction, making species immigration critical for community resilience. Moreover, we detected signals of antibiotic-resistance evolution occurring within species at the same time scale, leaving evolutionary changes in communities despite recovery at the species compositional level. Together, these observations reveal a disturbance response that presents as classic species sorting, but is nevertheless accompanied by rapid within-species evolution.}, }
@article {pmid32775155, year = {2020}, author = {Méhes, G and Roy, A and Strakosas, X and Berggren, M and Stavrinidou, E and Simon, DT}, title = {Organic Microbial Electrochemical Transistor Monitoring Extracellular Electron Transfer.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {7}, number = {15}, pages = {2000641}, pmid = {32775155}, issn = {2198-3844}, abstract = {Extracellular electron transfer (EET) denotes the process of microbial respiration with electron transfer to extracellular acceptors and has been exploited in a range of microbial electrochemical systems (MESs). To further understand EET and to optimize the performance of MESs, a better understanding of the dynamics at the microscale is needed. However, the real-time monitoring of EET at high spatiotemporal resolution would require sophisticated signal amplification. To amplify local EET signals, a miniaturized bioelectronic device, the so-called organic microbial electrochemical transistor (OMECT), is developed, which includes Shewanella oneidensis MR-1 integrated onto organic electrochemical transistors comprising poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) combined with poly(vinyl alcohol) (PVA). Bacteria are attached to the gate of the transistor by a chronoamperometric method and the successful attachment is confirmed by fluorescence microscopy. Monitoring EET with the OMECT configuration is achieved due to the inherent amplification of the transistor, revealing fast time-responses to lactate. The limits of detection when using microfabricated gates as charge collectors are also investigated. The work is a first step toward understanding and monitoring EET in highly confined spaces via microfabricated organic electronic devices, and it can be of importance to study exoelectrogens in microenvironments, such as those of the human microbiome.}, }
@article {pmid32772665, year = {2020}, author = {Chomicki, G and Werner, GDA and West, SA and Kiers, ET}, title = {Compartmentalization drives the evolution of symbiotic cooperation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {375}, number = {1808}, pages = {20190602}, pmid = {32772665}, issn = {1471-2970}, abstract = {Across the tree of life, hosts have evolved mechanisms to control and mediate interactions with symbiotic partners. We suggest that the evolution of physical structures that allow hosts to spatially separate symbionts, termed compartmentalization, is a common mechanism used by hosts. Such compartmentalization allows hosts to: (i) isolate symbionts and control their reproduction; (ii) reward cooperative symbionts and punish or stop interactions with non-cooperative symbionts; and (iii) reduce direct conflict among different symbionts strains in a single host. Compartmentalization has allowed hosts to increase the benefits that they obtain from symbiotic partners across a diversity of interactions, including legumes and rhizobia, plants and fungi, squid and Vibrio, insects and nutrient provisioning bacteria, plants and insects, and the human microbiome. In cases where compartmentalization has not evolved, we ask why not. We argue that when partners interact in a competitive hierarchy, or when hosts engage in partnerships which are less costly, compartmentalization is less likely to evolve. We conclude that compartmentalization is key to understanding the evolution of symbiotic cooperation. This article is part of the theme issue 'The role of the microbiome in host evolution'.}, }
@article {pmid32771801, year = {2020}, author = {Eggers, S and Gennings, C and Malecki, KMC and Safdar, N and Arora, M}, title = {Exposure to environmental chemical mixtures is associated with nasal colonization by Staphylococcus aureus: NHANES 2001-2004.}, journal = {Environmental research}, volume = {190}, number = {}, pages = {109994}, pmid = {32771801}, issn = {1096-0953}, support = {R01 ES026033/ES/NIEHS NIH HHS/United States ; DP2 ES025453/ES/NIEHS NIH HHS/United States ; P30 ES023515/ES/NIEHS NIH HHS/United States ; T32 HD049311/HD/NICHD NIH HHS/United States ; U2C ES030859/ES/NIEHS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carrier State ; Child ; Female ; Humans ; *Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Nutrition Surveys ; Prevalence ; Risk Factors ; *Staphylococcal Infections/epidemiology ; Staphylococcus aureus ; Young Adult ; }, abstract = {BACKGROUND: Understanding the health effects of exposure to chemical mixtures is critically important given the broad range of concurrent exposures throughout the life-course. While investigations of environmental chemicals and components of the human microbiome are becoming more common, few have examined associations with chemical mixtures. This study assesses the association between exposure to mixtures of 66 different environmental chemicals and nasal colonization of Staphylococcus aureus (SA) and methicillin resistant SA (MRSA).
METHODS: Data came from the National Health and Nutrition Examination Survey (NHANES) 2001-2004. The analytical sample consists of 10,312 participants, age 6 years and older, subdivided into 8 groups with different chemical exposure mixtures. Within each of 6 chemical classes (metals, phthalates, polycyclic aromatic hydrocarbons (PAHs), polybrominated diphenyl ethers (PBDEs), polyfluorochemicals (PFCs), and phenols), weighted quantile sum (WQS) regression was used to analyze the joint association of the component compounds and nasal SA colonization. WQS was also used to assess the joint association of 3 chemical mixtures (metals, metal and PAHs, and metal and triclosan) and nasal MRSA colonization. All regression models were adjusted for confounders.
RESULTS: The analytical sample was between ages 6-85, slightly more female, and predominantly non-smokers. Prevalence of SA carriage was 29.2%, and MRSA colonization prevalence was 1.2%. Within each chemical class, odds of SA colonization increased statistically significantly with exposure to mixtures of metals (OR = 1.11, 95% CI = 1.02-1.20), phthalates (OR = 1.09, 95% CI = 1.04-1.14), and phenols (OR = 1.08, 95% CI = 1.01-1.15). Exposure to a mixture of metals combined with PAHs was also associated with increased odds of MRSA carriage (OR = 1.38, 95% CI = 1.02-1.86).
CONCLUSION: Results indicate an association between multiple environmental chemical mixtures and SA colonization, including MRSA. These findings support the need for further analysis of associations between chemical mixtures and SA colonization, as well as other components of the human microbiome.}, }
@article {pmid32770635, year = {2020}, author = {Tan, Y and Shen, J and Si, T and Ho, CL and Li, Y and Dai, L}, title = {Engineered Live Biotherapeutics: Progress and Challenges.}, journal = {Biotechnology journal}, volume = {15}, number = {10}, pages = {e2000155}, doi = {10.1002/biot.202000155}, pmid = {32770635}, issn = {1860-7314}, support = {2019YFA09006700//National Key R&D Program of China/ ; DWKF20190001//Shenzhen Institute of Synthetic Biology/ ; Y8G023//SIAT Innovation Program for Excellent Young Researchers/ ; 2019M663166//China Postdoctoral Science Foundation/ ; //IDG-McGovern Institute for Brain Research and the School of Pharmaceutical Sciences at Tsinghua University/ ; 31971513//National Natural Science Foundation of China/ ; }, abstract = {The human microbiome plays an important role in human health, from metabolism to immunity. In the last few decades, advances in synthetic biology have enabled scientists to design and engineer live microorganisms for therapeutic purposes. In this review, major strategies for manipulating the microbiome are outlined, which include three emerging areas with promising therapeutic applications: engineered commensal bacteria, synthetic microbial consortia, and targeted modulation by phages. Furthermore, the applications of engineered live biotherapeutics in treating a variety of human diseases, including pathogenic infections, metabolic disorders, inflammatory bowel disease, and colorectal cancer, are highlighted. Finally, an overview of the challenges and opportunities in the future development of engineered live biotherapeutics is provided.}, }
@article {pmid32767183, year = {2020}, author = {Tan, GSE and Tay, HL and Tan, SH and Lee, TH and Ng, TM and Lye, DC}, title = {Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.}, journal = {Advances in therapy}, volume = {37}, number = {10}, pages = {4054-4067}, doi = {10.1007/s12325-020-01458-z}, pmid = {32767183}, issn = {1865-8652}, abstract = {The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.}, }
@article {pmid32762083, year = {2020}, author = {Kantonen, J and Mahzabin, S and Mäyränpää, MI and Tynninen, O and Paetau, A and Andersson, N and Sajantila, A and Vapalahti, O and Carpén, O and Kekäläinen, E and Kantele, A and Myllykangas, L}, title = {Neuropathologic features of four autopsied COVID-19 patients.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {30}, number = {6}, pages = {1012-1016}, doi = {10.1111/bpa.12889}, pmid = {32762083}, issn = {1750-3639}, support = {//Juho Vainion Säätiö/International ; //Suomen Lääketieteen Säätiö/International ; //Medicinska Understödsföreningen Liv och Hälsa/International ; //Helsingin ja Uudenmaan Sairaanhoitopiiri/International ; 294817//Academy of Finland/International ; 334812//Academy of Finland/International ; 308913//Academy of Finland/International ; }, mesh = {Adult ; Aged, 80 and over ; Autopsy ; Brain/*pathology ; COVID-19/*pathology ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; }, }
@article {pmid32760391, year = {2020}, author = {Jouhten, H and Ronkainen, A and Aakko, J and Salminen, S and Mattila, E and Arkkila, P and Satokari, R}, title = {Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1663}, pmid = {32760391}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.}, }
@article {pmid32756341, year = {2020}, author = {Sierra, MA and Li, Q and Pushalkar, S and Paul, B and Sandoval, TA and Kamer, AR and Corby, P and Guo, Y and Ruff, RR and Alekseyenko, AV and Li, X and Saxena, D}, title = {The Influences of Bioinformatics Tools and Reference Databases in Analyzing the Human Oral Microbial Community.}, journal = {Genes}, volume = {11}, number = {8}, pages = {}, pmid = {32756341}, issn = {2073-4425}, support = {CA206105/NH/NIH HHS/United States ; DE025992/NH/NIH HHS/United States ; DE027074/NH/NIH HHS/United States ; NYU Mega grant initiative//New York University/ ; }, abstract = {There is currently no criterion to select appropriate bioinformatics tools and reference databases for analysis of 16S rRNA amplicon data in the human oral microbiome. Our study aims to determine the influence of multiple tools and reference databases on α-diversity measurements and β-diversity comparisons analyzing the human oral microbiome. We compared the results of taxonomical classification by Greengenes, the Human Oral Microbiome Database (HOMD), National Center for Biotechnology Information (NCBI) 16S, SILVA, and the Ribosomal Database Project (RDP) using Quantitative Insights Into Microbial Ecology (QIIME) and the Divisive Amplicon Denoising Algorithm (DADA2). There were 15 phyla present in all of the analyses, four phyla exclusive to certain databases, and different numbers of genera were identified in each database. Common genera found in the oral microbiome, such as Veillonella, Rothia, and Prevotella, are annotated by all databases; however, less common genera, such as Bulleidia and Paludibacter, are only annotated by large databases, such as Greengenes. Our results indicate that using different reference databases in 16S rRNA amplicon data analysis could lead to different taxonomic compositions, especially at genus level. There are a variety of databases available, but there are no defined criteria for data curation and validation of annotations, which can affect the accuracy and reproducibility of results, making it difficult to compare data across studies.}, }
@article {pmid32755361, year = {2020}, author = {Afzal, M and Mazhar, SF and Sana, S and Naeem, M and Rasool, MH and Saqalein, M and Nisar, MA and Rasool, M and Bilal, M and Khan, AA and Khurshid, M}, title = {Neurological and cognitive significance of probiotics: a holy grail deciding individual personality.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1059-1074}, doi = {10.2217/fmb-2019-0143}, pmid = {32755361}, issn = {1746-0921}, abstract = {The role of the human microbiome in the brain and behavioral development is an area of increasing attention. Recent investigations have found that diverse mechanisms and signals including the immune, endocrine and neural associations are responsible for the communication between gut microbiota and the brain. The studies have suggested that alteration of intestinal microbiota using probiotic formulations may offer a significant role in the maturation and organization of the brain and can shape the brain and behavior as well as mood and cognition in human subjects. The understanding of the possible impact of gut microflora on neurological function is a promising phenomenon that can surely transform the neurosciences and may decipher the novel etiologies for neurodegenerative and psychiatric disorders.}, }
@article {pmid32754400, year = {2020}, author = {Achufusi, TGO and Sharma, A and Zamora, EA and Manocha, D}, title = {Small Intestinal Bacterial Overgrowth: Comprehensive Review of Diagnosis, Prevention, and Treatment Methods.}, journal = {Cureus}, volume = {12}, number = {6}, pages = {e8860}, pmid = {32754400}, issn = {2168-8184}, abstract = {Small intestinal bacterial overgrowth (SIBO) is a commonly diagnosed gastrointestinal disorder affecting millions of individuals throughout the United States. It refers to a condition in which there is an excess and imbalance of small intestinal bacteria. Despite its prevalence, it remains underdiagnosed due to the invasive nature of diagnostic testing. Symptoms observed in SIBO, including abdominal distension, bloating, diarrhea, and gas formation, are nonspecific and can overlap with other gastrointestinal disorders. Frequently cited predisposing factors include gastric acid suppression, dysmotility, gastric bypass, and opioids. The diagnostic gold standard remains small bowel aspirate and culture. However, due to its invasive nature, it remains an unpopular method among patients and clinicians alike. Glucose and lactulose breath testing have become the go-to diagnostic method in clinical practice due to its noninvasive nature and low cost. Treatment is guided towards the eradication of bacteria in the small bowel and usually consists of a prolonged course of oral antibiotics. Due to recent advances in our understanding of the human microbiome, we are surely poised for a transformation in our approach to diagnosing and treating this condition.}, }
@article {pmid32753361, year = {2020}, author = {García-Velasco, JA and Budding, D and Campe, H and Malfertheiner, SF and Hamamah, S and Santjohanser, C and Schuppe-Koistinen, I and Nielsen, HS and Vieira-Silva, S and Laven, J}, title = {The reproductive microbiome - clinical practice recommendations for fertility specialists.}, journal = {Reproductive biomedicine online}, volume = {41}, number = {3}, pages = {443-453}, doi = {10.1016/j.rbmo.2020.06.014}, pmid = {32753361}, issn = {1472-6491}, abstract = {The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for assisted reproductive technologies. Combining these trends, it makes sense that clinicians are eager to understand and exploit the microbiome of their patients, i.e. the reproductive microbiome, in order to help them achieve their goal of becoming parents. This paper aims to provide an overview of the current and future research into the reproductive microbiome in relation to fertility and also share clinical practice recommendations for physicians who are new to this field or unsure about how they can utilise what is known to help their patients.}, }
@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}, 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 {pmid32733788, year = {2020}, author = {Guan, X and Ma, F and Sun, X and Li, C and Li, L and Liang, F and Li, S and Yi, Z and Liu, B and Xu, B}, title = {Gut Microbiota Profiling in Patients With HER2-Negative Metastatic Breast Cancer Receiving Metronomic Chemotherapy of Capecitabine Compared to Those Under Conventional Dosage.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {902}, pmid = {32733788}, issn = {2234-943X}, abstract = {Purpose: Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage. Methods: The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing. Results: A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (P = 0.025). Besides that, the Bray-Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of Slackia (9.2 vs. 32.7 months, P = 0.004), while the patients with Blautia obeum had a significantly prolonged PFS than those without (32.7 vs. 12.9 months, P = 0.013). Conclusions: The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.}, }
@article {pmid32729247, year = {2020}, author = {Fontana, F and Lindstedt, H and Correia, A and Chiaro, J and Kari, OK and Ndika, J and Alenius, H and Buck, J and Sieber, S and Mäkilä, E and Salonen, J and Urtti, A and Cerullo, V and Hirvonen, JT and Santos, HA}, title = {Influence of Cell Membrane Wrapping on the Cell-Porous Silicon Nanoparticle Interactions.}, journal = {Advanced healthcare materials}, volume = {9}, number = {17}, pages = {e2000529}, doi = {10.1002/adhm.202000529}, pmid = {32729247}, issn = {2192-2659}, abstract = {Biohybrid nanosystems represent the cutting-edge research in biofunctionalization of micro- and nano-systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane-coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell-specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage-mediated uptake.}, }
@article {pmid32727720, year = {2020}, author = {Huybrechts, I and Zouiouich, S and Loobuyck, A and Vandenbulcke, Z and Vogtmann, E and Pisanu, S and Iguacel, I and Scalbert, A and Indave, I and Smelov, V and Gunter, MJ and Michels, N}, title = {The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies.}, journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology}, volume = {29}, number = {10}, pages = {1856-1868}, pmid = {32727720}, issn = {1538-7755}, support = {ZIA CP010127/ImNIH/Intramural NIH HHS/United States ; }, abstract = {The microbiome has been hypothesized to play a role in cancer development. Because of the diversity of published data, an overview of available epidemiologic evidence linking the microbiome with cancer is now needed. We conducted a systematic review using a tailored search strategy in Medline and EMBASE databases to identify and summarize the current epidemiologic literature on the relationship between the microbiome and different cancer outcomes published until December 2019. We identified 124 eligible articles. The large diversity of parameters used to describe microbial composition made it impossible to harmonize the different studies in a way that would allow meta-analysis, therefore only a qualitative description of results could be performed. Fifty studies reported differences in the gut microbiome between patients with colorectal cancer and various control groups. The most consistent findings were for Fusobacterium, Porphyromonas, and Peptostreptococcus being significantly enriched in fecal and mucosal samples from patients with colorectal cancer. For the oral microbiome, significantly increased and decreased abundance was reported for Fusobacterium and Streptococcus, respectively, in patients with oral cancer compared with controls. Overall, although there was a large amount of evidence for some of these alterations, most require validation in high-quality, preferably prospective, epidemiologic studies.}, }
@article {pmid32725676, year = {2020}, author = {Druart, C and Plovier, H and Van Hul, M and Brient, A and Phipps, KR and de Vos, WM and Cani, PD}, title = {Toxicological safety evaluation of pasteurized Akkermansia muciniphila.}, journal = {Journal of applied toxicology : JAT}, volume = {}, number = {}, pages = {}, doi = {10.1002/jat.4044}, pmid = {32725676}, issn = {1099-1263}, support = {1410053//Walloon Region Microbe4U/ ; //Fonds de la Recherche Scientifique (FRS-FNRS)/ ; Microbes4U_713547//PoC ERC/ ; }, abstract = {Gut microorganisms are vital for many aspects of human health, and the commensal bacterium Akkermansia muciniphila has repeatedly been identified as a key component of intestinal microbiota. Reductions in A. muciniphila abundance are associated with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. It was recently discovered that administration of A. muciniphila has beneficial effects and that these are not diminished, but rather enhanced after pasteurization. Pasteurized A. muciniphila is proposed for use as a food ingredient, and was therefore subjected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day toxicity study. For the latter, Han Wistar rats were administered with the vehicle or pasteurized A. muciniphila at doses of 75, 375 or 1500 mg/kg body weight/day (equivalent to 4.8 × 109 , 2.4 × 1010 , or 9.6 × 1010 A. muciniphila cells/kg body weight/day) by oral gavage for 90 consecutive days. The study assessed potential effects on clinical observations (including detailed arena observations and a modified Irwin test), body weight, food and water consumption, clinical pathology, organ weights, and macroscopic and microscopic pathology. The results of both in vitro genotoxicity studies were negative. No test item-related adverse effects were observed in the 90-day study; therefore, 1500 mg/kg body weight/day (the highest dose tested, equivalent to 9.6 × 1010 A. muciniphila cells/kg body weight/day) was established as the no-observed-adverse-effect-level. These results support that pasteurized A. muciniphila is safe for use as a food ingredient.}, }
@article {pmid32723799, year = {2020}, author = {Rojas, MI and Cavalcanti, GS and McNair, K and Benler, S and Alker, AT and Cobián-Güemes, AG and Giluso, M and Levi, K and Rohwer, F and Bailey, BA and Beyhan, S and Edwards, RA and Shikuma, NJ}, title = {A Distinct Contractile Injection System Gene Cluster Found in a Majority of Healthy Adult Human Microbiomes.}, journal = {mSystems}, volume = {5}, number = {4}, pages = {}, pmid = {32723799}, issn = {2379-5077}, abstract = {Many commensal bacteria antagonize each other or their host by producing syringe-like secretion systems called contractile injection systems (CIS). Members of the Bacteroidales family have been shown to produce only one type of CIS-a contact-dependent type 6 secretion system that mediates bacterium-bacterium interactions. Here, we show that a second distinct cluster of genes from Bacteroidales bacteria from the human microbiome may encode yet-uncharacterized injection systems that we term Bacteroidales injection systems (BIS). We found that BIS genes are present in the gut microbiomes of 99% of individuals from the United States and Europe and that BIS genes are more prevalent in the gut microbiomes of healthy individuals than in those individuals suffering from inflammatory bowel disease. Gene clusters similar to that of the BIS mediate interactions between bacteria and diverse eukaryotes, like amoeba, insects, and tubeworms. Our findings highlight the ubiquity of the BIS gene cluster in the human gut and emphasize the relevance of the gut microbiome to the human host. These results warrant investigations into the structure and function of the BIS and how they might mediate interactions between Bacteroidales bacteria and the human host or microbiome.IMPORTANCE To engage with host cells, diverse pathogenic bacteria produce syringe-like structures called contractile injection systems (CIS). CIS are evolutionarily related to the contractile tails of bacteriophages and are specialized to puncture membranes, often delivering effectors to target cells. Although CIS are key for pathogens to cause disease, paradoxically, similar injection systems have been identified within healthy human microbiome bacteria. Here, we show that gene clusters encoding a predicted CIS, which we term Bacteroidales injection systems (BIS), are present in the microbiomes of nearly all adult humans tested from Western countries. BIS genes are enriched within human gut microbiomes and are expressed both in vitro and in vivo Further, a greater abundance of BIS genes is present within healthy gut microbiomes than in those humans with with inflammatory bowel disease (IBD). Our discovery provides a potentially distinct means by which our microbiome interacts with the human host or its microbiome.}, }
@article {pmid32722412, year = {2020}, author = {Nazik, H and Sass, G and Déziel, E and Stevens, DA}, title = {Aspergillus Is Inhibited by Pseudomonas aeruginosa Volatiles.}, journal = {Journal of fungi (Basel, Switzerland)}, volume = {6}, number = {3}, pages = {}, pmid = {32722412}, issn = {2309-608X}, support = {CIMR no. 3770//The Flatley Foundation/ ; }, abstract = {BACKGROUND: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons with cystic fibrosis, particularly the airways. These intermicrobial studies have largely been conducted in liquid medium or on agar, and thus focus on soluble or diffusible microbial products. Several key inhibitory molecules were defined in such studies.
METHODS: in the present report, we examine several methodologies which can be conveniently used to study the interaction of microbial volatiles, including capture methods and kinetics.
RESULTS: Pa volatiles inhibit Af, and the inhibitory mechanism appears to be the incorporation of the inhibitory molecules into the substrate nourishing the Af, rather than directly onto Af structures. We define by mass spectroscopy some specific volatile Pa products that can inhibit Af. Some of these molecules are selected for interest by the study of gene deletion mutants, producing a few Pa strains that were impaired in inhibition. We presumed the volatiles of these latter strains could be excluded from the search for inhibitors.
CONCLUSION: the Pa inhibition of Af via a gaseous phase could be critical components in their competition, particularly in airways, where more direct contact may not be extensive.}, }
@article {pmid32721621, year = {2020}, author = {Pearson, AL and Pechal, J and Lin, Z and Benbow, ME and Schmidt, C and Mavoa, S}, title = {Associations detected between measures of neighborhood environmental conditions and human microbiome diversity.}, journal = {The Science of the total environment}, volume = {745}, number = {}, pages = {141029}, doi = {10.1016/j.scitotenv.2020.141029}, pmid = {32721621}, issn = {1879-1026}, mesh = {Humans ; *Microbiota ; Plants ; Soil ; *Soil Microbiology ; Trees ; }, abstract = {While emerging research suggests urban green space revegetation increases soil microbiota diversity and native plant species affect skin microbiome diversity, there is still a paucity of knowledge on relationships between neighborhood environmental conditions and the human microbiome. This study leveraged data on human microbiome samples (nose, mouth, rectum) taken at autopsy at the Wayne County Medical Examiner's Office (2014-2015). We evaluated relationships between the microbiome and five measures of environmental conditions (NDVI standard deviation, NDVI mean, percent trees, percent grassland and soil type) near the home of 126 decedents. For the rectum microbiome, NDVI sd had negative, significant associations with diversity (ASVs β = -0.20, p = 0.045; Faith PD β = -0.22, p = 0.026). In contrast, while insignificant, there were consistent, positive associations between diversity and NDVI sd for the mouth microbiome (ASVs β = 0.09, p = 0.337, Faith PD β = 0.14, p = 0.149, Shannon diversity β = 0.14, p = 0.159, Heip's evenness β = 0.11, p = 0.259) and a significant association for the nose microbiome (eigenvalues 3 β = 0.18, p = 0.057). We found consistent, significant, negative associations between percent grassland and diversity of the nose microbiome (ASVs β = -0.25, p = 0.008, Faith PD β = -0.25, p = 0.009, Shannon diversity β = -0.17, p = 0.062). For the mouth microbiome, we found a small effect of percent trees on diversity (eigenvalues 1 β = -0.08, p = 0.053). Clay loam soil was negatively (eigenvalues 2 β = -0.47, p = 0.053) and positively associated (eigenvalues 3 β = 0.65, p = 0.008) with rectum microbiome diversity, compared to loam soil. There was no potential indicator taxon among NDVI quartiles. These findings may be relevant for urban planning and management of urban outdoor spaces in ways that may support healthy human microbiomes. Still, future research is needed to link variation in NDVI, vegetation, plant and/or soil microbe diversity and to confirm or negate our findings that environmental conditions may have contrasting influence on the microbiome of the rectum versus the nose and mouth and that grasslands affect the nose microbiome.}, }
@article {pmid32717337, year = {2020}, 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 = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.07.010}, pmid = {32717337}, issn = {1096-3650}, 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 {pmid32714306, year = {2020}, author = {Spacova, I and Dodiya, HB and Happel, AU and Strain, C and Vandenheuvel, D and Wang, X and Reid, G}, title = {Future of Probiotics and Prebiotics and the Implications for Early Career Researchers.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1400}, pmid = {32714306}, issn = {1664-302X}, abstract = {The opportunities in the fields of probiotics and prebiotics to a great degree stem from what we can learn about how they influence the microbiota and interact with the host. We discuss recent insights, cutting-edge technologies and controversial results from the perspective of early career researchers innovating in these areas. This perspective emerged from the 2019 meeting of the International Scientific Association for Probiotics and Prebiotics - Student and Fellows Association (ISAPP-SFA). Probiotic and prebiotic research is being driven by genetic characterization and modification of strains, state-of-the-art in vitro, in vivo, and in silico techniques designed to uncover the effects of probiotics and prebiotics on their targets, and metabolomic tools to identify key molecules that mediate benefits on the host. These research tools offer unprecedented insights into the functionality of probiotics and prebiotics in the host ecosystem. Young scientists need to acquire these diverse toolsets, or form inter-connected teams to perform comprehensive experiments and systematic analysis of data. This will be critical to identify microbial structure and co-dependencies at body sites and determine how administered probiotic strains and prebiotic substances influence the host. This and other strategies proposed in this review will pave the way for translating the health benefits observed during research into real-life outcomes. Probiotic strains and prebiotic products can contribute greatly to the amelioration of global issues threatening society. The intent of this article is to provide an early career researcher's perspective on where the biggest opportunities lie to advance science and impact human health.}, }
@article {pmid32708627, year = {2020}, author = {Garvey, M}, title = {Bacteriophages and the One Health Approach to Combat Multidrug Resistance: Is This the Way?.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {7}, pages = {}, pmid = {32708627}, issn = {2079-6382}, abstract = {Antimicrobial resistance necessitates action to reduce and eliminate infectious disease, ensure animal and human health, and combat emerging diseases. Species such as Acinetobacter baumanniii, vancomycin resistant Enterococcus, methicillin resistance Staphylococcus aureus, and Pseudomonas aeruginosa, as well as other WHO priority pathogens, are becoming extremely difficult to treat. In 2017, the EU adopted the "One Health" approach to combat antibiotic resistance in animal and human medicine and to prevent the transmission of zoonotic disease. As the current therapeutic agents become increasingly inadequate, there is a dire need to establish novel methods of treatment under this One Health Framework. Bacteriophages (phages), viruses infecting bacterial species, demonstrate clear antimicrobial activity against an array of resistant species, with high levels of specificity and potency. Bacteriophages play key roles in bacterial evolution and are essential components of all ecosystems, including the human microbiome. Factors such are their specificity, potency, biocompatibility, and bactericidal activity make them desirable options as therapeutics. Issues remain, however, relating to their large-scale production, formulation, stability, and bacterial resistance, limiting their implementation globally. Phages used in therapy must be virulent, purified, and well characterized before administration. Clinical studies are warranted to assess the in vivo pharmacokinetics and pharmacodynamic characteristics of phages to fully establish their therapeutic potential.}, }
@article {pmid32706929, year = {2020}, author = {Wisgrill, L and Werner, P and Jalonen, E and Berger, A and Lauerma, A and Alenius, H and Fyhrquist, N}, title = {Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.14519}, pmid = {32706929}, issn = {1398-9995}, support = {2018-00601//FORTE: Forskningsrådet för hälsa, arbetsliv och välfärd/ ; 113314//Finnish Work Environment Fund/ ; }, abstract = {BACKGROUND: Nickel-induced allergic contact dermatitis (nACD) remains a major occupational skin disorder, significantly impacting the quality of life of suffering patients. Complex cellular compositional changes and associated immunological pathways are partly resolved in humans; thus, the impact of nACD on human skin needs to be further elucidated.
METHODS: To decipher involved immunological players and pathways, human skin biopsies were taken at 0, 2, 48, and 96 hours after nickel patch test in six nickel-allergic patients. Gene expression profiles were analyzed via microarray.
RESULTS: Leukocyte deconvolution of nACD-affected skin identified major leukocyte compositional changes at 48 and 96 hours, including natural killer (NK) cells, macrophage polarization, and T-cell immunity. Gene set enrichment analysis mirrored cellular-linked functional pathways enriched over time. NK cell infiltration and cytotoxic pathways were uniquely found in nACD-affected skin compared to sodium lauryl sulfate-induced irritant skin reactions.
CONCLUSION: These results highlight key immunological leukocyte subsets as well as associated pathways in nACD, providing insights into pathophysiology with the potential to unravel novel therapeutic targets.}, }
@article {pmid32689930, year = {2020}, author = {Buongermino Pereira, M and Österlund, T and Eriksson, KM and Backhaus, T and Axelson-Fisk, M and Kristiansson, E}, title = {A comprehensive survey of integron-associated genes present in metagenomes.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {495}, pmid = {32689930}, issn = {1471-2164}, abstract = {BACKGROUND: Integrons are genomic elements that mediate horizontal gene transfer by inserting and removing genetic material using site-specific recombination. Integrons are commonly found in bacterial genomes, where they maintain a large and diverse set of genes that plays an important role in adaptation and evolution. Previous studies have started to characterize the wide range of biological functions present in integrons. However, the efforts have so far mainly been limited to genomes from cultivable bacteria and amplicons generated by PCR, thus targeting only a small part of the total integron diversity. Metagenomic data, generated by direct sequencing of environmental and clinical samples, provides a more holistic and unbiased analysis of integron-associated genes. However, the fragmented nature of metagenomic data has previously made such analysis highly challenging.
RESULTS: Here, we present a systematic survey of integron-associated genes in metagenomic data. The analysis was based on a newly developed computational method where integron-associated genes were identified by detecting their associated recombination sites. By processing contiguous sequences assembled from more than 10 terabases of metagenomic data, we were able to identify 13,397 unique integron-associated genes. Metagenomes from marine microbial communities had the highest occurrence of integron-associated genes with levels more than 100-fold higher than in the human microbiome. The identified genes had a large functional diversity spanning over several functional classes. Genes associated with defense mechanisms and mobility facilitators were most overrepresented and more than five times as common in integrons compared to other bacterial genes. As many as two thirds of the genes were found to encode proteins of unknown function. Less than 1% of the genes were associated with antibiotic resistance, of which several were novel, previously undescribed, resistance gene variants.
CONCLUSIONS: Our results highlight the large functional diversity maintained by integrons present in unculturable bacteria and significantly expands the number of described integron-associated genes.}, }
@article {pmid32687052, year = {2020}, author = {Descheemaeker, L and de Buyl, S}, title = {Stochastic logistic models reproduce experimental time series of microbial communities.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32687052}, issn = {2050-084X}, support = {SRP31//Vrije Universiteit Brussel/International ; }, abstract = {We analyze properties of experimental microbial time series, from plankton and the human microbiome, and investigate whether stochastic generalized Lotka-Volterra models could reproduce those properties. We show that this is the case when the noise term is large and a linear function of the species abundance, while the strength of the self-interactions varies over multiple orders of magnitude. We stress the fact that all the observed stochastic properties can be obtained from a logistic model, that is, without interactions, even the niche character of the experimental time series. Linear noise is associated with growth rate stochasticity, which is related to changes in the environment. This suggests that fluctuations in the sparsely sampled experimental time series may be caused by extrinsic sources.}, }
@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 ; R01 MH095458/MH/NIMH NIH HHS/United States ; }, 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 {pmid32680791, year = {2020}, author = {Daisley, BA and Chmiel, JA and Pitek, AP and Thompson, GJ and Reid, G}, title = {Missing Microbes in Bees: How Systematic Depletion of Key Symbionts Erodes Immunity.}, journal = {Trends in microbiology}, volume = {28}, number = {12}, pages = {1010-1021}, doi = {10.1016/j.tim.2020.06.006}, pmid = {32680791}, issn = {1878-4380}, abstract = {Pesticide exposure, infectious disease, and nutritional stress contribute to honey bee mortality and a high rate of colony loss. This realization has fueled a decades-long investigation into the single and combined effects of each stressor and their overall bearing on insect physiology. However, one element largely missing from this research effort has been the evaluation of underlying microbial communities in resisting environmental stressors and their influence on host immunity and disease tolerance. In humans, multigenerational bombardment by antibiotics is linked with many contemporary diseases. Here, we draw a parallel conclusion for the case in honey bees and suggest that chronic exposure to antimicrobial xenobiotics can systematically deplete honey bees of their microbes and hamper cross-generational preservation of host-adapted symbionts that are crucial to health.}, }
@article {pmid32679247, year = {2020}, author = {Le, ST and Toussi, A and Maverakis, N and Marusina, AI and Barton, VR and Merleev, AA and Luxardi, G and Raychaudhuri, SP and Maverakis, E}, title = {The cutaneous and intestinal microbiome in psoriatic disease.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {218}, number = {}, pages = {108537}, doi = {10.1016/j.clim.2020.108537}, pmid = {32679247}, issn = {1521-7035}, abstract = {Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases of multifactorial etiology. In addition to genetic and environmental factors, evidence supports involvement of a dysregulated human microbiome in the pathogenesis of psoriatic disease. In particular, alterations in the composition of the microbiome, termed dysbiosis, can result in downstream proinflammatory effects in the gut, skin, and joints. Both the cutaneous and intestinal microbial populations are implicated in the pathogenesis of psoriatic disease, although exact mechanisms are unclear. Herein, we review the relationship between the human microbiome and psoriatic disease. Further insight into the functions of the microbiome may allow for greater understanding of inflammatory disease processes and identification of additional therapeutic targets.}, }
@article {pmid32677447, year = {2020}, author = {Gao, W and Baumgartel, KL and Alexander, SA}, title = {The Gut Microbiome as a Component of the Gut-Brain Axis in Cognitive Health.}, journal = {Biological research for nursing}, volume = {22}, number = {4}, pages = {485-494}, doi = {10.1177/1099800420941923}, pmid = {32677447}, issn = {1552-4175}, abstract = {INTRODUCTION: The human microbiome, the microorganisms living in and on the body, plays a vital role in brain physiology and pathophysiology. The gut microbiome (GMB) has been identified as a link in the gut-brain axis moderating cognitive development and health.
OBJECTIVES: The objectives of this scoping review are to discuss mechanisms of the microbiome-gut-brain axis in cognition, review the existing literature on the GMB and cognition, and discuss implications for nursing research.
METHODS: We searched Pubmed using the terms "gut microbiome," "brain," and "cognition" and the terms "gut brain axis," "microbiome," and "cognition"; removed duplicates, studies not published in English, and unrelated publications; and added additional articles identified through references. We retained the 85 most relevant publications for this review.
RESULTS: Common themes in the current literature include GMB components; interactions on cognitive development; effects of GMB-gut-brain interactions on cognition, mild cognitive impairment and Alzheimer's disease; effects of GMB interactions with physiologic stress on cognition in critical care; and GMB modification for improved cognition. Review of the literature on each of these topics reveals multiple theoretical mechanisms of action for GMB-gut-brain interaction that modify cognitive development and function across the lifespan.
DISCUSSION: GMB components and dysbiosis have been implicated in many cognitive states, and specific microbiota constituents contribute to cognitive development, stability, and impairment. The study of these interactions is relevant to nursing research as it addresses the holistic human experience and microbiome constituents are modifiable, facilitating translation into the clinical setting.}, }
@article {pmid32675857, year = {2020}, author = {Dupont, HL and Jiang, ZD and Dupont, AW and Utay, NS}, title = {THE INTESTINAL MICROBIOME IN HUMAN HEALTH AND DISEASE.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {131}, number = {}, pages = {178-197}, pmid = {32675857}, issn = {0065-7778}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.}, }
@article {pmid32673603, year = {2020}, author = {Giannoni, E and Baud, D and Agri, VD and Gibson, GR and Reid, G}, title = {Probiotics and COVID-19.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {5}, number = {8}, pages = {720-721}, doi = {10.1016/S2468-1253(20)30195-3}, pmid = {32673603}, issn = {2468-1253}, mesh = {*Betacoronavirus ; COVID-19 ; *Coronavirus Infections ; Humans ; *Pandemics ; *Pneumonia, Viral ; *Probiotics ; SARS-CoV-2 ; }, }
@article {pmid32670603, year = {2020}, author = {Hadrich, D}, title = {New EU projects delivering human microbiome applications.}, journal = {Future science OA}, volume = {6}, number = {6}, pages = {FSO474}, pmid = {32670603}, issn = {2056-5623}, abstract = {Over recent years, the number of studies and projects showing correlations between the human microbiome and diseases has increased enormously. The potential of the human microbiome for healthcare is big. However, many confounders have been discovered and the relevant disease mechanisms and the causalities of these diseases still require more efforts and better understanding. The EU called for project proposals exploiting the application potential of human microbiome research and finally decided to fund the three top excellent new H2020 projects ONCOBIOME, MICROB-PREDICT and GEMMA. They get a total EU funding of €44 M and started in January 2019 with the aim to deliver high impact through validated clinical tools that are helpful for end-users.}, }
@article {pmid32668369, year = {2020}, author = {Matenchuk, BA and Mandhane, PJ and Kozyrskyj, AL}, title = {Sleep, circadian rhythm, and gut microbiota.}, journal = {Sleep medicine reviews}, volume = {53}, number = {}, pages = {101340}, doi = {10.1016/j.smrv.2020.101340}, pmid = {32668369}, issn = {1532-2955}, abstract = {From asthma and heart disease to diabetes and obesity, the human microbiome plays a role in the pathogenesis of each chronic health condition plaguing today's society. Recent work has shown that the gut microbiota and its metabolites exhibit diurnal rhythmicity which predominantly respond to the feeding/fasting cycle. Persistent jet lag, an obesogenic diet, and clock gene deficiency can dampen the oscillatory nature of gut bacterial composition, which can subsequently be rescued by time restricted feeding. Contrastingly, gut microbial metabolites influence central and hepatic clock gene expression and sleep duration in the host and regulate body composition through circadian transcription factors. Both sleep fragmentation and short sleep duration are associated with gut dysbiosis which may be due to activation of the HPA-axis. Metabolic disturbances associated with sleep loss may in fact be mediated through the overgrowth of specific gut bacteria. Reciprocally, the end products of bacterial species which grow in response to sleep loss are able to induce fatigue. Furthermore, probiotic supplementation has been found to improve subjective sleep quality. Sleep quality and duration may be an important target for supporting healthy gut microbiota composition, but the cyclic nature of this relationship should not be overlooked.}, }
@article {pmid32665329, year = {2020}, author = {Zhao, C and Wei, Z and Yang, J and Zhang, J and Yu, C and Yang, A and Zhang, M and Zhang, L and Wang, Y and Mu, X and Heng, X and Yang, H and Gai, Z and Wang, X and Zhang, L}, title = {Characterization of the Vaginal Microbiome in Women with Infertility and Its Potential Correlation with Hormone Stimulation during In Vitro Fertilization Surgery.}, journal = {mSystems}, volume = {5}, number = {4}, pages = {}, pmid = {32665329}, issn = {2379-5077}, abstract = {Perturbation of vaginal microbiome of reproductive-age women influences all the phases of a woman's reproductive life. Although studies have shown that dynamic changes in vaginal microbiome can affect pregnancy, its role in secondary infertility (i.e., inability to become pregnant or to carry a pregnancy successfully after previous success in delivering a child) and in vitrofertilization (IVF) remains to be unraveled. To determine the vaginal microbiome in women undergoing in vitrofertilization and embryo transfer (IVF-ET) and investigate its potential correlations with hormone stimulation, we recruited 30 patients with secondary infertility and receiving IVF and 92 matched healthy women and analyzed their vaginal microbiome composition using 16S rRNA gene sequencing. Our results show that women suffering from infertility (infertile women) exhibit a significant decrease in microbiome diversity and richness compared with healthy women during the nonovulation period (follicular phase) (P < 0.01), whereas vaginal microbiome of healthy women reveals dramatic fluctuations during ovulation (P < 0.05). Interestingly, infertility patients show no change of the vaginal microbiome under conditions of gonadotropin-releasing hormone (GnRH) agonist and recombinant human chorionic gonadotropin (r-hCG) induction (P > 0.05). Moreover, our results indicate that infertile women show characteristic variations in vaginal microbiome, such as increased abundance of Atopobium, Aerococcus, and Bifidobacterium and decreased abundance of Lactobacillus and LeuconostocIMPORTANCE The microbiome had been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction before the first success in IVF, while the data supporting or refuting this hypothesis were less than conclusive. Thanks to sequencing data from the 16S rRNA subunit, we characterized the microbiome in the reproductive tract of infertile women, and we found that changes in the vaginal microbiome are related to female infertility. We also found that the characteristic microbiome bacteria are mainly members of several genera and that the vaginal microbiome of infertile women is not sensitive to hormonal changes during IVF. In conclusion, our report provides data that can be used for discovering the role of the vaginal microbiome in patients suffering from secondary infertility.}, }
@article {pmid32663769, year = {2020}, author = {Arnolds, KL and Martin, CG and Lozupone, CA}, title = {Blood type and the microbiome- untangling a complex relationship with lessons from pathogens.}, journal = {Current opinion in microbiology}, volume = {56}, number = {}, pages = {59-66}, doi = {10.1016/j.mib.2020.06.008}, pmid = {32663769}, issn = {1879-0364}, support = {T32 AI007405/AI/NIAID NIH HHS/United States ; }, abstract = {The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors. Here, we address how a fundamental aspect of human biology, blood type, contributes to shaping this microscopic ecosystem. Although this question remains largely unexplored, we glean insights from decades of work describing relationships between pathogens and blood type. The bacterial strategies, molecular mechanisms, and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact. Understanding these nuanced interactions will expand our capacity to analyze and manipulate the human microbiome.}, }
@article {pmid32660471, year = {2020}, author = {Koslovsky, MD and Vannucci, M}, title = {MicroBVS: Dirichlet-tree multinomial regression models with Bayesian variable selection - an R package.}, journal = {BMC bioinformatics}, volume = {21}, number = {1}, pages = {301}, pmid = {32660471}, issn = {1471-2105}, mesh = {Algorithms ; Bacteroides/classification ; *Bayes Theorem ; Diet ; Humans ; Microbiota ; Phylogeny ; Prevotella/classification ; *Software ; }, abstract = {BACKGROUND: Understanding the relation between the human microbiome and modulating factors, such as diet, may help researchers design intervention strategies that promote and maintain healthy microbial communities. Numerous analytical tools are available to help identify these relations, oftentimes via automated variable selection methods. However, available tools frequently ignore evolutionary relations among microbial taxa, potential relations between modulating factors, as well as model selection uncertainty.
RESULTS: We present MicroBVS, an R package for Dirichlet-tree multinomial models with Bayesian variable selection, for the identification of covariates associated with microbial taxa abundance data. The underlying Bayesian model accommodates phylogenetic structure in the abundance data and various parameterizations of covariates' prior probabilities of inclusion.
CONCLUSION: While developed to study the human microbiome, our software can be employed in various research applications, where the aim is to generate insights into the relations between a set of covariates and compositional data with or without a known tree-like structure.}, }
@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 ; }, 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 {pmid32658296, year = {2020}, author = {Sutherland, VL and McQueen, CA and Mendrick, D and Gulezian, D and Cerniglia, C and Foley, S and Forry, S and Khare, S and Liang, X and Manautou, JE and Tweedie, D and Young, H and Alekseyenko, AV and Burns, F and Dietert, R and Wilson, A and Chen, C}, title = {The Gut Microbiome and Xenobiotics: Identifying Knowledge Gaps.}, journal = {Toxicological sciences : an official journal of the Society of Toxicology}, volume = {176}, number = {1}, pages = {1-10}, doi = {10.1093/toxsci/kfaa060}, pmid = {32658296}, issn = {1096-0929}, abstract = {There is an increasing awareness that the gut microbiome plays a critical role in human health and disease, but mechanistic insights are often lacking. In June 2018, the Health and Environmental Sciences Institute (HESI) held a workshop, "The Gut Microbiome: Markers of Human Health, Drug Efficacy and Xenobiotic Toxicity" (https://hesiglobal.org/event/the-gut-microbiome-workshop) to identify data gaps in determining how gut microbiome alterations may affect human health. Speakers and stakeholders from academia, government, and industry addressed multiple topics including the current science on the gut microbiome, endogenous and exogenous metabolites, biomarkers, and model systems. The workshop presentations and breakout group discussions formed the basis for identifying data gaps and research needs. Two critical issues that emerged were defining the microbial composition and function related to health and developing standards for models, methods and analysis in order to increase the ability to compare and replicate studies. A series of key recommendations were formulated to focus efforts to further understand host-microbiome interactions and the consequences of exposure to xenobiotics as well as identifying biomarkers of microbiome-associated disease and toxicity.}, }
@article {pmid32656839, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {3}, pages = {557-558}, doi = {10.1111/apt.15875}, pmid = {32656839}, issn = {1365-2036}, mesh = {*Anemia ; Azathioprine ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; *Leukopenia ; }, }
@article {pmid32654186, year = {2020}, author = {Cavaleiro Rufo, J and Paciência, I and Hoffimann, E and Moreira, A and Barros, H and Ribeiro, AI}, title = {The neighbourhood natural environment is associated with asthma in children: A birth cohort study.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.14493}, pmid = {32654186}, issn = {1398-9995}, support = {PTDC/GES-AMB/30193/2017//Fundação para a Ciência e a Tecnologia/ ; CEECIND/02386/2018//Fundação para a Ciência e a Tecnologia/ ; POCI-01-0145-FEDER-006862//European Regional Development Fund/ ; UID/DTP/04750/2019//European Regional Development Fund/ ; POCI-01-0145-FEDER-030193//European Regional Development Fund/ ; 02/SAICT/2017//European Regional Development Fund/ ; }, abstract = {BACKGROUND: A lower exposure to the natural environment has been hypothesized to adversely affect the human microbiome and its immunomodulatory capacity. However, the underlying effects of this hypothesis are still not understood. We aimed to evaluate the effect of early-life exposure to greenness and species richness on the development of allergic diseases and asthma in children.
METHODS: A longitudinal study was conducted comprising 1050 children from a population-based birth cohort recruited in Portugal. Residential normalized difference vegetation index (NDVI) and species richness index (SRI) were assessed at baseline to estimate their association with allergic diseases and asthma at the ages of 4 and 7.
RESULTS: Significant predisposing associations were observed between the exposure to species richness at baseline and the onset of asthma and wheezing at the age of 7. Children living in neighbourhoods surrounded by high levels of SRI were at a significantly higher risk developing allergic sensitization(OR [95% CI] = 2.00 [1.04:3.86] at age 4; 2.35 [1.20:4.63] at age 7). Living surrounded by greener environments was significantly associated with a lower prevalence of asthma and rhinitis at the age of 7(0.41 [0.18:0.97] and 0.37 [0.15:0.93], respectively).
CONCLUSIONS: Living in close proximity to a greener environment at birth has a protective effect on the development of allergic diseases and asthma at the age of 7. Conversely, living in neighbourhoods with a high number of fauna species appears to be associated with a higher risk for allergy, asthma and wheezing.}, }
@article {pmid32647884, year = {2020}, author = {Wiley, CA}, title = {Emergent Viral Infections of the CNS.}, journal = {Journal of neuropathology and experimental neurology}, volume = {79}, number = {8}, pages = {823-842}, doi = {10.1093/jnen/nlaa054}, pmid = {32647884}, issn = {1554-6578}, mesh = {Animals ; Birds ; Central Nervous System Viral Diseases/*epidemiology/prevention & control/*transmission ; Ecosystem ; Humans ; Influenza in Birds/epidemiology/prevention & control/transmission ; Influenza, Human/epidemiology/prevention & control/transmission ; West Nile Fever/epidemiology/prevention & control/transmission ; Zika Virus Infection/epidemiology/prevention & control/transmission ; Zoonoses/*epidemiology/prevention & control/*transmission ; }, abstract = {Biological evolution of the microbiome continually drives the emergence of human viral pathogens, a subset of which attack the nervous system. The sheer number of pathogens that have appeared, along with their abundance in the environment, demand our attention. For the most part, our innate and adaptive immune systems have successfully protected us from infection; however, in the past 5 decades, through pathogen mutation and ecosystem disruption, a dozen viruses emerged to cause significant neurologic disease. Most of these pathogens have come from sylvatic reservoirs having made the energetically difficult, and fortuitously rare, jump into humans. But the human microbiome is also replete with agents already adapted to the host that need only minor mutations to create neurotropic/toxic agents. While each host/virus symbiosis is unique, this review examines virologic and immunologic principles that govern the pathogenesis of different viral CNS infections that were described in the past 50 years (Influenza, West Nile Virus, Zika, Rift Valley Fever Virus, Hendra/Nipah, Enterovirus-A71/-D68, Human parechovirus, HIV, and SARS-CoV). Knowledge of these pathogens provides us the opportunity to respond and mitigate infection while at the same time prepare for inevitable arrival of unknown agents.}, }
@article {pmid32636826, year = {2020}, author = {Filik, K and Szermer-Olearnik, B and Wernecki, M and Happonen, LJ and Pajunen, MI and Nawaz, A and Qasim, MS and Jun, JW and Mattinen, L and Skurnik, M and Brzozowska, E}, title = {The Podovirus ϕ80-18 Targets the Pathogenic American Biotype 1B Strains of Yersinia enterocolitica.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1356}, pmid = {32636826}, issn = {1664-302X}, abstract = {We report here the complete genome sequence and characterization of Yersinia bacteriophage vB_YenP_ϕ80-18. ϕ80-18 was isolated in 1991 using a Y. enterocolitica serotype O:8 strain 8081 as a host from a sewage sample in Turku, Finland, and based on its morphological and genomic features is classified as a podovirus. The genome is 42 kb in size and has 325 bp direct terminal repeats characteristic for podoviruses. The genome contains 57 predicted genes, all encoded in the forward strand, of which 29 showed no similarity to any known genes. Phage particle proteome analysis identified altogether 24 phage particle-associated proteins (PPAPs) including those identified as structural proteins such as major capsid, scaffolding and tail component proteins. In addition, also the DNA helicase, DNA ligase, DNA polymerase, 5'-exonuclease, and the lytic glycosylase proteins were identified as PPAPs, suggesting that they might be injected together with the phage genome into the host cell to facilitate the take-over of the host metabolism. The phage-encoded RNA-polymerase and DNA-primase were not among the PPAPs. Promoter search predicted the presence of four phage and eleven host RNA polymerase -specific promoters in the genome, suggesting that early transcription of the phage is host RNA-polymerase dependent and that the phage RNA polymerase takes over later. The phage tolerates pH values between 2 and 12, and is stable at 50°C but is inactivated at 60°C. It grows slowly with a 50 min latent period and has apparently a low burst size. Electron microscopy revealed that the phage has a head diameter of about 60 nm, and a short tail of 20 nm. Whole-genome phylogenetic analysis confirmed that ϕ80-18 belongs to the Autographivirinae subfamily of the Podoviridae family, that it is 93.2% identical to Yersinia phage fHe-Yen3-01. Host range analysis showed that ϕ80-18 can infect in addition to Y. enterocolitica serotype O:8 strains also strains of serotypes O:4, O:4,32, O:20 and O:21, the latter ones representing similar to Y. enterocolitica serotype O:8, the American pathogenic biotype 1B strains. In conclusion, the phage ϕ80-18 is a promising candidate for the biocontrol of the American biotype 1B Y. enterocolitica.}, }
@article {pmid32635461, year = {2020}, author = {Puccetti, M and Xiroudaki, S and Ricci, M and Giovagnoli, S}, title = {Postbiotic-Enabled Targeting of the Host-Microbiota-Pathogen Interface: Hints of Antibiotic Decline?.}, journal = {Pharmaceutics}, volume = {12}, number = {7}, pages = {}, pmid = {32635461}, issn = {1999-4923}, support = {FFC#24/2018//Fondazione per la Ricerca sulla Fibrosi Cistica/ ; }, abstract = {Mismanagement of bacterial infection therapies has undermined the reliability and efficacy of antibiotic treatments, producing a profound crisis of the antibiotic drug market. It is by now clear that tackling deadly infections demands novel strategies not only based on the mere toxicity of anti-infective compounds. Host-directed therapies have been the first example as novel treatments with alternate success. Nevertheless, recent advances in the human microbiome research have provided evidence that compounds produced by the microbial metabolism, namely postbiotics, can have significant impact on human health. Such compounds target the host-microbe-pathogen interface rescuing biotic and immune unbalances as well as inflammation, thus providing novel therapeutic opportunities. This work discusses critically, through literature review and personal contributions, these novel nonantibiotic treatment strategies for infectious disease management and resistance prevention, which could represent a paradigm change rocking the foundation of current antibiotic therapy tenets.}, }
@article {pmid32634783, year = {2020}, author = {Yang, Y and Liu, S and Wang, Y and Wang, Z and Ding, W and Sun, X and He, K and Feng, Q and Zhang, X}, title = {Changes of saliva microbiota in the onset and after the treatment of diabetes in patients with periodontitis.}, journal = {Aging}, volume = {12}, number = {13}, pages = {13090-13114}, pmid = {32634783}, issn = {1945-4589}, abstract = {The relationship between type 2 diabetes mellitus (T2DM) and oral microbiota is still insufficiently recognized. In the present study, we compared the salivary microbiome of nondiabetic individuals, treatment-naïve diabetic patients, and diabetic patients treated with metformin or a combination of insulin and other drugs. The α- and β-diversity demonstrated significant differences in the salivary microbiome between the nondiabetic people and patients with a history of diabetes, while little divergence was found among individuals with a history of diabetes. After characterizing the effects of periodontitis on the microbial composition of each group, the salivary microbiome of the treatment-naïve diabetic patient group was compared with that of nondiabetic people and the metformin/combined treatment groups. The results revealed changes in the contents of certain bacteria after both the onset and the treatment of diabetes; among these differential bacteria, Blautia_wexlerae, Lactobacillus_fermentum, Nocardia_coeliaca and Selenomonas_artemidis varied in all processes. A subsequent correlational analysis of the differential bacteria and clinical characteristics demonstrated that salivary microbes were related to drug treatment and certain pathological changes. Finally, the four common differential bacteria were employed for distinguishing the treatment-naïve diabetic patients from the nondiabetic people and the treated patients, with prediction accuracies of 83.3%, 75% and 75%, respectively.}, }
@article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1555-1563}, pmid = {32620549}, issn = {1468-3288}, mesh = {Betacoronavirus ; COVID-19 ; Change Management ; Clostridium Infections/microbiology/*therapy ; *Coronavirus Infections/epidemiology/prevention & control ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastroenterology/organization & administration/trends ; Gastrointestinal Microbiome ; Humans ; Infection Control/methods/standards ; *Pandemics/prevention & control ; *Patient Selection ; *Pneumonia, Viral/epidemiology/prevention & control ; Risk Adjustment/methods/standards ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, }
@article {pmid32620143, year = {2020}, author = {Creswell, R and Tan, J and Leff, JW and Brooks, B and Mahowald, MA and Thieroff-Ekerdt, R and Gerber, GK}, title = {High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {59}, pmid = {32620143}, issn = {1756-994X}, support = {1R01GM130777/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics.
METHODS: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants' microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns.
RESULTS: Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes.
CONCLUSIONS: Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome.}, }
@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}, 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 {pmid32612660, year = {2020}, author = {Ogunrinola, GA and Oyewale, JO and Oshamika, OO and Olasehinde, GI}, title = {The Human Microbiome and Its Impacts on Health.}, journal = {International journal of microbiology}, volume = {2020}, number = {}, pages = {8045646}, pmid = {32612660}, issn = {1687-918X}, abstract = {The human microbiome comprises bacteria, archaea, viruses, and eukaryotes which reside within and outside our bodies. These organisms impact human physiology, both in health and in disease, contributing to the enhancement or impairment of metabolic and immune functions. Micro-organisms colonise various sites on and in the human body, where they adapt to specific features of each niche. Facultative anaerobes are more dominant in the gastrointestinal tract, whereas strict aerobes inhabit the respiratory tract, nasal cavity, and skin surface. The indigenous organisms in the human body are well adapted to the immune system, due to the biological interaction of the organisms with the immune system over time. An alteration in the intestinal microbial community plays a major role in human health and disease pathogenesis. These alterations result from lifestyle and the presence of an underlying disease. Dysbiosis increases host susceptibility to infection, and the nature of which depends on the anatomical site involved. The unique diversity of the human microbiota accounts for the specific metabolic activities and functions of these micro-organisms within each body site. It is therefore important to understand the microbial composition and activities of the human microbiome as they contribute to health and disease.}, }
@article {pmid32607819, year = {2020}, author = {Ohadian Moghadam, S and Momeni, SA}, title = {Human microbiome and prostate cancer development: current insights into the prevention and treatment.}, journal = {Frontiers of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11684-019-0731-7}, pmid = {32607819}, issn = {2095-0225}, abstract = {The huge communities of microorganisms that symbiotically colonize humans are recognized as significant players in health and disease. The human microbiome may influence prostate cancer development. To date, several studies have focused on the effect of prostate infections as well as the composition of the human microbiome in relation to prostate cancer risk. Current studies suggest that the microbiota of men with prostate cancer significantly differs from that of healthy men, demonstrating that certain bacteria could be associated with cancer development as well as altered responses to treatment. In healthy individuals, the microbiome plays a crucial role in the maintenance of homeostasis of body metabolism. Dysbiosis may contribute to the emergence of health problems, including malignancy through affecting systemic immune responses and creating systemic inflammation, and changing serum hormone levels. In this review, we discuss recent data about how the microbes colonizing different parts of the human body including urinary tract, gastrointestinal tract, oral cavity, and skin might affect the risk of developing prostate cancer. Furthermore, we discuss strategies to target the microbiome for risk assessment, prevention, and treatment of prostate cancer.}, }
@article {pmid32605552, year = {2020}, author = {Rees, J and Christophersen, CC and Lewis, JR and Lo, J and Sambell, R and Costello, L and Walker, C and Byrne, MF and Boyce, MC and Newton, RU and Devine, A}, title = {The study protocol for a pseudo-randomised pre-post designed controlled intervention trial to study the effects of a 7-week cooking program on self-efficacy and biomarkers of health: the ECU lifestyle and biomarkers get connected study (ECULABJMOF) including the Jamie's Ministry of Food WA participant experience.}, journal = {BMC public health}, volume = {20}, number = {1}, pages = {1037}, pmid = {32605552}, issn = {1471-2458}, mesh = {Adult ; Australia ; Biomarkers ; Chronic Disease ; *Cooking ; Diet/adverse effects/statistics & numerical data ; Female ; *Health Knowledge, Attitudes, Practice ; Health Promotion/*methods ; Humans ; Life Style ; Male ; Obesity/epidemiology/prevention & control ; Personal Satisfaction ; Program Evaluation ; Research Design ; *Self Efficacy ; Surveys and Questionnaires ; Western Australia/epidemiology ; }, abstract = {BACKGROUND: Australia, like other nations, has experienced a shift in dietary patterns away from home cooking of nutritious foods, towards a reliance on pre-prepared convenience meals. These are typically energy-dense, nutrient-poor and contribute to the rising prevalence of obesity and chronic disease burden. The aims of this study were to evaluate whether a community-based cooking program instigated a change to participants' skills, attitudes, knowledge, enjoyment and satisfaction of cooking and cooking confidence (self-efficacy).
METHODS: The pseudo-random, pre-post study design consisted of an intervention and a control group. Participant recruitment and group allocation was based on their program start dates. Intervention participants were surveyed three times (baseline, 7 weeks and 6 months) and the control group were surveyed at baseline and 5 weeks. All participants were registered via an online website and were 18 years or over. Upon consent, participants were offered four levels of commitment, defined by different assessments. The minimum participation level included an online survey and levels 2, 3 and 4 involved attendance at a clinic with increasing functional, anthropometric and biomarker measurements. Primary endpoints were participants' cooking confidence as a proxy for self-efficacy. Secondary endpoints were dietary intake, physical activity levels, body composition, anthropometry, blood, urine and faecal biomarkers of systemic, physical and mental health.
DISCUSSION: The community cooking program provided participants with information and advice on food sourcing, preparation and nutrition to improve home cooking skills. The study was designed to explore whether food literacy programs are efficacious in improving participant physical health and well-being in order to combat the rise in obesity and diet-related disease. It will support future use of public health cooking program initiatives aimed at improving food literacy, self-efficacy and physical and mental health. The extensive data collected will inform future research into the relationship between diet, the gut-microbiota and human health.
TRIAL REGISTRATION: Retrospectively registered on 16.08.2019 with the Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12619001144101 . Protocol version 4.}, }
@article {pmid32605102, year = {2020}, author = {Roder, T and Wüthrich, D and Bär, C and Sattari, Z and Ah, UV and Ronchi, F and Macpherson, AJ and Ganal-Vonarburg, SC and Bruggmann, R and Vergères, G}, title = {In Silico Comparison Shows that the Pan-Genome of a Dairy-Related Bacterial Culture Collection Covers Most Reactions Annotated to Human Microbiomes.}, journal = {Microorganisms}, volume = {8}, number = {7}, pages = {}, pmid = {32605102}, issn = {2076-2607}, support = {GRS-070/17//Gebert Rüf Stiftung/ ; }, abstract = {The diversity of the human microbiome is positively associated with human health. However, this diversity is endangered by Westernized dietary patterns that are characterized by a decreased nutrient variety. Diversity might potentially be improved by promoting dietary patterns rich in microbial strains. Various collections of bacterial cultures resulting from a century of dairy research are readily available worldwide, and could be exploited to contribute towards this end. We have conducted a functional in silico analysis of the metagenome of 24 strains, each representing one of the species in a bacterial culture collection composed of 626 sequenced strains, and compared the pathways potentially covered by this metagenome to the intestinal metagenome of four healthy, although overweight, humans. Remarkably, the pan-genome of the 24 strains covers 89% of the human gut microbiome's annotated enzymatic reactions. Furthermore, the dairy microbial collection covers biological pathways, such as methylglyoxal degradation, sulfate reduction, g-aminobutyric (GABA) acid degradation and salicylate degradation, which are differently covered among the four subjects and are involved in a range of cardiometabolic, intestinal, and neurological disorders. We conclude that microbial culture collections derived from dairy research have the genomic potential to complement and restore functional redundancy in human microbiomes.}, }
@article {pmid32604176, year = {2020}, author = {Qian, XB and Chen, T and Xu, YP and Chen, L and Sun, FX and Lu, MP and Liu, YX}, title = {A guide to human microbiome research: study design, sample collection, and bioinformatics analysis.}, journal = {Chinese medical journal}, volume = {133}, number = {15}, pages = {1844-1855}, pmid = {32604176}, issn = {2542-5641}, abstract = {The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods.}, }
@article {pmid32602257, year = {2020}, author = {Delbeke, H and Younas, S and Casteels, I and Joossens, M}, title = {Current knowledge on the human eye microbiome: a systematic review of available amplicon and metagenomic sequencing data.}, journal = {Acta ophthalmologica}, volume = {}, number = {}, pages = {}, doi = {10.1111/aos.14508}, pmid = {32602257}, issn = {1755-3768}, abstract = {Insights in the ocular surface microbiome are still at an early stage and many more questions remain unanswered compared with other human-associated microbial communities. The current knowledge on the human microbiome changed our viewpoint on bacteria and human health and significantly enhanced our understanding of human pathophysiology. Also in ocular medicine, microbiome research might impact treatment. Here, we summarize the current knowledge on ocular microbiome research with a particular focus on potential confounding factors and their effects on microbiome composition. Moreover, we present the ocular surface core microbiome based on current available data and defined it as genera present in almost half of the published control cohorts with a relative abundance of at least 1%.}, }
@article {pmid32600759, year = {2020}, author = {Simões da Silva, TM and Piazentin, ACM and Mendonça, CMN and Converti, A and Bogsan, CSB and Mora, D and de Souza Oliveira, RP}, title = {Buffalo milk increases viability and resistance of probiotic bacteria in dairy beverages under in vitro simulated gastrointestinal conditions.}, journal = {Journal of dairy science}, volume = {103}, number = {9}, pages = {7890-7897}, doi = {10.3168/jds.2019-18078}, pmid = {32600759}, issn = {1525-3198}, mesh = {Animals ; Beverages ; *Buffaloes ; Cattle ; Cultured Milk Products/microbiology ; Dairy Products/*microbiology ; Female ; Fermentation ; Food Storage ; Gastrointestinal Tract/*metabolism ; Humans ; Lactobacillus acidophilus/metabolism ; *Microbial Viability ; Microbiota ; *Milk/metabolism ; *Probiotics/analysis ; Streptococcus thermophilus/metabolism ; Whey Proteins/analysis ; }, abstract = {Probiotic dairy beverages prepared from buffalo and cow milks with different levels of whey (0, 25, and 50%) were evaluated for kinetic fermentation parameters, protein and fat contents, post-acidification profile, viability of Streptococcus thermophilus, Lactobacillus bulgaricus, and Lactobacillus acidophilus during 21 d of refrigerated storage, and resistance to in vitro gastrointestinal conditions. Progressive acidification that occurred during storage of all dairy products was reduced in the presence of whey. Lactic acid bacteria showed viable cell counts at the end of shelf life, with the highest values (7.33 to 8.83 log cfu/mL) detected in buffalo dairy products. Compared with fermented cow milk products, those made with buffalo milk showed better bacterial viability during in vitro simulated gastrointestinal digestion, which suggests a beneficial protective effect on human microbiome.}, }
@article {pmid32599802, year = {2020}, author = {Marzano, V and Pane, S and Foglietta, G and Levi Mortera, S and Vernocchi, P and Onetti Muda, A and Putignani, L}, title = {Mass Spectrometry Based-Proteomic Analysis of Anisakis spp.: A Preliminary Study towards a New Diagnostic Tool.}, journal = {Genes}, volume = {11}, number = {6}, pages = {}, pmid = {32599802}, issn = {2073-4425}, abstract = {Anisakiasis is nowadays a well-known infection, mainly caused by the accidental ingestion of Anisakis larvae, following the consumption of raw or undercooked fishes and cephalopods. Due to the similarity of symptoms with those of common gastrointestinal disorders, this infection is often underestimated, and the need for new specific diagnostic tools is becoming crucial. Given the remarkable impact that MALDI-TOF MS biotyping had in the last decade in clinical routine practice for the recognition of bacterial and fungi strains, a similar scenario could be foreseen for the identification of parasites, such as nematodes. In this work, a MALDI-TOF MS profiling of Anisakis proteome was pursued with a view to constructing a first spectral library for the diagnosis of Anisakis infections. At the same time, a shotgun proteomics approach by LC-ESI-MS/MS was performed on the two main fractions obtained from protein extraction, to evaluate the protein species enriched by the protocol. A set of MALDI-TOF MS signals associated with proteins originating in the ribosomal fraction of the nematode extract was selected as a potential diagnostic tool for the identification of Anisakis spp.}, }
@article {pmid32592144, year = {2020}, author = {Ouabbou, S and He, Y and Butler, K and Tsuang, M}, title = {Inflammation in Mental Disorders: Is the Microbiota the Missing Link?.}, journal = {Neuroscience bulletin}, volume = {36}, number = {9}, pages = {1071-1084}, pmid = {32592144}, issn = {1995-8218}, abstract = {Research suggests that inflammation is important in the pathophysiology of mental disorders. In addition, a growing body of evidence has led to the concept of the microbiota-gut-brain axis. To understand the potential interactions, we begin by exploring the liaison between the immune system and mental disorders, then we describe the evidence that the microbiota impact the immune response in the developing brain. Next, we review the literature that has documented microbiome alterations in major mental disorders. We end with a summary of therapeutic applications, ranging from psycho-biotics to immunomodulatory drugs that could affect the microbiota-gut-brain axis, and potential treatments to alleviate the adverse effects of antipsychotics. We conclude that there is promising evidence to support the position that the microbiota plays an important role in the immunological pathophysiology of mental disorders with an emphasis on psychotic disorders and mood disorders. However, more research is needed to elucidate the mechanisms.}, }
@article {pmid32587451, year = {2020}, author = {Xue, AJ and Miao, SJ and Sun, H and Qiu, XX and Wang, SN and Wang, L and Ye, ZQ and Zheng, CF and Huang, ZH and Wang, YH and Huang, Y}, title = {Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.}, journal = {World journal of gastroenterology}, volume = {26}, number = {22}, pages = {3098-3109}, pmid = {32587451}, issn = {2219-2840}, abstract = {BACKGROUND: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome.
AIM: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity.
METHODS: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.
RESULTS: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.
CONCLUSION: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.}, }
@article {pmid32584047, year = {2020}, author = {Tavakoli, S and Kari, OK and Turunen, T and Lajunen, T and Schmitt, M and Lehtinen, J and Tasaka, F and Parkkila, P and Ndika, J and Viitala, T and Alenius, H and Urtti, A and Subrizi, A}, title = {Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations.}, journal = {Molecular pharmaceutics}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.molpharmaceut.0c00411}, pmid = {32584047}, issn = {1543-8392}, abstract = {The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.}, }
@article {pmid32582274, year = {2020}, author = {Jiang, S and Xiao, G and Koh, AY and Chen, Y and Yao, B and Li, Q and Zhan, X}, title = {HARMONIES: A Hybrid Approach for Microbiome Networks Inference via Exploiting Sparsity.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {445}, pmid = {32582274}, issn = {1664-8021}, support = {P30 CA142543/CA/NCI NIH HHS/United States ; R01 GM126479/GM/NIGMS NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; }, abstract = {The human microbiome is a collection of microorganisms. They form complex communities and collectively affect host health. Recently, the advances in next-generation sequencing technology enable the high-throughput profiling of the human microbiome. This calls for a statistical model to construct microbial networks from the microbiome sequencing count data. As microbiome count data are high-dimensional and suffer from uneven sampling depth, over-dispersion, and zero-inflation, these characteristics can bias the network estimation and require specialized analytical tools. Here we propose a general framework, HARMONIES, Hybrid Approach foR MicrobiOme Network Inferences via Exploiting Sparsity, to infer a sparse microbiome network. HARMONIES first utilizes a zero-inflated negative binomial (ZINB) distribution to model the skewness and excess zeros in the microbiome data, as well as incorporates a stochastic process prior for sample-wise normalization. This approach infers a sparse and stable network by imposing non-trivial regularizations based on the Gaussian graphical model. In comprehensive simulation studies, HARMONIES outperformed four other commonly used methods. When using published microbiome data from a colorectal cancer study, it discovered a novel community with disease-enriched bacteria. In summary, HARMONIES is a novel and useful statistical framework for microbiome network inference, and it is available at https://github.com/shuangj00/HARMONIES.}, }
@article {pmid32581284, year = {2020}, author = {Hermes, GDA and Eckermann, HA and de Vos, WM and de Weerth, C}, title = {Does entry to center-based childcare affect gut microbial colonization in young infants?.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {10235}, doi = {10.1038/s41598-020-66404-z}, pmid = {32581284}, issn = {2045-2322}, mesh = {Bacteria/*classification/genetics/isolation & purification ; Bayes Theorem ; Case-Control Studies ; Child Day Care Centers ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant Care/*methods ; Longitudinal Studies ; Male ; Netherlands ; Phylogeny ; Sequence Analysis, DNA/*methods ; }, abstract = {Entry to center-based childcare (CC) at three months of life can be an important challenge for infants as it includes major stressors such as long maternal separations and frequently changing caregivers. Stress and the new environment may in turn alter the composition of the gut microbiota with possible implications for future health outcomes. As part of an ongoing longitudinal study, we investigated whether CC, as compared to being cared for by the parents at home, alters the composition of the gut microbiota, while accounting for known covariates of the infant gut microbiota. Stool samples of infants who entered CC (n = 49) and control infants (n = 49) were obtained before and four weeks after CC entrance. Using Redundancy analysis, Random Forests and Bayesian linear models we found that infant gut microbiota was not affected in a uniform way by entry to CC. In line with the literature, breastfeeding, birth mode, age, and the presence of siblings were shown to significantly impact the microbial composition.}, }
@article {pmid32578402, year = {2020}, author = {López-Laguna, H and Sánchez-García, L and Serna, N and Voltà-Durán, E and Sánchez, JM and Sánchez-Chardi, A and Unzueta, U and Łoś, M and Villaverde, A and Vázquez, E}, title = {Engineering Protein Nanoparticles Out from Components of the Human Microbiome.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {16}, number = {30}, pages = {e2001885}, doi = {10.1002/smll.202001885}, pmid = {32578402}, issn = {1613-6829}, support = {//Agencia Estatal de Investigación/ ; BIO2016-76063-R//Fondo Europeo de Desarrollo Regional/ ; 2017SGR-229//AGAUR/ ; //Networking Research Center on Bioengineering, Biomaterials and Nanomedicine/ ; //Instituto de Salud Carlos III/ ; }, abstract = {Nanoscale protein materials are highly convenient as vehicles for targeted drug delivery because of their structural and functional versatility. Selective binding to specific cell surface receptors and penetration into target cells require the use of targeting peptides. Such homing stretches should be incorporated to larger proteins that do not interact with body components, to prevent undesired drug release into nontarget organs. Because of their low interactivity with human body components and their tolerated immunogenicity, proteins derived from the human microbiome are appealing and fully biocompatible building blocks for the biofabrication of nonreactive, inert protein materials within the nanoscale. Several phage and phage-like bacterial proteins with natural structural roles are produced in Escherichia coli as polyhistidine-tagged recombinant proteins, looking for their organization as discrete, nanoscale particulate materials. While all of them self-assemble in a variety of sizes, the stability of the resulting constructs at 37 °C is found to be severely compromised. However, the fine adjustment of temperature and Zn2+ concentration allows the formation of robust nanomaterials, fully stable in complex media and under physiological conditions. Then, microbiome-derived proteins show promise for the regulatable construction of scaffold protein nanomaterials, which can be tailored and strengthened by simple physicochemical approaches.}, }
@article {pmid32574814, year = {2020}, author = {Chauhan, V and Kanwar, SS}, title = {Lipopeptide(s) associated with human microbiome as potent cancer drug.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.06.012}, pmid = {32574814}, issn = {1096-3650}, abstract = {Human microbiota comprises of trillions of microbes which have evolved with and continued to live on/ within their human hosts. Different environmental factors and diet have a large impact upon human microbiota population. These microorganisms live in synergy with their hosts and are beneficial to the host in many different ways. Many microorganisms help to fight against human diseases. Cancer is one such diseases which effects a large human population often leading to death. Cancer is also one of the most fatal human diseases killing millions of people world-wide every year. Though many treatment procedures are available but none is 100 % effective in curing cancer. In this review, we seek to understand the role of human microbiota in cancer treatment. Lipopeptide(s) (LPs) produced by different microorganisms can act as efficient drug(s) against cancer. LPs are low molecular weight lipo-proteins that are also known for their anti-cancer activities. As human microbiota belongs to an environment within the host body, a drug prepared using these microorganisms will be easily accepted by the body. This novel approach of using LPs produced by human microbiota can be considered for the much needed change in cancer treatment. Therefore, it is proposed that research should focus on the host-microbe interaction which could pave the way in understanding role played by these microorganisms in cancer treatment.}, }
@article {pmid32574290, year = {2020}, author = {Baud, D and Dimopoulou Agri, V and Gibson, GR and Reid, G and Giannoni, E}, title = {Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic.}, journal = {Frontiers in public health}, volume = {8}, number = {}, pages = {186}, pmid = {32574290}, issn = {2296-2565}, mesh = {*COVID-19/prevention & control/therapy ; Diarrhea/prevention & control ; Gastrointestinal Microbiome ; Humans ; *Infection Control ; Probiotics/*administration & dosage ; Respiratory Tract Infections/prevention & control ; SARS-CoV-2 ; }, }
@article {pmid32571986, year = {2020}, author = {Alverdy, JC and Keskey, R and Thewissen, R}, title = {Can the Cecal Ligation and Puncture Model Be Repurposed To Better Inform Therapy in Human Sepsis?.}, journal = {Infection and immunity}, volume = {88}, number = {9}, pages = {}, pmid = {32571986}, issn = {1098-5522}, abstract = {A recent report by the National Institutes of Health on sepsis research has implied there is a trend to move away from mouse models of sepsis. The most commonly used animal model to study the pathogenesis of human sepsis is cecal ligation and puncture (CLP) in mice. The model has been the mainstay of sepsis research for decades and continues to be considered the gold standard to inform novel pathways of sepsis physiology and its therapeutic direction. As there have been many criticisms of the model, particularly regarding its relevance to human disease, how this model might be repurposed to be more reflective of the human condition begs discussion. In this piece, we compare and contrast the mouse microbiome of the CLP model to the emerging science of the microbiome of human sepsis and discuss the relevance for mice to harbor the specific pathogens present in the human microbiome during sepsis, as well as an underlying disease process to mimic the characteristics of those patients with undesirable outcomes. How to repurpose this model to incorporate these "human factors" is discussed in detail and suggestions offered.}, }
@article {pmid32564483, year = {2020}, author = {Rattan, P and Minacapelli, CD and Rustgi, V}, title = {The Microbiome and Hepatocellular Carcinoma.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {26}, number = {10}, pages = {1316-1327}, doi = {10.1002/lt.25828}, pmid = {32564483}, issn = {1527-6473}, abstract = {The human microbiome is a vast and complex system encompassing all of the microbes and their genes that occupy the environmentally exposed surfaces of the human body. The gut microbiota and its associated microbiome play an integral role in mammalian metabolism and immune tolerance as well as in immunocompetence. Disruptions in the human gut microbiome are associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. The persistence of this inflammation has been shown to induce the accumulation of genetic and epigenetic changes leading to hepatocellular carcinoma (HCC). Therefore, the importance and prognostic influence of the gut microbiome on hepatocarcinogenesis has been increasingly studied in recent years. This review discusses the mechanisms by which imbalances in the gut microbiome disturb the gut-liver axis to impact hepatocarcinogenesis, including disruption of the intestinal barrier, changes in bile acid metabolism, and reduction in tumor-suppressing microRNA. Furthermore, this review summarizes recent advances in potential microbiome-based therapeutic opportunities in HCC.}, }
@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}, doi = {10.1016/j.isci.2020.101223}, 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 {pmid32559728, year = {2020}, author = {Ma, ZS}, title = {Critical Network Structures and Medical Ecology Mechanisms Underlying Human Microbiome-Associated Diseases.}, journal = {iScience}, volume = {23}, number = {6}, pages = {101195}, doi = {10.1016/j.isci.2020.101195}, pmid = {32559728}, issn = {2589-0042}, abstract = {A fundamental problem in studies on human microbiome-associated diseases (MADs) is to understand the relationships between microbiome structures and health status of hosts. For example, species diversity metrics have been routinely evaluated in virtually all studies on MADs, yet a recent meta-analysis revealed that, in only approximately one-third of the cases, diversity and diseases were related. In this study, we ask whether Hubbell's neutral theory (supplemented with the normalized stochasticity ratio [NSR]) or critical microbiome network structures may offer better alternatives. Whereas neutral theory and NSR focus on stochastic processes, we use core/periphery and high-salience skeleton networks to evaluate deterministic, asymmetrical niche effects, assuming that all species or their interactions were not "born" equal and focusing on non-neutral, critical network structures. We found that properties of critical network structures are more indicative of disease effects. Finally, seven findings (mechanisms, interpretations, and postulations) regarding medical ecology mechanisms underlying MADs were summarized.}, }
@article {pmid32559614, year = {2020}, author = {Hampton-Marcell, JT and Larsen, P and Anton, T and Cralle, L and Sangwan, N and Lax, S and Gottel, N and Salas-Garcia, M and Young, C and Duncan, G and Lopez, JV and Gilbert, JA}, title = {Detecting personal microbiota signatures at artificial crime scenes.}, journal = {Forensic science international}, volume = {313}, number = {}, pages = {110351}, doi = {10.1016/j.forsciint.2020.110351}, pmid = {32559614}, issn = {1872-6283}, abstract = {When mapped to the environments we interact with on a daily basis, the 36 million microbial cells per hour that humans emit leave a trail of evidence that can be leveraged for forensic analysis. We employed 16S rRNA amplicon sequencing to map unique microbial sequence variants between human skin and building surfaces in three experimental conditions: over time during controlled and uncontrolled incidental interactions with a door handle, and during multiple mock burglaries in ten real residences. We demonstrate that humans (n = 30) leave behind microbial signatures that can be used to track interaction with various surfaces within a building, but the likelihood of accurately detecting the specific burglar for a given home was between 20-25%. Also, the human microbiome contains rare microbial taxa that can be combined to create a unique microbial profile, which when compared to 600 other individuals can improve our ability to link an individual 'burglar' to a residence. In total, 5512 discriminating, non-singleton unique exact sequence variants (uESVs) were identified as unique to an individual, with a minimum of 1 and a maximum of 568, suggesting some people maintain a greater degree of unique taxa compared to our population of 600. Approximate 60-77% of the unique exact sequence variants originated from the hands of participants, and these microbial discriminators spanned 36 phyla but were dominated by the Proteobacteria (34%). A fitted regression generated to determine whether an intruder's uESVs found on door handles in an office decayed over time in the presence or absence of office workers, found no significant shift in proportion of uESVs over time irrespective of the presence of office workers. While it was possible to detect the correct burglars' microbiota as having contributed to the invaded space, the predictions were very weak in comparison to accepted forensic standards. This suggests that at this time 16S rRNA amplicon sequencing of the built environment microbiota cannot be used as a reliable trace evidence standard for criminal investigations.}, }
@article {pmid32556166, year = {2020}, author = {De Filippis, F and Pasolli, E and Ercolini, D}, title = {The food-gut axis: lactic acid bacteria and their link to food, the gut microbiome and human health.}, journal = {FEMS microbiology reviews}, volume = {44}, number = {4}, pages = {454-489}, pmid = {32556166}, issn = {1574-6976}, abstract = {Lactic acid bacteria (LAB) are present in foods, the environment and the animal gut, although fermented foods (FFs) are recognized as the primary niche of LAB activity. Several LAB strains have been studied for their health-promoting properties and are employed as probiotics. FFs are recognized for their potential beneficial effects, which we review in this article. They are also an important source of LAB, which are ingested daily upon FF consumption. In this review, we describe the diversity of LAB and their occurrence in food as well as the gut microbiome. We discuss the opportunities to study LAB diversity and functional properties by considering the availability of both genomic and metagenomic data in public repositories, as well as the different latest computational tools for data analysis. In addition, we discuss the role of LAB as potential probiotics by reporting the prevalence of key genomic features in public genomes and by surveying the outcomes of LAB use in clinical trials involving human subjects. Finally, we highlight the need for further studies aimed at improving our knowledge of the link between LAB-fermented foods and the human gut from the perspective of health promotion.}, }
@article {pmid32551196, year = {2020}, author = {Coil, DA and Neches, RY and Lang, JM and Jospin, G and Brown, WE and Cavalier, D and Hampton-Marcell, J and Gilbert, JA and Eisen, JA}, title = {Bacterial communities associated with cell phones and shoes.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e9235}, pmid = {32551196}, issn = {2167-8359}, abstract = {Background: Every human being carries with them a collection of microbes, a collection that is likely both unique to that person, but also dynamic as a result of significant flux with the surrounding environment. The interaction of the human microbiome (i.e., the microbes that are found directly in contact with a person in places such as the gut, mouth, and skin) and the microbiome of accessory objects (e.g., shoes, clothing, phones, jewelry) is of potential interest to both epidemiology and the developing field of microbial forensics. Therefore, the microbiome of personal accessories are of interest because they serve as both a microbial source and sink for an individual, they may provide information about the microbial exposure experienced by an individual, and they can be sampled non-invasively.
Findings: We report here a large-scale study of the microbiome found on cell phones and shoes. Cell phones serve as a potential source and sink for skin and oral microbiome, while shoes can act as sampling devices for microbial environmental experience. Using 16S rRNA gene sequencing, we characterized the microbiome of thousands of paired sets of cell phones and shoes from individuals at sporting events, museums, and other venues around the United States.
Conclusions: We place this data in the context of previous studies and demonstrate that the microbiome of phones and shoes are different. This difference is driven largely by the presence of "environmental" taxa (taxa from groups that tend to be found in places like soil) on shoes and human-associated taxa (taxa from groups that are abundant in the human microbiome) on phones. This large dataset also contains many novel taxa, highlighting the fact that much of microbial diversity remains uncharacterized, even on commonplace objects.}, }
@article {pmid32546787, year = {2020}, author = {Puebla-Barragan, S and Renaud, J and Sumarah, M and Reid, G}, title = {Malodorous biogenic amines in Escherichia coli-caused urinary tract infections in women-a metabolomics approach.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9703}, doi = {10.1038/s41598-020-66662-x}, pmid = {32546787}, issn = {2045-2322}, mesh = {Biogenic Amines/*metabolism ; Cadaverine/metabolism ; Escherichia coli Infections/metabolism/*microbiology ; Metabolomics ; Methylamines/metabolism ; Odorants ; Putrescine/metabolism ; Tyramine/metabolism ; Urinary Tract Infections/*microbiology ; Uropathogenic Escherichia coli/*metabolism ; }, abstract = {Many women suffer from urinary tract infections (UTIs). In addition to pain and increased urgency to urinate, malodour is a significant issue for these patients. The specific factors causing this malodour are unclear, and there are no targeted treatment options to counteract it effectively. We used a metabolomics approach to compare the chemical composition of metabolites in the urine of women with E. coli UTIs (n = 15) and those who are healthy (n = 10). The biogenic amines trimethylamine and putrescine, which cause malodour in other urogenital conditions, were significantly increased in UTI patients. Conversely, the precursor of trimethylamine, trimethylamine N-oxide, was lower. To further confirm the source of the malodorous compounds, in vitro experiments were conducted by incubating strains of uropathogenic E. coli in sterilized urine from healthy women. All tested strains accumulated trimethylamine and putrescine. Notably, cadaverine was also produced by E. coli strains in vitro; however, it was not significantly different between both groups. We confirmed that the malodorous amines TMA and putrescine are found in higher concentrations in the urine of patients with an E.coli-caused UTI.}, }
@article {pmid32544460, year = {2020}, author = {Kenny, DJ and Plichta, DR and Shungin, D and Koppel, N and Hall, AB and Fu, B and Vasan, RS and Shaw, SY and Vlamakis, H and Balskus, EP and Xavier, RJ}, title = {Cholesterol Metabolism by Uncultured Human Gut Bacteria Influences Host Cholesterol Level.}, journal = {Cell host & microbe}, volume = {28}, number = {2}, pages = {245-257.e6}, pmid = {32544460}, issn = {1934-6069}, support = {R01 HL131015/HL/NHLBI NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; HHSN268201500001I/HL/NHLBI NIH HHS/United States ; T32 GM095450/GM/NIGMS NIH HHS/United States ; N01HC25195/HL/NHLBI NIH HHS/United States ; 75N92019D00031/HL/NHLBI NIH HHS/United States ; F32 MH095450/MH/NIMH NIH HHS/United States ; HHSN268201500001C/HL/NHLBI NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; }, abstract = {The human microbiome encodes extensive metabolic capabilities, but our understanding of the mechanisms linking gut microbes to human metabolism remains limited. Here, we focus on the conversion of cholesterol to the poorly absorbed sterol coprostanol by the gut microbiota to develop a framework for the identification of functional enzymes and microbes. By integrating paired metagenomics and metabolomics data from existing cohorts with biochemical knowledge and experimentation, we predict and validate a group of microbial cholesterol dehydrogenases that contribute to coprostanol formation. These enzymes are encoded by ismA genes in a clade of uncultured microorganisms, which are prevalent in geographically diverse human cohorts. Individuals harboring coprostanol-forming microbes have significantly lower fecal cholesterol levels and lower serum total cholesterol with effects comparable to those attributed to variations in lipid homeostasis genes. Thus, cholesterol metabolism by these microbes may play important roles in reducing intestinal and serum cholesterol concentrations, directly impacting human health.}, }
@article {pmid32541790, year = {2020}, author = {Diakite, A and Dubourg, G and Dione, N and Afouda, P and Bellali, S and Ngom, II and Valles, C and Tall, ML and Lagier, JC and Raoult, D}, title = {Optimization and standardization of the culturomics technique for human microbiome exploration.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9674}, pmid = {32541790}, issn = {2045-2322}, mesh = {Bacteria/*classification/*growth & development/isolation & purification ; Bacteriological Techniques/methods/*standards ; Culture Media/chemistry ; Feces/*microbiology ; Humans ; Microbiota ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Workflow ; }, abstract = {Culturomics is a high-throughput culture approach that has dramatically contributed to the recent renewal of culture. While metagenomics enabled substantial advances in exploring the microbiota, culturomics significantly expanded our knowledge regarding the bacterial gut repertoire through the discovery and the description of hundreds of new taxa. While this approach relies on the variation of culture conditions and media, we have tested so far more than 300 conditions since the beginning of culturomics studies. In this context, we aimed herein to identify the most profitable conditions for optimizing culturomics approach. For this purpose, we have analysed a set of 58 culturomics conditions that were previously applied to 8 faecal specimens, enabling the isolation of 497 bacterial species. As a result, we were able to reduce the number of conditions used to isolate these 497 of more than a half (i.e. to 25 culture conditions). We have also established a list of the 16 conditions that allowed to capture 98% of the total number of species previously isolated. These data constitute a methodological starting point for culture-based microbiota studies by improving the culturomics workflow without any loss of captured bacterial diversity.}, }
@article {pmid32539695, year = {2020}, author = {Philips, A and Stolarek, I and Handschuh, L and Nowis, K and Juras, A and Trzciński, D and Nowaczewska, W and Wrzesińska, A and Potempa, J and Figlerowicz, M}, title = {Analysis of oral microbiome from fossil human remains revealed the significant differences in virulence factors of modern and ancient Tannerella forsythia.}, journal = {BMC genomics}, volume = {21}, number = {1}, pages = {402}, pmid = {32539695}, issn = {1471-2164}, support = {2014/12/W/NZ2/00466//Narodowe Centrum Nauki/ ; 2016/21/B/NZ1/00292//Narodowe Centrum Nauki/ ; R21DE026280/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Recent advances in the next-generation sequencing (NGS) allowed the metagenomic analyses of DNA from many different environments and sources, including thousands of years old skeletal remains. It has been shown that most of the DNA extracted from ancient samples is microbial. There are several reports demonstrating that the considerable fraction of extracted DNA belonged to the bacteria accompanying the studied individuals before their death.
RESULTS: In this study we scanned 344 microbiomes from 1000- and 2000- year-old human teeth. The datasets originated from our previous studies on human ancient DNA (aDNA) and on microbial DNA accompanying human remains. We previously noticed that in many samples infection-related species have been identified, among them Tannerella forsythia, one of the most prevalent oral human pathogens. Samples containing sufficient amount of T. forsythia aDNA for a complete genome assembly were selected for thorough analyses. We confirmed that the T. forsythia-containing samples have higher amounts of the periodontitis-associated species than the control samples. Despites, other pathogens-derived aDNA was found in the tested samples it was too fragmented and damaged to allow any reasonable reconstruction of these bacteria genomes. The anthropological examination of ancient skulls from which the T. forsythia-containing samples were obtained revealed the pathogenic alveolar bone loss in tooth areas characteristic for advanced periodontitis. Finally, we analyzed the genetic material of ancient T. forsythia strains. As a result, we assembled four ancient T. forsythia genomes - one 2000- and three 1000- year-old. Their comparison with contemporary T. forsythia genomes revealed a lower genetic diversity within the four ancient strains than within contemporary strains. We also investigated the genes of T. forsythia virulence factors and found that several of them (KLIKK protease and bspA genes) differ significantly between ancient and modern bacteria.
CONCLUSIONS: In summary, we showed that NGS screening of the ancient human microbiome is a valid approach for the identification of disease-associated microbes. Following this protocol, we provided a new set of information on the emergence, evolution and virulence factors of T. forsythia, the member of the oral dysbiotic microbiome.}, }
@article {pmid32536582, year = {2021}, author = {Jian, C and Luukkonen, P and Sädevirta, S and Yki-Järvinen, H and Salonen, A}, title = {Impact of short-term overfeeding of saturated or unsaturated fat or sugars on the gut microbiota in relation to liver fat in obese and overweight adults.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {40}, number = {1}, pages = {207-216}, doi = {10.1016/j.clnu.2020.05.008}, pmid = {32536582}, issn = {1532-1983}, abstract = {BACKGROUNDS & AIMS: Intestinal microbiota may be causally involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aimed to study the effect of short-term overfeeding on human gut microbiota in relation to baseline and overfeeding-induced liver steatosis. We also asked whether the baseline microbiota composition is associated to the overfeeding-induced increase in liver fat.
METHODS: In a randomized trial, 38 overweight and obese subjects were assigned to consume an excess of 1000 kcal/day of diets rich in either saturated fat, unsaturated fat, or simple sugars for 3 weeks. Fasting blood samples and 1H-MR spectroscopy were used for extensive clinical phenotyping as previously reported (PMID: 29844096). Fecal samples were collected for the analysis of the gut microbiota using 16S rRNA amplicon sequencing, imputed metagenomics and qPCR. Microbiota results were correlated with dietary intakes and clinical measurements before and during overfeeding.
RESULTS: The overall community structure of the microbiota remained highly stable and personalized during overfeeding based on between-sample Bray-Curtis dissimilarity, but the relative abundances of individual taxa were altered in a diet-specific manner: overfeeding saturated fat increased Proteobacteria, while unsaturated fat increased butyrate producers. Sugar overfeeding increased Lactococcus and Escherichia coli. Imputed functions of the gut microbiota were not affected by overfeeding. Several taxa affected by overfeeding significantly correlated with the changes in host metabolic markers. The baseline levels of proteobacterial family Desulfovibrionaceae, and especially genus Bilophila, were significantly associated to overfeeding-induced liver fat increase independently of the diet arm. In general, limited overlap was observed between the overfeeding-induced microbiota changes and the liver fat-associated microbiota features at baseline.
CONCLUSIONS: Our work indicates that the human gut microbiota is resilient to short-term overfeeding on community level, but specific taxa are altered on diet composition-dependent manner. Generalizable microbiota signatures directly associated with liver steatosis could not be identified. Instead, the carriage of Bilophila was identified as a potential novel risk factor for diet-induced liver steatosis in humans. Clinical trial registry number: NCT02133144 listed on NIH website: ClinicalTrials.gov.}, }
@article {pmid32536356, year = {2020}, author = {Ooi, DS and Tan, CP and Tay, MJ and Ong, SG and Tham, EH and Siah, KTH and Eriksson, JG and Godfrey, KM and Shek, LP and Loo, EX}, title = {Developmental Origins of Health and Disease: Impact of environmental dust exposure in modulating microbiome and its association with non-communicable diseases.}, journal = {Journal of developmental origins of health and disease}, volume = {11}, number = {6}, pages = {545-556}, pmid = {32536356}, issn = {2040-1752}, support = {MC_UU_12011/4/MRC_/Medical Research Council/United Kingdom ; U24 AG047867/AG/NIA NIH HHS/United States ; NF-SI-0515-10042/DH_/Department of Health/United Kingdom ; /BB_/Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Non-communicable diseases (NCDs) including obesity, diabetes, and allergy are chronic, multi-factorial conditions that are affected by both genetic and environmental factors. Over the last decade, the microbiome has emerged as a possible contributor to the pathogenesis of NCDs. Microbiome profiles were altered in patients with NCDs, and shift in microbial communities was associated with improvement in these health conditions. Since the genetic component of these diseases cannot be altered, the ability to manipulate the microbiome holds great promise for design of novel therapies in the prevention and treatment of NCDs. Together, the Developmental Origins of Health and Disease concept and the microbial hypothesis propose that early life exposure to environmental stimuli will alter the development and composition of the human microbiome, resulting in health consequences. Recent studies indicated that the environment we are exposed to in early life is instrumental in shaping robust immune development, possibly through modulation of the human microbiome (skin, airway, and gut). Despite much research into human microbiome, the origin of their constituent microbiota remains unclear. Dust (also known as particulate matter) is a key determinant of poor air quality in the modern urban environment. It is ubiquitous and serves as a major source and reservoir of microbial communities that modulates the human microbiome, contributing to health and disease. There are evidence that reported significant associations between environmental dust and NCDs. In this review, we will focus on the impact of dust exposure in shaping the human microbiome and its possible contribution to the development of NCDs.}, }
@article {pmid32533793, year = {2020}, author = {Rotz, SJ and Dandoy, CE}, title = {The microbiome in pediatric oncology.}, journal = {Cancer}, volume = {126}, number = {16}, pages = {3629-3637}, pmid = {32533793}, issn = {1097-0142}, support = {KL2 TR002547/TR/NCATS NIH HHS/United States ; 2KL2TR002547 (PI: Dweik) (SJR)//NIH NCATS/ ; }, abstract = {The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.}, }
@article {pmid32528717, year = {2020}, author = {Galli, I and Fasanelli, R}, title = {Public understanding of science and common sense: Social representations of the human microbiome among the expert and non-expert public.}, journal = {Health psychology open}, volume = {7}, number = {1}, pages = {2055102920913239}, pmid = {32528717}, issn = {2055-1029}, abstract = {The aim of this investigation is to examine the structure and the content of different social groups' representations of the human microbiome. We employed a non-probabilistic sample comprising two groups of participants. The first group (n = 244) included university students. The second group included lay people (n = 355). We chose a mixed-method approach. The data obtained were processed using IRaMuTeQ software. The results allow us to identify the anchoring and objectification processes activated by the two different groups of interviewees. The results could be useful to those in charge of implementing campaigns aimed at promoting health literacy.}, }
@article {pmid32528434, year = {2020}, author = {Sui, HY and Weil, AA and Nuwagira, E and Qadri, F and Ryan, ET and Mezzari, MP and Phipatanakul, W and Lai, PS}, title = {Impact of DNA Extraction Method on Variation in Human and Built Environment Microbial Community and Functional Profiles Assessed by Shotgun Metagenomics Sequencing.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {953}, pmid = {32528434}, issn = {1664-302X}, support = {U01 AI110397/AI/NIAID NIH HHS/United States ; K08 AI123494/AI/NIAID NIH HHS/United States ; R01 AI106878/AI/NIAID NIH HHS/United States ; K23 ES023700/ES/NIEHS NIH HHS/United States ; U01 AI058935/AI/NIAID NIH HHS/United States ; R01 AI144119/AI/NIAID NIH HHS/United States ; K24 AI106822/AI/NIAID NIH HHS/United States ; }, abstract = {Both the host microbiome and the microbiome of the built environment can have profound impacts on human health. While prior studies have suggested that the variability introduced by DNA extraction method is less than typical biologic variation, most studies have focused on 16S rRNA amplicon sequencing or on high biomass fecal samples. Shotgun metagenomic sequencing provides advantages over amplicon sequencing for surveying the microbiome, but is a challenge to perform in lower microbial biomass samples with high human DNA content such as sputum or vacuumed dust. Here we systematically evaluate the impact of four different extraction methods (phenol:choloroform, and three high-throughput kit-based approaches, the Promega Maxwell gDNA, Qiagen MagAttract PowerSoil DNA, and ZymoBIOMICS 96 MagBead). We report the variation in microbial community structure and predicted microbial function assessed by shotgun metagenomics sequencing in human stool, sputum, and vacuumed dust obtained from ongoing cohort studies or clinical trials. The same beadbeating protocol was used for all samples to focus our evaluation on the impact of kit chemistries on sequencing results. DNA yield was overall highest in the phenol:choloroform and Promega approaches. Only the phenol:choloroform approach showed evidence of contamination in negative controls. Bias was evaluated using mock community controls, and was noted across all extraction methods, although Promega exhibited the least amount of bias. The extraction method did not impact the proportion of human reads, although stool had the lowest proportion of human reads (0.1%) as compared to dust (44.1%) and sputum (80%). We calculated Bray-Curtis dissimilarity and Aitchison distances to evaluate the impact of extraction method on microbial community structure by sample type. Extraction method had the lowest impact in stool (extraction method responsible for 3.0-3.9% of the variability), the most impact in vacuumed dust (12-16% of the variability) and intermediate values for sputum (9.2-12% variability). Similar differences were noted when evaluating microbial community function. Our results will inform investigators planning microbiome studies using diverse sample types in large clinical studies. A consistent DNA extraction approach across all sample types is recommended, particularly with lower microbial biomass samples that are more heavily influenced by extraction method.}, }
@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}, doi = {10.1038/s41598-020-66178-4}, 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 {pmid32524177, year = {2020}, author = {Dekaboruah, E and Suryavanshi, MV and Chettri, D and Verma, AK}, title = {Human microbiome: an academic update on human body site specific surveillance and its possible role.}, journal = {Archives of microbiology}, volume = {202}, number = {8}, pages = {2147-2167}, pmid = {32524177}, issn = {1432-072X}, mesh = {Computational Biology/*trends ; Disease ; *Human Body ; Humans ; Microbiota/*physiology ; }, abstract = {Human body is inhabited by vast number of microorganisms which form a complex ecological community and influence the human physiology, in the aspect of both health and diseases. These microbes show a relationship with the human immune system based on coevolution and, therefore, have a tremendous potential to contribute to the metabolic function, protection against the pathogen and in providing nutrients and energy. However, of these microbes, many carry out some functions that play a crucial role in the host physiology and may even cause diseases. The introduction of new molecular technologies such as transcriptomics, metagenomics and metabolomics has contributed to the upliftment on the findings of the microbiome linked to the humans in the recent past. These rapidly developing technologies are boosting our capacity to understand about the human body-associated microbiome and its association with the human health. The highlights of this review are inclusion of how to derive microbiome data and the interaction between human and associated microbiome to provide an insight on the role played by the microbiome in biological processes of the human body as well as the development of major human diseases.}, }
@article {pmid32518182, year = {2020}, author = {Topçuoğlu, BD and Lesniak, NA and Ruffin, MT and Wiens, J and Schloss, PD}, title = {A Framework for Effective Application of Machine Learning to Microbiome-Based Classification Problems.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, pmid = {32518182}, issn = {2150-7511}, support = {R01 CA215574/CA/NCI NIH HHS/United States ; P30 DK034933/DK/NIDDK NIH HHS/United States ; }, abstract = {Machine learning (ML) modeling of the human microbiome has the potential to identify microbial biomarkers and aid in the diagnosis of many diseases such as inflammatory bowel disease, diabetes, and colorectal cancer. Progress has been made toward developing ML models that predict health outcomes using bacterial abundances, but inconsistent adoption of training and evaluation methods call the validity of these models into question. Furthermore, there appears to be a preference by many researchers to favor increased model complexity over interpretability. To overcome these challenges, we trained seven models that used fecal 16S rRNA sequence data to predict the presence of colonic screen relevant neoplasias (SRNs) (n = 490 patients, 261 controls and 229 cases). We developed a reusable open-source pipeline to train, validate, and interpret ML models. To show the effect of model selection, we assessed the predictive performance, interpretability, and training time of L2-regularized logistic regression, L1- and L2-regularized support vector machines (SVM) with linear and radial basis function kernels, a decision tree, random forest, and gradient boosted trees (XGBoost). The random forest model performed best at detecting SRNs with an area under the receiver operating characteristic curve (AUROC) of 0.695 (interquartile range [IQR], 0.651 to 0.739) but was slow to train (83.2 h) and not inherently interpretable. Despite its simplicity, L2-regularized logistic regression followed random forest in predictive performance with an AUROC of 0.680 (IQR, 0.625 to 0.735), trained faster (12 min), and was inherently interpretable. Our analysis highlights the importance of choosing an ML approach based on the goal of the study, as the choice will inform expectations of performance and interpretability.IMPORTANCE Diagnosing diseases using machine learning (ML) is rapidly being adopted in microbiome studies. However, the estimated performance associated with these models is likely overoptimistic. Moreover, there is a trend toward using black box models without a discussion of the difficulty of interpreting such models when trying to identify microbial biomarkers of disease. This work represents a step toward developing more-reproducible ML practices in applying ML to microbiome research. We implement a rigorous pipeline and emphasize the importance of selecting ML models that reflect the goal of the study. These concepts are not particular to the study of human health but can also be applied to environmental microbiology studies.}, }
@article {pmid32517038, year = {2020}, author = {Leskinen, K and Pajunen, MI and Vilanova, MVG and Kiljunen, S and Nelson, A and Smith, D and Skurnik, M}, title = {YerA41, a Yersinia ruckeri Bacteriophage: Determination of a Non-Sequencable DNA Bacteriophage Genome via RNA-Sequencing.}, journal = {Viruses}, volume = {12}, number = {6}, pages = {}, pmid = {32517038}, issn = {1999-4915}, abstract = {YerA41 is a Myoviridae bacteriophage that was originally isolated due its ability to infect Yersinia ruckeri bacteria, the causative agent of enteric redmouth disease of salmonid fish. Several attempts to determine its genomic DNA sequence using traditional and next generation sequencing technologies failed, indicating that the phage genome is modified in such a way that it is an unsuitable template for PCR amplification and for conventional sequencing. To determine the YerA41 genome sequence, we performed RNA-sequencing from phage-infected Y. ruckeri cells at different time points post-infection. The host-genome specific reads were subtracted and de novo assembly was performed on the remaining unaligned reads. This resulted in nine phage-specific scaffolds with a total length of 143 kb that shared only low level and scattered identity to known sequences deposited in DNA databases. Annotation of the sequences revealed 201 predicted genes, most of which found no homologs in the databases. Proteome studies identified altogether 63 phage particle-associated proteins. The RNA-sequencing data were used to characterize the transcriptional control of YerA41 and to investigate its impact on the bacterial gene expression. Overall, our results indicate that RNA-sequencing can be successfully used to obtain the genomic sequence of non-sequencable phages, providing simultaneous information about the phage-host interactions during the process of infection.}, }
@article {pmid32516025, year = {2020}, author = {Satokari, R and Pietilä, L and Mattila, E and Lahtinen, P and Arkkila, PET}, title = {Faecal banking at -20 °C facilitates faecal microbiota transplantation for recurrent Clostridioides difficile infection in clinical practice.}, journal = {Infectious diseases (London, England)}, volume = {52}, number = {9}, pages = {662-665}, doi = {10.1080/23744235.2020.1774075}, pmid = {32516025}, issn = {2374-4243}, }
@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}, }
@article {pmid32514485, year = {2020}, author = {Hahn, A and Burrell, A and Ansusinha, E and Peng, D and Chaney, H and Sami, I and Perez, GF and Koumbourlis, AC and McCarter, R and Freishtat, RJ and Crandall, KA and Zemanick, ET}, title = {Airway microbial diversity is decreased in young children with cystic fibrosis compared to healthy controls but improved with CFTR modulation.}, journal = {Heliyon}, volume = {6}, number = {6}, pages = {e04104}, pmid = {32514485}, issn = {2405-8440}, support = {K12 HL119994/HL/NHLBI NIH HHS/United States ; R21 TR002513/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; }, abstract = {Background: Culture-independent next generation sequencing has identified diverse microbial communities within the cystic fibrosis (CF) airway. The study objective was to test for differences in the upper airway microbiome of children with CF and healthy controls and age-related differences in children with CF.
Methods: Oropharyngeal swabs and clinical data were obtained from 25 children with CF and 50 healthy controls aged ≤6 years. Bacterial DNA was amplified and sequenced for the V4 region of 16S rRNA marker-gene. Alpha diversity was measured using operational taxonomic units (OTUs), Shannon diversity, and the inverse Simpson's index. Beta diversity was measured using Morisita-Horn and Bray-Curtis and Jaccard distances. General linear models were used for comparison of alpha diversity measures between groups to account for differences in demographics and exposures. Mixed effects general linear models were used for longitudinal comparisons 1) between children with CF of different ages and 2) between children with CF receiving CF transmembrane conductance regulator (CFTR) modulators, children with CF not receiving CFTR modulators, and healthy controls to adjust for repeated measures per subject.
Results: Children with CF were more likely to have received antibiotics in the prior year than healthy controls (92% vs 24%, p < 0.001). Controlling age, race, ethnicity, length of breastfeeding, and having siblings, children with CF had a lower richness than healthy controls: OTUs 62.1 vs 83, p = 0.022; and trended toward lower diversity: Shannon 2.09 vs 2.35, p = 0.057; inverse Simpson 5.7 vs 6.92, p = 0.118. Staphylococcus, three Rothia OTUs, and two Streptococcus OTUs were more abundant in CF children versus healthy controls (all p < 0.05). Bray-Curtis and Jaccard distances, which reflect overall microbial community composition, were also significantly different (both p = 0.001). In longitudinally collected samples from children with CF, Morisita-Horn trended toward more similarity in those aged 0-2 years compared to those aged 3-6 years (p = 0.070). In children >2 years of age, there was a significant trend in increasing alpha diversity measures between children with CF not receiving CFTR modulators, children with CF receiving CFTR modulators, and healthy controls: OTUs 63.7 vs 74.7 vs 97.6, p < 0.001; Shannon 2.11 vs 2.34 vs 2.56, p < 0.001; inverse Simpson 5.78 vs 7.23 vs 7.96, p < 0.001.
Conclusions: Children with CF have lower bacterial diversity and different composition of organisms compared with healthy controls. This appears to start in early childhood, is possibly related to the use of antibiotics, and may be partially corrected with the use of CFTR modulators.}, }
@article {pmid32514171, year = {2020}, author = {Chng, KR and Li, C and Bertrand, D and Ng, AHQ and Kwah, JS and Low, HM and Tong, C and Natrajan, M and Zhang, MH and Xu, L and Ko, KKK and Ho, EXP and Av-Shalom, TV and Teo, JWP and Khor, CC and , and Chen, SL and Mason, CE and Ng, OT and Marimuthu, K and Ang, B and Nagarajan, N}, title = {Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment.}, journal = {Nature medicine}, volume = {26}, number = {6}, pages = {941-951}, doi = {10.1038/s41591-020-0894-4}, pmid = {32514171}, issn = {1546-170X}, mesh = {Beds/microbiology ; Biofilms ; Cross Infection/drug therapy/*microbiology/transmission ; Disinfection ; Drug Resistance, Bacterial/*genetics ; Drug Resistance, Multiple, Bacterial/genetics ; Equipment Contamination ; Equipment and Supplies, Hospital/*microbiology ; Geographic Mapping ; Humans ; *Infection Control ; Metagenomics ; Microbiota/*genetics ; Opportunistic Infections/drug therapy/microbiology/transmission ; Patients' Rooms ; Singapore ; Spatio-Temporal Analysis ; Tertiary Care Centers ; }, abstract = {Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (>60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (>8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.}, }
@article {pmid32513310, year = {2020}, author = {Douglas, GM and Bielawski, JP and Langille, MGI}, title = {Re-evaluating the relationship between missing heritability and the microbiome.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {87}, pmid = {32513310}, issn = {2049-2618}, support = {CMF-108026//CIHR/Canada ; }, abstract = {Human genome-wide association studies (GWASs) have recurrently estimated lower heritability estimates than familial studies. Many explanations have been suggested to explain these lower estimates, including that a substantial proportion of genetic variation and gene-by-environment interactions are unmeasured in typical GWASs. The human microbiome is potentially related to both of these explanations, but it has been more commonly considered as a source of unmeasured genetic variation. In particular, it has recently been argued that the genetic variation within the human microbiome should be included when estimating trait heritability. We outline issues with this argument, which in its strictest form depends on the holobiont model of human-microbiome interactions. Instead, we argue that the microbiome could be leveraged to help control for environmental variation across a population, although that remains to be determined. We discuss potential approaches that could be explored to determine whether integrating microbiome sequencing data into GWASs is useful. Video abstract.}, }
@article {pmid32513256, year = {2020}, author = {Chopyk, J and Akrami, K and Bavly, T and Shin, JH and Schwanemann, LK and Ly, M and Kalia, R and Xu, Y and Kelley, ST and Malhotra, A and Torriani, FJ and Sweeney, DA and Pride, DT}, title = {Temporal variations in bacterial community diversity and composition throughout intensive care unit renovations.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {86}, pmid = {32513256}, issn = {2049-2618}, support = {K24 HL132105/HL/NHLBI NIH HHS/United States ; R01 AG063925/AG/NIA NIH HHS/United States ; R01 HL085188/HL/NHLBI NIH HHS/United States ; R01 HL148436/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Inanimate surfaces within a hospital serve as a reservoir of microbial life that may colonize patients and ultimately result in healthcare associated infections (HAIs). Critically ill patients in intensive care units (ICUs) are particularly vulnerable to HAIs. Little is known about how the microbiome of the ICU is established or what factors influence its evolution over time. A unique opportunity to bridge the knowledge gap into how the ICU microbiome evolves emerged in our health system, where we were able to characterize microbial communities in an established hospital ICU prior to closing for renovations, during renovations, and then after re-opening.
RESULTS: We collected swab specimens from ICU bedrails, computer keyboards, and sinks longitudinally at each renovation stage, and analyzed the bacterial compositions on these surfaces by 16S rRNA gene sequencing. Specimens collected before ICU closure had the greatest alpha diversity, while specimens collected after the ICU had been closed for over 300 days had the least. We sampled the ICU during the 45 days after re-opening; however, within that time frame, the alpha diversity never reached pre-closure levels. There were clear and significant differences in microbiota compositions at each renovation stage, which was driven by environmental bacteria after closure and human-associated bacteria after re-opening and before closure.
CONCLUSIONS: Overall, we identified significant differences in microbiota diversity and community composition at each renovation stage. These data help to decipher the evolution of the microbiome in the most critical part of the hospital and demonstrate the significant impacts that microbiota from patients and staff have on the evolution of ICU surfaces. Video Abstract.}, }
@article {pmid32503672, year = {2020}, author = {Liu, Y and Liu, Y and Du, Z and Zhang, L and Chen, J and Shen, Z and Liu, Q and Qin, J and Lv, H and Wang, H and He, L and Liu, J and Huang, Q and Sun, Y and Otto, M and Li, M}, title = {Skin microbiota analysis-inspired development of novel anti-infectives.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {85}, doi = {10.1186/s40168-020-00866-1}, pmid = {32503672}, issn = {2049-2618}, support = {81873957//National Natural Science Foundation of China/International ; 81671975//National Natural Science Foundation of China/International ; 81861138043//National Natural Science Foundation of China/International ; 81421001//Foundation for Innovative Research Groups of the National Natural Science Foundation of China/International ; 2017BR001//Shanghai Health System Talents Training Program/International ; ZIA AI001080/ImNIH/Intramural NIH HHS/United States ; 19JC1413005//Science and Technology Commission of Shanghai Municipality/International ; }, abstract = {BACKGROUND: The alarming spread of antimicrobial resistance requires the development of novel anti-infective drugs. Despite the recent research focus on the human microbiome and its likely value to understand and exploit inter-bacterial inhibitory phenomena as a source for antimicrobial strategies, the human microbiota has barely been investigated for the purpose of drug development.
RESULTS: We performed a large screen analyzing over 3000 human skin isolates to evaluate bacterial competition within the human skin microbiota as a basis for the development of anti-infective therapeutics. We discovered a Staphylococcus hominis strain with strong and broad activity against Gram-positive pathogens that was mediated by the bacteriocin micrococcin P1 (MP1). In "probiotic" approaches, this strain led to reduced Staphylococcus aureus infection and accelerated closure of S. aureus-infected wounds. Furthermore, we used a nanoparticle strategy to overcome the physico-chemical limitations often encountered with natural substances such as MP1 and demonstrate a significant reduction of S. aureus infection by MP1-loaded nanoparticles.
CONCLUSIONS: Our study gives examples of how analysis of bacterial interactions in the human microbiota can be explored for the development of novel, effective anti-infective strategies. Video Abstract.}, }
@article {pmid32498430, year = {2020}, author = {Moles, L and Otaegui, D}, title = {The Impact of Diet on Microbiota Evolution and Human Health. Is Diet an Adequate Tool for Microbiota Modulation?.}, journal = {Nutrients}, volume = {12}, number = {6}, pages = {}, pmid = {32498430}, issn = {2072-6643}, abstract = {The human microbiome is emerging as an interesting field in research into the prevention of health problems and recovery from illness in humans. The complex ecosystem formed by the microbiota is continuously interacting with its host and the environment. Diet could be assumed to be one of the most prominent factors influencing the microbiota composition. Nevertheless, and in spite of numerous strategies proposed to modulate the human microbiota through dietary means, guidelines to achieve this goal have yet to be established. This review assesses the correlation between social and dietary changes over the course of human evolution and the adaptation of the human microbiota to those changes. In addition, it discusses the main dietary strategies for modulating the microbiota and the difficulties of putting them properly into practice.}, }
@article {pmid32496571, year = {2020}, author = {Wang, CZ and Wan, JY and Wan, J and Wang, S and Luo, Y and Zeng, J and Yao, H and Zhang, CF and Zhang, QH and Sawadogo, WR and Xu, M and Du, W and Qi, LW and Li, P and Yuan, CS}, title = {Human intestinal microbiota derived metabolism signature from a North American native botanical Oplopanax horridus with UPLC/Q-TOF-MS analysis.}, journal = {Biomedical chromatography : BMC}, volume = {34}, number = {10}, pages = {e4911}, doi = {10.1002/bmc.4911}, pmid = {32496571}, issn = {1099-0801}, support = {AT004418//National Institutes of Health/National Center for Complementary and Alternative Medicine (NIH/NCCAM)/ ; AT005362//National Institutes of Health/National Center for Complementary and Alternative Medicine (NIH/NCCAM)/ ; BK20160545//Natural Science Foundation of Jiangsu Province/ ; 81603378//National Natural Science Foundation of China/ ; B16046//111 Project from the Ministry of Education of China and the State Administration of Foreign Experts Affairs of China/ ; }, abstract = {Oplopanax horridus, widely distributed in North America, is an herbal medicine traditionally used by Pacific indigenous peoples for various medical conditions. After oral ingestion, constituents in O. horridus extract (OhE) could be converted to their metabolites by the enteric microbiome before absorption. In this study, in order to mimic gut environment, the OhE was biotransformed using the enteric microbiome of healthy human subjects. For accurate and reliable data collection with optimized approaches in sample preparation and analytical conditions, ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry were used to characterize parent constituents and their metabolites. In the extract, 20 parent compounds were identified including polyynes, sesquiterpenes, monoterpeondids, phenylpropanoids and phenolic acids. After the biotransformation, a total of 78 metabolites were identified, of which 37 belonged to polyynes metabolites. The common biotransformation pathways are hydroxylation, acetylization, methylation and demethylation. Based on the pathway distributions, the metabolism signature of OhE has been explored. The metabolism pathways of OhE compounds are dependent on their structural classifications and hydrophilic/hydrophobic properties. In summary, with comprehensive analysis, we systematically investigated human microbiome-derived OhE metabolites. The enteric microbial metabolism signature provides novel information for future effective use of O. horridus.}, }
@article {pmid32495698, year = {2020}, author = {Gascon, M and Harrall, KK and Beavers, AW and Glueck, DH and Stanislawski, MA and Alaimo, K and Villalobos, A and Hebert, JR and Dexter, K and Li, K and Litt, J}, title = {Feasibility of collection and analysis of microbiome data in a longitudinal randomized trial of community gardening.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {633-648}, pmid = {32495698}, issn = {1746-0921}, support = {P2C HD066613/HD/NICHD NIH HHS/United States ; R25 GM111901/GM/NIGMS NIH HHS/United States ; }, abstract = {Aim: We explored the feasibility of collecting and analyzing human microbiome data in a longitudinal randomized controlled trial of community gardening. Methods & materials: Participants were randomly assigned to gardening (N = 8) or control (N = 8). Participants provided stool, mouth, hand and forehead microbiome samples at six timepoints. Analyses combined mixed models with Qiita output. Results: Participant satisfaction was high, with 75% of participants completing evaluations. While no microbial effects were statistically significant due to small sample size, the analysis pipeline utility was tested. Conclusion: Longitudinal collection and analysis of microbiome data in a community gardening randomized controlled trial is feasible. The analysis pipeline will be useful in larger studies for assessment of the pathway between microbiota, gardening and health outcomes.}, }
@article {pmid32488167, year = {2020}, author = {Rasmussen, MA and Thorsen, J and Dominguez-Bello, MG and Blaser, MJ and Mortensen, MS and Brejnrod, AD and Shah, SA and Hjelmsø, MH and Lehtimäki, J and Trivedi, U and Bisgaard, H and Sørensen, SJ and Stokholm, J}, title = {Ecological succession in the vaginal microbiota during pregnancy and birth.}, journal = {The ISME journal}, volume = {14}, number = {9}, pages = {2325-2335}, pmid = {32488167}, issn = {1751-7370}, abstract = {The mother's vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota.}, }
@article {pmid32487674, year = {2020}, author = {Brenes, LR and Lohse, MB and Hartooni, N and Johnson, AD}, title = {A Set of Diverse Genes Influence the Frequency of White-Opaque Switching in Candida albicans.}, journal = {G3 (Bethesda, Md.)}, volume = {10}, number = {8}, pages = {2593-2600}, pmid = {32487674}, issn = {2160-1836}, support = {R01 AI049187/AI/NIAID NIH HHS/United States ; }, abstract = {The fungal species Candida albicans is both a member of the human microbiome and a fungal pathogen. C. albicans undergoes several different morphological transitions, including one called white-opaque switching. Here, cells reversibly switch between two states, "white" and "opaque," and each state is heritable through many cell generations. Each cell type has a distinct cellular and colony morphology and they differ in many other properties including mating, nutritional specialization, and interactions with the innate immune system. Previous genetic screens to gain insight into white-opaque switching have focused on certain classes of genes (for example transcriptional regulators or chromatin modifying enzymes). In this paper, we examined 172 deletion mutants covering a broad range of cell functions. We identified 28 deletion mutants with at least a fivefold effect on switching frequencies; these cover a wide variety of functions ranging from membrane sensors to kinases to proteins of unknown function. In agreement with previous reports, we found that components of the pheromone signaling cascade affect white-to-opaque switching; however, our results suggest that the major effect of Cek1 on white-opaque switching occurs through the cell wall damage response pathway. Most of the genes we identified have not been previously implicated in white-opaque switching and serve as entry points to understand new aspects of this morphological transition.}, }
@article {pmid32486497, year = {2020}, author = {Badawy, S and Pajunen, MI and Haiko, J and Baka, ZAM and Abou-Dobara, MI and El-Sayed, AKA and Skurnik, M}, title = {Identification and Functional Analysis of Temperate Siphoviridae Bacteriophages of Acinetobacter baumannii.}, journal = {Viruses}, volume = {12}, number = {6}, pages = {}, pmid = {32486497}, issn = {1999-4915}, abstract = {Acinetobacter baumannii is an opportunistic pathogen that presents a serious clinical challenge due to its increasing resistance to all available antibiotics. Phage therapy has been introduced recently to treat antibiotic-incurable A. baumannii infections. In search for new A. baumannii specific bacteriophages, 20 clinical A. baumannii strains were used in two pools in an attempt to enrich phages from sewage. The enrichment resulted in induction of resident prophage(s) and three temperate bacteriophages, named vB_AbaS_fEg-Aba01, vB_AbaS_fLi-Aba02 and vB_AbaS_fLi-Aba03, all able to infect only one strain (#6597) of the 20 clinical strains, were isolated. Morphological characteristics obtained by transmission electron microscopy together with the genomic information revealed that the phages belong to the family Siphoviridae. The ca. 35 kb genomic sequences of the phages were >99% identical to each other. The linear ds DNA genomes of the phages contained 10 nt cohesive end termini, 52-54 predicted genes, an attP site and one tRNA gene each. A database search revealed an >99% identical prophage in the genome of A.baumannii strain AbPK1 (acc. no. CP024576.1). Over 99% identical prophages were also identified from two of the original 20 clinical strains (#5707 and #5920) and both were shown to be spontaneously inducible, thus very likely being the origins of the isolated phages. The phage vB_AbaS_fEg-Aba01 was also able to lysogenize the susceptible strain #6597 demonstrating that it was fully functional. The phages showed a very narrow host range infecting only two A.baumannii strains. In conclusion, we have isolated and characterized three novel temperate Siphoviridae phages that infect A.baumannii.}, }
@article {pmid32479952, year = {2020}, author = {Singh, A and Nayak, N and Rathi, P and Verma, D and Sharma, R and Chaudhary, A and Agarwal, A and Tripathi, YB and Garg, N}, title = {Microbiome and host crosstalk: A new paradigm to cancer therapy.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.05.014}, pmid = {32479952}, issn = {1096-3650}, abstract = {The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.}, }
@article {pmid32475524, year = {2020}, author = {Dahl, WJ and Rivero Mendoza, D and Lambert, JM}, title = {Diet, nutrients and the microbiome.}, journal = {Progress in molecular biology and translational science}, volume = {171}, number = {}, pages = {237-263}, doi = {10.1016/bs.pmbts.2020.04.006}, pmid = {32475524}, issn = {1878-0814}, abstract = {Although there is associative evidence linking fecal microbiome profile to health and disease, many studies have not considered the confounding effects of dietary intake. Consuming food provides fermentable substrate which sustains the microbial ecosystem that resides with most abundance in the colon. Western, Mediterranean and vegetarian dietary patterns have a role in modulating the gut microbiota, as do trending restrictive diets such the paleolithic and ketogenic. Altering the amount or ratio of carbohydrate, protein and fat, particularly at the extremes of intake, impacts the microbiome. Diets high in fermentable carbohydrates support the relative abundance of Bifidobacterium, Prevotella, Ruminococcus, Dorea and Roseburia, among others, capable of degrading polysaccharides, oligosaccharides and sugars. Conversely, very high fat diets increase bile-resistant organisms such as Bilophila and Bacteroides. Food form, whole foods vs. ultra-processed, alters the provision of macronutrient substrate to the colon due to differing digestibility, and thereby may impact the microbiota and its metabolic activity. In addition, phytochemicals in plant-based foods have specific and possibly prebiotic effects on the microbiome. Further, food ingredients such as certain low-calorie sweeteners enhance Bifidobacterium spp. The weight of evidence to date suggests a high level of interindividual variability in the human microbiome vs. clearly defined, dietary-induced profiles. Healthful dietary patterns, emphasizing plant foods high in microbial-available carbohydrate, support favorable microbiome profiles active in saccharolytic fermentation. Future research into diet and microbiome should consider the balance of gut microbial-generated metabolites, an important link between microbiome profile and human health.}, }
@article {pmid32474160, year = {2020}, author = {Prescott, SL}, title = {A butterfly flaps its wings: Extinction of biological experience and the origins of allergy.}, journal = {Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology}, volume = {125}, number = {5}, pages = {528-534}, doi = {10.1016/j.anai.2020.05.025}, pmid = {32474160}, issn = {1534-4436}, mesh = {Allergens/administration & dosage/*immunology ; Betacoronavirus/immunology/pathogenicity ; Biodiversity ; COVID-19 ; Coronavirus Infections/genetics/immunology/*prevention & control/virology ; Disease Susceptibility/*immunology ; Ecosystem ; Environmental Exposure/analysis ; Extinction, Biological ; Gastrointestinal Tract/immunology/microbiology/virology ; Gene-Environment Interaction ; Humans ; Hypersensitivity/genetics/immunology/microbiology/*prevention & control ; Immune System/drug effects ; Microbiota/*immunology ; Pandemics/*prevention & control ; Pneumonia, Viral/genetics/immunology/*prevention & control/virology ; SARS-CoV-2 ; Skin/immunology/microbiology/virology ; }, abstract = {OBJECTIVE: To explore links between biodiversity on all scales and allergic disease as a measure of immune dysregulation.
DATA SOURCES: PubMed and Web of Science were searched using the keywords biodiversity, nature relatedness, allergic disease, microbiome, noncommunicable diseases, coronavirus disease 2019, and associated terms.
STUDY SELECTIONS: Studies were selected based on relevance to human health and biodiversity.
RESULTS: Contact with natural environments enriches the human microbiome, promotes regulated immune responses, and protects against allergy and both acute and chronic inflammatory disorders. These important links to ecopsychological constructs of the extinction of experience, which indicates that loss of direct, personal contact with biodiversity (wildlife and the more visible elements of the natural world), might lead to emotional apathy and irresponsible behaviors toward the environment.
CONCLUSION: The immune system is a useful early barometer of environmental effects and, by means of the microbiome, is a measure of the way in which our current experiences differ from our ancestral past. Although we would benefit from further research, efforts to increase direct, personal contact with biodiversity have clear benefits for multiple aspects of physical and mental health, the skin and gut microbiome, immune function, food choices, sleep, and physical activity and promote environmental responsibility.}, }
@article {pmid32468338, year = {2020}, author = {Wu, AH and Tseng, C and Vigen, C and Yu, Y and Cozen, W and Garcia, AA and Spicer, D}, title = {Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study.}, journal = {Breast cancer research and treatment}, volume = {182}, number = {2}, pages = {451-463}, doi = {10.1007/s10549-020-05702-6}, pmid = {32468338}, issn = {1573-7217}, support = {20IB-0105//California Breast Cancer Research Program/ ; }, abstract = {OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors.
METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity.
RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors.
CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.}, }
@article {pmid32456257, year = {2020}, author = {Vernocchi, P and Del Chierico, F and Putignani, L}, title = {Gut Microbiota Metabolism and Interaction with Food Components.}, journal = {International journal of molecular sciences}, volume = {21}, number = {10}, pages = {}, pmid = {32456257}, issn = {1422-0067}, abstract = {The human gut contains trillions of microbes that play a central role in host biology, including the provision of key nutrients from the diet. Food is a major source of precursors for metabolite production; in fact, diet modulates the gut microbiota (GM) as the nutrients, derived from dietary intake, reach the GM, affecting both the ecosystem and microbial metabolic profile. GM metabolic ability has an impact on human nutritional status from childhood. However, there is a wide variability of dietary patterns that exist among individuals. The study of interactions with the host via GM metabolic pathways is an interesting field of research in medicine, as microbiota members produce myriads of molecules with many bioactive properties. Indeed, much evidence has demonstrated the importance of metabolites produced by the bacterial metabolism from foods at the gut level that dynamically participate in various biochemical mechanisms of a cell as a reaction to environmental stimuli. Hence, the GM modulate homeostasis at the gut level, and the alteration in their composition can concur in disease onset or progression, including immunological, inflammatory, and metabolic disorders, as well as cancer. Understanding the gut microbe-nutrient interactions will increase our knowledge of how diet affects host health and disease, thus enabling personalized therapeutics and nutrition.}, }
@article {pmid32453194, year = {2020}, author = {Thapa, S and Runge, JK and Venkatachalam, A and Denne, C and Luna, RA and Anon, JB}, title = {The Nasopharyngeal and Gut Microbiota in Children in a Pediatric Otolaryngology Practice.}, journal = {The Pediatric infectious disease journal}, volume = {39}, number = {9}, pages = {e226-e233}, doi = {10.1097/INF.0000000000002703}, pmid = {32453194}, issn = {1532-0987}, abstract = {BACKGROUND: The human microbiome evolves rapidly in early life with contributions from various factors such as diet, delivery mode, medical history, antibiotics exposure, genetics, immunomodulators and the environment. A high use of antibiotics in pediatric outpatient settings has been well documented, and improvement in antibiotic selection is required to reduce the risks of antibiotic resistance and disruption of the microbiome.
METHODS: We performed an exploratory study using 16S rRNA gene-based sequencing to characterize the gut and nasopharyngeal microbiome of children (n = 50) age 1-6 years of age in a pediatric otolaryngology practice.
RESULTS: Relative abundance of Haemophilus and Moraxella were higher in nasopharyngeal swabs, while Prevotella, Bacteroides, Porphyromonas and Faecalibacterium were highly abundant in rectal swabs. The gut microbiome composition in children <2 years old was different compared with children ≥2 years age. Gut bacterial diversity increased with an increase in age of the children. Children taking probiotics had a notable increase in abundance of potentially beneficial gut bacteria such as Bacteroides and Akkermansia. The nasopharyngeal microbiome differed between children who received antibiotics in the 3 months before sample collection compared with those that did not. Haemophilus spp. was highly abundant in children who received antibiotics 3 months before sampling.
CONCLUSIONS: The pediatric nasopharyngeal and rectal microbiomes differ in bacterial composition and diversity. The increased abundance of Haemophilus spp. in the nasopharyngeal microbiome of children who received antibiotics during the 3 months before sampling suggests a potential impact of antibiotics in colonization with the otopathogen and may be relevant to clinical practice.}, }
@article {pmid32449747, year = {2020}, author = {Sharma, D and Paterson, AD and Xu, W}, title = {TaxoNN: ensemble of neural networks on stratified microbiome data for disease prediction.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {17}, pages = {4544-4550}, doi = {10.1093/bioinformatics/btaa542}, pmid = {32449747}, issn = {1367-4811}, abstract = {MOTIVATION: Research supports the potential use of microbiome as a predictor of some diseases. Motivated by the findings that microbiome data is complex in nature, and there is an inherent correlation due to hierarchical taxonomy of microbial Operational Taxonomic Units (OTUs), we propose a novel machine learning method incorporating a stratified approach to group OTUs into phylum clusters. Convolutional Neural Networks (CNNs) were used to train within each of the clusters individually. Further, through an ensemble learning approach, features obtained from each cluster were then concatenated to improve prediction accuracy. Our two-step approach comprising stratification prior to combining multiple CNNs, aided in capturing the relationships between OTUs sharing a phylum efficiently, as compared to using a single CNN ignoring OTU correlations.
RESULTS: We used simulated datasets containing 168 OTUs in 200 cases and 200 controls for model testing. Thirty-two OTUs, potentially associated with risk of disease were randomly selected and interactions between three OTUs were used to introduce non-linearity. We also implemented this novel method in two human microbiome studies: (i) Cirrhosis with 118 cases, 114 controls; (ii) type 2 diabetes (T2D) with 170 cases, 174 controls; to demonstrate the model's effectiveness. Extensive experimentation and comparison against conventional machine learning techniques yielded encouraging results. We obtained mean AUC values of 0.88, 0.92, 0.75, showing a consistent increment (5%, 3%, 7%) in simulations, Cirrhosis and T2D data, respectively, against the next best performing method, Random Forest.
https://github.com/divya031090/TaxoNN_OTU.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid32446759, year = {2020}, author = {Dannenberg, L and Zikeli, D and Benkhoff, M and Ahlbrecht, S and Kelm, M and Levkau, B and Polzin, A}, title = {Targeting the human microbiome and its metabolite TMAO in cardiovascular prevention and therapy.}, journal = {Pharmacology & therapeutics}, volume = {213}, number = {}, pages = {107584}, doi = {10.1016/j.pharmthera.2020.107584}, pmid = {32446759}, issn = {1879-016X}, abstract = {The human gut microbiota is the most important active part of the intestinal micro-ecosystem. Lifestyle modification, drug intake and nutrition have an impact on the composition of the gut microbiota and its metabolites. This review focuses on the effects of changes in the gut microbiota as well as the important metabolite Trimethylamine-N-oxide (TMAO). Furthermore, relevant therapeutic options to target the human microbiome in patients with cardiovascular disease are presented.}, }
@article {pmid32437658, year = {2020}, author = {Ang, QY and Alexander, M and Newman, JC and Tian, Y and Cai, J and Upadhyay, V and Turnbaugh, JA and Verdin, E and Hall, KD and Leibel, RL and Ravussin, E and Rosenbaum, M and Patterson, AD and Turnbaugh, PJ}, title = {Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells.}, journal = {Cell}, volume = {181}, number = {6}, pages = {1263-1275.e16}, doi = {10.1016/j.cell.2020.04.027}, pmid = {32437658}, issn = {1097-4172}, support = {R21 CA227232/CA/NCI NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 HL122593/HL/NHLBI NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; K08 AG048354/AG/NIA NIH HHS/United States ; }, abstract = {Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.}, }
@article {pmid32435232, year = {2020}, author = {Ma, ZS}, title = {Assessing and Interpreting the Metagenome Heterogeneity With Power Law.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {648}, pmid = {32435232}, issn = {1664-302X}, abstract = {There are two major sequencing technologies for investigating the microbiome: the amplicon sequencing that generates the OTU (operational taxonomic unit) tables of marker genes (e.g., bacterial 16S-rRNA), and the metagenomic shotgun sequencing that generates metagenomic gene abundance (MGA) tables. The OTU table is the counterpart of species abundance tables in macrobial ecology of plants and animals, and has been the target of numerous ecological and network analyses in recent gold rush for microbiome research and in great efforts for establishing an inclusive theoretical ecology. Nevertheless, MGA analyses have been largely limited to bioinformatics pipelines and ad hoc statistical methods, and systematic approaches to MGAs guided by classic ecological theories are still few. Here, we argue that, the difference between "gene kinds" and "gene species" are nominal, and the metagenome that a microbiota carries is essentially a 'community' of metagenomic genes (MGs). Each row of a MGA table represents a metagenome of a microbiota, and the whole MGA table represents a 'meta-metagenome' (or an assemblage of metagenomes) of N microbiotas (microbiome samples). Consequently, the same ecological/network analyses used in OTU analyses should be equally applicable to MGA tables. Here we choose to analyze the heterogeneity of metagenome by introducing classic Taylor's power law (TPL) and its recent extensions in community ecology. Heterogeneity is a fundamental property of metagenome, particularly in the context of human microbiomes. Recent studies have shown that the heterogeneity of human metagenomes is far more significant than that of human genomes. Therefore, without deep understanding of the human metagenome heterogeneity, personalized medicine of the human microbiome-associated diseases is hardly feasible. The TPL extensions have been successfully applied to measure the heterogeneity of human microbiome based on amplicon-sequencing reads of marker genes (e.g., 16s-rRNA). In this article, we demonstrate the analysis of the metagenomic heterogeneity of human gut microbiome at whole metagenome scale (with type-I power law extension) and metagenomic gene scale (type-III), as well as the heterogeneity of gene clusters, respectively. We further examine the influences of obesity, IBD and diabetes on the heterogeneity, which is of important ramifications for the diagnosis and treatment of human microbiome-associated diseases.}, }
@article {pmid32431776, year = {2020}, author = {Sewall, JM and Oliver, A and Denaro, K and Chase, AB and Weihe, C and Lay, M and Martiny, JBH and Whiteson, K}, title = {Fiber Force: A Fiber Diet Intervention in an Advanced Course-Based Undergraduate Research Experience (CURE) Course.}, journal = {Journal of microbiology & biology education}, volume = {21}, number = {1}, pages = {}, pmid = {32431776}, issn = {1935-7877}, abstract = {Course-based undergraduate research experiences (CUREs) are an effective way to introduce students to contemporary scientific research. Research experiences have been shown to promote critical thinking, improve understanding and proper use of the scientific method, and help students learn practical skills including writing and oral communication. We aimed to improve scientific training by engaging students enrolled in an upper division elective course in a human microbiome CURE. The "Fiber Force" course is aimed at studying the effect of a wholesome high-fiber diet (40 to 50 g/day for two weeks) on the students' gut microbiomes. Enrolled students participated in a noninvasive diet intervention, designed health surveys, tested hypotheses on the effect of a diet intervention on the gut microbiome, and analyzed their own samples (as anonymized aggregates). The course involved learning laboratory techniques (e.g., DNA extraction, PCR, and 16S sequencing) and the incorporation of computational techniques to analyze microbiome data with QIIME2 and within the R software environment. In addition, the learning objectives focused on effective student performance in writing, data analysis, and oral communication. Enrolled students showed high performance grades on writing, data analysis and oral communication assignments. Pre- and post-course surveys indicate that the students found the experience favorable, increased their interest in science, and heightened awareness of their diet habits. Fiber Force constitutes a validated case of a research experience on microbiology with the capacity to improve research training and promote healthy dietary habits.}, }
@article {pmid32430415, year = {2020}, author = {Gosens, R and Hiemstra, PS and Adcock, IM and Bracke, KR and Dickson, RP and Hansbro, PM and Krauss-Etschmann, S and Smits, HH and Stassen, FRM and Bartel, S}, title = {Host-microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease.}, journal = {The European respiratory journal}, volume = {56}, number = {2}, pages = {}, pmid = {32430415}, issn = {1399-3003}, abstract = {Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.}, }
@article {pmid32429141, year = {2020}, author = {Spruit, CM and Wicklund, A and Wan, X and Skurnik, M and Pajunen, MI}, title = {Discovery of Three Toxic Proteins of Klebsiella Phage fHe-Kpn01.}, journal = {Viruses}, volume = {12}, number = {5}, pages = {}, pmid = {32429141}, issn = {1999-4915}, abstract = {The lytic phage, fHe-Kpn01 was isolated from sewage water using an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae as a host. The genome is 43,329 bp in size and contains direct terminal repeats of 222 bp. The genome contains 56 predicted genes, of which proteomics analysis detected 29 different proteins in purified phage particles. Comparison of fHe-Kpn01 to other phages, both morphologically and genetically, indicated that the phage belongs to the family Podoviridae and genus Drulisvirus. Because fHe-Kpn01 is strictly lytic and does not carry any known resistance or virulence genes, it is suitable for phage therapy. It has, however, a narrow host range since it infected only three of the 72 tested K. pneumoniae strains, two of which were of capsule type KL62. After annotation of the predicted genes based on the similarity to genes of known function and proteomics results on the virion-associated proteins, 22 gene products remained annotated as hypothetical proteins of unknown function (HPUF). These fHe-Kpn01 HPUFs were screened for their toxicity in Escherichia coli. Three of the HPUFs, encoded by the genes g10, g22, and g38, were confirmed to be toxic.}, }
@article {pmid32426004, year = {2020}, author = {Herman, RA}, title = {Increasing allergy: are antibiotics the elephant in the room?.}, journal = {Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology}, volume = {16}, number = {}, pages = {35}, pmid = {32426004}, issn = {1710-1484}, abstract = {Antibiotics cause dramatic changes to the human microbiome. The composition of the microbiome has been associated with changes in the immune system and these changes are beginning to be linked to immune diseases. Thus, antibiotics have been implicated as a significant contributor to the continual rise of allergies and autoimmune disease in developed countries. This recognition will hopefully result in the development of post-antibiotic therapies that restore a healthy microbiome and reduce immune system disorders.}, }
@article {pmid32414567, year = {2020}, author = {Chipollini, J and Wright, JR and Nwanosike, H and Kepler, CY and Batai, K and Lee, BR and Spiess, PE and Stewart, DB and Lamendella, R}, title = {Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study.}, journal = {Urologic oncology}, volume = {38}, number = {7}, pages = {615-621}, doi = {10.1016/j.urolonc.2020.04.014}, pmid = {32414567}, issn = {1873-2496}, abstract = {OBJECTIVES: The human microbiome has been linked to the development of several malignancies, but there is scarcity of data on the microbiome of bladder cancer patients. In this study, we analyzed microbial composition and diversity among patients with and without bladder cancer.
MATERIAL AND METHODS: Samples were collected from 38 urothelial carcinoma (UC) patients and 10 noncancer controls from August 2018 to May 2019. DNA was extracted and processed for 16 S ribosomal RNA sequencing. Alpha diversity community characteristics including evenness and richness as well as beta diversity metrics were obtained. Linear discriminant analysis effect size was used to identify microbial components whose sequences were more abundant. Pairwise statistics provided quantitative assessment of significant distributions among groups.
RESULTS: Thirty seven total samples contained high quality sequence data for subsequent analyses and divided into 3 cohorts: control (n = 10), muscle-invasive (n = 15) and superficial UC (n = 12). Control samples had significantly higher species evenness when compared to invasive (P = 0.031) and superficial tumors (P = 0.002). In addition, higher species richness was observed in noncancer versus cancer samples (Faith phylogenetic diversity, P < 0.05). Significantly enriched taxa were found in both control (Bacteroides, Lachnoclostridium, Burkholderiaceae) and cancer samples (Bacteroides and Faecalbacterium).
CONCLUSION: Significantly decreased microbial community diversity was seen in the urine of patients with bladder cancer when compared to a noncancer group. Distinct taxa were noted suggesting unique microbial communities in the urine of bladder cancer patients.}, }
@article {pmid32411613, year = {2020}, author = {Pinto, D and Calabrese, FM and De Angelis, M and Celano, G and Giuliani, G and Gobbetti, M and Rinaldi, F}, title = {Predictive Metagenomic Profiling, Urine Metabolomics, and Human Marker Gene Expression as an Integrated Approach to Study Alopecia Areata.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {146}, pmid = {32411613}, issn = {2235-2988}, abstract = {Involvement of the microbiome in many different scalp conditions has been investigated over the years. Studies on the role of the scalp microbiome in specific diseases, such as those involving hair growth alterations like non-cicatricial [androgenetic alopecia (AGA), alopecia areata (AA)] and cicatricial alopecia lichen planopilaris, are of major importance. In the present work, we highlighted the differences in microbial populations inhabiting the scalp of AA subjects and a healthy sample cohort by using an integrated approach relying on metagenomic targeted 16S sequencing analysis, urine metabolomics, and human marker gene expression. Significant differences in genera abundances (p < 0.05) were found in the hypodermis and especially the dermis layer. Based on 16S sequencing data, we explored the differences in predicted KEGG pathways and identified some significant differences in predicted pathways related to the AA pathologic condition such as flagellar, assembly, bacterial chemotaxis, mineral absorption, ABC transporters, cellular antigens, glycosaminoglycan degradation, lysosome, sphingolipid metabolism, cell division, protein digestion and absorption, and energy metabolism. All predicted pathways were significantly enhanced in AA samples compared to expression in healthy samples, with the exceptions of mineral absorption, and ABC transporters. We also determined the expression of TNF-α, FAS, KCNA3, NOD-2, and SOD-2 genes and explored the relationships between human gene expression levels and microbiome composition by Pearson's correlation analysis; here, significant correlations both positive (SOD vs. Staphylococcus, Candidatus Aquiluna) and negative (FAS and SOD2 vs. Anaerococcus, Neisseria, and Acinetobacter) were highlighted. Finally, we inspected volatile organic metabolite profiles in urinary samples and detected statistically significant differences (menthol, methanethiol, dihydrodehydro-beta-ionone, 2,5-dimethylfuran, 1,2,3,4, tetrahydro-1,5,7-trimethylnapthalene) when comparing AA and healthy subject groups. This multiple comparison approach highlighted potential traits associated with AA and their relationship with the microbiota inhabiting the scalp, opening up novel therapeutic interventions in such kind of hair growth disorders mainly by means of prebiotics, probiotics, and postbiotics.}, }
@article {pmid32410293, year = {2020}, author = {Qureshi, SS and Kedo, M and Berthrong, ST}, title = {Gender-neutral bathroom surfaces recolonized by microbes more quickly than single-gender bathrooms.}, journal = {Letters in applied microbiology}, volume = {71}, number = {2}, pages = {134-137}, doi = {10.1111/lam.13316}, pmid = {32410293}, issn = {1472-765X}, support = {//Butler University's Center for High Achievement and Scholarly Engagement Honors Program/ ; }, mesh = {Bacteria/classification/*growth & development/isolation & purification ; Bacterial Load/*statistics & numerical data ; Female ; Humans ; Male ; Microbiota/*physiology ; Sex Factors ; Sexual and Gender Minorities/statistics & numerical data ; Toilet Facilities/*statistics & numerical data ; United States ; }, abstract = {As humans become increasingly urban and spend more time inside the built environment, there will be increased interactions between humans and shared public surface microbiomes. Recent cultural changes in the United States have led to increased numbers of gender-neutral bathrooms. Given that bathroom surfaces are frequently sanitized, we used this increased availability of gender-neutral bathrooms to examine how single-gender or gender-neutral surfaces are recolonized with microbes. Given that male and female microbiomes vary, we hypothesized that rates of recolonization would differ between male, female and gender-neutral bathroom surfaces. We collected swabs from common hand-contacted surfaces in bathrooms and cultured microbes on selective and rich media to determine microbial abundance after cleaning. Recolonization was dominated by Gram-positive bacteria and was slowest on male, intermediate on female and fastest on gender-neutral surfaces. These results imply that gender-neutral surfaces approach normal climax microbial communities more quickly than single-gender bathrooms. SIGNIFICANCE OF IMPACT OF THE STUDY: Humans now spend substantial amount of time within the built environment, and as a consequence the human microbiome interacts frequently with indoor surfaces. Social changes are making gender-neutral public bathrooms more common, so it is important to study how humans and microbiomes interact with these bathroom surfaces. We found that the gender-neutral bathroom surfaces recolonize more quickly than single-gender, which suggests that there are more potential human-surface microbiome connections in these public spaces. These results will potentially add a new layer to our understanding of the interactions of humans, our microbiomes and how we design our built environment.}, }
@article {pmid32408372, year = {2020}, author = {Whitmont, RD}, title = {The Human Microbiome, Conventional Medicine, and Homeopathy.}, journal = {Homeopathy : the journal of the Faculty of Homeopathy}, volume = {109}, number = {4}, pages = {248-255}, doi = {10.1055/s-0040-1709665}, pmid = {32408372}, issn = {1476-4245}, abstract = {Human health is intimately linked to the ecology and diversity of the human microbiome. Together, the human organism and the human microbiome work as a complex super-organism throughout the human life cycle. Microbiome science provides direct evidence and substantiation of the fundamental principles of homeopathy, including holism, psychosomatics, direction of cure, the Law of Similars, individuality and susceptibility, minimum dose, and homeostasis. Whilst many conventional (allopathic) medical treatments irreversibly damage the ecology of the microbiome and trigger chronic immune dysfunction and inflammation, the future sustainability of the entire field of medicine depends on the ability to recognize these inconvenient biological truths and to embrace a safer approach based on this evidence. Fortunately, one of the oldest forms of clinically verifiable, evidence-based, and ecologically sustainable medicine, that does not harm the microbiome, already exists in the form of homeopathy.}, }
@article {pmid32407510, year = {2020}, author = {Ma, ZS}, title = {Heterogeneity-disease relationship in the human microbiome-associated diseases.}, journal = {FEMS microbiology ecology}, volume = {96}, number = {7}, pages = {}, doi = {10.1093/femsec/fiaa093}, pmid = {32407510}, issn = {1574-6941}, mesh = {Humans ; *Microbiota ; *Models, Biological ; }, abstract = {Space is a critical and also challenging frontier in human microbiome research. It has been found that lack of consideration of scales beyond individual and ignoring of microbe dispersal are two crucial roadblocks in preventing deep understanding of the spatial heterogeneity of human microbiome. Assessing and interpreting the heterogeneity and dispersal in microbiomes explicitly are particularly challenging, but implicit approaches such as Taylor's power law (TPL) can be rather effective. Based on TPL, which achieved a rare status of ecological laws, we introduce a general methodology for characterizing the spatial heterogeneity of microbiome (i.e. characterization of microbial spatial distribution) and further apply it for investigating the heterogeneity-disease relationship (HDR) via analyzing a big dataset of 26 MAD (microbiome-associated disease) studies covering nearly all high-profile MADs including obesity, diabetes and gout. It was found that in majority of the MAD cases, the microbiome was sufficiently resilient to endure the disease disturbances. Specifically, in ∼10-16% cases, disease effects were significant-the healthy and diseased cohorts exhibited statistically significant differences in the TPL heterogeneity parameters. We further compared HDR with classic diversity-disease relationship (DDR) and explained their mechanistic differences. Both HDR and DDR cross-verified remarkable resilience of the human microbiomes against MADs.}, }
@article {pmid32406914, year = {2020}, author = {Wang, Y and Bhattacharya, T and Jiang, Y and Qin, X and Wang, Y and Liu, Y and Saykin, AJ and Chen, L}, title = {A novel deep learning method for predictive modeling of microbiome data.}, journal = {Briefings in bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1093/bib/bbaa073}, pmid = {32406914}, issn = {1477-4054}, abstract = {With the development and decreasing cost of next-generation sequencing technologies, the study of the human microbiome has become a rapid expanding research field, which provides an unprecedented opportunity in various clinical applications such as drug response predictions and disease diagnosis. It is thus essential and desirable to build a prediction model for clinical outcomes based on microbiome data that usually consist of taxon abundance and a phylogenetic tree. Importantly, all microbial species are not uniformly distributed in the phylogenetic tree but tend to be clustered at different phylogenetic depths. Therefore, the phylogenetic tree represents a unique correlation structure of microbiome, which can be an important prior to improve the prediction performance. However, prediction methods that consider the phylogenetic tree in an efficient and rigorous way are under-developed. Here, we develop a novel deep learning prediction method MDeep (microbiome-based deep learning method) to predict both continuous and binary outcomes. Conceptually, MDeep designs convolutional layers to mimic taxonomic ranks with multiple convolutional filters on each convolutional layer to capture the phylogenetic correlation among microbial species in a local receptive field and maintain the correlation structure across different convolutional layers via feature mapping. Taken together, the convolutional layers with its built-in convolutional filters capture microbial signals at different taxonomic levels while encouraging local smoothing and preserving local connectivity induced by the phylogenetic tree. We use both simulation studies and real data applications to demonstrate that MDeep outperforms competing methods in both regression and binary classifications. Availability and Implementation: MDeep software is available at https://github.com/lichen-lab/MDeep Contact:chen61@iu.edu.}, }
@article {pmid32400169, year = {2020}, author = {Salehi, B and Dimitrijević, M and Aleksić, A and Neffe-Skocińska, K and Zielińska, D and Kołożyn-Krajewska, D and Sharifi-Rad, J and Stojanović-Radić, Z and Prabu, SM and Rodrigues, CF and Martins, N}, title = {Human microbiome and homeostasis: insights into the key role of prebiotics, probiotics, and symbiotics.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-14}, doi = {10.1080/10408398.2020.1760202}, pmid = {32400169}, issn = {1549-7852}, abstract = {The interest in the study of the gut microbiome has grown exponentially. Indeed, its impact on health and disease has been increasingly reported, and the importance of keeping gut microbiome homeostasis clearly highlighted. However, and despite many advances, there are still some gaps, as well as the real discernment on the contribution of some species falls far short of what is needed. Anyway, it is already more than a solid fact of its importance in maintaining health and preventing disease, as well as in the treatment of some pathologies. In this sense, and given the existence of some ambiguous opinions, the present review aims to discuss the importance of gut microbiome in homeostasis maintenance, and even the role of probiotics, prebiotics, and symbiotics in both health promotion and disease prevention.}, }
@article {pmid32397233, year = {2020}, author = {Satokari, R}, title = {High Intake of Sugar and the Balance between Pro- and Anti-Inflammatory Gut Bacteria.}, journal = {Nutrients}, volume = {12}, number = {5}, pages = {}, pmid = {32397233}, issn = {2072-6643}, abstract = {The so-called Western diet is rich in saturated fat and sugars and poor in plant-derived fibers, and it is associated with an increased risk of metabolic and cardiovascular diseases, as well as chronic (low grade) inflammation. The detrimental effects of poor diet are in part mediated by gut microbiota, whose composition, functionality and metabolic end products respond to dietary changes. Recent studies have shown that high intake of sugars increase the relative abundance of Proteobacteria in the gut, while simultaneously decreasing the abundance of Bacteroidetes, which can mitigate the effects of endotoxin, as well as reinforce gut barrier function. Thus, a high sugar intake may stagger the balance of microbiota to have increased pro-inflammatory properties and decreased the capacity to regulate epithelial integrity and mucosal immunity. Consequently, high dietary sugar can, through the modulation of microbiota, promote metabolic endotoxemia, systemic (low grade) inflammation and the development of metabolic dysregulation and thereby, high dietary sugar may have many-fold deleterious health effects, in addition to providing excess energy.}, }
@article {pmid32397065, year = {2020}, author = {Bangayan, NJ and Shi, B and Trinh, J and Barnard, E and Kasimatis, G and Curd, E and Li, H}, title = {MG-MLST: Characterizing the Microbiome at the Strain Level in Metagenomic Data.}, journal = {Microorganisms}, volume = {8}, number = {5}, pages = {}, pmid = {32397065}, issn = {2076-2607}, support = {R01 GM099530/GM/NIGMS NIH HHS/United States ; UH2 AR057503/AR/NIAMS NIH HHS/United States ; UH2AR057503/NH/NIH HHS/United States ; R01GM099530/NH/NIH HHS/United States ; }, abstract = {The microbiome plays an important role in human physiology. The composition of the human microbiome has been described at the phylum, class, genus, and species levels, however, it is largely unknown at the strain level. The importance of strain-level differences in microbial communities has been increasingly recognized in understanding disease associations. Current methods for identifying strain populations often require deep metagenomic sequencing and a comprehensive set of reference genomes. In this study, we developed a method, metagenomic multi-locus sequence typing (MG-MLST), to determine strain-level composition in a microbial community by combining high-throughput sequencing with multi-locus sequence typing (MLST). We used a commensal bacterium, Propionibacterium acnes, as an example to test the ability of MG-MLST in identifying the strain composition. Using simulated communities, MG-MLST accurately predicted the strain populations in all samples. We further validated the method using MLST gene amplicon libraries and metagenomic shotgun sequencing data of clinical skin samples. MG-MLST yielded consistent results of the strain composition to those obtained from nearly full-length 16S rRNA clone libraries and metagenomic shotgun sequencing analysis. When comparing strain-level differences between acne and healthy skin microbiomes, we demonstrated that strains of RT2/6 were highly associated with healthy skin, consistent with previous findings. In summary, MG-MLST provides a quantitative analysis of the strain populations in the microbiome with diversity and richness. It can be applied to microbiome studies to reveal strain-level differences between groups, which are critical in many microorganism-related diseases.}, }
@article {pmid32393397, year = {2020}, author = {Koh, H and Zhao, N}, title = {A powerful microbial group association test based on the higher criticism analysis for sparse microbial association signals.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {63}, pmid = {32393397}, issn = {2049-2618}, support = {P30 AI094189/AI/NIAID NIH HHS/United States ; U24 OD023382/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: In human microbiome studies, it is crucial to evaluate the association between microbial group (e.g., community or clade) composition and a host phenotype of interest. In response, a number of microbial group association tests have been proposed, which account for the unique features of the microbiome data (e.g., high-dimensionality, compositionality, phylogenetic relationship). These tests generally fall in the class of aggregation tests which amplify the overall group association by combining all the underlying microbial association signals, and, therefore, they are powerful when many microbial species are associated with a given host phenotype (i.e., low sparsity). However, in practice, the microbial association signals can be highly sparse, and this is especially the situation where we have a difficulty to discover the microbial group association.
METHODS: Here, we introduce a powerful microbial group association test for sparse microbial association signals, namely, microbiome higher criticism analysis (MiHC). MiHC is a data-driven omnibus test taken in a search space spanned by tailoring the higher criticism test to incorporate phylogenetic information and/or modulate sparsity levels and including the Simes test for excessively high sparsity levels. Therefore, MiHC robustly adapts to diverse phylogenetic relevance and sparsity levels.
RESULTS: Our simulations show that MiHC maintains a high power at different phylogenetic relevance and sparsity levels with correct type I error controls. We also apply MiHC to four real microbiome datasets to test the association between respiratory tract microbiome and smoking status, the association between the infant's gut microbiome and delivery mode, the association between the gut microbiome and type 1 diabetes status, and the association between the gut microbiome and human immunodeficiency virus status.
CONCLUSIONS: In practice, the true underlying association pattern on the extent of phylogenetic relevance and sparsity is usually unknown. Therefore, MiHC can be a useful analytic tool because of its high adaptivity to diverse phylogenetic relevance and sparsity levels. MiHC can be implemented in the R computing environment using our software package freely available at https://github.com/hk1785/MiHC.}, }
@article {pmid32391057, year = {2020}, author = {Thomas, G and Bain, JM and Budge, S and Brown, AJP and Ames, RM}, title = {Identifying Candida albicans Gene Networks Involved in Pathogenicity.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {375}, pmid = {32391057}, issn = {1664-8021}, abstract = {Candida albicans is a normal member of the human microbiome. It is also an opportunistic pathogen, which can cause life-threatening systemic infections in severely immunocompromized individuals. Despite the availability of antifungal drugs, mortality rates of systemic infections are high and new drugs are needed to overcome therapeutic challenges including the emergence of drug resistance. Targeting known disease pathways has been suggested as a promising avenue for the development of new antifungals. However, <30% of C. albicans genes are verified with experimental evidence of a gene product, and the full complement of genes involved in important disease processes is currently unknown. Tools to predict the function of partially or uncharacterized genes and generate testable hypotheses will, therefore, help to identify potential targets for new antifungal development. Here, we employ a network-extracted ontology to leverage publicly available transcriptomics data and identify potential candidate genes involved in disease processes. A subset of these genes has been phenotypically screened using available deletion strains and we present preliminary data that one candidate, PEP8, is involved in hyphal development and immune evasion. This work demonstrates the utility of network-extracted ontologies in predicting gene function to generate testable hypotheses that can be applied to pathogenic systems. This could represent a novel first step to identifying targets for new antifungal therapies.}, }
@article {pmid32391012, year = {2020}, author = {Peroni, DG and Nuzzi, G and Trambusti, I and Di Cicco, ME and Comberiati, P}, title = {Microbiome Composition and Its Impact on the Development of Allergic Diseases.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {700}, pmid = {32391012}, issn = {1664-3224}, abstract = {Allergic diseases, such as food allergy (FA), atopic dermatitis (AD), and asthma, are heterogeneous inflammatory immune-mediated disorders that currently constitute a public health issue in many developed countries worldwide. The significant increase in the prevalence of allergic diseases reported over the last few years has closely paralleled substantial environmental changes both on a macro and micro scale, which have led to reduced microbial exposure in early life and perturbation of the human microbiome composition. Increasing evidence shows that early life interactions between the human microbiome and the immune cells play a pivotal role in the development of the immune system. Therefore, the process of early colonization by a "healthy" microbiome is emerging as a key determinant of life-long health. In stark contrast, the perturbation of such a process, which results in changes in the host-microbiome biodiversity and metabolic activities, has been associated with greater susceptibility to immune-mediated disorders later in life, including allergic diseases. Here, we outline recent findings on the potential contribution of the microbiome in the gastrointestinal tract, skin, and airways to the development of FA, AD, and asthma. Furthermore, we address how the modulation of the microbiome composition in these different body districts could be a potential strategy for the prevention and treatment of allergic diseases.}, }
@article {pmid32390974, year = {2020}, author = {Jiang, T and Chen, W and Cao, L and He, Y and Zhou, H and Mao, H}, title = {Abundance, Functional, and Evolutionary Analysis of Oxalyl-Coenzyme A Decarboxylase in Human Microbiota.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {672}, pmid = {32390974}, issn = {1664-302X}, abstract = {Oxalic acid and its oxalate salts have been linked to kidney stones and other health problems and about 80% kidney stones are made up of calcium oxalate. Oxalyl coenzyme A decarboxylase (OXC) is a key enzyme in the catabolism of oxalate. In this study, we performed bioinformatic and biochemical analysis of OXC. First, we mined the OXC sequences from a public protein database and collected 1396 putative OXC sequences. These sequences were widely spread and mainly distributed in Actinobacteria, Alphaproteobacteria, Gammaproteobacteria, and Betaproteobacteria and classified into seven clusters. The phylogenetic relationship and evolutionary rate of the 7 clusters showed that OXC are highly conserved. Second, the abundance of the different clusters of OXC was explored in 380 human microbiome datasets, which showed that OXCs in Cluster 1 were relatively high in the gut while OXCs in Clusters 2-4 were relatively enriched in the vagina. Third, we measured the activity of one OXC from Mycobacterium mageritense (OXCmm) in Cluster 3, in which there was no experimentally characterized enzymes. Mutation analysis showed that OXCmm shared the same active sites with the OXC from Oxalobacter formigenes. Taken together, this analysis provides a better insight into the distribution and catalysis of OXC and further potential alternative application of OXC active bacteria as probiotics in the management of kidney stone disease.}, }
@article {pmid32384684, year = {2020}, author = {Caparrós-Martín, JA and Flynn, S and Reen, FJ and Woods, DF and Agudelo-Romero, P and Ranganathan, SC and Stick, SM and O'Gara, F}, title = {The Detection of Bile Acids in the Lungs of Paediatric Cystic Fibrosis Patients Is Associated with Altered Inflammatory Patterns.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {10}, number = {5}, pages = {}, pmid = {32384684}, issn = {2075-4418}, support = {FP7-PEOPLE-2013-ITN, 607786//European Comission/ ; FP7-KBBE-2012-6, CP-TP-312184//European Comission/ ; FP7-KBBE-2012-6, 311975//European Comission/ ; OCEAN 2011-2, 287589//European Comission/ ; Marie Curie 256596//European Comission/ ; EU-634486//European Comission/ ; SSPC-2, 12/RC/2275/SFI_/Science Foundation Ireland/Ireland ; SSP3-Pharm5:13/TIDA/B2625/SFI_/Science Foundation Ireland/Ireland ; 12/TIDA/B2411/SFI_/Science Foundation Ireland/Ireland ; 12/TIDA/B2405/SFI_/Science Foundation Ireland/Ireland ; 14/TIDA/2438/SFI_/Science Foundation Ireland/Ireland ; 15/TIDA/2977/SFI_/Science Foundation Ireland/Ireland ; FIRM/RSF/CoFoRD//The Department of Agriculture and Food/ ; FIRM 08/RDC/629//The Department of Agriculture and Food/ ; FIRM 1/F009/MabS//The Department of Agriculture and Food/ ; FIRM 13/F/516//The Department of Agriculture and Food/ ; HRB-ILP-POR-2019-004/HRBI_/Health Research Board/Ireland ; MRCG-2014-6//Health Research Board/Irish Thoracic Society/ ; Beaufort award C2CRA 2007/082//The Marine Institute/ ; Walsh Fellowship 2013//Teagasc/ ; The Glenn Brown Memorial Grant 2017//The Institute for Respiratory Health/ ; MRCG-2018-16/HRBI_/Health Research Board/Ireland ; Grant CFF 1710//US CF Foundation/ ; }, abstract = {Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.}, }
@article {pmid32380174, year = {2020}, author = {Price, TK and Lin, H and Gao, X and Thomas-White, KJ and Hilt, EE and Mueller, ER and Wolfe, AJ and Dong, Q and Brubaker, L}, title = {Bladder bacterial diversity differs in continent and incontinent women: a cross-sectional study.}, journal = {American journal of obstetrics and gynecology}, volume = {223}, number = {5}, pages = {729.e1-729.e10}, pmid = {32380174}, issn = {1097-6868}, support = {P20 DK108268/DK/NIDDK NIH HHS/United States ; R01 DK104718/DK/NIDDK NIH HHS/United States ; R21 DK097435/DK/NIDDK NIH HHS/United States ; R56 DK104718/DK/NIDDK NIH HHS/United States ; }, mesh = {Actinomycetaceae/isolation & purification ; Adult ; Aerococcus/isolation & purification ; Aged ; Aged, 80 and over ; *Biodiversity ; Corynebacterium/isolation & purification ; Cross-Sectional Studies ; Female ; Gardnerella vaginalis/isolation & purification ; Humans ; Lactobacillus/isolation & purification ; Lactobacillus crispatus/isolation & purification ; Lactobacillus gasseri/isolation & purification ; *Microbiota ; Middle Aged ; Staphylococcus epidermidis/isolation & purification ; Streptococcus anginosus/isolation & purification ; Urinary Bladder/*microbiology ; Urinary Incontinence, Stress/*microbiology ; Urinary Incontinence, Urge/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: Since the discovery of the bladder microbiome (urobiome), interest has grown in learning whether urobiome characteristics have a role in clinical phenotyping and provide opportunities for novel therapeutic approaches for women with common forms of urinary incontinence.
OBJECTIVE: This study aimed to test the hypothesis that the bladder urobiome differs among women in the control cohort and women affected by urinary incontinence by assessing associations between urinary incontinence status and the cultured urobiome.
STUDY DESIGN: With institutional review board oversight, urine specimens from 309 adult women were collected through transurethral catheterization. These women were categorized into 3 cohorts (continent control, stress urinary incontinence [SUI], and urgency urinary incontinence [UUI]) based on their responses to the validated Pelvic Floor Distress Inventory (PFDI) questionnaire. Among 309 women, 150 were in the continent control cohort, 50 were in the SUI cohort, and 109 were in the UUI cohort. Symptom severity was assessed by subscale scoring with the Urinary Distress Inventory (UDI), subscale of the Pelvic Floor Distress Inventory. Microbes were assessed by expanded quantitative urine culture protocol, which detects the most common bladder microbes (bacteria and yeast). Microbes were identified to the species level by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. Alpha diversity indices were calculated for culture-positive samples and compared across the 3 cohorts. The correlations of UDI scores, alpha diversity indices, and species abundance were estimated.
RESULTS: Participants had a mean age of 53 years (range 22-90); most were whites (65%). Women with urinary incontinence were slightly older (control, 47; SUI, 54; UUI, 61). By design, UDI symptom scores differed (control, 8.43 [10.1]; SUI, 97.95 [55.36]; UUI, 93.71 [49.12]; P<.001). Among 309 participants, 216 (70%) had expanded quantitative urine culture-detected bacteria; furthermore, the urinary incontinence cohorts had a higher detection frequency than the control cohort (control, 57%; SUI, 86%; UUI, 81%; P<.001). In addition, the most frequently detected species among the cohorts were as follows: continent control, Lactobacillus iners (12.7%), Streptococcus anginosus (12.7%), L crispatus (10.7%), and L gasseri (10%); SUI, S anginosus (26%), L iners (18%), Staphylococcus epidermidis (18%), and L jensenii (16%); and UUI, S anginosus (30.3%), L gasseri (22%), Aerococcus urinae (18.3%), and Gardnerella vaginalis (17.4%). However, only Actinotignum schaalii (formerly Actinobaculum schaalii), A urinae, A sanguinicola, and Corynebacterium lipophile group were found at significantly higher mean abundances in 1 of the urinary incontinence cohorts when compared with the control cohort (Wilcoxon rank sum test; P<.02), and no individual genus differed significantly between the 2 urinary incontinence cohorts. Both urinary incontinence cohorts had increased alpha diversity similar to continent control cohort with indices of species richness, but not evenness, strongly associated with urinary incontinence.
CONCLUSION: In adult women, the composition of the culturable bladder urobiome is associated with urinary incontinence, regardless of common incontinence subtype. Detection of more unique living microbes was associated with worsening incontinence symptom severity. Culturable species richness was significantly greater in the urinary incontinence cohorts than in the continent control cohort.}, }
@article {pmid32379704, year = {2020}, author = {Liu, S and Wang, Y and Zhao, L and Sun, X and Feng, Q}, title = {Microbiome succession with increasing age in three oral sites.}, journal = {Aging}, volume = {12}, number = {9}, pages = {7874-7907}, pmid = {32379704}, issn = {1945-4589}, abstract = {The incidence of oral diseases is remarkably increased with age, and it may be related to oral microbiota. In this study, we systematically investigated the microbiota of gingival crevicular fluid (GCF), tongue back (TB) and saliva (SAL) from various age groups in healthy populations. The microbial diversity results indicated that the α-diversity of bacteria had a tendency to decrease in aging mouth, whereas the β-diversity showed an opposite increasing trend in all three sites. Next, the microbial structure exploration revealed a divergence in bacterial profile in three sites in response to aging, but the intersite differential bacteria demonstrated a uniform bell-shaped variation trend with age. Meanwhile, several age-differentiated genera were shared by GCF, SAL and TB sites, and the bacterial correlation analysis demonstrated a clear shift in the pattern of bacterial correlations with age. Moreover, both the intra- and intersite "core microbiome" showed significantly decreased bacterial diversities with age. Finally, the trending differential bacteria species were used as a biomarker to distinguish the different age groups, and the prediction accuracies in GCF were 0.998, 0.809, 0.668, 0.675 and 0.956. Our results revealed the characteristics of intra- and intersite bacterial succession with age, providing novel insights into senile oral diseases.}, }
@article {pmid32375241, year = {2020}, author = {Tomaiuolo, R and Veneruso, I and Cariati, F and D'Argenio, V}, title = {Microbiota and Human Reproduction: The Case of Female Infertility.}, journal = {High-throughput}, volume = {9}, number = {2}, pages = {}, pmid = {32375241}, issn = {2571-5135}, support = {855720//H2020 Innovation In SMEs/ ; year 2016//EIT Health/ ; }, abstract = {During the last decade, the availability of next-generation sequencing-based approaches has revealed the presence of microbial communities in almost all the human body, including the reproductive tract. As for other body sites, this resident microbiota has been involved in the maintenance of a healthy status. As a consequence, alterations due to internal or external factors may lead to microbial dysbiosis and to the development of pathologies. Female reproductive microbiota has also been suggested to affect infertility, and it may play a key role in the success of assisted reproductive technologies, such as embryo implantation and pregnancy care. While the vaginal microbiota is well described, the uterine microbiota is underexplored. This could be due to technical issues, as the uterus is a low biomass environment. Here, we review the state of the art regarding the role of the female reproductive system microbiota in women's health and human reproduction, highlighting its contribution to infertility.}, }
@article {pmid32374853, year = {2020}, author = {Bartolomaeus, TUP and Birkner, T and Bartolomaeus, H and Löber, U and Avery, EG and Mähler, A and Weber, D and Kochlik, B and Balogh, A and Wilck, N and Boschmann, M and Müller, DN and Markó, L and Forslund, SK}, title = {Quantifying Technical Confounders in Microbiome Studies.}, journal = {Cardiovascular research}, volume = {}, number = {}, pages = {}, doi = {10.1093/cvr/cvaa128}, pmid = {32374853}, issn = {1755-3245}, abstract = {AIMS: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health and demographics.
METHODS AND RESULTS: An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution.
CONCLUSIONS: DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.
TRANSLATIONAL PERSPECTIVES: By applying a framework which is typical for the investigation of the microbiome in cardiovascular disease patients, we assess the role of these confounders under realistic circumstances. Our work allows quality control and design improvement for upcoming translational microbiome studies such as the search for disease biomarkers or efficacy predictors for personalized treatment regimes.}, }
@article {pmid32374655, year = {2020}, author = {Zhu, C and Yuan, C and Wei, FQ and Sun, XY and Zheng, SG}, title = {Intraindividual Variation and Personal Specificity of Salivary Microbiota.}, journal = {Journal of dental research}, volume = {99}, number = {9}, pages = {1062-1071}, doi = {10.1177/0022034520917155}, pmid = {32374655}, issn = {1544-0591}, abstract = {Salivary microbiota is a typical habitat of the human microbiome. This study intended to use salivary microbiota as a model aiming to systematically address the influence of collection methods and temporal dynamics on the human microbiota compared to personal specificity. We carried out a supervised short-term longitudinal study to evaluate the influence of the change of collection methods and sampling time point on salivary microbiota in 10 systemically and orally healthy individuals with certain confounding factors (sex, oral and general health state, medication history, physical exercise, diet, and oral hygiene behavior) controlled before and during the sampling period. The microbial profiles were analyzed by 16S rDNA V3 to V4 hypervariable region amplicon sequencing. The taxonomic structure represented by the dominant species and the weighted UniFrac distance algorithm were used to demonstrate the individual specificity and the intraindividual variation introduced by the change of collection method and sampling time point. The findings suggested individual specificity existed in salivary microbiota from individuals with similar oral and general health status. The intraindividual variation brought by the change of collection method or sampling time point might introduce remarkable perturbation with the personal specificity. Insights into the intraindividual variation and personal specificity of salivary microbiota will enhance our understanding in salivary microbiota-related research. We recommend keeping collection conditions consistent within a study to avoid interference brought by the sampling. The strategy of repeated sampling at multiple time points as representative samples, as well as thorough interpretation of the complex relationships and causality between microbiome composition and disease without the interference of temporal dynamics, is optimal for research exploring the relationship between the salivary microbiome and disease.}, }
@article {pmid32373093, year = {2020}, author = {Woods, DF and Kozak, IM and O'Gara, F}, title = {Microbiome and Functional Analysis of a Traditional Food Process: Isolation of a Novel Species (Vibrio hibernica) With Industrial Potential.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {647}, pmid = {32373093}, issn = {1664-302X}, abstract = {Traditional food preservation processes are vital for the food industry. They not only preserve a high-quality protein and nutrient source but can also provide important value-added organoleptic properties. The Wiltshire process is a traditional food curing method applied to meat, and special recognition is given to the maintenance of a live rich microflora within the curing brine. We have previously analyzed a curing brine from this traditional meat process and characterized a unique microbial core signature. The characteristic microbial community is actively maintained and includes the genera, Marinilactibacillus, Carnobacterium, Leuconostoc, and Vibrio. The bacteria present are vital for Wiltshire curing compliance. However, the exact function of this microflora is largely unknown. A microbiome profiling of three curing brines was conducted and investigated for functional traits by the robust bioinformatic tool, Tax4Fun. The key objective was to uncover putative metabolic functions associated with the live brine and to identify changes over time. The functional bioinformatic analysis revealed metabolic enrichments over time, with many of the pathways identified as being involved in organoleptic development. The core bacteria present in the brine are Lactic Acid Bacteria (LAB), with the exception of the Vibrio genus. LAB are known for their positive contribution to food processing, however, little work has been conducted on the use of Vibrio species for beneficial processes. The Vibrio genome was sequenced by Illumina MiSeq technologies and annotated in RAST. A phylogenetic reconstruction was completed using both the 16S rRNA gene and housekeeping genes, gapA, ftsZ, mreB, topA, gyrB, pyrH, recA, and rpoA. The isolated Vibrio species was defined as a unique novel species, named Vibrio hibernica strain B1.19. Metabolic profiling revealed that the bacterium has a unique substrate scope in comparison to other closely related Vibrio species tested. The possible function and industrial potential of the strain was investigated using carbohydrate metabolizing profiling under food processing relevant conditions. Vibrio hibernica is capable of metabolizing a unique carbohydrate profile at low temperatures. This characteristic provides new application options for use in the industrial food sector, as well as highlighting the key role of this bacterium in the Wiltshire curing process.}, }
@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 ; K08 HL148178/NH/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 ; }, 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}, mesh = {Bayes Theorem ; Firmicutes/physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Interleukin-17/*blood ; Interleukins/*blood ; Longitudinal Studies ; Microbiota/physiology ; Prediabetic State/immunology/microbiology ; }, 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 {pmid32360945, year = {2020}, author = {Piggott, DA and Tuddenham, S}, title = {The gut microbiome and frailty.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {221}, number = {}, pages = {23-43}, doi = {10.1016/j.trsl.2020.03.012}, pmid = {32360945}, issn = {1878-1810}, mesh = {*Frailty ; *Gastrointestinal Microbiome ; HIV Infections/microbiology/physiopathology ; Humans ; }, abstract = {The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. In this article, we review the complex interplay of biological, behavioral, and environmental factors that may influence shifts in gut microbiome composition and function in aging populations and the putative implications of such shifts for progression to frailty. We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.}, }
@article {pmid32351023, year = {2020}, author = {Ndika, J and Ilves, M and Kooter, IM and Gröllers-Mulderij, M and Duistermaat, E and Tromp, PC and Kuper, F and Kinaret, P and Greco, D and Karisola, P and Alenius, H}, title = {Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for Hazard Assessment.}, journal = {Small (Weinheim an der Bergstrasse, Germany)}, volume = {16}, number = {36}, pages = {e2000527}, doi = {10.1002/smll.202000527}, pmid = {32351023}, issn = {1613-6829}, support = {309329//Seventh Framework Programme/ ; 297885//Academy of Finland/ ; 307768//Academy of Finland/ ; }, abstract = {The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non-animal approaches to health hazard assessment for ethical and practical reasons. Although non-animal approaches are becoming increasingly popular, there are almost no studies of side-by-side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air-liquid interface (ALI) cultures of donor-derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.}, }
@article {pmid32350240, year = {2020}, author = {Xiao, J and Fiscella, KA and Gill, SR}, title = {Oral microbiome: possible harbinger for children's health.}, journal = {International journal of oral science}, volume = {12}, number = {1}, pages = {12}, pmid = {32350240}, issn = {2049-3169}, support = {K23 DE027412/DE/NIDCR NIH HHS/United States ; }, mesh = {Child ; *Child Health ; Humans ; Infant ; *Microbiota ; Mouth/*microbiology ; }, abstract = {The human microbiome functions as an intricate and coordinated microbial network, residing throughout the mucosal surfaces of the skin, oral cavity, gastrointestinal tract, respiratory tract, and reproductive system. The oral microbiome encompasses a highly diverse microbiota, consisting of over 700 microorganisms, including bacteria, fungi, and viruses. As our understanding of the relationship between the oral microbiome and human health has evolved, we have identified a diverse array of oral and systemic diseases associated with this microbial community, including but not limited to caries, periodontal diseases, oral cancer, colorectal cancer, pancreatic cancer, and inflammatory bowel syndrome. The potential predictive relationship between the oral microbiota and these human diseases suggests that the oral cavity is an ideal site for disease diagnosis and development of rapid point-of-care tests. The oral cavity is easily accessible with a non-invasive collection of biological samples. We can envision a future where early life salivary diagnostic tools will be used to predict and prevent future disease via analyzing and shaping the infant's oral microbiome. In this review, we present evidence for the establishment of the oral microbiome during early childhood, the capability of using childhood oral microbiome to predict future oral and systemic diseases, and the limitations of the current evidence.}, }
@article {pmid32343000, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.}, journal = {Alimentary pharmacology & therapeutics}, volume = {51}, number = {12}, pages = {1321-1331}, doi = {10.1111/apt.15740}, pmid = {32343000}, issn = {1365-2036}, mesh = {Adolescent ; Adult ; Aged ; Colonoscopy/*methods ; Double-Blind Method ; Dysbiosis/complications/microbiology/therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/complications/microbiology/*therapy ; Male ; Middle Aged ; Placebos ; Quality of Life ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis.
AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS.
METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight.
RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms.
CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.}, }
@article {pmid32340923, year = {2019}, author = {Gotschlich, EC and Colbert, RA and Gill, T}, title = {Methods in microbiome research: Past, present, and future.}, journal = {Best practice & research. Clinical rheumatology}, volume = {33}, number = {6}, pages = {101498}, pmid = {32340923}, issn = {1532-1770}, support = {ZIA AR041184/ImNIH/Intramural NIH HHS/United States ; }, mesh = {Dysbiosis ; Humans ; *Microbiota ; Research/trends ; }, abstract = {The human microbiome is impressively immense and participates in many aspects of our health and wellness, particularly involving the development and maintenance of a healthy immune system. Not only do our microbes teach the immune system to fight infection, they also teach immune tolerance and help maintain homeostasis. From this knowledge, we have learned that the loss of tolerance to microbiota in both innate and adaptive processes plays an important role in immune-mediated and autoimmune disease. In this chapter, we will be discussing about methods used to study the microbiome, both old and new methods, fundamental concepts that have taken hold within the field, and how these principles relate to rheumatology, including thoughts on how microbiome research may be focused in the next decade.}, }
@article {pmid32334114, year = {2020}, author = {Zhou, J and Sun, T and Kang, W and Tang, D and Feng, Q}, title = {Pathogenic and antimicrobial resistance genes in Streptococcus oralis strains revealed by comparative genome analysis.}, journal = {Genomics}, volume = {112}, number = {5}, pages = {3783-3793}, doi = {10.1016/j.ygeno.2020.04.014}, pmid = {32334114}, issn = {1089-8646}, abstract = {Streptococcus oralis is an early colonizer bacterium in dental plaques and is considered a potential pathogen of infective endocarditis (IE) disease. In this study, we built a complete genome map of Streptococcus oralis strain SOT, Streptococcus oralis strain SOD and Streptococcus infantis strain SO and performed comparative genomic analysis among these three strains. The results showed that there are five genomic islands (GIs) in strain SOT and one CRISPR in strain SOD. Each genome harbors various pathogenic genes related to diseases and drug resistance, while the antibiotic resistance genes in strains SOT and SOD were quite similar but different from those in strain SO. In addition, we identified 17 main virulence factors and capsule-related genes in three strains. These results suggest the pathogenic potential of Streptococcus strains, which lay a foundation for the prevention and treatment of a Streptococcus oralis infection.}, }
@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 {pmid32329665, year = {2020}, author = {Jia, B and Park, D and Hahn, Y and Jeon, CO}, title = {Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1300-1313}, pmid = {32329665}, issn = {1949-0984}, abstract = {Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (n = 1,605) and healthy controls (n = 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health.}, }
@article {pmid32327694, year = {2020}, author = {Yang, H and Zhang, J and Xue, Z and Zhao, C and Lei, L and Wen, Y and Dong, Y and Yang, J and Zhang, L}, title = {Potential Pathogenic Bacteria in Seminal Microbiota of Patients with Different Types of Dysspermatism.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6876}, pmid = {32327694}, issn = {2045-2322}, mesh = {Adult ; Asthenozoospermia/microbiology ; Bacteria/metabolism/pathogenicity ; Biodiversity ; Biomarkers/metabolism ; Case-Control Studies ; Discriminant Analysis ; Humans ; Infertility, Male/*microbiology ; Male ; Metagenome ; *Microbiota/genetics ; Oligospermia/microbiology ; Phylogeny ; Principal Component Analysis ; Semen/*microbiology ; }, abstract = {Human microbiota play an important role in the health of their human hosts. Recent studies have demonstrated that microbiota exist in seminal plasma. The current study aims to elucidate whether seminal microbiota exist in patients with different types of dysspermatism and whether bacterial biomarkers can be identified for them. A total of 159 study participants were recruited, including 22 patients with oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients with oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed using 16S rRNA gene-based sequencing. The results showed that the composition of seminal microbiota of patients with dysspermatism differed from those of healthy controls. Comparison of the microbiota composition in semen samples from patients with different types of dysspermatism showed that microbiota in patients with asthenospermia and oligoasthenospermia were distinct from healthy controls in beta diversity (P < 0.05). Characteristic biomarkers, including Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, were identified based on LEfSe analysis. Inferred functional analysis based on seminal microbiome data further indicated the presence of potential pathogenic biomarkers in patients with asthenospermia and oligoasthenospermia. These results provided profiles of seminal microbiota exhibited in different types of dysspermatism, thus providing new insights into their pathogenesis.}, }
@article {pmid32326394, year = {2020}, author = {Garcia-Mazcorro, JF and Minamoto, Y and Kawas, JR and Suchodolski, JS and de Vos, WM}, title = {Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity.}, journal = {Veterinary sciences}, volume = {7}, number = {2}, pages = {}, pmid = {32326394}, issn = {2306-7381}, abstract = {Akkermansia muciniphila is a mucin-degrading bacterium that has shown the potential to provide anti-inflammatory and anti-obesity effects in mouse and man. We here focus on companion animals, specifically cats and dogs, and evaluate the microbial degradation of mucus and its health impact in the context of the worldwide epidemic of pet obesity. A literature survey revealed that the two presently known Akkermansia spp., A. muciniphila and A. glycaniphila, as well as other members of the phylum of Verrucomicrobia seem to be neither very prevalent nor abundant in the digestive tract of cats and dog. While this may be due to methodological aspects, it suggests that bacteria related to Akkermansia are not the major mucus degraders in these pets and hence other mucus-utilizing taxa may deserve attention. Hence, we will discuss the potential of these endogenous mucus utilizers and dietary interventions to boost these as well as the use of Akkermansia spp. related bacteria or their components as strategies to target feline and canine obesity.}, }
@article {pmid32324967, year = {2020}, author = {Samples, RM and Balunas, MJ}, title = {Bridging the Gap: Plant-Endophyte Interactions as a Roadmap to Understanding Small-Molecule Communication in Marine Microbiomes.}, journal = {Chembiochem : a European journal of chemical biology}, volume = {21}, number = {19}, pages = {2708-2721}, doi = {10.1002/cbic.202000064}, pmid = {32324967}, issn = {1439-7633}, support = {IOS-1557914//National Science Foundation/ ; IOS-1656475//National Science Foundation/ ; }, abstract = {Probing the composition of the microbiome and its association with health and disease states is more accessible than ever due to the rise of affordable sequencing technology. Despite advances in our ability to identify members of symbiont communities, untangling the chemical signaling that they use to communicate with host organisms remains challenging. In order to gain a greater mechanistic understanding of how the microbiome impacts health, and how chemical ecology can be leveraged to advance small-molecule drug discovery from microorganisms, the principals governing communication between host and symbiont must be elucidated. Herein, we review common modes of interkingdom small-molecule communication in terrestrial and marine environments, describe the differences between these environments, and detail the advantages and disadvantages for studies focused on the marine environment. Finally, we propose the use of plant-endophyte interactions as a stepping stone to a greater understanding of similar interactions in marine invertebrates, and ultimately in humans.}, }
@article {pmid32319703, year = {2020}, author = {Vangoitsenhoven, R and Cresci, GAM}, title = {Role of Microbiome and Antibiotics in Autoimmune Diseases.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {35}, number = {3}, pages = {406-416}, doi = {10.1002/ncp.10489}, pmid = {32319703}, issn = {1941-2452}, support = {R00AA023266//GAC National Institutes of Health, NIAAA/ ; }, abstract = {The global rise in the incidence of autoimmune diseases has paralleled the widespread use of antibiotics. Recently, the gut microbiome has been shown to be key in the development and maturation of a normal immune system, and a range of microbial disturbances have been associated with the development and activity of several autoimmune diseases. Here, we aim to provide an overview of the mechanistic crosstalk between the human microbiome, the immune system, and antibiotics. The disease-associated microbial gut dysbiosis, the potential role of antibiotics in the development and treatment of autoimmune diseases, and the manipulation of the gut microbiome with prebiotics and probiotics is discussed using 2 key autoimmune diseases as an example: inflammatory bowel disease and type 1 diabetes. Although some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis, there are also data to suggest antibiotics may hold the potential to improve disease activity. Currently, the effect of fecal microbiota transplantation on several autoimmune diseases is being studied in clinical trials, and several preclinical studies are revealing promising results with probiotic and prebiotic therapies.}, }
@article {pmid32318028, year = {2020}, author = {Eetemadi, A and Rai, N and Pereira, BMP and Kim, M and Schmitz, H and Tagkopoulos, I}, title = {The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {393}, pmid = {32318028}, issn = {1664-302X}, abstract = {Food and human health are inextricably linked. As such, revolutionary impacts on health have been derived from advances in the production and distribution of food relating to food safety and fortification with micronutrients. During the past two decades, it has become apparent that the human microbiome has the potential to modulate health, including in ways that may be related to diet and the composition of specific foods. Despite the excitement and potential surrounding this area, the complexity of the gut microbiome, the chemical composition of food, and their interplay in situ remains a daunting task to fully understand. However, recent advances in high-throughput sequencing, metabolomics profiling, compositional analysis of food, and the emergence of electronic health records provide new sources of data that can contribute to addressing this challenge. Computational science will play an essential role in this effort as it will provide the foundation to integrate these data layers and derive insights capable of revealing and understanding the complex interactions between diet, gut microbiome, and health. Here, we review the current knowledge on diet-health-gut microbiota, relevant data sources, bioinformatics tools, machine learning capabilities, as well as the intellectual property and legislative regulatory landscape. We provide guidance on employing machine learning and data analytics, identify gaps in current methods, and describe new scenarios to be unlocked in the next few years in the context of current knowledge.}, }
@article {pmid32316935, year = {2020}, author = {Koliada, A and Moseiko, V and Romanenko, M and Piven, L and Lushchak, O and Kryzhanovska, N and Guryanov, V and Vaiserman, A}, title = {Seasonal variation in gut microbiota composition: cross-sectional evidence from Ukrainian population.}, journal = {BMC microbiology}, volume = {20}, number = {1}, pages = {100}, pmid = {32316935}, issn = {1471-2180}, abstract = {BACKGROUND: Gut microbiota composition is known to depend on environmental (diet, day length, infections, xenobiotic exposure) and lifestyle (alcohol/drug intake, physical activity) factors. All these factors fluctuate seasonally, especially in areas with highly variable climatic conditions between seasons. Seasonal microbiota changes were reported in several previous studies. The purpose of our study was to investigate whether there is a seasonal variability in the gut microbiota composition in Ukrainian population. In contrast to previous studies performed on small-size samples using a longitudinal design, we used cross-sectional design with a large sample size (n = 769). Determination of microbial composition at the level of major microbial phyla was performed by qRT-PCR.
RESULTS: The relative abundance of major taxonomic groups of gut microbiota was found to be affected by month of sampling. Actinobacteria were more abundant and Bacteroidetes were less abundant in summer-derived samples compared to those obtained during other seasons, whereas Firmicutes content was seasonally independent. The Firmicutes to Bacteroidetes (F/B) ratio was significantly higher in summer-derived samples than in winter-derived ones. Odds to have F/B > 1 were 3.3 times higher in summer samples and 1.9 times higher in autumn samples than in winter ones; neither age, nor sex were significant confounding factors.
CONCLUSIONS: Seasonality of sampling could influence results of human microbiome research, thereby potentially biasing estimates. This factor must be taken into consideration in further microbiome research.}, }
@article {pmid32305861, year = {2020}, author = {Ma, ZS}, title = {Testing the Anna Karenina Principle in Human Microbiome-Associated Diseases.}, journal = {iScience}, volume = {23}, number = {4}, pages = {101007}, doi = {10.1016/j.isci.2020.101007}, pmid = {32305861}, issn = {2589-0042}, abstract = {The AKP (Anna Karenina principle), which refers to observations inspired by the opening line of Leo Tolstoy's Anna Karenina, "all happy families are all alike; each unhappy family is unhappy in its own way," predicts that all "healthy" microbiomes are alike and each disease-associated microbiome is "sick" in its own way in human microbiome-associated diseases (MADs). The AKP hypothesis predicts the rise of heterogeneity/stochasticity in human microbiomes associated with dysbiosis due to MADs. We used the beta-diversity in Hill numbers and stochasticity analysis to detect AKP and anti-AKP effects. We tested the AKP with 27 human MAD studies and discovered that the AKP, anti-AKP, and non-AKP effects were exhibited in approximately 50%, 25%, and 25% of the MAD cases, respectively. Mechanistically, AKP effects are primarily influenced by highly dominant microbial species and less influenced by rare species. In contrast, all species appear to play equal roles in influencing anti-AKP effects.}, }
@article {pmid32298967, year = {2020}, author = {Otto, M}, title = {Staphylococci in the human microbiome: the role of host and interbacterial interactions.}, journal = {Current opinion in microbiology}, volume = {53}, number = {}, pages = {71-77}, doi = {10.1016/j.mib.2020.03.003}, pmid = {32298967}, issn = {1879-0364}, support = {ZIA AI000904/ImNIH/Intramural NIH HHS/United States ; }, abstract = {Staphylococci are common commensals on human epithelial surfaces. Some species, most notably Staphylococcus aureus, have considerable pathogenic potential and can cause severe and sometimes fatal infections. Despite the long-known fact that staphylococcal infection arises from colonizing isolates, research on staphylococcal colonization has been limited, in particular regarding interactions with the colonizing microbiota. However, several recent studies are beginning to decipher such interactions, which range from bacteriocin-based or signaling interference-mediated inhibitory interactions to cooperation with host defenses to outcompete co-colonizers. This review will give an outline of recent research on the mechanistic underpinnings of staphylococcal interference with other members of the colonizing microbiota, some of which suggest new avenues for the development of novel anti-infectives or decolonization strategies.}, }
@article {pmid32298612, year = {2020}, author = {Ligthart, K and Belzer, C and de Vos, WM and Tytgat, HLP}, title = {Bridging Bacteria and the Gut: Functional Aspects of Type IV Pili.}, journal = {Trends in microbiology}, volume = {28}, number = {5}, pages = {340-348}, doi = {10.1016/j.tim.2020.02.003}, pmid = {32298612}, issn = {1878-4380}, abstract = {Cell-surface-located proteinaceous appendages, such as flagella and fimbriae or pili, are ubiquitous in bacterial communities. Here, we focus on conserved type IV pili (T4P) produced by bacteria in the intestinal tract, one of the most densely populated human ecosystems. Computational analysis revealed that approximately 30% of known intestinal bacteria are predicted to produce T4P. To rationalize how T4P allow intestinal bacteria to interact with their environment, other microbiota members, and host cells, we review their established role in gut commensals and pathogens with respect to adherence, motility, and biofilm formation, as well as protein secretion and DNA uptake. This work indicates that T4P are widely spread among the known members of the intestinal microbiota and that their contribution to human health might be underestimated.}, }
@article {pmid32294988, year = {2020}, author = {Tomaiuolo, R and Veneruso, I and Cariati, F and D'Argenio, V}, title = {Microbiota and Human Reproduction: The Case of Male Infertility.}, journal = {High-throughput}, volume = {9}, number = {2}, pages = {}, pmid = {32294988}, issn = {2571-5135}, support = {855720//H2020 Innovation In SMEs/ ; year 2016//EIT Health/ ; }, abstract = {The increasing interest in metagenomics is enhancing our knowledge regarding the composition and role of the microbiota in human physiology and pathology. Indeed, microbes have been reported to play a role in several diseases, including infertility. In particular, the male seminal microbiota has been suggested as an important factor able to influence couple's health and pregnancy outcomes, as well as offspring health. Nevertheless, few studies have been carried out to date to deeper investigate semen microbiome origins and functions, and its correlations with the partner's reproductive tract microbiome. Here, we report the state of the art regarding the male reproductive system microbiome and its alterations in infertility.}, }
@article {pmid32291445, year = {2020}, author = {Wu, K and Yuan, Y and Yu, H and Dai, X and Wang, S and Sun, Z and Wang, F and Fei, H and Lin, Q and Jiang, H and Chen, T}, title = {The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice.}, journal = {Blood}, volume = {136}, number = {4}, pages = {501-515}, pmid = {32291445}, issn = {1528-0020}, abstract = {The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow-derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage's response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.}, }
@article {pmid32277534, year = {2020}, author = {Meng, X and Zhang, G and Cao, H and Yu, D and Fang, X and de Vos, WM and Wu, H}, title = {Gut dysbacteriosis and intestinal disease: mechanism and treatment.}, journal = {Journal of applied microbiology}, volume = {129}, number = {4}, pages = {787-805}, doi = {10.1111/jam.14661}, pmid = {32277534}, issn = {1365-2672}, support = {No. 31670796//National Natural Science Foundation of China/ ; //Jilin University/ ; }, abstract = {The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) inflammatory bowel disease, primary sclerosing cholangitis-IBD, irritable bowel syndrome, chronic constipation, osmotic diarrhoea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota-derived signalling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, faecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.}, }
@article {pmid32269511, year = {2020}, author = {Elmassry, MM and Piechulla, B}, title = {Volatilomes of Bacterial Infections in Humans.}, journal = {Frontiers in neuroscience}, volume = {14}, number = {}, pages = {257}, pmid = {32269511}, issn = {1662-4548}, abstract = {Sense of smell in humans has the capacity to detect certain volatiles from bacterial infections. Our olfactory senses were used in ancient medicine to diagnose diseases in patients. As humans are considered holobionts, each person's unique odor consists of volatile organic compounds (VOCs, volatilome) produced not only by the humans themselves but also by their beneficial and pathogenic micro-habitants. In the past decade it has been well documented that microorganisms (fungi and bacteria) are able to emit a broad range of olfactory active VOCs [summarized in the mVOC database (http://bioinformatics.charite.de/mvoc/)]. During microbial infection, the equilibrium between the human and its microbiome is altered, followed by a change in the volatilome. For several decades, physicians have been trying to utilize these changes in smell composition to develop fast and efficient diagnostic tools, particularly because volatiles detection is non-invasive and non-destructive, which would be a breakthrough in many therapies. Within this review, we discuss bacterial infections including gastrointestinal, respiratory or lung, and blood infections, focusing on the pathogens and their known corresponding volatile biomarkers. Furthermore, we cover the potential role of the human microbiota and their volatilome in certain diseases such as neurodegenerative diseases. We also report on discrete mVOCs that affect humans.}, }
@article {pmid32266088, year = {2020}, author = {Xu, J and Peng, JJ and Yang, W and Fu, K and Zhang, Y}, title = {Vaginal microbiomes and ovarian cancer: a review.}, journal = {American journal of cancer research}, volume = {10}, number = {3}, pages = {743-756}, pmid = {32266088}, issn = {2156-6976}, abstract = {The human microbiome, often termed as "the forgotten organ", is an aggregation of microorganisms and their genomes that forms a mutualistic complex with the host. Recent research has shown the symbiotic merits of a microbiome ecosystem and its crucial role in the hosts' physiological functions. Disruption of this symbiotic relationship is prone to cause a broad spectrum of ailments, including cancer. The compositional and environmental factors that tip the scales from beneficial co-existence to the development of malignancy is actively investigated. Herein we review the latest research in knowledge regarding the association between the vaginal microbiomes and oncogenesis, with a particular focus on ovarian carcinoma.}, }
@article {pmid32257965, year = {2020}, author = {Fernández de Ullivarri, M and Arbulu, S and Garcia-Gutierrez, E and Cotter, PD}, title = {Antifungal Peptides as Therapeutic Agents.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {105}, pmid = {32257965}, issn = {2235-2988}, abstract = {Fungi have been used since ancient times in food and beverage-making processes and, more recently, have been harnessed for the production of antibiotics and in processes of relevance to the bioeconomy. Moreover, they are starting to gain attention as a key component of the human microbiome. However, fungi are also responsible for human infections. The incidence of community-acquired and nosocomial fungal infections has increased considerably in recent decades. Antibiotic resistance development, the increasing number of immunodeficiency- and/or immunosuppression-related diseases and limited therapeutic options available are triggering the search for novel alternatives. These new antifungals should be less toxic for the host, with targeted or broader antimicrobial spectra (for diseases of known and unknown etiology, respectively) and modes of actions that limit the potential for the emergence of resistance among pathogenic fungi. Given these criteria, antimicrobial peptides with antifungal properties, i.e., antifungal peptides (AFPs), have emerged as powerful candidates due to their efficacy and high selectivity. In this review, we provide an overview of the bioactivity and classification of AFPs (natural and synthetic) as well as their mode of action and advantages over current antifungal drugs. Additionally, natural, heterologous and synthetic production of AFPs with a view to greater levels of exploitation is discussed. Finally, we evaluate the current and potential applications of these peptides, along with the future challenges relating to antifungal treatments.}, }
@article {pmid32255860, year = {2020}, author = {Yu, B and Yu, B and Yu, L}, title = {Commentary: Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome.}, journal = {Indian journal of microbiology}, volume = {60}, number = {2}, pages = {259-261}, pmid = {32255860}, issn = {0046-8991}, abstract = {Human beings have co-evolved with the microorganisms in our environment for millions of years, and have developed into a symbiosis in a mutually beneficial/defensive way. Human beings have significant multifaceted relationships with the diverse microbial community. Apart from the important protective role of microbial community exposure in development of early immunity, millions of inimitable bacterial genes of the diverse microbial community are the indispensable source of essential nutrients like essential amino acids and essential fatty acids for human body. The essential nutrition from microbiome is harvested through xenophagy. As an immune effector, xenophagy will capture any microorganisms that touch the epithelial cells of our gastrointestinal tract, degrade them and turn them into nutrients for the use of our body.}, }
@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}, 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 {pmid32246318, year = {2020}, author = {Chen, B and Wang, Z and Wang, J and Su, X and Yang, J and Zhang, Q and Zhang, L}, title = {The oral microbiome profile and biomarker in Chinese type 2 diabetes mellitus patients.}, journal = {Endocrine}, volume = {68}, number = {3}, pages = {564-572}, doi = {10.1007/s12020-020-02269-6}, pmid = {32246318}, issn = {1559-0100}, support = {31471202//National Natural Science Foundation of China/International ; 2016YYSP009//Shandong Provincial Key Research and Development Program/International ; }, abstract = {PURPOSE: Oral microbiota maintains a dynamic ecological balance with the host. However, a disruption in this balance can lead to oral diseases such as dental caries and periodontitis. Several studies suggest differences in microbial composition in the oral cavity between patients with T2DM and nondiabetic patients. However, there is inadequate oral microbiome-related data from Chinese patients with T2DM, and the difference in microbiome profile between Chinese patients with T2DM and other ethnicities needs to be investigated further.
METHOD: Oral swab samples were collected from 280 adult patients with T2DM and 162 healthy controls. Illumina sequencing was performed on oral samples targeting V1-V2 region of 16S rRNA gene and sequence analysis was carried in the QIIME.
RESULTS: Patients with T2DM and healthy cohorts exhibited distinct oral microbial clusters based on principal coordinate analysis (PCoA). The Firmicutes/Bacteroidetes ratio increased in T2DM and T2DM patients presented significantly higher numbers of Neisseria, Streptococcus, Haemophilus, and Pseudomonas genera, and lower numbers of Acinetobacteria compared with healthy controls. When compared with the available published data of oral and gut microbiome associated with T2DM patients, we found the ratio of Firmicutes/Bacteroidetes and the abundance of Haemophilus could be a specific microbial biomarker in Chinese patients with T2DM.
CONCLUSIONS: Our study revealed a significant difference in the oral microbiota between T2DM patients and healthy individuals. We identified 25 taxa, including 6 genera, with significant difference in abundance between T2DM and healthy controls.}, }
@article {pmid32246263, year = {2020}, author = {Swann, JR and Rajilic-Stojanovic, M and Salonen, A and Sakwinska, O and Gill, C and Meynier, A and Fança-Berthon, P and Schelkle, B and Segata, N and Shortt, C and Tuohy, K and Hasselwander, O}, title = {Considerations for the design and conduct of human gut microbiota intervention studies relating to foods.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3347-3368}, pmid = {32246263}, issn = {1436-6215}, abstract = {With the growing appreciation for the influence of the intestinal microbiota on human health, there is increasing motivation to design and refine interventions to promote favorable shifts in the microbiota and their interactions with the host. Technological advances have improved our understanding and ability to measure this indigenous population and the impact of such interventions. However, the rapid growth and evolution of the field, as well as the diversity of methods used, parameters measured and populations studied, make it difficult to interpret the significance of the findings and translate their outcomes to the wider population. This can prevent comparisons across studies and hinder the drawing of appropriate conclusions. This review outlines considerations to facilitate the design, implementation and interpretation of human gut microbiota intervention studies relating to foods based upon our current understanding of the intestinal microbiota, its functionality and interactions with the human host. This includes parameters associated with study design, eligibility criteria, statistical considerations, characterization of products and the measurement of compliance. Methodologies and markers to assess compositional and functional changes in the microbiota, following interventions are discussed in addition to approaches to assess changes in microbiota-host interactions and host responses. Last, EU legislative aspects in relation to foods and health claims are presented. While it is appreciated that the field of gastrointestinal microbiology is rapidly evolving, such guidance will assist in the design and interpretation of human gut microbiota interventional studies relating to foods.}, }
@article {pmid32243703, year = {2020}, author = {Adams, LA and Wang, Z and Liddle, C and Melton, PE and Ariff, A and Chandraratna, H and Tan, J and Ching, H and Coulter, S and de Boer, B and Christophersen, CT and O'Sullivan, TA and Morrison, M and Jeffrey, GP}, title = {Bile acids associate with specific gut microbiota, low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease.}, journal = {Liver international : official journal of the International Association for the Study of the Liver}, volume = {40}, number = {6}, pages = {1356-1365}, doi = {10.1111/liv.14453}, pmid = {32243703}, issn = {1478-3231}, abstract = {BACKGROUND: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non-alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships.
METHODS: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high-performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next-generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3-day food diary.
RESULTS: Serum and faecal BA concentrations increased progressively among non-NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0-2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other.
CONCLUSIONS: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low-level alcohol consumption.}, }
@article {pmid32240601, year = {2020}, author = {Yan, Y and Drew, DA and Markowitz, A and Lloyd-Price, J and Abu-Ali, G and Nguyen, LH and Tran, C and Chung, DC and Gilpin, KK and Meixell, D and Parziale, M and Schuck, M and Patel, Z and Richter, JM and Kelsey, PB and Garrett, WS and Chan, AT and Stadler, ZK and Huttenhower, C}, title = {Structure of the Mucosal and Stool Microbiome in Lynch Syndrome.}, journal = {Cell host & microbe}, volume = {27}, number = {4}, pages = {585-600.e4}, pmid = {32240601}, issn = {1934-6069}, support = {R01 CA202704/CA/NCI NIH HHS/United States ; L30 CA209764/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; T32 CA009001/CA/NCI NIH HHS/United States ; K01 DK120742/DK/NIDDK NIH HHS/United States ; /CRUK_/Cancer Research UK/United Kingdom ; }, abstract = {The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosal biopsies. A classifier leveraging stool metatranscriptomes resulted in modest power to predict interval development of preneoplastic colonic adenoma. Predictive transcripts corresponded with a shift in flagellin contributors and oxidative metabolic microenvironment, potentially factors in local CRC pathogenesis. This suggests that the effectiveness of prospective microbiome monitoring for adenomas may be limited but supports the potential causality of these consistent, early microbial changes in colonic neoplasia.}, }
@article {pmid32239808, year = {2020}, author = {Kim, MH and Choi, JH}, title = {An Update on Sepsis Biomarkers.}, journal = {Infection & chemotherapy}, volume = {52}, number = {1}, pages = {1-18}, pmid = {32239808}, issn = {2093-2340}, abstract = {Sepsis is a dysregulated systemic reaction to a common infection, that can cause life-threatening organ dysfunction. Over the last decade, the mortality rate of patients with sepsis has decreased as long as patients are treated according to the recommendations of the Surviving Sepsis Campaign, but is still unacceptably high. Patients at risk of sepsis should therefore be identified prior to the onset of organ dysfunction and this requires a rapid diagnosis and a prompt initiation of treatment. Unfortunately, there is no gold standard for the diagnosis of sepsis and traditional standard culture methods are time-consuming. Recently, in order to overcome these limitations, biomarkers which could help in predicting the diagnosis and prognosis of sepsis, as well as being useful for monitoring the response to treatments, have been identified. In addition, recent advances have led to the development of newly identified classes of biomarkers such as microRNAs, long-non-coding RNAs, and the human microbiome. This review focuses on the latest information on biomarkers that can be used to predict the diagnosis and prognosis of sepsis.}, }
@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}, 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 {pmid32236123, year = {2020}, author = {Stennett, CA and Dyer, TV and He, X and Robinson, CK and Ravel, J and Ghanem, KG and Brotman, RM}, title = {A cross-sectional pilot study of birth mode and vaginal microbiota in reproductive-age women.}, journal = {PloS one}, volume = {15}, number = {4}, pages = {e0228574}, pmid = {32236123}, issn = {1932-6203}, support = {U01 AI070921/AI/NIAID NIH HHS/United States ; R01 AI089878/AI/NIAID NIH HHS/United States ; R01 AI119012/AI/NIAID NIH HHS/United States ; T32 AG000262/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Cesarean Section ; Cross-Sectional Studies ; *Delivery, Obstetric ; Female ; Humans ; Lactobacillus/isolation & purification ; *Microbiota ; *Parturition ; Pilot Projects ; Pregnancy ; United States ; Vagina/*microbiology ; Vaginosis, Bacterial/epidemiology ; Young Adult ; }, abstract = {Recent studies suggest that birth mode (Cesarean section [C-section] or vaginal delivery) is an important event in the initial colonization of the human microbiome and may be associated with long-term health outcomes. We sought to determine the association between a woman's birth mode and her vaginal microbiota in adulthood. We re-contacted 144 adult women from two U.S. studies and administered a brief survey. Vaginal microbiota was characterized on a single sample by amplicon sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene and clustered into community state types (CSTs). We evaluated the association between birth mode and a CST with low relative abundance of Lactobacillus spp. ("molecular bacterial vaginosis" [Molecular-BV]) compared to Lactobacillus-dominated CSTs in logistic regression modeling which adjusted for body mass index, a confounder in this analysis. Twenty-seven women (19%) reported C-section. Overall, C-section showed a non-significant trend towards increased odds of Molecular-BV (aOR = 1.22, 95% CI: 0.45, 3.32), and Prevotella bivia was the strongest single taxa associated with C-section. However, because the two archived studies had different inclusion criteria (interaction p = 0.048), we stratified the analysis by study site. In the study with a larger sample size (n = 88), women born by C-section had 3-fold higher odds of Molecular-BV compared to vaginally-delivered women (aOR = 3.55, p = 0.06, 95% CI: 0.97-13.02). No association was found in the smaller study (n = 56, aOR = 0.19, p = 0.14, 95% CI: 0.02-1.71). This pilot cross-sectional study suggests a possible association between C-section and Molecular-BV in adulthood. However, the analysis is limited by small sample size and lack of comparability in participant age and other characteristics between the study sites. Future longitudinal studies could recruit larger samples of women, address the temporal dynamics of vaginal microbiota, and explore other confounders, including maternal factors, breastfeeding history, and socioeconomic status, which may affect the relationship between birth mode and vaginal microbiota.}, }
@article {pmid32235279, year = {2020}, author = {Lundy, SD and Vij, SC and Rezk, AH and Cohen, JA and Bajic, P and Ramasamy, R}, title = {The microbiome of the infertile male.}, journal = {Current opinion in urology}, volume = {30}, number = {3}, pages = {355-362}, doi = {10.1097/MOU.0000000000000742}, pmid = {32235279}, issn = {1473-6586}, mesh = {Humans ; Infertility, Male/*microbiology ; Male ; Metagenomics ; *Microbiota ; RNA, Ribosomal, 16S ; Semen/*microbiology ; Semen Analysis ; }, abstract = {PURPOSE OF REVIEW: Contrary to historic dogma, many tissues and organs in the human body contain a resident population of bacteria, fungi, and viruses collectively known as the microbiome. The microbiome plays a role in both homeostatic symbiosis and also pathogenic dysbiosis in a wide array of diseases. Our understanding of the relationship between the microbiome and male factor infertility is in its infancy but is slowly evolving.
RECENT FINDINGS: Recent literature indicates that semen (and likely the testis) is not sterile and contains a distinct microbiome, and these changes in its composition are associated with alterations in semen quality and fertility status. Preliminary investigation indicates that manipulating the human microbiome may have implications in improving semen parameters and fertility.
SUMMARY: In this review, we describe relationships between the microbiome and the genitourinary system, discuss the prior work on the relationship among bacteriospermia, leukocytospermia and male factor infertility, and summarize the current literature utilizing 16s rRNA-based next-generation sequencing on the seminal and testicular microbiome. We explore the specific microbial taxa implicated in various aspects of spermatic dysfunction and introduce preliminary evidence for therapeutic approaches to alter the microbiome and improve fertility status.}, }
@article {pmid32231681, year = {2020}, author = {Carter, KM and Lu, M and Jiang, H and An, L}, title = {An Information-Based Approach for Mediation Analysis on High-Dimensional Metagenomic Data.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {148}, pmid = {32231681}, issn = {1664-8021}, abstract = {The human microbiome plays a critical role in the development of gut-related illnesses such as inflammatory bowel disease and clinical pouchitis. A mediation model can be used to describe the interaction between host gene expression, the gut microbiome, and clinical/health situation (e.g., diseased or not, inflammation level) and may provide insights into underlying disease mechanisms. Current mediation regression methodology cannot adequately model high-dimensional exposures and mediators or mixed data types. Additionally, regression based mediation models require some assumptions for the model parameters, and the relationships are usually assumed to be linear and additive. With the microbiome being the mediators, these assumptions are violated. We propose two novel nonparametric procedures utilizing information theory to detect significant mediation effects with high-dimensional exposures and mediators and varying data types while avoiding standard regression assumptions. Compared with available methods through comprehensive simulation studies, the proposed method shows higher power and lower error. The innovative method is applied to clinical pouchitis data as well and interesting results are obtained.}, }
@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}, 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 {pmid32231240, year = {2020}, author = {Chaudhari, DS and Dhotre, DP and Agarwal, DM and Gaike, AH and Bhalerao, D and Jadhav, P and Mongad, D and Lubree, H and Sinkar, VP and Patil, UK and Salvi, S and Bavdekar, A and Juvekar, SK and Shouche, YS}, title = {Gut, oral and skin microbiome of Indian patrilineal families reveal perceptible association with age.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5685}, pmid = {32231240}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; *Age Factors ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Child ; Child, Preschool ; Family ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; India/epidemiology ; Male ; Metagenome/genetics ; Metagenomics/methods ; Microbiota/*genetics ; Middle Aged ; Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Skin/microbiology ; }, abstract = {The human microbiome plays a key role in maintaining host homeostasis and is influenced by age, geography, diet, and other factors. Traditionally, India has an established convention of extended family arrangements wherein three or more generations, bound by genetic relatedness, stay in the same household. In the present study, we have utilized this unique family arrangement to understand the association of age with the microbiome. We characterized stool, oral and skin microbiome of 54 healthy individuals from six joint families by 16S rRNA gene-based metagenomics. In total, 69 (1.03%), 293 (2.68%) and 190 (8.66%) differentially abundant OTUs were detected across three generations in the gut, skin and oral microbiome, respectively. Age-associated changes in the gut and oral microbiome of patrilineal families showed positive correlations in the abundance of phyla Proteobacteria and Fusobacteria, respectively. Genera Treponema and Fusobacterium showed a positive correlation with age while Granulicatella and Streptococcus showed a negative correlation with age in the oral microbiome. Members of genus Prevotella illustrated high abundance and prevalence as a core OTUs in the gut and oral microbiome. In conclusion, this study highlights that precise and perceptible association of age with microbiome can be drawn when other causal factors are kept constant.}, }
@article {pmid32230951, year = {2020}, author = {Hiippala, K and Kainulainen, V and Suutarinen, M and Heini, T and Bowers, JR and Jasso-Selles, D and Lemmer, D and Valentine, M and Barnes, R and Engelthaler, DM and Satokari, R}, title = {Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, pmid = {32230951}, issn = {2072-6643}, support = {304490//Academy of Finland/ ; 323156//Academy of Finland/ ; 285632//Academy of Finland/ ; Reetta Satokari//Sigrid Juséliuksen Säätiö/ ; }, abstract = {Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P.distasonis, B.caccae, B. intestinalis, B.uniformis, B. fragilis, B.vulgatus and B.ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.}, }
@article {pmid32229436, year = {2020}, author = {Zheng, JS and Wahlqvist, ML}, title = {Regulobiosis: A regulatory and food system-sensitive role for fungal symbionts in human evolution and ecobiology.}, journal = {Asia Pacific journal of clinical nutrition}, volume = {29}, number = {1}, pages = {9-15}, doi = {10.6133/apjcn.202003_29(1).0002}, pmid = {32229436}, issn = {1440-6047}, abstract = {The role of microbiomes in human biology and health are being extensively investigated, yet how the fungal community or mycobiome contributes to an integral microbiome is unclear and probably underestimated. We review the roles of fungi from the perspectives of their functionality in human biology, their cross-kingdom talk with other human microbial organisms, their dependence on diet and their involvement in human health and diseases. We hypothesize that members of the fungal community may interact as necessary symbionts with members of other human microbiome communities, and play a key role in human biology, yet to be fully understood. We propose further that "regulobiosis", whereby fungi play a regulatory role in human ecobiology, is operative in humans as probably obtains in other forms of life. Fungally-dependent regulobiosis would characterise, at first, microbiomes which include, but are not limited to, bacteria, archaea, and viruses; then, their human host; and, next, provide ecological connectedness.}, }
@article {pmid32221294, year = {2020}, author = {Gilijamse, PW and Hartstra, AV and Levin, E and Wortelboer, K and Serlie, MJ and Ackermans, MT and Herrema, H and Nederveen, AJ and Imangaliyev, S and Aalvink, S and Sommer, M and Levels, H and Stroes, ESG and Groen, AK and Kemper, M and de Vos, WM and Nieuwdorp, M and Prodan, A}, title = {Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose-response effects on glucose metabolism in human subjects with metabolic syndrome.}, journal = {NPJ biofilms and microbiomes}, volume = {6}, number = {1}, pages = {16}, pmid = {32221294}, issn = {2055-5008}, abstract = {Dysbiosis of the intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic strain Anaerobutyricum soehngenii on glucose metabolism in 24 subjects with metabolic syndrome. We found that treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehngenii (defined as improved insulin sensitivity 4 weeks after A. soehngenii intake) is dependent on microbiota composition at baseline. These data in humans are promising, but additional studies are needed to reproduce our findings and to investigate long-term effects, as well as other modes of delivery.}, }
@article {pmid32219339, year = {2020}, author = {Kyrgyzov, O and Prost, V and Gazut, S and Farcy, B and Brüls, T}, title = {Binning unassembled short reads based on k-mer abundance covariance using sparse coding.}, journal = {GigaScience}, volume = {9}, number = {4}, pages = {}, pmid = {32219339}, issn = {2047-217X}, abstract = {BACKGROUND: Sequence-binning techniques enable the recovery of an increasing number of genomes from complex microbial metagenomes and typically require prior metagenome assembly, incurring the computational cost and drawbacks of the latter, e.g., biases against low-abundance genomes and inability to conveniently assemble multi-terabyte datasets.
RESULTS: We present here a scalable pre-assembly binning scheme (i.e., operating on unassembled short reads) enabling latent genome recovery by leveraging sparse dictionary learning and elastic-net regularization, and its use to recover hundreds of metagenome-assembled genomes, including very low-abundance genomes, from a joint analysis of microbiomes from the LifeLines DEEP population cohort (n = 1,135, >1010 reads).
CONCLUSION: We showed that sparse coding techniques can be leveraged to carry out read-level binning at large scale and that, despite lower genome reconstruction yields compared to assembly-based approaches, bin-first strategies can complement the more widely used assembly-first protocols by targeting distinct genome segregation profiles. Read enrichment levels across 6 orders of magnitude in relative abundance were observed, indicating that the method has the power to recover genomes consistently segregating at low levels.}, }
@article {pmid32214138, year = {2020}, author = {Kummen, M and Solberg, OG and Storm-Larsen, C and Holm, K and Ragnarsson, A and Trøseid, M and Vestad, B and Skårdal, R and Yndestad, A and Ueland, T and Svardal, A and Berge, RK and Seljeflot, I and Gullestad, L and Karlsen, TH and Aaberge, L and Aukrust, P and Hov, JR}, title = {Rosuvastatin alters the genetic composition of the human gut microbiome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {5397}, pmid = {32214138}, issn = {2045-2322}, support = {2016067//Helse Sør-øst RHF/International ; 240787/F20//Norges Forskningsråd/International ; }, abstract = {The gut microbiome contributes to the variation of blood lipid levels, and secondary bile acids are associated with the effect of statins. Yet, our knowledge of how statins, one of our most common drug groups, affect the human microbiome is scarce. We aimed to characterize the effect of rosuvastatin on gut microbiome composition and inferred genetic content in stool samples from a randomized controlled trial (n = 66). No taxa were significantly altered by rosuvastatin during the study. However, rosuvastatin-treated participants showed a reduction in the collective genetic potential to transport and metabolize precursors of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO, p < 0.01), and an increase of related metabolites betaine and γ-butyrobetaine in plasma (p < 0.01). Exploratory analyses in the rosuvastatin group showed that participants with the least favorable treatment response (defined as < median change in high-density/low-density lipoprotein (HDL/LDL) ratio) showed a marked increase in TMAO-levels compared to those with a more favorable response (p < 0.05). Our data suggest that while rosuvastatin has a limited effect on gut microbiome composition, it could exert broader collective effects on the microbiome relevant to their function, providing a rationale for further studies of the influence of statins on the gut microbiome.}, }
@article {pmid32200333, year = {2020}, author = {Ben, Y and Hu, M and Zhang, X and Wu, S and Wong, MH and Wang, M and Andrews, CB and Zheng, C}, title = {Efficient detection and assessment of human exposure to trace antibiotic residues in drinking water.}, journal = {Water research}, volume = {175}, number = {}, pages = {115699}, doi = {10.1016/j.watres.2020.115699}, pmid = {32200333}, issn = {1879-2448}, mesh = {Anti-Bacterial Agents ; China ; Cities ; *Drinking Water ; Humans ; }, abstract = {Human exposure to antibiotic residues in drinking water has not been well evaluated. This study is the first attempt to simultaneously and efficiently identify and quantify 92 antibiotic residues in filtered tap water (multistage filtration at the tap) (n = 36) collected from 10 areas of a large city in southern China, 10 Chinese brands of bottled/barreled water (n = 30) and six foreign brands of bottled water (n = 18) obtained from the Chinese market. The average and median concentrations of all the detected antibiotic compounds was 182 and 92 ng/L in filtered tap water, 180 and 105 ng/L in Chinese brands of bottled/barreled water, and 666 and 146 ng/L in foreign brands of bottled water, respectively. A total of 58 antibiotics were detected in the filtered tap water, and 45 and 36 antibiotics were detected in the Chinese and foreign brands of bottled water, respectively. More types of antibiotics were detected in Chinese brands of bottled water than in the other bottled waters. In addition, Chinese waters had high roxithromycin concentrations, while the foreign brands of bottled water had high concentrations of dicloxacillin. The average and median values of the estimated overall daily intake of all the detected antibiotics were 4.3 and 2.3 ng/kg/day when only filtered tap water was drunk, 4.0 and 2.5 ng/kg/day when Chinese brands of bottled water was drunk, and 16.0 and 4.9 ng/kg/day when foreign brands of bottled water was drunk. Further study is needed to develop a more comprehensive estimation of human exposure to antibiotic residues in the environment and a more in-depth understanding of the potential hazard of ingested antibiotic residues to the human microbiome.}, }
@article {pmid32199025, year = {2020}, author = {Puhlmann, ML and de Vos, WM}, title = {Back to the Roots: Revisiting the Use of the Fiber-Rich Cichorium intybusL. Taproots.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {11}, number = {4}, pages = {878-889}, pmid = {32199025}, issn = {2156-5376}, abstract = {Fibers are increasingly recognized as an indispensable part of our diet and vital for maintaining health. Notably, complex mixtures of fibers have been found to improve metabolic health. Following an analysis of the fiber content of plant-based products, we found the taproot of the chicory plant (Cichorium intybusL.) to be 1 of the vegetables with the highest fiber content, comprising nearly 90% of its dry weight. Chicory roots consist of a mixture of inulin, pectin, and (hemi-)cellulose and also contain complex phytochemicals, such as sesquiterpene lactones that have been characterized in detail. Nowaday, chicory roots are mainly applied as a source for the extraction of inulin, which is used as prebiotic fiber and food ingredient. Chicory roots, however, have long been consumed as a vegetable by humans. The whole root has been used for thousands of years for nutritional, medicinal, and other purposes, and it is still used in traditional dishes in various parts of the world. Here, we summarize the composition of chicory roots to explain their historic success in the human diet. We revisit the intake of chicory roots by humans and describe the different types of use along with their various methods of preparation. Hereby, we focus on the whole root in its complex, natural form, as well as in relation to its constituents, and discuss aspects regarding legal regulation and the safety of chicory root extracts for human consumption. Finally, we provide an overview of the current and future applications of chicory roots and their contribution to a fiber-rich diet.}, }
@article {pmid32194617, year = {2020}, author = {Jensen, CS and Norsigian, CJ and Fang, X and Nielsen, XC and Christensen, JJ and Palsson, BO and Monk, JM}, title = {Reconstruction and Validation of a Genome-Scale Metabolic Model of Streptococcus oralis (iCJ415), a Human Commensal and Opportunistic Pathogen.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {116}, pmid = {32194617}, issn = {1664-8021}, abstract = {The mitis group of streptococci (MGS) is a member of the healthy human microbiome in the oral cavity and upper respiratory tract. Troublingly, some MGS are able to escape this niche and cause infective endocarditis, a severe and devastating disease. Genome-scale models have been shown to be valuable in investigating metabolism of bacteria. Here we present the first genome-scale model, iCJ415, for Streptococcus oralis SK141. We validated the model using gene essentiality and amino acid auxotrophy data from closely related species. iCJ415 has 71-76% accuracy in predicting gene essentiality and 85% accuracy in predicting amino acid auxotrophy. Further, the phenotype of S. oralis was tested using the Biolog Phenotype microarrays, giving iCJ415 a 82% accuracy in predicting carbon sources. iCJ415 can be used to explore the metabolic differences within the MGS, and to explore the complicated metabolic interactions between different species in the human oral cavity.}, }
@article {pmid32186326, year = {2020}, author = {Fragiadakis, GK and Wastyk, HC and Robinson, JL and Sonnenburg, ED and Sonnenburg, JL and Gardner, CD}, title = {Long-term dietary intervention reveals resilience of the gut microbiota despite changes in diet and weight.}, journal = {The American journal of clinical nutrition}, volume = {111}, number = {6}, pages = {1127-1136}, pmid = {32186326}, issn = {1938-3207}, mesh = {Adult ; Bacteria/classification/genetics/isolation & purification ; Diet, Carbohydrate-Restricted ; Diet, Fat-Restricted ; Diet, Reducing ; Feces ; Female ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Obesity/*diet therapy/metabolism/microbiology/physiopathology ; Weight Loss ; Young Adult ; }, abstract = {BACKGROUND: With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood.
OBJECTIVES: Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota.
METHODS: We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet.
RESULTS: While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study.
CONCLUSIONS: These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.}, }
@article {pmid32180472, year = {2020}, author = {Zou, Y and Wu, L and Xu, W and Zhou, X and Ye, K and Xiong, H and Song, C and Xie, Y}, title = {Correlation between antibiotic use in childhood and subsequent inflammatory bowel disease: a systematic review and meta-analysis.}, journal = {Scandinavian journal of gastroenterology}, volume = {55}, number = {3}, pages = {301-311}, doi = {10.1080/00365521.2020.1737882}, pmid = {32180472}, issn = {1502-7708}, abstract = {Background: Antibiotic use leads to a cascade of inflammatory reaction in the gastrointestinal tract due to its association with a temporary disruption of human microbiome.Objectives: To explore the undetermined correlation between antibiotic use in childhood and subsequent inflammatory bowel disease (IBD).Methods: PUBMED, EMBASE and Cochrane Central Register of Controlled Trials were searched to identify related articles. We extracted and pooled the (adjusted) odds ratio (OR) and (adjusted) risk ratio (RR).Results: This systematic review and meta-analysis included 11 studies. The pooled OR of all 11 studies was 1.5 (95% confidence interval (CI): 1.22-1.85). The pooled ORs of the subsequent Crohn's disease and ulcerative colitis after antibiotic use in childhood were 1.59 (95% CI: 1.06-2.4) and 1.22 (95% CI: 0.82-1.8). The sensitivity analysis showed no change. The meta-regression showed there was not statistical significance for the publication year, research area and research methods. Egger's test showed publication bias in the IBD studies (p = .006 < .05) but no publication bias for the CD (p = .275>.05) and UC studies (p = .537>.05).Conclusions: There was a positive association between antibiotic use in childhood and the subsequently risk of Crohn's disease in non-European countries in the west during 2010-2013. Children in the United States taking antibiotics will have a higher risk of subsequently IBD than Europe, Asia and Australia. Registration number: CRD42019147648 (PROSPERO).}, }
@article {pmid32179736, year = {2019}, author = {El-Awady, A and de Sousa Rabelo, M and Meghil, MM and Rajendran, M and Elashiry, M and Stadler, AF and Foz, AM and Susin, C and Romito, GA and Arce, RM and Cutler, CW}, title = {Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members.}, journal = {NPJ biofilms and microbiomes}, volume = {5}, number = {1}, pages = {11}, pmid = {32179736}, issn = {2055-5008}, support = {R01 DE014328/DE/NIDCR NIH HHS/United States ; }, mesh = {Biofilms/*growth & development ; Coinfection/*microbiology ; Dendritic Cells/*microbiology ; Fimbriae, Bacterial/genetics ; Fusobacterium nucleatum/genetics/physiology ; Gingiva/*microbiology ; Humans ; Inflammation ; *Microbial Consortia ; Microbiota ; Periodontitis/*microbiology ; Porphyromonas gingivalis/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Streptococcus gordonii/genetics/physiology ; }, abstract = {Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses.}, }
@article {pmid32179576, year = {2020}, author = {Tuompo, R and Lääveri, T and Hannu, T and Pakkanen, SH and Kirveskari, J and Leirisalo-Repo, M and Kantele, A}, title = {Reactive arthritis and other musculoskeletal symptoms associated with acquisition of diarrhoeagenic Escherichia coli (DEC).}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {5}, pages = {605-611}, pmid = {32179576}, issn = {1468-2060}, mesh = {Academic Medical Centers ; Anti-Bacterial Agents/*therapeutic use ; Arthritis, Reactive/*epidemiology/etiology/physiopathology ; Cohort Studies ; Diarrhea/*complications/diagnosis/microbiology ; Escherichia coli/pathogenicity ; Escherichia coli Infections/*complications/diagnosis ; Female ; Finland ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Multiplex Polymerase Chain Reaction/methods ; Multivariate Analysis ; Musculoskeletal Diseases/*epidemiology/etiology/physiopathology ; Prognosis ; Prospective Studies ; Risk Assessment ; Severity of Illness Index ; *Travel-Related Illness ; }, abstract = {OBJECTIVES: Using a prospective research design, we evaluated the association between acquisition of diarrhoeagenic Escherichia coli (DEC) and development of reactive arthritis (ReA) and other reactive musculoskeletal (MSK) symptoms among international travellers.
METHODS: A total of 526 study participants were asked to provide pretravel and post-travel stool samples and fill in questionnaires (pretravel, post-travel and 3-week follow-up). A multiplex quantitative PCR assay was deployed to detect five DEC comprising enteroaggregative E. coli, enteropathogenic E. coli, enterotoxigenic E. coli, enterohaemorrhagic E. coli and enteroinvasive E. coli and Salmonella, Shigella, Campylobacter, Yersinia, and Vibrio cholerae. Multivariate analysis was employed to identify factors predisposing to MSK symptoms. New post-travel MSK symptoms reported by participants with DEC were assessed by phone interviews and, if needed, clinically confirmed.
RESULTS: From among the total of 224 volunteers who returned all questionnaires and stool specimens, 38 (17.0%) reported MSK symptoms. Multivariate analysis revealed that acquisition of DEC was associated with MSK symptoms (OR 3.9; 95% CI 1.2 to 13.3). Of the 151 with only-DEC, four (2.6%) had ReA, two (1.3%) reactive tendinitis and three (2.0%) reactive arthralgia. ReA was mostly mild, and all patients with ReA were negative for human leucocyte antigen B27. Antibiotic treatment of travellers' diarrhoea did not prevent development of MSK symptoms.
CONCLUSION: A total of 17% of volunteers reported post-travel MSK symptoms. DEC acquisition was associated with an increased risk of developing them, yet the ReA incidence remained low and the clinical picture mild. Antibiotic treatment did not protect against development of MSK symptoms.}, }
@article {pmid32174900, year = {2020}, author = {Sarra, A and Celluzzi, A and Bruno, SP and Ricci, C and Sennato, S and Ortore, MG and Casciardi, S and Del Chierico, F and Postorino, P and Bordi, F and Masotti, A}, title = {Biophysical Characterization of Membrane Phase Transition Profiles for the Discrimination of Outer Membrane Vesicles (OMVs) From Escherichia coli Grown at Different Temperatures.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {290}, pmid = {32174900}, issn = {1664-302X}, abstract = {Dynamic Light Scattering (DLS), Small Angle X-ray Scattering (SAXS) and Transmission Electron Microscopy (TEM) are physical techniques widely employed to characterize the morphology and the structure of vesicles such as liposomes or human extracellular vesicles (exosomes). Bacterial extracellular vesicles are similar in size to human exosomes, although their function and membrane properties have not been elucidated in such detail as in the case of exosomes. Here, we applied the above cited techniques, in synergy with the thermotropic characterization of the vesicles lipid membrane using a turbidimetric technique to the study of vesicles produced by Gram-negative bacteria (Outer Membrane Vesicles, OMVs) grown at different temperatures. This study demonstrated that our combined approach is useful to discriminate vesicles of different origin or coming from bacteria cultured under different experimental conditions. We envisage that in a near future the techniques employed in our work will be further implemented to discriminate complex mixtures of bacterial vesicles, thus showing great promises for biomedical or diagnostic applications.}, }
@article {pmid32170007, year = {2020}, author = {Bhatt, AP and Pellock, SJ and Biernat, KA and Walton, WG and Wallace, BD and Creekmore, BC and Letertre, MM and Swann, JR and Wilson, ID and Roques, JR and Darr, DB and Bailey, ST and Montgomery, SA and Roach, JM and Azcarate-Peril, MA and Sartor, RB and Gharaibeh, RZ and Bultman, SJ and Redinbo, MR}, title = {Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {13}, pages = {7374-7381}, pmid = {32170007}, issn = {1091-6490}, support = {P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 CA207416/CA/NCI NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; R01 CA098468/CA/NCI NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Bacteria/drug effects ; Disease Models, Animal ; Dysbiosis/drug therapy ; Enzyme Inhibitors/pharmacology ; Female ; Gastrointestinal Microbiome/*drug effects ; Glucuronidase/*antagonists & inhibitors/*drug effects/metabolism ; Humans ; Irinotecan/pharmacology ; Mice ; Mice, Nude ; Neoplasms/drug therapy ; }, abstract = {Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial β-glucuronidase (GUS) enzymes. Targeted bacterial GUS inhibitors have been shown to partially alleviate irinotecan-induced GI tract damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for GI protection by gut microbial GUS inhibitors using in vivo models. We use in vitro, in fimo, and in vivo models to determine whether GUS inhibition alters the anticancer efficacy of irinotecan. We demonstrate that a single dose of irinotecan increases GI bacterial GUS activity in 1 d and reduces intestinal epithelial cell proliferation in 5 d, both blocked by a single dose of a GUS inhibitor. In a tumor xenograft model, GUS inhibition prevents intestinal toxicity and maintains the antitumor efficacy of irinotecan. Remarkably, GUS inhibitor also effectively blocks the striking irinotecan-induced bloom of Enterobacteriaceae in immune-deficient mice. In a genetically engineered mouse model of cancer, GUS inhibition alleviates gut damage, improves survival, and does not alter gut microbial composition; however, by allowing dose intensification, it dramatically improves irinotecan's effectiveness, reducing tumors to a fraction of that achieved by irinotecan alone, while simultaneously promoting epithelial regeneration. These results indicate that targeted gut microbial enzyme inhibitors can improve cancer chemotherapeutic outcomes by protecting the gut epithelium from microbial dysbiosis and proliferative crypt damage.}, }
@article {pmid32169076, year = {2020}, author = {Murugesan, S and Al Ahmad, SF and Singh, P and Saadaoui, M and Kumar, M and Al Khodor, S}, title = {Profiling the Salivary microbiome of the Qatari population.}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {127}, pmid = {32169076}, issn = {1479-5876}, abstract = {BACKGROUND: The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions.
MATERIALS AND METHODS: We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1-V3 region of the 16S rRNA gene.
RESULTS: In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers.
CONCLUSION: This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.}, }
@article {pmid32167855, year = {2020}, author = {Belmok, A and de Cena, JA and Kyaw, CM and Damé-Teixeira, N}, title = {The Oral Archaeome: A Scoping Review.}, journal = {Journal of dental research}, volume = {99}, number = {6}, pages = {630-643}, doi = {10.1177/0022034520910435}, pmid = {32167855}, issn = {1544-0591}, abstract = {The Archaea domain was recognized as a separate phylogenetic lineage in the tree of life nearly 3 decades ago. It is now known as part of the human microbiome; however, given that its roles in oral sites are still poorly understood, this review aimed to establish the current level of evidence regarding archaea in the oral cavity to guide future research, providing insights on the present knowledge about the human oral archaeome. A scoping review was conducted with the PRISMA Extension for Scoping Reviews checklist. Five electronic databases were searched, as well as gray literature. Two independent reviewers performed the selection and characterization of the studies. Clinical studies were included when the target population consisted of humans of any age who were donors of samples from the oral cavity. A qualitative analysis was performed, based on the type of oral site and by considering the methods employed for archaeal identification and taxonomy, including the DNA extraction protocols, primers, and probes used. Fifty articles were included in the final scoping review, published from 1987 to 2019. Most studies sampled periodontal sites. Methanogens were the most abundant archaea in those sites, and their presence could be associated with other periodontal pathogens. No consistent relationship with different disease conditions was observed in studies that evaluated the microbiota surviving in endodontic sites. Few articles analyzed the presence of archaea in dental caries, saliva, or tongue microbiota, as well as in archaeologic samples, also showing a relationship with healthy microbiota. Archaea have been detected in different oral niches of individuals from diverse geographic locations and clinical conditions, suggesting potential roles in oral diseases. Methodological limitations may hamper our current knowledge about archaeal diversity and prevalence in oral samples, and future research with diversified methodological approaches may lead to a better comprehension of the human oral archaeome.}, }
@article {pmid32167023, year = {2020}, author = {Depommier, C and Van Hul, M and Everard, A and Delzenne, NM and De Vos, WM and Cani, PD}, title = {Pasteurized Akkermansia muciniphila increases whole-body energy expenditure and fecal energy excretion in diet-induced obese mice.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1231-1245}, pmid = {32167023}, issn = {1949-0984}, abstract = {Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.}, }
@article {pmid32166902, year = {2020}, author = {Antosca, K and Hoen, AG and Palys, T and Hilliard, M and Morrison, HG and Coker, M and Madan, J and Karagas, MR}, title = {Reliability of stool microbiome methods for DNA yields and sequencing among infants and young children.}, journal = {MicrobiologyOpen}, volume = {9}, number = {5}, pages = {e1018}, pmid = {32166902}, issn = {2045-8827}, support = {UH3 OD023275/OD/NIH HHS/United States ; R01 LM012723/LM/NLM NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; T32 HL134598/HL/NHLBI NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, abstract = {With the emergence of large-scale epidemiologic human microbiome studies, there is a need to understand the reproducibility of microbial DNA sequencing and the impact of specimen collection and processing methods on measures of microbial community composition and structure, with reproducibility studies in infants and young children particularly lacking. Here, we examined batch-to-batch variability and reliability of collection, handling, and processing protocols, testing replicate stool samples from infants and young children using Illumina MiSeq sequencing of the bacterial 16S rRNA gene V4-V5 hypervariable region, evaluating 33 conditions with different protocols and extraction methods. We detected no evidence of batch effects in replicate DNA samples or extractions from the same stool sample. Variability in DNA yield and alpha diversity was observed between the different collection, handling, and processing protocols. However, across all protocols, subject variability was the dominant contributor to microbiome structure, with comparatively little impact of the protocol used. While collection method and DNA extraction kit may affect DNA yield, and correspondingly alpha diversity, our findings suggest that characterization of the structure and composition of the fecal microbiome of infants and young children are reliably measurable by standardized collection, handling, and processing protocols and DNA extraction methods within an individual longitudinal study.}, }
@article {pmid32158700, year = {2020}, author = {Romani, L and Del Chierico, F and Chiriaco, M and Foligno, S and Reddel, S and Salvatori, G and Cifaldi, C and Faraci, S and Finocchi, A and Rossi, P and Bagolan, P and D'Argenio, P and Putignani, L and Fusaro, F}, title = {Gut Mucosal and Fecal Microbiota Profiling Combined to Intestinal Immune System in Neonates Affected by Intestinal Ischemic Injuries.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {59}, pmid = {32158700}, issn = {2235-2988}, abstract = {Background and Purpose: Early life microbiota plays a crucial role in human health by acting as a barrier from pathogens' invasion and maintaining the intestinal immune homoeostasis. Altered fecal microbiota (FM) ecology was reported in newborns affected by intestinal ischemia. Our purpose was to describe, in these patients, the FM, the mucosal microbiota (MM) and the mucosal immunity. Methods: Fourteen newborns underwent intestinal resection because of intestinal ischemia. FM and MM were determined through targeted-metagenomics, diversity assignment and Kruskal-Wallis analyses of Operational taxonomic units (OTUs). The mucosal immune cells were analyzed through cytofluorimetry. Results and Conclusion: Based on the severity intestinal injueris we identified two groups: extensive (EII) and focal intestinal ischemia (FII). FM and MM varied in EII and FII groups, showing in the EII group the predominance of Proteobacteria and Enterobacteriaceae and the reduction of Bacteroidetes and Verrucomicrobia for both microbiota. The MM was characterized by a statistically significant reduction of Bacteroides, Lachnospiraceae and Ruminococcaceae and by a higher diversity in the EII compared to FII group. FM showed a prevalence of Proteobacteria, while the Shannon index was lower in the EII compared to FII group. An overall increment in B- and T-lymphocytes and Natural killer (NK) T-like cells was found for EII mucosal samples associated to an increment of TNF-α and INF-γ expressing cells, compared to FII group. FM and MM carry specific signatures of intestinal ischemic lesions. Further research may be crucial to address the role of specific taxa in EII, expecially with reference to inflammation grade and ischemia extension.}, }
@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 {pmid32153643, year = {2020}, author = {Ma, Y and Liu, G and Ma, Y and Chen, Q}, title = {Integrative Analysis for Identifying Co-Modules of Microbe-Disease Data by Matrix Tri-Factorization With Phylogenetic Information.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {83}, pmid = {32153643}, issn = {1664-8021}, abstract = {Microbe-disease association relationship mining is drawing more and more attention due to its potential in capturing disease-related microbes. Hence, it is essential to develop new tools or algorithms to study the complex pathogenic mechanism of microbe-related diseases. However, previous research studies mainly focused on the paradigm of "one disease, one microbe," rarely investigated the cooperation and associations between microbes, diseases or microbe-disease co-modules from system level. In this study, we propose a novel two-level module identifying algorithm (MDNMF) based on nonnegative matrix tri-factorization which integrates two similarity matrices (disease and microbe similarity matrices) and one microbe-disease association matrix into the objective of MDNMF. MDNMF can identify the modules from different levels and reveal the connections between these modules. In order to improve the efficiency and effectiveness of MDNMF, we also introduce human symptoms-disease network and microbial phylogenetic distance into this model. Furthermore, we applied it to HMDAD dataset and compared it with two NMF-based methods to demonstrate its effectiveness. The experimental results show that MDNMF can obtain better performance in terms of enrichment index (EI) and the number of significantly enriched taxon sets. This demonstrates the potential of MDNMF in capturing microbial modules that have significantly biological function implications.}, }
@article {pmid32133297, year = {2020}, author = {Cheng, H and Wang, Z and Cui, L and Wen, Y and Chen, X and Gong, F and Yi, H}, title = {Opportunities and Challenges of the Human Microbiome in Ovarian Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {163}, pmid = {32133297}, issn = {2234-943X}, abstract = {Ovarian cancer is the most lethal malignancy among gynecological cancers worldwide. Most ovarian cancer patients are diagnosed at an advanced stage because of non-specific clinical symptoms. The human microbiome plays a crucial role in maintaining the normal physiological and pathological state of the body. With the development of technologies such as DNA and 16S rRNA sequencing, an increasing number of findings on the role of microbiome in cancers are being reported. Microbiome abnormalities are increasingly associated with diseases, including cancer development, and response to therapies. Some studies have shown the relationship between microbiome changes and ovarian cancer. However, the mechanisms underlying this relationship are not yet fully understood. Here, we summarize the key findings in this regard by focusing on estrogen metabolism and host recognition receptors in microorganisms and changes in the gut or pelvic microbiome in patients with ovarian cancer. We further discuss the potential of using the microbiome as a novel biomarker for cancers. We also highlight the possibility to use microorganisms as a treatment modality to enhance the immune system, activate anti-tumor response, mediate chemotherapy resistance, and ameliorate the adverse effects of the treatment.}, }
@article {pmid32132244, year = {2020}, author = {Bellone, M and Brevi, A and Huber, S}, title = {Microbiota-Propelled T Helper 17 Cells in Inflammatory Diseases and Cancer.}, journal = {Microbiology and molecular biology reviews : MMBR}, volume = {84}, number = {2}, pages = {}, pmid = {32132244}, issn = {1098-5557}, abstract = {Technologies allowing genetic sequencing of the human microbiome are opening new realms to discovery. The host microbiota substantially impacts immune responses both in immune-mediated inflammatory diseases (IMIDs) and in tumors affecting tissues beyond skin and mucosae. However, a mechanistic link between host microbiota and cancer or IMIDs has not been well established. Here, we propose T helper 17 (TH17) lymphocytes as the connecting factor between host microbiota and rheumatoid or psoriatic arthritides, multiple sclerosis, breast or ovarian cancer, and multiple myeloma. We theorize that similar mechanisms favor the expansion of gut-borne TH17 cells and their deployment at the site of inflammation in extraborder IMIDs and tumors, where TH17 cells are driving forces. Thus, from a pathogenic standpoint, tumors may share mechanistic routes with IMIDs. A review of similarities and divergences in microbiota-TH17 cell interactions in IMIDs and cancer sheds light on previously ignored pathways in either one of the two groups of pathologies and identifies novel therapeutic avenues.}, }
@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}, 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 {pmid32121205, year = {2020}, author = {Sare, AR and Stouvenakers, G and Eck, M and Lampens, A and Goormachtig, S and Jijakli, MH and Massart, S}, title = {Standardization of Plant Microbiome Studies: Which Proportion of the Microbiota is Really Harvested?.}, journal = {Microorganisms}, volume = {8}, number = {3}, pages = {}, pmid = {32121205}, issn = {2076-2607}, support = {FIRA 5200818F//Fonds De La Recherche Scientifique - FNRS/ ; }, abstract = {Studies in plant-microbiome currently use diverse protocols, making their comparison difficult and biased. Research in human microbiome have faced similar challenges, but the scientific community proposed various recommendations which could also be applied to phytobiome studies. Here, we addressed the isolation of plant microbiota through apple carposphere and lettuce root microbiome. We demonstrated that the fraction of the culturable epiphytic microbiota harvested by a single wash might only represent one-third of the residing microbiota harvested after four successive washes. In addition, we observed important variability between the efficiency of washing protocols (up to 1.6-fold difference for apple and 1.9 for lettuce). QIIME2 analysis of 16S rRNA gene, showed a significant difference of the alpha and beta diversity between protocols in both cases. The abundance of 76 taxa was significantly different between protocols used for apple. In both cases, differences between protocols disappeared when sequences of the four washes were pooled. Hence, pooling the four successive washes increased the alpha diversity for apple in comparison to a single wash. These results underline the interest of repeated washing to leverage abundance of microbial cells harvested from plant epiphytic microbiota whatever the washing protocols, thus minimizing bias.}, }
@article {pmid32117102, year = {2020}, author = {Tsigalou, C and Konstantinidis, T and Stavropoulou, E and Bezirtzoglou, EE and Tsakris, A}, title = {Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {50}, pmid = {32117102}, issn = {1664-302X}, abstract = {Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the "gut resistome." ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.}, }
@article {pmid32112046, year = {2020}, author = {Domingue, JC and Drewes, JL and Merlo, CA and Housseau, F and Sears, CL}, title = {Host responses to mucosal biofilms in the lung and gut.}, journal = {Mucosal immunology}, volume = {13}, number = {3}, pages = {413-422}, pmid = {32112046}, issn = {1935-3456}, support = {/CRUK_/Cancer Research UK/United Kingdom ; U2C CA233291/CA/NCI NIH HHS/United States ; K99 CA230192/CA/NCI NIH HHS/United States ; R01 CA203891/CA/NCI NIH HHS/United States ; R01 CA196845/CA/NCI NIH HHS/United States ; }, abstract = {The impact of the human microbiome on health and disease is of utmost importance and has been studied intensively in recent years. Microbes promote immune system development and are essential to the production and absorption of nutrients for the host but are also implicated in disease pathogenesis. Particularly, bacterial biofilms have long been recognized as contributors to chronic infections and diseases in humans. However, our understanding of how the host responds to the presence of biofilms, specifically the immune response to biofilms, and how this contributes to disease pathogenesis is limited. This review aims to highlight what is known about biofilm formation and in vivo models available for the biofilm study. We critique the contribution of biofilms to human diseases, focusing on the lung diseases, cystic fibrosis and chronic obstructive pulmonary disease, and the gut diseases, inflammatory bowel disease and colorectal cancer.}, }
@article {pmid32109571, year = {2020}, author = {Tarsillo, B and Priefer, R}, title = {Proteobiotics as a new antimicrobial therapy.}, journal = {Microbial pathogenesis}, volume = {142}, number = {}, pages = {104093}, doi = {10.1016/j.micpath.2020.104093}, pmid = {32109571}, issn = {1096-1208}, abstract = {Antibiotic resistance is a major concern for healthcare. The emergence of resistant bacteria has contributed to an increase in cost, morbidity, and mortality rates of patients. There is evidence to suggest that the inhibition of bacteria's virulence strategies would downregulate their pathogenesis and stop infections while also preventing more resistance. This concept became the backbone of many studies in the arena of human microbiome. Through probiotic studies, novel compounds were discovered that possessed antimicrobial activity. These have become labeled as proteobiotics, i.e. metabolites from probiotics. Proteobiotics have demonstrated the ability to interrupt bacteria cell-to-cell communication. Currently, there is one approved product containing proteobiotic technologies for swine showing positive outcomes.}, }
@article {pmid32109360, year = {2020}, author = {de Jesus, VC and Shikder, R and Oryniak, D and Mann, K and Alamri, A and Mittermuller, B and Duan, K and Hu, P and Schroth, RJ and Chelikani, P}, title = {Sex-Based Diverse Plaque Microbiota in Children with Severe Caries.}, journal = {Journal of dental research}, volume = {99}, number = {6}, pages = {703-712}, doi = {10.1177/0022034520908595}, pmid = {32109360}, issn = {1544-0591}, support = {//CIHR/Canada ; }, abstract = {Severe early childhood caries (S-ECC) is a multifactorial disease that can lead to suffering and reduced oral health-related quality of life in young children. The bacterial and fungal composition of dental plaque and how children's sex is associated with S-ECC are largely unknown. In this study, V4-16S rRNA and ITS1 rRNA gene amplicon sequencing was used to compare the plaque bacteriome and mycobiome of children <72 mo of age: 40 with S-ECC (15 males, 25 females) and 40 caries-free (19 males, 21 females). Health- and nutrition-related questionnaire data were also investigated. This study aimed to analyze potential sex-based differences in the supragingival plaque microbiota of young children with S-ECC and those caries-free. Behavioral and nutritional habit differences were observed between children with S-ECC and those caries-free and between male and female children. Overall, higher levels of Veillonella dispar, Streptococcus mutans, and other bacterial species were found in the S-ECC group as compared with caries-free controls (P < 0.05). A significant difference in the abundance of Neisseria was observed between males and females with S-ECC (P < .05). Fungal taxonomic analysis showed significantly higher levels of Candida dubliniensis in the plaque of children with S-ECC as compared with those caries-free (P < 0.05), but no differences were observed with Candida albicans (P > 0.05). Significant differences in the relative abundance of Mycosphaerella, Cyberlindnera, and Trichosporon fungal species were also observed between the caries-free and S-ECC groups (P < 0.05). Machine learning analysis revealed the most important bacterial and fungal species for classifying S-ECC versus caries-free. Different patterns of crosstalk between microbial species were observed between male and female children. Our work demonstrates that plaque microbiota and sex may be important determinants for S-ECC and could be factors to consider for inclusion in caries risk assessment tools.}, }
@article {pmid32108360, year = {2020}, author = {Ruokolainen, L and Parkkola, A and Karkman, A and Sinkko, H and Peet, A and Hämäläinen, AM and von Hertzen, L and Tillmann, V and Koski, K and Virtanen, SM and Niemelä, O and Haahtela, T and Knip, M}, title = {Contrasting microbiotas between Finnish and Estonian infants: Exposure to Acinetobacter may contribute to the allergy gap.}, journal = {Allergy}, volume = {75}, number = {9}, pages = {2342-2351}, doi = {10.1111/all.14250}, pmid = {32108360}, issn = {1398-9995}, abstract = {BACKGROUND: Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures.
METHODS: We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children.
RESULTS: Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genus Acinetobacter was more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile of Acinetobacter lwoffii was more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genus Acinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization.
CONCLUSIONS: In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genus Acinetobacter in the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.}, }
@article {pmid32103766, year = {2020}, author = {Shen, L}, title = {Gut, oral and nasal microbiota and Parkinson's disease.}, journal = {Microbial cell factories}, volume = {19}, number = {1}, pages = {50}, pmid = {32103766}, issn = {1475-2859}, mesh = {Humans ; Intestines/*microbiology ; *Microbiota ; Mouth/*microbiology ; Nose/*microbiology ; Parkinson Disease/*microbiology ; }, abstract = {Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, and in an effort to identify novel therapeutic target for this disease in recent years, human microbiota has attracted much interest. This paper briefly summarizes the main findings concerning the differences of human microbiome across several important mucosal interfaces, including nose, mouth, and gut between PD patients and controls as obtained from a total of 13 studies published since 2015, which covered a total of 943 PD patients and 831 matched controls from 6 countries. Overall, these studies supported the differences of gut microbiota between PD patients and matched controls, while significantly altered bacterial taxa among studies were not identical. Due to relatively limited number of available studies and covered patients, the associations between oral and nasal microbiota and PD remain inconclusive. The therapeutic and diagnostic potentials of gut microbiota for PD are discussed. More well-designed clinical studies recruiting large-scale PD patients are encouraged in future.}, }
@article {pmid32103319, year = {2020}, author = {Ulaszewska, MM and Koutsos, A and Trošt, K and Stanstrup, J and Garcia-Aloy, M and Scholz, M and Fava, F and Natella, F and Scaccini, C and Vrhovsek, U and Tuohy, K and Lovegrove, J and Mattivi, F}, title = {Two apples a day modulate human:microbiome co-metabolic processing of polyphenols, tyrosine and tryptophan.}, journal = {European journal of nutrition}, volume = {59}, number = {8}, pages = {3691-3714}, doi = {10.1007/s00394-020-02201-8}, pmid = {32103319}, issn = {1436-6215}, support = {FOODBALL//Joint Programming Initiative A healthy diet for a healthy life/ ; CABALA_DIET&HEALTH//Joint Programming Initiative A healthy diet for a healthy life/ ; }, abstract = {PURPOSE: Validated biomarkers of food intake (BFIs) have recently been suggested as a useful tool to assess adherence to dietary guidelines or compliance in human dietary interventions. Although many new candidate biomarkers have emerged in the last decades for different foods from metabolic profiling studies, the number of comprehensively validated biomarkers of food intake is limited. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fibers, an important mediator for their health-protective properties.
METHODS: Using an untargeted metabolomics approach, we aimed to identify biomarkers of long-term apple intake and explore how apples impact on the human plasma and urine metabolite profiles. Forty mildly hypercholesterolemic volunteers consumed two whole apples or a sugar and energy-matched control beverage, daily for 8 weeks in a randomized, controlled, crossover intervention study. The metabolome in plasma and urine samples was analyzed via untargeted metabolomics.
RESULTS: We found 61 urine and 9 plasma metabolites being statistically significant after the whole apple intake compared to the control beverage, including several polyphenol metabolites that could be used as BFIs. Furthermore, we identified several endogenous indole and phenylacetyl-glutamine microbial metabolites significantly increasing in urine after apple consumption. The multiomic dataset allowed exploration of the correlations between metabolites modulated significantly by the dietary intervention and fecal microbiota species at genus level, showing interesting interactions between Granulicatella genus and phenyl-acetic acid metabolites. Phloretin glucuronide and phloretin glucuronide sulfate appeared promising biomarkers of apple intake; however, robustness, reliability and stability data are needed for full BFI validation.
CONCLUSION: The identified apple BFIs can be used in future studies to assess compliance and to explore their health effects after apple intake. Moreover, the identification of polyphenol microbial metabolites suggests that apple consumption mediates significant gut microbial metabolic activity which should be further explored.}, }
@article {pmid32103176, year = {2020}, author = {Quinn, RA and Melnik, AV and Vrbanac, A and Fu, T and Patras, KA and Christy, MP and Bodai, Z and Belda-Ferre, P and Tripathi, A and Chung, LK and Downes, M and Welch, RD and Quinn, M and Humphrey, G and Panitchpakdi, M and Weldon, KC and Aksenov, A and da Silva, R and Avila-Pacheco, J and Clish, C and Bae, S and Mallick, H and Franzosa, EA and Lloyd-Price, J and Bussell, R and Thron, T and Nelson, AT and Wang, M and Leszczynski, E and Vargas, F and Gauglitz, JM and Meehan, MJ and Gentry, E and Arthur, TD and Komor, AC and Poulsen, O and Boland, BS and Chang, JT and Sandborn, WJ and Lim, M and Garg, N and Lumeng, JC and Xavier, RJ and Kazmierczak, BI and Jain, R and Egan, M and Rhee, KE and Ferguson, D and Raffatellu, M and Vlamakis, H and Haddad, GG and Siegel, D and Huttenhower, C and Mazmanian, SK and Evans, RM and Nizet, V and Knight, R and Dorrestein, PC}, title = {Global chemical effects of the microbiome include new bile-acid conjugations.}, journal = {Nature}, volume = {579}, number = {7797}, pages = {123-129}, pmid = {32103176}, issn = {1476-4687}, support = {P01 HL088093/HL/NHLBI NIH HHS/United States ; GMS10RR029121/NH/NIH HHS/United States ; R01 HL105278/HL/NHLBI NIH HHS/United States ; R24DK110499/NH/NIH HHS/United States ; 1 DP1 AT010885/NH/NIH HHS/United States ; DP1 AT010885/AT/NCCIH NIH HHS/United States ; 1R03CA211211-01/NH/NIH HHS/United States ; 1R01HL116235/NH/NIH HHS/United States ; KL2 TR001444/TR/NCATS NIH HHS/United States ; R37 DK057978/DK/NIDDK NIH HHS/United States ; R03 CA211211/CA/NCI NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 HD084163/HD/NICHD NIH HHS/United States ; S10 RR029121/RR/NCRR NIH HHS/United States ; CA014195/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 AI124316/AI/NIAID NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; R01 HL116235/HL/NHLBI NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; U54DE023798/NH/NIH HHS/United States ; 5U01AI124316-03/NH/NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/*biosynthesis/*chemistry/metabolism ; Cholic Acid/biosynthesis/chemistry/metabolism ; Cystic Fibrosis/genetics/metabolism/microbiology ; Germ-Free Life ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism/microbiology ; *Metabolomics ; Mice ; Microbiota/*physiology ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; }, abstract = {A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease1-9. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units10), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches11-13 to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry14. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis.}, }
@article {pmid32102941, year = {2020}, author = {Wu, L and Zeng, T and Deligios, M and Milanesi, L and Langille, MGI and Zinellu, A and Rubino, S and Carru, C and Kelvin, DJ}, title = {Age-Related Variation of Bacterial and Fungal Communities in Different Body Habitats across the Young, Elderly, and Centenarians in Sardinia.}, journal = {mSphere}, volume = {5}, number = {1}, pages = {}, pmid = {32102941}, issn = {2379-5042}, mesh = {Adult ; *Age Factors ; Aged ; Aged, 80 and over ; *Aging ; Bacteria/*classification ; DNA, Intergenic/genetics ; Ecosystem ; Feces/microbiology ; Female ; Fungi/classification/*genetics ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Italy ; Male ; *Microbiota ; Mouth/microbiology ; *Mycobiome ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/microbiology ; Young Adult ; }, abstract = {Human body microbes interact with the host, forming microbial communities that are in continual flux during the aging process. Previous studies have mostly focused on surveying a single body habitat to determine the age-related variation in the bacterial and fungal communities. A more comprehensive understanding of the variation in the human microbiota and mycobiota across multiple body habitats related to aging is still unclear. To obtain an integrated view of the spatial distribution of microbes in a specific Mediterranean population across a wide age range, we surveyed the bacterial and fungal communities in the skin, oral cavity, and gut in the young, elderly, and centenarians in Sardinia using 16S rRNA gene and internal transcribed spacer 1 (ITS1) sequencing. We found that the distribution and correlation of bacterial and fungal communities in Sardinians were largely determined by body site. In each age group, the bacterial and fungal communities found in the skin were significantly different in structure. In the oral cavity, age had a marginal impact on the structures of the bacterial and fungal communities. Furthermore, the gut bacterial communities in centenarians clustered separately from those of the young and elderly, while the fungal communities in the gut habitat could not be separated by host age.IMPORTANCE Site-specific microbial communities are recognized as important factors in host health and disease. To better understand how the human microbiota potentially affects and is affected by its host during the aging process, the fundamental issue to address is the distribution of microbiota related to age. Here, we show an integrated view of the spatial distribution of microbes in a specific Mediterranean population (Sardinians) across a wide age range. Our study indicates that age plays a critical role in shaping the human microbiota in a habitat-dependent manner. The dynamic age-related microbiota changes we observed across multiple body sites may provide possibilities for modulating microbe communities to maintain or improve health during aging.}, }
@article {pmid32102343, year = {2020}, author = {Lopez-Santamarina, A and Miranda, JM and Mondragon, ADC and Lamas, A and Cardelle-Cobas, A and Franco, CM and Cepeda, A}, title = {Potential Use of Marine Seaweeds as Prebiotics: A Review.}, journal = {Molecules (Basel, Switzerland)}, volume = {25}, number = {4}, pages = {}, pmid = {32102343}, issn = {1420-3049}, mesh = {Animals ; Chlorophyceae/chemistry ; Dietary Fiber/metabolism/*pharmacology ; Fermentation ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Mice ; Microbiota/*drug effects/physiology ; Phaeophyta/chemistry ; Polysaccharides/chemistry/isolation & purification/*pharmacology ; Prebiotics/*analysis/supply & distribution ; Rats ; Rhodophyta/chemistry ; Seaweed/*chemistry ; }, abstract = {Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main sources of complex carbohydrates destined for human consumption are terrestrial plants. However, fresh water is an increasingly scarce commodity and world agricultural productivity is in a persistent decline, thus demanding the exploration of other sources of complex carbohydrates. As an interesting option, marine seaweeds show rapid growth and do not require arable land, fresh water or fertilizers. The present review offers an objective perspective of the current knowledge surrounding the impacts of seaweeds and their derived polysaccharides on the human microbiome and the profound need for more in-depth investigations into this topic. Animal experiments and in vitro colonic-simulating trials investigating the effects of seaweed ingestion on human gut microbiota are discussed.}, }
@article {pmid32101723, year = {2020}, author = {Xavier, JB and Young, VB and Skufca, J and Ginty, F and Testerman, T and Pearson, AT and Macklin, P and Mitchell, A and Shmulevich, I and Xie, L and Caporaso, JG and Crandall, KA and Simone, NL and Godoy-Vitorino, F and Griffin, TJ and Whiteson, KL and Gustafson, HH and Slade, DJ and Schmidt, TM and Walther-Antonio, MRS and Korem, T and Webb-Robertson, BM and Styczynski, MP and Johnson, WE and Jobin, C and Ridlon, JM and Koh, AY and Yu, M and Kelly, L and Wargo, JA}, title = {The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View.}, journal = {Trends in cancer}, volume = {6}, number = {3}, pages = {192-204}, pmid = {32101723}, issn = {2405-8025}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA208179/CA/NCI NIH HHS/United States ; R01 CA227479/CA/NCI NIH HHS/United States ; U54 CA209975/CA/NCI NIH HHS/United States ; }, abstract = {The collection of microbes that live in and on the human body - the human microbiome - can impact on cancer initiation, progression, and response to therapy, including cancer immunotherapy. The mechanisms by which microbiomes impact on cancers can yield new diagnostics and treatments, but much remains unknown. The interactions between microbes, diet, host factors, drugs, and cell-cell interactions within the cancer itself likely involve intricate feedbacks, and no single component can explain all the behavior of the system. Understanding the role of host-associated microbial communities in cancer systems will require a multidisciplinary approach combining microbial ecology, immunology, cancer cell biology, and computational biology - a systems biology approach.}, }
@article {pmid32099373, year = {2020}, author = {Michael, H and Mpofana, T and Ramlall, S and Oosthuizen, F}, title = {The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside.}, journal = {Neuropsychiatric disease and treatment}, volume = {16}, number = {}, pages = {355-367}, pmid = {32099373}, issn = {1176-6328}, abstract = {Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains prevalent in the anti-retroviral (ART) era. While there is a complex interplay of many factors in the neuropathogenesis of HAND, decreased neurotrophic synthesis has been shown to contribute to synaptic degeneration which is a hallmark of HAND neuropathology. Brain derived neurotrophic factor (BDNF) is the most abundant and synaptic-promoting neurotrophic factor in the brain and plays a critical role in both learning and memory. Reduced BDNF levels can worsen neurocognitive impairment in HIV-positive individuals across several domains. In this paper, we review the evidence from pre-clinical and clinical studies showing the neuroprotective roles of BDNF against viral proteins, effect on co-morbid mental health disorders, altered human microbiome and ART in HAND management. Potential applications of BDNF modulation in pharmacotherapeutic, cognitive and behavioral interventions in HAND are also discussed. Finally, research gaps and future research direction are identified with the aim of helping researchers to direct efforts to make these BDNF driven interventions improve the quality of life of patients living with HAND.}, }
@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 {pmid32089572, year = {2020}, author = {Gupta, V and Kumar, R and Sood, U and Singhvi, N}, title = {Reconciling Hygiene and Cleanliness: A New Perspective from Human Microbiome.}, journal = {Indian journal of microbiology}, volume = {60}, number = {1}, pages = {37-44}, pmid = {32089572}, issn = {0046-8991}, abstract = {The term hygiene is deeply rooted with the concept of maintaining sound health and alertness towards cleanliness, while "hygiene hypothesis" depicts the protective role of microbial community exposure in development of early immunity and initial allergic and aesthetic reactions. The tug-of-war has now been pushed toward the literal term "hygiene" over the "hygiene hypothesis" and has continued with disinfection of all microbial loads from the related environments to avoid infections in humans. With the advancement in the microbiome studies, it became clear that humans possess warm, and significant relationships with diverse microbial community. With this opinion article, we have emphasized on the importance of hygiene hypothesis in immunological responses. We also propose the individual/targeted hygiene instead of application of unanimous hygiene hypothesis. This review also elaborates the common practices that should be employed to maintain hygiene along with the balanced microbiome.}, }
@article {pmid32089571, year = {2020}, author = {Singhvi, N and Gupta, V and Gaur, M and Sharma, V and Puri, A and Singh, Y and Dubey, GP and Lal, R}, title = {Interplay of Human Gut Microbiome in Health and Wellness.}, journal = {Indian journal of microbiology}, volume = {60}, number = {1}, pages = {26-36}, pmid = {32089571}, issn = {0046-8991}, abstract = {The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the pathogenesis and wellness. Although in-depth investigations of gut microbiome, 'the Black Boxes', complexities and functionalities are yet at its infancy, profound evidences are being reported for their concurrent involvement in disease etiology and its treatment. Interestingly, studies from the 'minimal murine' (Oligo-MM12), 'humanized' microbiota gnotobiotic mice models and patient samples, combined with multi-omics and cell biology approaches, have been revealing the implications of these findings in the treatment of gut dysbiosis associated diseases. Nonetheless, due to the inherent heterogeneity of the gut commensals and their unified co-existence with opportunistic pathobionts, it is utmost essential to highlight their functionalities in 'good or bad' gut in human wellness. We have specifically reviewed dietary lifestyle and infectious diseases linked with the gut bacterial consortia to delineate the ecobiotic approaches towards their treatment. This notably includes gut mucosal immunity mediated diseases such as Tuberculosis, IBD, CDI, Type 2 Diabetes, etc. Alongside of each dysbiosis, we have described the current therapeutic advancements of the pre- and probiotics derived from human microbiome studies to restore gut microbial homeostasis. With a continuous running debate on the role of microbiota in above mentioned diseases, we have collected numerous scientific evidences highlighting a previously unanticipated complex involvement of gut microbiome in the potential of human health.}, }
@article {pmid32080334, year = {2020}, author = {Piersigilli, F and Syed, M and Lam, TT and Dotta, A and Massoud, M and Vernocchi, P and Quagliariello, A and Putignani, L and Auriti, C and Salvatori, G and Bagolan, P and Bhandari, V}, title = {An omic approach to congenital diaphragmatic hernia: a pilot study of genomic, microRNA, and metabolomic profiling.}, journal = {Journal of perinatology : official journal of the California Perinatal Association}, volume = {40}, number = {6}, pages = {952-961}, doi = {10.1038/s41372-020-0623-3}, pmid = {32080334}, issn = {1476-5543}, abstract = {INTRODUCTION: The omic approach can help identify a signature that can be potentially used as biomarkers in babies with congenital diaphragmatic hernia (CDH).
OBJECTIVES: To find a specific microRNA (miR) and metabolic fingerprint of the tracheal aspirates (TA) of CDH patients. We conducted a genetic analysis from blood samples.
METHODS: TA samples collected in the first 48 h of life in patients with CDH, compared with age-matched controls. Metabolomics done by a mass spectroscopy-based assay. Genomics done using chromosomal microarray analysis.
RESULTS: CDH (n = 17) and 16 control neonates enrolled. miR-16, miR-17, miR-18, miR-19b, and miR-20a had an increased expression, while miR-19a had a twofold decreased expression in CDH patients, compared with age-matched control patients. Specific metabolites separated neonates with CDH from controls. A genetic mutation found in a small subset of patients.
CONCLUSIONS: Specific patterns of metabolites and miR expression can be discerned in TA samples in infants with CDH.}, }
@article {pmid32077339, year = {2020}, author = {Grosse, CSJ and Christophersen, CT and Devine, A and Lawrance, IC}, title = {The role of a plant-based diet in the pathogenesis, etiology and management of the inflammatory bowel diseases.}, journal = {Expert review of gastroenterology & hepatology}, volume = {14}, number = {3}, pages = {137-145}, doi = {10.1080/17474124.2020.1733413}, pmid = {32077339}, issn = {1747-4132}, abstract = {Introduction: Inflammatory Bowel Disease (IBD) carries a significant burden on an individual's quality-of-life and on the healthcare system. The majority of patients use dietary modifications to manage their symptoms, despite limited research to support these changes. There is emerging data that a plant-based diet will be of benefit to IBD patients.Areas covered: A literature review on the pathogenesis and potential benefits of dietary management of IBD.Expert opinion: A Westernized diet has been associated with IBD risk and relapse; hence a plant-based diet may be of benefit to IBD patients through reducing inflammation and restoring symbiosis. Dietary therapy can be an important adjunct therapy, however, better quality studies are still required.}, }
@article {pmid32076932, year = {2020}, author = {Bresalier, RS and Chapkin, RS}, title = {Human Microbiome in Health and Disease: The Good, the Bad, and the Bugly.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {671-673}, doi = {10.1007/s10620-020-06059-y}, pmid = {32076932}, issn = {1573-2568}, mesh = {Gastrointestinal Diseases/metabolism/*microbiology/pathology ; *Health Status ; Humans ; Microbiota/*physiology ; }, }
@article {pmid32076128, year = {2020}, author = {Darcy, JL and Washburne, AD and Robeson, MS and Prest, T and Schmidt, SK and Lozupone, CA}, title = {A phylogenetic model for the recruitment of species into microbial communities and application to studies of the human microbiome.}, journal = {The ISME journal}, volume = {14}, number = {6}, pages = {1359-1368}, doi = {10.1038/s41396-020-0613-7}, pmid = {32076128}, issn = {1751-7370}, support = {T15 LM009451/LM/NLM NIH HHS/United States ; 5 T15 LM009451-12//U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/International ; }, mesh = {Bacteria/classification/*genetics/isolation & purification ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Male ; *Microbiota ; *Phylogeny ; }, abstract = {Understanding when and why new species are recruited into microbial communities is a formidable problem with implications for managing microbial systems, for instance by helping us better understand whether a probiotic or pathogen would be expected to colonize a human microbiome. Much theory in microbial temporal dynamics is focused on how phylogenetic relationships between microbes impact the order in which those microbes are recruited; for example, species that are closely related may competitively exclude each other. However, several recent human microbiome studies have observed closely related bacteria being recruited into microbial communities in short succession, suggesting that microbial community assembly is historically contingent, but competitive exclusion of close relatives may not be important. To address this, we developed a mathematical model that describes the order in which new species are detected in microbial communities over time within a phylogenetic framework. We use our model to test three hypothetical assembly modes: underdispersion (species recruitment is more likely if a close relative was previously detected), overdispersion (recruitment is more likely if a close relative has not been previously detected), and the neutral model (recruitment likelihood is not related to phylogenetic relationships among species). We applied our model to longitudinal human microbiome data, and found that for the individuals we analyzed, the human microbiome generally follows the underdispersion (i.e., nepotism) hypothesis. Exceptions were oral communities and the fecal communities of two infants that had undergone heavy antibiotic treatment. None of the datasets we analyzed showed statistically significant phylogenetic overdispersion.}, }
@article {pmid32075244, year = {2020}, author = {Benedetti, F and Cocchi, F and Latinovic, OS and Curreli, S and Krishnan, S and Munawwar, A and Gallo, RC and Zella, D}, title = {Role of Mycoplasma Chaperone DnaK in Cellular Transformation.}, journal = {International journal of molecular sciences}, volume = {21}, number = {4}, pages = {}, pmid = {32075244}, issn = {1422-0067}, mesh = {Apoptosis/genetics ; Cell Transformation, Neoplastic/genetics ; DNA Damage/genetics ; DNA Repair/genetics ; Humans ; Inflammation/*genetics/microbiology/pathology ; Molecular Chaperones/*genetics ; Mycoplasma/*genetics/pathogenicity ; Mycoplasma Infections/*genetics/microbiology ; Neoplasms/*genetics/pathology ; Poly (ADP-Ribose) Polymerase-1/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin Thiolesterase/genetics ; }, abstract = {Studies of the human microbiome have elucidated an array of complex interactions between prokaryotes and their hosts. However, precise bacterial pathogen-cancer relationships remain largely elusive, although several bacteria, particularly those establishing persistent intra-cellular infections, like mycoplasmas, can alter host cell cycles, affect apoptotic pathways, and stimulate the production of inflammatory substances linked to DNA damage, thus potentially promoting abnormal cell growth and transformation. Consistent with this idea, in vivo experiments in several chemically induced or genetically deficient mouse models showed that germ-free conditions reduce colonic tumor formation. We demonstrate that mycoplasma DnaK, a chaperone protein belonging to the Heath shock protein (Hsp)-70 family, binds Poly-(ADP-ribose) Polymerase (PARP)-1, a protein that plays a critical role in the pathways involved in recognition of DNA damage and repair, and reduces its catalytic activity. It also binds USP10, a key p53 regulator, reducing p53 stability and anti-cancer functions. Finally, we showed that bystander, uninfected cells take up exogenous DnaK-suggesting a possible paracrine function in promoting cellular transformation, over and above direct mycoplasma infection. We propose that mycoplasmas, and perhaps certain other bacteria with closely related DnaK, may have oncogenic activity, mediated through the inhibition of DNA repair and p53 functions, and may be involved in the initiation of some cancers but not necessarily involved nor necessarily even be present in later stages.}, }
@article {pmid32073295, year = {2020}, author = {Swanson, KS and de Vos, WM and Martens, EC and Gilbert, JA and Menon, RS and Soto-Vaca, A and Hautvast, J and Meyer, PD and Borewicz, K and Vaughan, EE and Slavin, JL}, title = {Effect of fructans, prebiotics and fibres on the human gut microbiome assessed by 16S rRNA-based approaches: a review.}, journal = {Beneficial microbes}, volume = {11}, number = {2}, pages = {101-129}, doi = {10.3920/BM2019.0082}, pmid = {32073295}, issn = {1876-2891}, mesh = {*Diet ; *Dietary Fiber ; Feces/microbiology ; *Fructans ; Gastrointestinal Microbiome/*genetics ; Humans ; Phylogeny ; *Prebiotics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.}, }
@article {pmid32066625, year = {2020}, author = {Ghosh, TS and Rampelli, S and Jeffery, IB and Santoro, A and Neto, M and Capri, M and Giampieri, E and Jennings, A and Candela, M and Turroni, S and Zoetendal, EG and Hermes, GDA and Elodie, C and Meunier, N and Brugere, CM and Pujos-Guillot, E and Berendsen, AM and De Groot, LCPGM and Feskins, EJM and Kaluza, J and Pietruszka, B and Bielak, MJ and Comte, B and Maijo-Ferre, M and Nicoletti, C and De Vos, WM and Fairweather-Tait, S and Cassidy, A and Brigidi, P and Franceschi, C and O'Toole, PW}, title = {Mediterranean diet intervention alters the gut microbiome in older people reducing frailty and improving health status: the NU-AGE 1-year dietary intervention across five European countries.}, journal = {Gut}, volume = {69}, number = {7}, pages = {1218-1228}, pmid = {32066625}, issn = {1468-3288}, abstract = {OBJECTIVE: Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty.
DESIGN: We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet).
RESULTS: Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks.
CONCLUSION: Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.}, }
@article {pmid32065252, year = {2020}, author = {Peñalver Bernabé, B and Maki, PM and Dowty, SM and Salas, M and Cralle, L and Shah, Z and Gilbert, JA}, title = {Precision medicine in perinatal depression in light of the human microbiome.}, journal = {Psychopharmacology}, volume = {237}, number = {4}, pages = {915-941}, pmid = {32065252}, issn = {1432-2072}, support = {Arnold O Beckman Postdoctoral Award//Arnold and Mabel Beckman Foundation (US)/ ; }, mesh = {Brain/metabolism ; Depressive Disorder, Major/metabolism/psychology/*therapy ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Infant ; Microbiota/physiology ; Postpartum Period/metabolism/psychology ; Precision Medicine/*methods/psychology ; Pregnancy ; Pregnancy Complications/metabolism/psychology/*therapy ; }, abstract = {Perinatal depression is the most common complication of pregnancy and affects the mother, fetus, and infant. Recent preclinical studies and a limited number of clinical studies have suggested an influence of the gut microbiome on the onset and course of mental health disorders. In this review, we examine the current state of knowledge regarding genetics, epigenetics, heritability, and neuro-immuno-endocrine systems biology in perinatal mood disorders, with a particular focus on the interaction between these factors and the gut microbiome, which is mediated via the gut-brain axis. We also provide an overview of experimental and analytical methods that are currently available to researchers interested in elucidating the influence of the gut microbiome on mental health disorders during pregnancy and postpartum.}, }
@article {pmid32060812, year = {2020}, author = {Wilson, AS and Koller, KR and Ramaboli, MC and Nesengani, LT and Ocvirk, S and Chen, C and Flanagan, CA and Sapp, FR and Merritt, ZT and Bhatti, F and Thomas, TK and O'Keefe, SJD}, title = {Diet and the Human Gut Microbiome: An International Review.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {723-740}, doi = {10.1007/s10620-020-06112-w}, pmid = {32060812}, issn = {1573-2568}, support = {R01 CA135379/CA/NCI NIH HHS/United States ; R01 CA204403/CA/NCI NIH HHS/United States ; }, mesh = {*Diet/trends ; Diet, Western/adverse effects ; Dietary Fiber/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Internationality ; Milk, Human/*microbiology/physiology ; }, abstract = {This review summarizes the key results of recently published studies on the effects of dietary change and nutritional intervention on the human microbiome from around the world, focusing on the USA, Canada, Europe, Asia, and Africa. It first explores mechanisms that might explain the ability of fiber-rich foods to suppress the incidence and mortality from westernized diseases, notably cancers of the colon, breast, liver, cardiovascular, infectious, and respiratory diseases, diabetes, and obesity (O'Keefe in Lancet Gastroenterol Hepatol 4(12):984-996, 2019; Am J Clin Nutr 110:265-266, 2019). It summarizes studies from Africa which suggest that disturbance of the colonic microbiome may exacerbate chronic malnutrition and growth failure in impoverished communities and highlights the importance of breast feeding. The American section discusses the role of the microbiome in the swelling population of patients with obesity and type 2 diabetes and examines the effects of race, ethnicity, geography, and climate on microbial diversity and metabolism. The studies from Europe and Asia extoll the benefits of whole foods and plant-based diets. The Asian studies examine the worrying changes from low-fat, high-carbohydrate diets to high-fat, low-carbohydrate ones and the increasing appearance of westernized diseases as in Africa and documents the ability of high-fiber traditional Chinese diets to reverse type 2 diabetes and control weight loss. In conclusion, most of the studies reviewed demonstrate clear changes in microbe abundances and in the production of fermentation products, such as short-chain fatty acids and phytochemicals following dietary change, but the significance of the microbiota changes to human health, with the possible exception of the stimulation of butyrogenic taxa by fiber-rich foods, is generally implied and not measured. Further studies are needed to determine how these changes in microbiota composition and metabolism can improve our health and be used to prevent and treat disease.}, }
@article {pmid32055399, year = {2020}, author = {Garza, DR and Taddese, R and Wirbel, J and Zeller, G and Boleij, A and Huynen, MA and Dutilh, BE}, title = {Metabolic models predict bacterial passengers in colorectal cancer.}, journal = {Cancer & metabolism}, volume = {8}, number = {}, pages = {3}, pmid = {32055399}, issn = {2049-3002}, abstract = {Background: Colorectal cancer (CRC) is a complex multifactorial disease. Increasing evidence suggests that the microbiome is involved in different stages of CRC initiation and progression. Beyond specific pro-oncogenic mechanisms found in pathogens, metagenomic studies indicate the existence of a microbiome signature, where particular bacterial taxa are enriched in the metagenomes of CRC patients. Here, we investigate to what extent the abundance of bacterial taxa in CRC metagenomes can be explained by the growth advantage resulting from the presence of specific CRC metabolites in the tumor microenvironment.
Methods: We composed lists of metabolites and bacteria that are enriched on CRC samples by reviewing metabolomics experimental literature and integrating data from metagenomic case-control studies. We computationally evaluated the growth effect of CRC enriched metabolites on over 1500 genome-based metabolic models of human microbiome bacteria. We integrated the metabolomics data and the mechanistic models by using scores that quantify the response of bacterial biomass production to CRC-enriched metabolites and used these scores to rank bacteria as potential CRC passengers.
Results: We found that metabolic networks of bacteria that are significantly enriched in CRC metagenomic samples either depend on metabolites that are more abundant in CRC samples or specifically benefit from these metabolites for biomass production. This suggests that metabolic alterations in the cancer environment are a major component shaping the CRC microbiome.
Conclusion: Here, we show with in sillico models that supplementing the intestinal environment with CRC metabolites specifically predicts the outgrowth of CRC-associated bacteria. We thus mechanistically explain why a range of CRC passenger bacteria are associated with CRC, enhancing our understanding of this disease. Our methods are applicable to other microbial communities, since it allows the systematic investigation of how shifts in the microbiome can be explained from changes in the metabolome.}, }
@article {pmid32054471, year = {2020}, author = {Nazareth, R and Chasqueira, MJ and Rodrigues, ML and Paulino, C and Conceição, C and Lêdo, L and Segura, Ú and Santos, M and Messias, A and Póvoa, P and Paixão, P}, title = {Respiratory viruses in mechanically ventilated patients: a pilot study.}, journal = {BMC pulmonary medicine}, volume = {20}, number = {1}, pages = {39}, pmid = {32054471}, issn = {1471-2466}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; *Respiration, Artificial ; Respiratory Insufficiency/*therapy/*virology ; Respiratory Tract Infections/*complications/diagnosis/therapy ; Virus Diseases/*complications/*diagnosis/virology ; Young Adult ; }, abstract = {BACKGROUND: Respiratory virome is an integral part of the human microbiome and its characterization may contribute to a better understanding of the changes that arise in the disease and, consequently, influence the approach and treatment of patients with acute lower respiratory infections. The aim of this study was to evaluate the presence of respiratory viruses in the lower airways of individuals undergoing invasive mechanical ventilation, with and without acute lower respiratory infection (respectively WRI and WORI groups).
METHODS: We studied 44 mini-bronchoalveolar lavage samples (collected with a double catheter, Combicath® kit) from patients with mean age in the seventh decade, 20 from WORI group and 24 from WRI group, who were hospitalized for acute respiratory failure in Intensive Care Units of two hospitals in the Lisbon area. Real-time PCR was applied to verify analyse the presence of 15 common respiratory viruses (adenovirus, human bocavirus, influenza virus A and B, repiratory syncytial virus, human parainfluenza virus types 1, 2, 3 and 4, human enterovirus, human rhinovirus, human metapneumovirus, human coronavirus group 1 (229E, NL63) and 2 (OC43, HKU1).
RESULTS: Respiratory viruses were detected in six of the 20 patients in the WORI group: influenza AH3 (n = 2), parainfluenza virus 1/3 (n = 2), human rhinovirus (n = 2), respiratory syncytial virus (n = 1) and human metapneumovirus (n = 1). In the WRI group, respiratory viruses were detected in 12 of the 24 patients: influenza AH3 (n = 3), human rhinovirus (n = 3), respiratory syncytial virus (n = 3), human metapneumovirus (n = 3), human bocavirus (n = 2) and human enterovirus (n = 1). Simultaneous detection of two viruses was recorded in two samples in both groups.
CONCLUSIONS: The results of this study suggest the presence of common respiratory viruses in the lower respiratory tract without causing symptomatic infection, even in carefully collected lower samples. This may have important implications on the interpretation of the results on the diagnostic setting.}, }
@article {pmid32040665, year = {2020}, author = {Engstrand, L and Graham, DY}, title = {Microbiome and Gastric Cancer.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {865-873}, doi = {10.1007/s10620-020-06101-z}, pmid = {32040665}, issn = {1573-2568}, mesh = {Gastric Mucosa/*microbiology/physiopathology ; Gastrointestinal Microbiome/*physiology ; Helicobacter pylori/isolation & purification/*physiology ; Host Microbial Interactions/physiology ; Humans ; Stomach Neoplasms/*microbiology/pathology/physiopathology ; }, abstract = {The late 1800s Louis Pasteur and Robert Koch introduced and popularized the germ theory of disease. At that time, gastric cancer was the most common cause of cancer deaths in most countries making the stomach an early site of microbial research with a focus on gastric luminal and mucosal bacteria and the role of Boas-Oppler bacillus (Lactobacillus) in the diagnosis of gastric cancer. In the 1970s, the research focus evolved to studies of the gastric microbiome in the production of nitrosamines and included development of the Correa cascade. Interest in nitrosamine production peaked in the late 1980s and was replaced by studies of the newly described Helicobacter pylori and studies of its role in gastritis, gastric atrophy, and gastric cancer. The last decade has witnessed a rebirth in interest in the gastric microbiota as part of worldwide interest in the human microbiome. Although fungi were prominent in the studies of gastric microbiology in the nineteenth century, their potential role in disease pathogenesis has yet to be addressed using modern techniques. Overall, current studies of the gastric bacterial microbiome do not provide convincing evidence to expand the role of the gastric microbiome in cancer pathogenesis beyond what is directly attributable to the oncogenic potential of H. pylori and its role in persisting acute-on-chronic inflammation.}, }
@article {pmid32040250, year = {2020}, author = {Guo, XY and Liu, XJ and Hao, JY}, title = {Gut microbiota in ulcerative colitis: insights on pathogenesis and treatment.}, journal = {Journal of digestive diseases}, volume = {21}, number = {3}, pages = {147-159}, doi = {10.1111/1751-2980.12849}, pmid = {32040250}, issn = {1751-2980}, support = {81300294//Youth Program of National Natural Science Foundation of China/ ; XXT11//Project of Digestive Medical Coordinated Development Center of Beijing Hospitals Authority/ ; PX2018011//Incubation Program Project of Beijing Municipal Administration of Hospitals of China/ ; 7192072//Beijing Natural Science Foundation/ ; }, abstract = {Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.}, }
@article {pmid32037278, year = {2020}, author = {Rao, BC and Lou, JM and Wang, WJ and Li, A and Cui, GY and Yu, ZJ and Ren, ZG}, title = {Human microbiome is a diagnostic biomarker in hepatocellular carcinoma.}, journal = {Hepatobiliary & pancreatic diseases international : HBPD INT}, volume = {19}, number = {2}, pages = {109-115}, doi = {10.1016/j.hbpd.2020.01.003}, pmid = {32037278}, issn = {1499-3872}, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Increasing evidence indicates a close relationship between HCC and the human microbiota. Herein, we reviewed the important potential of the human microbiota as a diagnostic biomarker of HCC.
DATA SOURCES: Several innovative studies have investigated the characteristics of the gut and oral microbiomes in patients with HCC and proposed that the human microbiome has the potential to be a diagnostic biomarker of HCC. Literature from February 1999 to February 2019 was searched in the PubMed database using the keywords "microbiota" or "microbiome" or "microbe" and "liver cancer" or "hepatocellular carcinoma", and the results of clinical and experimental studies were analyzed.
RESULTS: Specific changes occur in the human microbiome of patients with HCC. Moreover, the gut microbiome and oral microbiome can be used as non-invasive diagnostic biomarkers for HCC. Furthermore, they also have certain diagnostic potential for precancerous diseases of HCC. The diagnostic potential of the blood microbiota and ascites microbiota in HCC will be gradually discovered in the future.
CONCLUSIONS: The human microbiome is valuable to the diagnosis of HCC and provides a novel strategy for targeted therapy of HCC. The human microbiome may be widely used in the diagnosis, treatment and prognosis for multiple system diseases or cancers in the future.}, }
@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 {pmid32023871, year = {2020}, author = {Panyukov, VV and Kiselev, SS and Ozoline, ON}, title = {Unique k-mers as Strain-Specific Barcodes for Phylogenetic Analysis and Natural Microbiome Profiling.}, journal = {International journal of molecular sciences}, volume = {21}, number = {3}, pages = {}, pmid = {32023871}, issn = {1422-0067}, support = {18-14-00348//Russian Science Foundation/ ; 18-07-00899//Российский Фонд Фундаментальных Исследований (РФФИ)/ ; }, mesh = {Algorithms ; Case-Control Studies ; Computational Biology ; Crohn Disease/*genetics/microbiology ; DNA Barcoding, Taxonomic/*methods ; Escherichia coli/classification/*genetics/isolation & purification ; Escherichia coli Infections/*genetics/microbiology ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Metagenome ; *Microbiota ; }, abstract = {The need for a comparative analysis of natural metagenomes stimulated the development of new methods for their taxonomic profiling. Alignment-free approaches based on the search for marker k-mers turned out to be capable of identifying not only species, but also strains of microorganisms with known genomes. Here, we evaluated the ability of genus-specific k-mers to distinguish eight phylogroups of Escherichia coli (A, B1, C, E, D, F, G, B2) and assessed the presence of their unique 22-mers in clinical samples from microbiomes of four healthy people and four patients with Crohn's disease. We found that a phylogenetic tree inferred from the pairwise distance matrix for unique 18-mers and 22-mers of 124 genomes was fully consistent with the topology of the tree, obtained with concatenated aligned sequences of orthologous genes. Therefore, we propose strain-specific "barcodes" for rapid phylotyping. Using unique 22-mers for taxonomic analysis, we detected microbes of all groups in human microbiomes; however, their presence in the five samples was significantly different. Pointing to the intraspecies heterogeneity of E. coli in the natural microflora, this also indicates the feasibility of further studies of the role of this heterogeneity in maintaining population homeostasis.}, }
@article {pmid32014010, year = {2020}, author = {Botticelli, A and Vernocchi, P and Marini, F and Quagliariello, A and Cerbelli, B and Reddel, S and Del Chierico, F and Di Pietro, F and Giusti, R and Tomassini, A and Giampaoli, O and Miccheli, A and Zizzari, IG and Nuti, M and Putignani, L and Marchetti, P}, title = {Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment.}, journal = {Journal of translational medicine}, volume = {18}, number = {1}, pages = {49}, pmid = {32014010}, issn = {1479-5876}, abstract = {BACKGROUND: Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.
METHODS: The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.
RESULTS: Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.
CONCLUSIONS: Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.}, }
@article {pmid32011231, year = {2020}, author = {Cepko, LCS and Garling, EE and Dinsdale, MJ and Scott, WP and Bandy, L and Nice, T and Faber-Hammond, J and Mellies, JL}, title = {Myoviridae phage PDX kills enteroaggregative Escherichia coli without human microbiome dysbiosis.}, journal = {Journal of medical microbiology}, volume = {69}, number = {2}, pages = {309-323}, pmid = {32011231}, issn = {1473-5644}, mesh = {Animals ; Bacteria/classification/genetics/isolation & purification ; Bacteriophages/classification/genetics/isolation & purification/*physiology ; Dysbiosis/microbiology ; Escherichia coli/physiology/*virology ; Escherichia coli Infections/microbiology/*therapy ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Myoviridae/classification/genetics/isolation & purification/*physiology ; Phylogeny ; }, abstract = {Introduction. Bacteriophage therapy can be developed to target emerging diarrhoeal pathogens, but doing so in the absence of microbiome disruption, which occurs with antibiotic treatment, has not been established.Aim. Identify a therapeutic bacteriophage that kills diarrhoeagenic enteroaggregative Escherichia coli (EAEC) while leaving the human microbiome intact.Methodology. Phages from wastewater in Portland, OR, USA were screened for bacteriolytic activity by overlay assay. One isolated phage, PDX, was classified by electron microscopy and genome sequencing. A mouse model of infection determined whether the phage was therapeutic against EAEC. 16S metagenomic analysis of anaerobic cultures determined whether a normal human microbiome was altered by treatment.Results.Escherichia virus PDX, a member of the strictly lytic family Myoviridae, killed a case-associated EAEC isolate from a child in rural Tennessee in a dose-dependent manner, and killed EAEC isolates from Columbian children. A single dose of PDX (multiplicity of infection: 100) 1 day post-infection reduced EAEC recovered from mouse faeces. PDX also killed EAEC when cultured anaerobically in the presence of human faecal bacteria. While the addition of EAEC reduced the β-diversity of the human microbiota, that of the cultures with either faeces alone, faeces with EAEC and PDX, or with just PDX phage was not different statistically.Conclusion.PDX killed EAEC isolate EN1E-0007 in vivo and in vitro, while not altering the diversity of normal human microbiota in anaerobic culture, and thus could be part of an effective therapy for children in developing countries and those suffering from EAEC-mediated traveller's diarrhoea without causing dysbiosis.}, }
@article {pmid32010645, year = {2019}, author = {Zhang, L and Liu, Y and Zheng, HJ and Zhang, CP}, title = {The Oral Microbiota May Have Influence on Oral Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {476}, pmid = {32010645}, issn = {2235-2988}, mesh = {Bacteria/*classification/genetics/isolation & purification ; Carcinoma, Squamous Cell/*etiology/*microbiology ; DNA, Ribosomal/genetics ; Female ; Fusobacterium nucleatum ; Humans ; Lipopolysaccharides ; Male ; Microbiota/*physiology ; Middle Aged ; Mouth/*microbiology ; Mouth Mucosa/microbiology ; Peptostreptococcus ; Prevotella intermedia ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (Prevotellaceae, Fusobacteriaceae, Flavobacteriaceae, Lachnospiraceae, Peptostreptococcaceae, and Campylobacteraceae) and 13 genera, including Fusobacterium, Alloprevotella and Porphyromonas. At the species level, the abundances of Fusobacterium nucleatum, Prevotella intermedia, Aggregatibacter segnis, Capnocytophaga leadbetteri, Peptostreptococcus stomatis, and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).}, }
@article {pmid31996419, year = {2020}, author = {Ghannam, RB and Schaerer, LG and Butler, TM and Techtmann, SM}, title = {Biogeographic Patterns in Members of Globally Distributed and Dominant Taxa Found in Port Microbial Communities.}, journal = {mSphere}, volume = {5}, number = {1}, pages = {}, pmid = {31996419}, issn = {2379-5042}, mesh = {Actinobacteria/*classification ; Asia ; Bacteroidetes/*classification ; *Biodiversity ; Cyanobacteria/*classification ; DNA, Bacterial/genetics ; Europe ; Fresh Water/microbiology ; Machine Learning ; Microbiota ; Phylogeography ; Proteobacteria/*classification ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Ships ; United States ; *Water Microbiology ; }, abstract = {We conducted a global characterization of the microbial communities of shipping ports to serve as a novel system to investigate microbial biogeography. The community structures of port microbes from marine and freshwater habitats house relatively similar phyla, despite spanning large spatial scales. As part of this project, we collected 1,218 surface water samples from 604 locations across eight countries and three continents to catalogue a total of 20 shipping ports distributed across the East and West Coast of the United States, Europe, and Asia to represent the largest study of port-associated microbial communities to date. Here, we demonstrated the utility of machine learning to leverage this robust system to characterize microbial biogeography by identifying trends in biodiversity across broad spatial scales. We found that for geographic locations sharing similar environmental conditions, subpopulations from the dominant phyla of these habitats (Actinobacteria, Bacteroidetes, Cyanobacteria, and Proteobacteria) can be used to differentiate 20 geographic locations distributed globally. These results suggest that despite the overwhelming diversity within microbial communities, members of the most abundant and ubiquitous microbial groups in the system can be used to differentiate a geospatial location across global spatial scales. Our study provides insight into how microbes are dispersed spatially and robust methods whereby we can interrogate microbial biogeography.IMPORTANCE Microbes are ubiquitous throughout the world and are highly diverse. Characterizing the extent of variation in the microbial diversity across large geographic spatial scales is a challenge yet can reveal a lot about what biogeography can tell us about microbial populations and their behavior. Machine learning approaches have been used mostly to examine the human microbiome and, to some extent, microbial communities from the environment. Here, we display how supervised machine learning approaches can be useful to understand microbial biodiversity and biogeography using microbes from globally distributed shipping ports. Our findings indicate that the members of globally dominant phyla are important for differentiating locations, which reduces the reliance on rare taxa to probe geography. Further, this study displays how global biogeographic patterning of aquatic microbial communities (and other systems) can be assessed through populations of the highly abundant and ubiquitous taxa that dominant the system.}, }
@article {pmid31993418, year = {2019}, author = {Kang, W and Sun, T and Tang, D and Zhou, J and Feng, Q}, title = {Time-Course Transcriptome Analysis of Gingiva-Derived Mesenchymal Stem Cells Reveals That Fusobacterium nucleatum Triggers Oncogene Expression in the Process of Cell Differentiation.}, journal = {Frontiers in cell and developmental biology}, volume = {7}, number = {}, pages = {359}, pmid = {31993418}, issn = {2296-634X}, abstract = {Fusobacterium nucleatum has pathogenic effects on oral squamous cell carcinoma and colon cancer, while the effects of continuously altered gene expression in normal human cells, as induced by persistent exposure to F. nucleatum, remain unclear. In this study, a microarray Significant Profiles (maSigPro) analysis was used to obtain the transcriptome profile of gingiva-derived mesenchymal stem cells (GMSCs) stimulated by F. nucleatum for 3, 7, 14, and 21 day, and the results revealed 790 (nine clusters) differentially expressed genes (DEGs), which were significantly enriched in cell adherens junctions and cancer-related pathways. On the basis of a short time-series expression miner (STEM) analysis, all the expressed genes in the GMSCs were grouped into 50 clusters according to dynamic gene expression patterns, and the expression levels of three gene clusters in the F. nucleatum-treated GMSCs were significantly different than the predicted values. Among the 790 DEGs, 50 tumor-associated genes (TAGs; such as L3MBTL4, CD163, CCCND2, CADM1, BCL7A, and IGF1) and five core dynamic DEGs (PLCG2, CHI3L2, L3MBTL4, SH2D2A, and NLRP3) were identified during F. nucleatum stimulation. Results from a GeneMANIA database analysis showed that PLCG2, CHI3L2, SH2D2A, and NLRP3 and 20 other proteins formed a complex network of which 12 genes were enriched in cancer-related pathways. Based on the five core dynamic DEGs, the related microRNAs (miRNAs) and transcription factors (TFs) were obtained from public resources, and an integrated network composed of the related TFs, miRNAs, and mRNAs was constructed. The results indicated that these genes were regulated by several miRNAs, such as miR-372-3p, miR-603, and miR-495-3p, and several TFs, including CREB3, GATA2, and SOX4. Our study suggests that long-term stimulation by F. nucleatum may trigger the expression of cancer-related genes in normal gingiva-derived stem cells.}, }
@article {pmid31991821, year = {2020}, author = {Simões-Silva, L and Araujo, R and Pestana, M and Soares-Silva, I and Sampaio-Maia, B}, title = {Peritoneal Microbiome in End-Stage Renal Disease Patients and the Impact of Peritoneal Dialysis Therapy.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, pmid = {31991821}, issn = {2076-2607}, support = {Research Grant 2014 to ISS//European Society of Clinical Microbiology and Infectious Diseases/ ; SFRH/BPD/101016/2014//Fundação para a Ciência e a Tecnologia/ ; POCI-01-0145-FEDER-029777//Fundação para a Ciência e a Tecnologia/ ; PTDC/MEC-MCI/29777/2017//Fundação para a Ciência e a Tecnologia/ ; UID/BIA/04050/2019//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Factors influencing the occurrence of peritoneal dialysis (PD)-related infections are still far from fully understood. Recent studies described the existence of specific microbiomes in body sites previously considered microbiome-free, unravelling new microbial pathways in the human body. In the present study, we analyzed the peritoneum of end-stage kidney disease (ESKD) patients to determine if they harbored a specific microbiome and if it is altered in patients on PD therapy. We conducted a cross-sectional study where the peritoneal microbiomes from ESKD patients with intact peritoneal cavities (ESKD non-PD, n = 11) and ESKD patients undergoing PD therapy (ESKD PD, n = 9) were analyzed with a 16S rRNA approach. Peritoneal tissue of ESKD patients contained characteristically low-abundance microbiomes dominated by Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. Patients undergoing PD therapy presented lower species richness, with dominance by the Pseudomonadaceae and Prevotelaceae families. This study provides the first characterization of the peritoneal microbiome in ESKD patients, bringing new insight to the human microbiome. Additionally, PD therapy may induce changes in this unique microbiome. The clinical relevance of these observations should be further explored to uncover the role of the peritoneal microbiome as a key element in the onset or aggravation of infection in ESKD patients, especially those undergoing PD.}, }
@article {pmid31988008, year = {2020}, author = {Zhang, Y and Ying, X and He, Y and Jiang, L and Zhang, S and Bartra, SS and Plano, GV and Klena, JD and Skurnik, M and Chen, H and Cai, H and Chen, T}, title = {Invasiveness of the Yersinia pestis ail protein contributes to host dissemination in pneumonic and oral plague.}, journal = {Microbial pathogenesis}, volume = {141}, number = {}, pages = {103993}, doi = {10.1016/j.micpath.2020.103993}, pmid = {31988008}, issn = {1096-1208}, abstract = {Yersinia pestis, a Gram-negative bacterium, is the etiologic agent of plague. A hallmark of Y. pestis infection is the organism's ability to rapidly disseminate through an animal host. Y. pestis expresses the outer membrane protein, Ail (Attachment invasion locus), which is associated with host invasion and serum resistance. However, whether Ail plays a role in host dissemination remains unclear. In this study, C57BL/6J mice were challenged with a defined Y. pestis strain, KimD27, or an isogenic ail-deleted mutant derived from KimD27 via metacarpal paw pad inoculation, nasal drops, orogastric infection, or tail vein injection to mimic bubonic, pneumonic, oral, or septicemic plague, respectively. Our results showed that ail-deleted Y. pestis KimD27 lost the ability to invade host cells, leading to failed host dissemination in the pneumonic and oral plague models but not in the bubonic or septicemic plague models, which do not require invasiveness. Therefore, this study demonstrated that whether Ail plays a role in Y. pestis pathogenesis depends on the infection route.}, }
@article {pmid31979276, year = {2020}, author = {Oduor, JMO and Kadija, E and Nyachieo, A and Mureithi, MW and Skurnik, M}, title = {Bioprospecting Staphylococcus Phages with Therapeutic and Bio-Control Potential.}, journal = {Viruses}, volume = {12}, number = {2}, pages = {}, pmid = {31979276}, issn = {1999-4915}, abstract = {Emergence of antibiotic-resistant bacteria is a serious threat to the public health. This is also true for Staphylococcus aureus and other staphylococci. Staphylococcus phages Stab20, Stab21, Stab22, and Stab23, were isolated in Albania. Based on genomic and phylogenetic analysis, they were classified to genus Kayvirus of the subfamily Twortvirinae. In this work, we describe the in-depth characterization of the phages that electron microscopy confirmed to be myoviruses. These phages showed tolerance to pH range of 5.4 to 9.4, to maximum UV radiation energy of 25 µJ/cm2, to temperatures up to 45 °C, and to ethanol concentrations up to 25%, and complete resistance to chloroform. The adsorption rate constants of the phages ranged between 1.0 × 10-9 mL/min and 4.7 × 10-9 mL/min, and the burst size was from 42 to 130 plaque-forming units. The phages Stab20, 21, 22, and 23, originally isolated using Staphylococcusxylosus as a host, demonstrated varied host ranges among different Staphylococcus strains suggesting that they could be included in cocktail formulations for therapeutic or bio-control purpose. Phage particle proteomes, consisting on average of ca 60-70 gene products, revealed, in addition to straight-forward structural proteins, also the presence of enzymes such DNA polymerase, helicases, recombinases, exonucleases, and RNA ligase polymer. They are likely to be injected into the bacteria along with the genomic DNA to take over the host metabolism as soon as possible after infection.}, }
@article {pmid31977194, year = {2020}, author = {Chevrette, MG and Handelsman, J}, title = {From Metagenomes to Molecules: Innovations in Functional Metagenomics Unlock Hidden Chemistry in the Human Microbiome.}, journal = {Biochemistry}, volume = {59}, number = {6}, pages = {729-730}, doi = {10.1021/acs.biochem.0c00033}, pmid = {31977194}, issn = {1520-4995}, mesh = {Humans ; Metagenome ; *Metagenomics ; *Microbiota ; }, }
@article {pmid31975449, year = {2020}, author = {Megrian, D and Taib, N and Witwinowski, J and Beloin, C and Gribaldo, S}, title = {One or two membranes? Diderm Firmicutes challenge the Gram-positive/Gram-negative divide.}, journal = {Molecular microbiology}, volume = {113}, number = {3}, pages = {659-671}, doi = {10.1111/mmi.14469}, pmid = {31975449}, issn = {1365-2958}, mesh = {Bacteria/genetics/metabolism ; Biological Evolution ; Cell Membrane/*genetics/ultrastructure ; Cell Wall/genetics/ultrastructure ; Evolution, Molecular ; Firmicutes/classification/genetics ; Gram-Negative Bacteria/genetics/metabolism/*ultrastructure ; Gram-Positive Bacteria/genetics/metabolism/*ultrastructure ; Lipopolysaccharides ; Phylogeny ; }, abstract = {How, when and why the transition between cell envelopes with one membrane (Gram-positives or monoderms) and two (Gram-negative or diderms) occurred in Bacteria is a key unanswered question in evolutionary biology. Different hypotheses have been put forward, suggesting that either the monoderm or the diderm phenotype is ancestral. The existence of diderm members in the classically monoderm Firmicutes challenges the Gram-positive/Gram-negative divide and provides a great opportunity to tackle the issue. In this review, we present current knowledge on the diversity of bacterial cell envelopes, including these atypical Firmicutes. We discuss how phylogenomic analysis supports the hypothesis that the diderm cell envelope architecture is an ancestral character in the Firmicutes, and that the monoderm phenotype in this phylum arose multiple times independently by loss of the outer membrane. Given the overwhelming distribution of diderm phenotypes with respect to monoderm ones, this scenario likely extends to the ancestor of all bacteria. Finally, we discuss the recent development of genetic tools for Veillonella parvula, a diderm Firmicute member of the human microbiome, which indicates it as an emerging new experimental model to investigate fundamental aspects of the diderm/monoderm transition.}, }
@article {pmid31967708, year = {2020}, author = {Napoli, E and Siracusa, L and Ruberto, G}, title = {New Tricks for Old Guys: Recent Developments in the Chemistry, Biochemistry, Applications and Exploitation of Selected Species from the Lamiaceae Family.}, journal = {Chemistry & biodiversity}, volume = {17}, number = {3}, pages = {e1900677}, doi = {10.1002/cbdv.201900677}, pmid = {31967708}, issn = {1612-1880}, abstract = {Lamiaceae is one of the largest families of flowering plants comprising about 250 genera and over 7,000 species. Most of the plants of this family are aromatic and therefore important source of essential oils. Lamiaceae are widely used as culinary herbs and reported as medicinal plants in several folk traditions. In the Mediterranean area oregano, sage, rosemary, thyme and lavender stand out for geographical diffusion and variety of uses. The aim of this review is to provide recent data dealing with the phytochemical and pharmacological studies, and the more recent applications of the essential oils and the non-volatile phytocomplexes. This literature survey suggests how the deeper understanding of biomolecular processes in the health and food sectors as per as pest control bioremediation of cultural heritage, or interaction with human microbiome, fields, leads to the rediscovery and new potential applications of well-known plants.}, }
@article {pmid31964769, year = {2020}, author = {Jia, Z and Zhao, X and Liu, X and Zhao, L and Jia, Q and Shi, J and Xu, X and Hao, L and Xu, Z and Zhong, Q and Yu, K and Cui, S and Chen, H and Guo, J and Li, X and Han, Y and Song, X and Zhao, C and Bo, X and Tian, Y and Wang, W and Xie, G and Feng, Q and He, K}, title = {Impacts of the Plateau Environment on the Gut Microbiota and Blood Clinical Indexes in Han and Tibetan Individuals.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31964769}, issn = {2379-5077}, abstract = {The intestinal microbiota is significantly affected by the external environment, but our understanding of the effects of extreme environments such as plateaus is far from adequate. In this study, we systematically analyzed the variation in the intestinal microbiota and 76 blood clinical indexes among 393 healthy adults with different plateau living durations (Han individuals with no plateau living, with plateau living for 4 to 6 days, with plateau living for >3 months, and who returned to the plain for 3 months, as well as plateau-living Tibetans). The results showed that the high-altitude environment rapidly (4 days) and continually (more than 3 months) shaped both the intestinal microbiota and clinical indexes of the Han population. With prolongation of plateau living, the general characteristics of the intestinal microbiota and clinical indexes of the Han population were increasingly similar to those of the Tibetan population. The intestinal microbiota of the Han population that returned to the plain area for 3 months still resembled that of the plateau-living Han population rather than that of the Han population on the plain. Moreover, clinical indexes such as blood glucose were significantly lower in the plateau groups than in the nonplateau groups, while the opposite result was obtained for testosterone. Interestingly, there were Tibetan-specific correlations between glucose levels and Succinivibrio and Sarcina abundance in the intestine. The results of this study suggest that a hypoxic environment could rapidly and lastingly affect both the human intestinal microbiota and blood clinical indexes, providing new insights for the study of plateau adaptability.IMPORTANCE The data presented in the present study demonstrate that the hypoxic plateau environment has a profound impact on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. The plateau-changed signatures of the gut microbiota and blood clinical indexes were not restored to the nonplateau status in the Han cohorts, even when the individuals returned to the plain from the plateau for several months. Our study will improve the understanding of the great impact of hypoxic environments on the gut microbiota and blood clinical indexes as well as the adaptation mechanism and intervention targets for plateau adaptation.}, }
@article {pmid31961709, year = {2020}, author = {Lawenius, L and Scheffler, JM and Gustafsson, KL and Henning, P and Nilsson, KH and Colldén, H and Islander, U and Plovier, H and Cani, PD and de Vos, WM and Ohlsson, C and Sjögren, K}, title = {Pasteurized Akkermansia muciniphila protects from fat mass gain but not from bone loss.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {318}, number = {4}, pages = {E480-E491}, pmid = {31961709}, issn = {1522-1555}, mesh = {Adipose Tissue/*growth & development/metabolism ; Akkermansia ; Animals ; Calcium Channels/metabolism ; Colon/drug effects/microbiology ; Female ; Femur/drug effects ; Gastrointestinal Microbiome/*physiology ; Lymph Nodes/cytology ; Mice ; Mice, Inbred C57BL ; Osteoporosis/*metabolism ; Ovariectomy ; Parathyroid Hormone/metabolism ; Pasteurization ; Probiotics/*pharmacology ; Serum Amyloid A Protein/metabolism ; Spine/drug effects ; T-Lymphocytes, Regulatory ; TRPV Cation Channels/metabolism ; Verrucomicrobia/*metabolism ; }, abstract = {Probiotic bacteria can protect from ovariectomy (ovx)-induced bone loss in mice. Akkermansia muciniphila is considered to have probiotic potential due to its beneficial effect on obesity and insulin resistance. The purpose of the present study was to determine if treatment with pasteurized Akkermansia muciniphila (pAkk) could prevent ovx-induced bone loss. Mice were treated with vehicle or pAkk for 4 wk, starting 3 days before ovx or sham surgery. Treatment with pAkk reduced fat mass accumulation confirming earlier findings. However, treatment with pAkk decreased trabecular and cortical bone mass in femur and vertebra of gonadal intact mice and did not protect from ovx-induced bone loss. Treatment with pAkk increased serum parathyroid hormone (PTH) levels and increased expression of the calcium transporter Trpv5 in kidney suggesting increased reabsorption of calcium in the kidneys. Serum amyloid A 3 (SAA3) can suppress bone formation and mediate the effects of PTH on bone resorption and bone loss in mice and treatment with pAkk increased serum levels of SAA3 and gene expression of Saa3 in colon. Moreover, regulatory T cells can be protective of bone and pAkk-treated mice had decreased number of regulatory T cells in mesenteric lymph nodes and bone marrow. In conclusion, treatment with pAkk protected from ovx-induced fat mass gain but not from bone loss and reduced bone mass in gonadal intact mice. Our findings with pAkk differ from some probiotics that have been shown to protect bone mass, demonstrating that not all prebiotic and probiotic factors have the same effect on bone.}, }
@article {pmid31961674, year = {2020}, author = {Chang, PT and Rao, K and Longo, LO and Lawton, ES and Scherer, G and Van Arnam, EB}, title = {Thiopeptide Defense by an Ant's Bacterial Symbiont.}, journal = {Journal of natural products}, volume = {83}, number = {3}, pages = {725-729}, doi = {10.1021/acs.jnatprod.9b00897}, pmid = {31961674}, issn = {1520-6025}, abstract = {Fungus-growing ants and their microbial symbionts have emerged as a model system for understanding antibiotic deployment in an ecological context. Here we establish that bacterial symbionts of the ant Trachymyrmex septentrionalis antagonize their most likely competitors, other strains of ant-associated bacteria, using the thiopeptide antibiotic GE37468. Genomic analysis suggests that these symbionts acquired the GE37468 gene cluster from soil bacteria. This antibiotic, with known activity against human pathogens, was previously identified in a biochemical screen but had no known ecological role. GE37468's host-associated defense role in this insect niche intriguingly parallels the function of similar thiopeptides in the human microbiome.}, }
@article {pmid31954376, year = {2020}, author = {Korpela, K and Salonen, A and Saxen, H and Nikkonen, A and Peltola, V and Jaakkola, T and de Vos, W and Kolho, KL}, title = {Antibiotics in early life associate with specific gut microbiota signatures in a prospective longitudinal infant cohort.}, journal = {Pediatric research}, volume = {88}, number = {3}, pages = {438-443}, doi = {10.1038/s41390-020-0761-5}, pmid = {31954376}, issn = {1530-0447}, abstract = {BACKGROUND: The effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota.
METHODS: Antibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians' discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home.
RESULTS: One hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions.
CONCLUSIONS: Antibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.}, }
@article {pmid31949191, year = {2020}, author = {Husso, A and Jalanka, J and Alipour, MJ and Huhti, P and Kareskoski, M and Pessa-Morikawa, T and Iivanainen, A and Niku, M}, title = {The composition of the perinatal intestinal microbiota in horse.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {441}, pmid = {31949191}, issn = {2045-2322}, mesh = {Animals ; Animals, Newborn ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Dosage ; Horses ; Mouth/microbiology ; RNA, Ribosomal, 16S/genetics ; Vagina/microbiology ; }, abstract = {The establishment of the intestinal microbiota is critical for the digestive and immune systems. We studied the early development of the rectal microbiota in horse, a hindgut fermenter, from birth until 7 days of age, by qPCR and 16S rRNA gene amplicon sequencing. To evaluate initial sources of the foal microbiota, we characterised dam fecal, vaginal and oral microbiotas. We utilised an amplicon sequence variant (ASV) pipeline to maximise resolution and reproducibility. Stringent ASV filtering based on prevalence and abundance in samples and controls purged contaminants while preserving intestinal taxa. Sampled within 20 minutes after birth, rectal meconium contained small amounts of diverse bacterial DNA, with a profile closer to mare feces than mouth. 24 hours after birth, rectum was colonised by Firmicutes and Proteobacteria, some foals dominated by single genera. At day 7, the rectal genera were still different from adult feces. The mare vaginal microbiota contributed to 24 h and 7 day microbiotas. It contained few lactobacilli, with Corynebacterium, Porphyromonas, Campylobacter and Helcococcus as the most abundant genera. In the oral mucosa, Gemella was extremely abundant. Our observations indicate that bacteria or bacterial components are present in the intestine immediately after birth, but the newborn microbiota changes rapidly.}, }
@article {pmid31944633, year = {2020}, author = {Selway, CA and Eisenhofer, R and Weyrich, LS}, title = {Microbiome applications for pathology: challenges of low microbial biomass samples during diagnostic testing.}, journal = {The journal of pathology. Clinical research}, volume = {6}, number = {2}, pages = {97-106}, pmid = {31944633}, issn = {2056-4538}, abstract = {The human microbiome can play key roles in disease, and diagnostic testing will soon have the ability to examine these roles in the context of clinical applications. Currently, most diagnostic testing in pathology applications focuses on a small number of disease-causing microbes and dismisses the whole microbial community that causes or is modulated by disease. Microbiome modifications have already provided clinically relevant insights in gut and oral diseases, such as irritable bowel disease, but there are currently limitations when clinically examining microbiomes outside of these body sites. This is critical, as the majority of microbial samples used in pathology originate from body sites that contain low concentrations of microbial DNA, including skin, tissue, blood, and urine. These samples, also known as low microbial biomass samples, are difficult to examine without careful consideration and precautions to mitigate contamination and biases. Here, we present the limitations when analysing low microbial biomass samples using current protocols and techniques and highlight the advantages that microbiome testing can offer diagnostics in the future, if the proper precautions are implemented. Specifically, we discuss the sources of contamination and biases that may result in false assessments for these sample types. Finally, we provide recommendations to mitigate contamination and biases from low microbial biomass samples during diagnostic testing, which will be especially important to effectively diagnose and treat patients using microbiome analyses.}, }
@article {pmid31940382, year = {2020}, author = {Jian, C and Luukkonen, P and Yki-Järvinen, H and Salonen, A and Korpela, K}, title = {Quantitative PCR provides a simple and accessible method for quantitative microbiota profiling.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0227285}, pmid = {31940382}, issn = {1932-6203}, mesh = {Bacteria/classification/genetics/*isolation & purification ; DNA, Bacterial/genetics/isolation & purification ; Feasibility Studies ; Gene Library ; High-Throughput Nucleotide Sequencing ; High-Throughput Screening Assays/*methods ; Humans ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Randomized Controlled Trials as Topic ; *Real-Time Polymerase Chain Reaction ; }, abstract = {The use of relative abundance data from next generation sequencing (NGS) can lead to misinterpretations of microbial community structures, as the increase of one taxon leads to the concurrent decrease of the other(s) in compositional data. Although different DNA- and cell-based methods as well as statistical approaches have been developed to overcome the compositionality problem, and the biological relevance of absolute bacterial abundances has been demonstrated, the human microbiome research has not yet adopted these methods, likely due to feasibility issues. Here, we describe how quantitative PCR (qPCR) done in parallel to NGS library preparation provides an accurate estimation of absolute taxon abundances from NGS data and hence provides an attainable solution to compositionality in high-throughput microbiome analyses. The advantages and potential challenges of the method are also discussed.}, }
@article {pmid31921929, year = {2019}, author = {Zangl, I and Pap, IJ and Aspöck, C and Schüller, C}, title = {The role of Lactobacillus species in the control of Candida via biotrophic interactions.}, journal = {Microbial cell (Graz, Austria)}, volume = {7}, number = {1}, pages = {1-14}, pmid = {31921929}, issn = {2311-2638}, support = {EP-C-16-016/EPA/EPA/United States ; }, abstract = {Microbial communities have an important role in health and disease. Candida spp. are ubiquitous commensals and sometimes opportunistic fungal pathogens of humans, colonizing mucosal surfaces of the genital, urinary, respiratory and gastrointestinal tracts and the oral cavity. They mainly cause local mucosal infections in immune competent individuals. However, in the case of an ineffective immune defense, Candida infections may become a serious threat. Lactobacillus spp. are part of the human microbiome and are natural competitors of Candida in the vaginal environment. Lactic acid, low pH and other secreted metabolites are environmental signals sensed by fungal species present in the microbiome. This review briefly discusses the ternary interaction between host, Lactobacillus species and Candida with regard to fungal infections and the potential antifungal and fungistatic effect of Lactobacillus species. Our understanding of these interactions is incomplete due to the variability of the involved species and isolates and the complexity of the human host.}, }
@article {pmid31921705, year = {2019}, author = {Kang, W and Ji, X and Zhang, X and Tang, D and Feng, Q}, title = {Persistent Exposure to Fusobacterium nucleatum Triggers Chemokine/Cytokine Release and Inhibits the Proliferation and Osteogenic Differentiation Capabilities of Human Gingiva-Derived Mesenchymal Stem Cells.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {429}, pmid = {31921705}, issn = {2235-2988}, mesh = {Adult ; Cell Differentiation/genetics/physiology ; Cell Movement/*physiology ; Cell Proliferation/*physiology ; Cells, Cultured ; Chemokines/*metabolism ; Fusobacterium Infections/immunology/pathology ; Fusobacterium nucleatum/*immunology ; Humans ; Mesenchymal Stem Cells/cytology/*metabolism ; Osteogenesis/physiology ; Periodontitis/microbiology/pathology ; Tooth Extraction ; Tooth, Impacted/surgery ; Young Adult ; }, abstract = {Fusobacterium nucleatum is one of the most frequent pathogenic bacteria causing periodontitis. The direct effect of Fusobacterium nucleatum (F. nucleatum) on oral stem cells has rarely been reported. In this study, we aimed to evaluate how gingiva-derived mesenchymal stem cells (GMSCs) respond to a direct challenge with F. nucleatum. GMSCs were isolated by the limiting dilution method and exposed to F. nucleatum at various multiplicities of infection (MOIs; F. nucleatum:cell ratios of 10:1, 50:1, and 100:1) for 24 h to 4 weeks. Our results indicated that F. nucleatum significantly inhibited cell proliferation in a dose-dependent manner and promoted cell migration and the release of chemokines/cytokines, such as CCL2, CXCL1, and IL-6. Additionally, F. nucleatum inhibited GMSC osteogenic differentiation partly by decreasing alkaline phosphatase (ALP) activity, mineralized nodule formation, and osteogenesis-related gene and protein expression. RNA-sequencing analyses indicated that F. nucleatum time-dependently activated cellular signaling pathways during the process of osteogenic differentiation. A total of 64 cell differentiation-related genes were found to be differentially expressed between non-infected and F. nucleatum-infected GMSCs at 3, 7, 14, and 21 d. Intriguingly, we discovered that the 64 cell differentiation-related differentially expressed genes (DEGs) were significantly enriched in cancer-related pathways, such as bone cancer, osteosarcoma and bone marrow cancer, which provides new insight into tumorigenesis during the process of GMSC osteogenic differentiation. In conclusion, this study demonstrates that persistent exposure to F. nucleatum promotes cell migration and chemokine/cytokine release and inhibits the proliferation and osteogenic differentiation of GMSCs. Our study provides a novel and long-time bacteria-cell co-culture in vitro model and makes a foundation for the future mechanistic studies of GMSCs under F. nucleatum infection.}, }
@article {pmid31919630, year = {2020}, author = {Nobile, V and Palumbo, F and Lanni, S and Ghisio, V and Vitali, A and Castagnola, M and Marzano, V and Maulucci, G and De Angelis, C and De Spirito, M and Pacini, L and D'Andrea, L and Ragno, R and Stazi, G and Valente, S and Mai, A and Chiurazzi, P and Genuardi, M and Neri, G and Tabolacci, E}, title = {Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.}, journal = {Human genetics}, volume = {139}, number = {2}, pages = {227-245}, pmid = {31919630}, issn = {1432-1203}, support = {GGP15257A//Fondazione Telethon/ ; Prot. 201789LFKB//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Ataxia/genetics/metabolism/*pathology ; Case-Control Studies ; Cells, Cultured ; *DNA Methylation ; Fibroblasts/metabolism/pathology ; Fragile X Mental Retardation Protein/genetics/*metabolism ; Fragile X Syndrome/genetics/metabolism/*pathology ; Humans ; Male ; Mitochondria/metabolism/*pathology ; Mitochondrial Proteins/genetics/*metabolism ; *Mutation ; Proteome/*analysis ; RNA, Small Interfering/genetics ; Superoxide Dismutase/antagonists & inhibitors/genetics/metabolism ; Tremor/genetics/metabolism/*pathology ; }, abstract = {Fragile X-related disorders are due to a dynamic mutation of the CGG repeat at the 5' UTR of the FMR1 gene, coding for the RNA-binding protein FMRP. As the CGG sequence expands from premutation (PM, 56-200 CGGs) to full mutation (> 200 CGGs), FMRP synthesis decreases until it is practically abolished in fragile X syndrome (FXS) patients, mainly due to FMR1 methylation. Cells from rare individuals with no intellectual disability and carriers of an unmethylated full mutation (UFM) produce slightly elevated levels of FMR1-mRNA and relatively low levels of FMRP, like in PM carriers. With the aim of clarifying how UFM cells differ from CTRL and FXS cells, a comparative proteomic approach was undertaken, from which emerged an overexpression of SOD2 in UFM cells, also confirmed in PM but not in FXS. The SOD2-mRNA bound to FMRP in UFM more than in the other cell types. The high SOD2 levels in UFM and PM cells correlated with lower levels of superoxide and reactive oxygen species (ROS), and with morphological anomalies and depolarization of the mitochondrial membrane detected through confocal microscopy. The same effect was observed in CTRL and FXS after treatment with MC2791, causing SOD2 overexpression. These mitochondrial phenotypes reverted after knock-down with siRNA against SOD2-mRNA and FMR1-mRNA in UFM and PM. Overall, these data suggest that in PM and UFM carriers, which have high levels of FMR1 transcription and may develop FXTAS, SOD2 overexpression helps to maintain low levels of both superoxide and ROS with signs of mitochondrial degradation.}, }
@article {pmid31918033, year = {2020}, author = {Marzano, V and Tilocca, B and Fiocchi, AG and Vernocchi, P and Levi Mortera, S and Urbani, A and Roncada, P and Putignani, L}, title = {Perusal of food allergens analysis by mass spectrometry-based proteomics.}, journal = {Journal of proteomics}, volume = {215}, number = {}, pages = {103636}, doi = {10.1016/j.jprot.2020.103636}, pmid = {31918033}, issn = {1876-7737}, abstract = {Food allergy is the disease where the immune system is elicited by antigens in food. Although innocuous for immune-tolerant individuals, an ever-growing number of food allergenic people are being registered worldwide. To date, no treatment to cure food allergy is available and the disease management relies on the careful exclusion of the allergenic food from the diet of the allergic individuals. Great efforts are ongoing to clarify the allergenic mechanisms of the diverse allergenic proteins of food origin, aimed to both designing suitable therapies and for a timely and precise diagnosis of the allergic condition. Among the other omics sciences, mass spectrometry (MS)-based proteomics is gaining a steadily increasing interest by the whole scientific community acknowledged its high versatility. In the present work, the latest proteomics based-studies on allergenic proteins are reviewed to provide guidance on the different MS-based methodologies adopted in the research on food allergens. Our review points to highlight the strengths of the MS-based proteomics and how these have been exploited to address specific research questions. Also, the most common drawbacks encountered in a proteomic study are discussed, providing an overview that helps novel researchers in choosing the more suitable experimental workflow. SIGNIFICANCE: Wide wealth of knowledge arising from the various MS-based proteomic investigations is improving our understanding of food allergy through molecular characterization of food allergens. The present work reviews the key aspects to be evaluated while investigating food allergens by means of MS-based proteomics and provide guidance to the novel research groups approaching to the fascinating world of MS-based food allergens detection.}, }
@article {pmid31905733, year = {2019}, author = {Signore, F and Gulìa, C and Votino, R and De Leo, V and Zaami, S and Putignani, L and Gigli, S and Santini, E and Bertacca, L and Porrello, A and Piergentili, R}, title = {The Role of Number of Copies, Structure, Behavior and Copy Number Variations (CNV) of the Y Chromosome in Male Infertility.}, journal = {Genes}, volume = {11}, number = {1}, pages = {}, pmid = {31905733}, issn = {2073-4425}, mesh = {Chromosome Aberrations ; Chromosomes, Human, Y/*genetics ; *DNA Copy Number Variations ; Humans ; Infertility, Male/*genetics ; Karyotyping ; Male ; Mutation ; Sequence Analysis, DNA ; }, abstract = {The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30-40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome.}, }
@article {pmid31904815, year = {2020}, author = {Zhang, X and Yi, N}, title = {Fast zero-inflated negative binomial mixed modeling approach for analyzing longitudinal metagenomics data.}, journal = {Bioinformatics (Oxford, England)}, volume = {36}, number = {8}, pages = {2345-2351}, doi = {10.1093/bioinformatics/btz973}, pmid = {31904815}, issn = {1367-4811}, mesh = {Humans ; Metagenome ; *Metagenomics ; *Microbiota/genetics ; Models, Statistical ; RNA, Ribosomal, 16S/genetics ; }, abstract = {MOTIVATION: Longitudinal metagenomics data, including both 16S rRNA and whole-metagenome shotgun sequencing data, enhanced our abilities to understand the dynamic associations between the human microbiome and various diseases. However, analytic tools have not been fully developed to simultaneously address the main challenges of longitudinal metagenomics data, i.e. high-dimensionality, dependence among samples and zero-inflation of observed counts.
RESULTS: We propose a fast zero-inflated negative binomial mixed modeling (FZINBMM) approach to analyze high-dimensional longitudinal metagenomic count data. The FZINBMM approach is based on zero-inflated negative binomial mixed models (ZINBMMs) for modeling longitudinal metagenomic count data and a fast EM-IWLS algorithm for fitting ZINBMMs. FZINBMM takes advantage of a commonly used procedure for fitting linear mixed models, which allows us to include various types of fixed and random effects and within-subject correlation structures and quickly analyze many taxa. We found that FZINBMM remarkably outperformed in computational efficiency and was statistically comparable with two R packages, GLMMadaptive and glmmTMB, that use numerical integration to fit ZINBMMs. Extensive simulations and real data applications showed that FZINBMM outperformed other previous methods, including linear mixed models, negative binomial mixed models and zero-inflated Gaussian mixed models.
FZINBMM has been implemented in the R package NBZIMM, available in the public GitHub repository http://github.com//nyiuab//NBZIMM.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.}, }
@article {pmid31904155, year = {2020}, author = {Cui, JJ and Wang, LY and Tan, ZR and Zhou, HH and Zhan, X and Yin, JY}, title = {MASS SPECTROMETRY-BASED PERSONALIZED DRUG THERAPY.}, journal = {Mass spectrometry reviews}, volume = {39}, number = {5-6}, pages = {523-552}, doi = {10.1002/mas.21620}, pmid = {31904155}, issn = {1098-2787}, abstract = {Personalized drug therapy aims to provide tailored treatment for individual patient. Mass spectrometry (MS) is revolutionarily involved in this area because MS is a rapid, customizable, cost-effective, and easy to be used high-throughput method with high sensitivity, specificity, and accuracy. It is driving the formation of a new field, MS-based personalized drug therapy, which currently mainly includes five subfields: therapeutic drug monitoring (TDM), pharmacogenomics (PGx), pharmacomicrobiomics, pharmacoepigenomics, and immunopeptidomics. Gas chromatography-MS (GC-MS) and liquid chromatography-MS (LC-MS) are considered as the gold standard for TDM, which can be used to optimize drug dosage. Matrix-assisted laser desorption ionization-time of flight-MS (MALDI-TOF-MS) significantly improves the capability of detecting biomacromolecule, and largely promotes the application of MS in PGx. It is becoming an indispensable tool for genotyping, which is used to discover and validate genetic biomarkers. In addition, MALDI-TOF-MS also plays important roles in identity of human microbiome whose diversity can explain interindividual differences of drug response. Pharmacoepigenetics is to study the role of epigenetic factors in individualized drug treatment. MS can be used to discover and validate pharmacoepigenetic markers (DNA methylation, histone modification, and noncoding RNA). For the emerging cancer immunotherapy, personalized cancer vaccine has effective immunotherapeutic activity in the clinic. MS-based immunopeptidomics can effectively discover and screen neoantigens. This article systematically reviewed MS-based personalized drug therapy in the above mentioned five subfields. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.}, }
@article {pmid31894374, year = {2020}, author = {Yang, J and Zhang, J and Zhao, C and Gai, Z and Mu, X and Wang, Y and Zhang, C and Su, Z and Gao, L and Zhu, D and Zuo, Z and Heng, X and Zhang, L}, title = {Blood Loss Leads to Increase in Relative Abundance of Opportunistic Pathogens in the Gut Microbiome of Rabbits.}, journal = {Current microbiology}, volume = {77}, number = {3}, pages = {415-424}, doi = {10.1007/s00284-019-01825-2}, pmid = {31894374}, issn = {1432-0991}, support = {81671362//The National Natural Science Foundation of China/ ; 31471202//The National Natural Science Foundation of China/ ; 2018CXGC1219//The Shandong Provincial Key Research and Development Program/ ; 2016YYSP009//The Shandong Provincial Key Research and Development Program/ ; 2016GNS023//Weihai Technique Extension Project/ ; tshw20120206//The Taishan Scholars Program of Shandong Province/ ; }, mesh = {Animals ; Bacteria/genetics/*pathogenicity ; Dysbiosis/*etiology ; Feces/microbiology ; *Gastrointestinal Microbiome ; Hemorrhage/*complications ; Male ; Opportunistic Infections/*etiology/microbiology ; RNA, Ribosomal, 16S/genetics ; Rabbits/microbiology ; }, abstract = {Massive blood loss, a common pathological complication in the clinic, is often accompanied by altered gut integrity and intestinal wall damage. Little is known to what extent the gut microbiome could be correlated with this process. The gut microbiome plays a crucial role in human health, especially in immune and inflammatory responses. This study aims to determine whether acute blood loss affects the gut microbiome and the dynamic variation of the gut microbiome following the loss of blood. We used New Zealand rabbits to mimic the blood loss complication and designed a five-time-point fecal sampling strategy including 24-h pre-blood loss procedure, 24 h, 36 h, 48 h, and 1-week post-blood loss procedure. Gut microbiome composition and diversity were analyzed using 16S rRNA gene sequencing and downstream α-diversity, β-diversity, and taxonomy analysis. The gut microbiome changed dramatically after blood loss procedure. There was a significant increase in diversity and richness of the gut microbiome at 24-h post-procedure (P = 0.038). Based on an analysis of similarities, the composition of gut microbiome in the samples collected at 24-h post-procedure was significantly different from that of pre-procedure samples (r = 0.79, P = 0.004 weighted unifrac distance; r = 0.99, P = 0.002, unweighted unifrac distance). The relative abundance of Lactobacillus was significantly decreased in the post-procedure samples (P = 0.0006), while the relative abundance of Clostridiales (P = 0.018) and Bacteroidales (P = 0.015) was significantly increased after procedure. We also found the relative abundance of Bacilli, Lactobacillus, Myroides, and Prevotella decreased gradually at different time points after blood loss. The relative abundance of the Clostridia, Alphaproteobacteria, and Sporosarcina increased at 24-h post-procedure and decreased thereafter. This preliminary study discovered potential connections between blood loss and dysbiosis of gut microbiome. The diversity and abundance of the gut microbiome was affected to various extents after acute blood loss and unable to be restored to the original microbiome profile even after one week. The increase in relative abundance of opportunistic pathogens after blood loss could be an important indication to reconsider immune and inflammatory responses after acute blood loss from the perspective of gut microbiome.}, }
@article {pmid31889089, year = {2019}, author = {Gavin, DP and Reen, FJ and Rocha-Martin, J and Abreu-Castilla, I and Woods, DF and Foley, AM and Sánchez-Murcia, PA and Schwarz, M and O'Neill, P and Maguire, AR and O'Gara, F}, title = {Genome mining and characterisation of a novel transaminase with remote stereoselectivity.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {20285}, pmid = {31889089}, issn = {2045-2322}, mesh = {Amino Acid Sequence ; *Computational Biology/methods ; *Data Mining ; Enzyme Activation ; *Genome ; *Genomics/methods ; Models, Molecular ; Molecular Structure ; Phylogeny ; Stereoisomerism ; Structure-Activity Relationship ; Transaminases/*chemistry/*genetics/metabolism ; }, abstract = {Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.}, }
@article {pmid31887978, year = {2019}, author = {Picca, A and Ponziani, FR and Calvani, R and Marini, F and Biancolillo, A and Coelho-Junior, HJ and Gervasoni, J and Primiano, A and Putignani, L and Del Chierico, F and Reddel, S and Gasbarrini, A and Landi, F and Bernabei, R and Marzetti, E}, title = {Gut Microbial, Inflammatory and Metabolic Signatures in Older People with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study.}, journal = {Nutrients}, volume = {12}, number = {1}, pages = {}, pmid = {31887978}, issn = {2072-6643}, support = {IMI-JU #115621//Innovative Medicines Initiative/ ; D3.2 2013//Intramural Research Grants from the Università Cattolica del Sacro Cuore/ ; D3.2 2015//Intramural Research Grants from the Università Cattolica del Sacro Cuore/ ; NA//Nonprofit research foundation "Centro Studi Achille e Linda Lorenzon"/ ; CAPES; Finance Code 001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Aged ; Amino Acids/metabolism ; Cohort Studies ; Cytokines/blood ; Female ; Frail Elderly ; *Frailty/complications/epidemiology/metabolism ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*metabolism ; Male ; *Sarcopenia/complications/epidemiology/metabolism ; }, abstract = {Physical frailty and sarcopenia (PF&S) share multisystem derangements, including variations in circulating amino acids and chronic low-grade inflammation. Gut microbiota balances inflammatory responses in several conditions and according to nutritional status. Therefore, an altered gut-muscle crosstalk has been hypothesized in PF&S. We analyzed the gut microbial taxa, systemic inflammation, and metabolic characteristics of older adults with and without PF&S. An innovative multi-marker analytical approach was applied to explore the classification performance of potential biomarkers for PF&S. Thirty-five community dwellers aged 70+, 18 with PF&S, and 17 nonPF&S controls were enrolled. Sequential and Orthogonalized Covariance Selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables, was applied. The SO-CovSel model with the best prediction ability using the smallest number of variables was built using seven mediators. The model correctly classified 91.7% participants with PF&S and 87.5% nonPF&S controls. Compared with the latter group, PF&S participants showed higher serum concentrations of aspartic acid, lower circulating levels of concentrations of threonine and macrophage inflammatory protein 1α, increased abundance of Oscillospira and Ruminococcus microbial taxa, and decreased abundance of Barnesiellaceae and Christensenellaceae. Future investigations are warranted to determine whether these biomediators are involved in PF&S pathophysiology and may, therefore, provide new targets for interventions.}, }
@article {pmid31886477, year = {2019}, author = {Tomassi, D and Forzani, L and Duarte, S and Pfeiffer, RM}, title = {Sufficient dimension reduction for compositional data.}, journal = {Biostatistics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/biostatistics/kxz060}, pmid = {31886477}, issn = {1468-4357}, 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 {pmid31883524, year = {2019}, author = {Manara, S and Asnicar, F and Beghini, F and Bazzani, D and Cumbo, F and Zolfo, M and Nigro, E and Karcher, N and Manghi, P and Metzger, MI and Pasolli, E and Segata, N}, title = {Microbial genomes from non-human primate gut metagenomes expand the primate-associated bacterial tree of life with over 1000 novel species.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {299}, pmid = {31883524}, issn = {1474-760X}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; Phylogeny ; Primates/*microbiology ; Treponema/genetics ; }, abstract = {BACKGROUND: Humans have coevolved with microbial communities to establish a mutually advantageous relationship that is still poorly characterized and can provide a better understanding of the human microbiome. Comparative metagenomic analysis of human and non-human primate (NHP) microbiomes offers a promising approach to study this symbiosis. Very few microbial species have been characterized in NHP microbiomes due to their poor representation in the available cataloged microbial diversity, thus limiting the potential of such comparative approaches.
RESULTS: We reconstruct over 1000 previously uncharacterized microbial species from 6 available NHP metagenomic cohorts, resulting in an increase of the mappable fraction of metagenomic reads by 600%. These novel species highlight that almost 90% of the microbial diversity associated with NHPs has been overlooked. Comparative analysis of this new catalog of taxa with the collection of over 150,000 genomes from human metagenomes points at a limited species-level overlap, with only 20% of microbial candidate species in NHPs also found in the human microbiome. This overlap occurs mainly between NHPs and non-Westernized human populations and NHPs living in captivity, suggesting that host lifestyle plays a role comparable to host speciation in shaping the primate intestinal microbiome. Several NHP-specific species are phylogenetically related to human-associated microbes, such as Elusimicrobia and Treponema, and could be the consequence of host-dependent evolutionary trajectories.
CONCLUSIONS: The newly reconstructed species greatly expand the microbial diversity associated with NHPs, thus enabling better interrogation of the primate microbiome and empowering in-depth human and non-human comparative and co-diversification studies.}, }
@article {pmid31876898, year = {2020}, author = {Harkins, CP and Kong, HH and Segre, JA}, title = {Manipulating the Human Microbiome to Manage Disease.}, journal = {JAMA}, volume = {323}, number = {4}, pages = {303-304}, doi = {10.1001/jama.2019.19602}, pmid = {31876898}, issn = {1538-3598}, mesh = {Child ; Child Nutrition Disorders/diet therapy/microbiology ; Clostridium Infections/therapy ; *Disease Management ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; HIV Infections/drug therapy ; Humans ; Infant, Newborn ; *Microbiota ; Neonatal Sepsis/prevention & control ; Vagina/microbiology ; }, }
@article {pmid31875448, year = {2019}, author = {Zhou, ZY and Xu, X and Zhou, Y}, title = {[Research progress on carbohydrate active enzymes of human microbiome].}, journal = {Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology}, volume = {37}, number = {6}, pages = {666-670}, pmid = {31875448}, issn = {2618-0456}, mesh = {Carbohydrates ; *Gastrointestinal Tract ; Humans ; *Microbiota ; }, abstract = {A massive variety of microorganisms live in and on the human body, especially at oral, skin, vaginal, gastroin-testinal, and respiratory sites. The complicated metabolic activities of microorganisms assist human digestive function and participate in a series of physiological and pathogenetic processes. Carbohydrate-active enzymes (CAZymes) are a series of enzymes that function in degradation, modification, and formation of glycoside bonds. Microbes regulate the physiological and pathogenetic processes of human body by producing various CAZymes to degrade and modify complex carbohydrates and generate signal molecules for further utilization in human cells. Here, we reviewed the mechanisms of complex carbohy-drate metabolism and related microbial CAZymes, especially in digestive tract and oral cavity. We also summarized the rela-tionship between microbial CAZymes and human health, and proposed potential applications.}, }
@article {pmid31874963, year = {2019}, author = {Majid, M and Andleeb, S}, title = {Designing a multi-epitopic vaccine against the enterotoxigenic Bacteroides fragilis based on immunoinformatics approach.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {19780}, pmid = {31874963}, issn = {2045-2322}, mesh = {*Bacterial Proteins/chemistry/genetics/immunology ; *Bacterial Vaccines/chemistry/genetics/immunology ; *Bacteroides fragilis/chemistry/genetics/immunology ; *Computational Biology ; *Epitopes/chemistry/genetics/immunology ; Humans ; *Molecular Docking Simulation ; Toll-Like Receptor 2/chemistry/genetics/immunology ; }, abstract = {Enterotoxigenic Bacteroides fragilis is an enteric pathogen which is described as a causative agent of various intestinal infections and inflammatory diseases. Moreover, various research studies have reported it to be a leading factor in the development of colorectal cancer. As a part of the normal human microbiome, its treatment has become quite a challenge due to the alarming resistance against the available antibiotics. Although, this particular strain of B. fragilis shows susceptibility to few antibiotics, it is pertinent to devise an effective vaccine strategy for its elimination. There is no vaccine available against this pathogen up to date; therefore, we systematically ventured the outer membrane toxin producing proteins found exclusively in the toxigenic B. fragilis through the in-silico approaches to predict a multi-epitopic chimeric vaccine construct. The designed protein constitutes of epitopes which are predicted for linear B cells, Helper and T cells of outer membrane proteins expected to be putative vaccine candidates. The finalized proteins are only expressed in the enterotoxigenic B. fragilis, thus proving them to be exclusive. The 3D structure of the protein was first predicted followed by its refinement and validation via utilizing the bioinformatic approaches. Docking of the designed protein with the TLR2 receptor forecasted apt binding. Upon immune simulation, notable levels were observed in the expression of the immune cells.}, }
@article {pmid31872558, year = {2019}, author = {Grosicki, GJ and Durk, RP and Bagley, JR}, title = {Rapid gut microbiome changes in a world-class ultramarathon runner.}, journal = {Physiological reports}, volume = {7}, number = {24}, pages = {e14313}, pmid = {31872558}, issn = {2051-817X}, mesh = {Adult ; Athletes ; *Gastrointestinal Microbiome ; Humans ; Lactic Acid/blood ; Male ; Oxygen Consumption ; Physical Exertion ; *Running ; }, abstract = {The human gut microbiome is a dynamic ecosystem with prolific health connotations. Physical activity is emerging as a potent regulator of human microbiome composition. This study examined changes in the gut microbiome of a world-class ultramarathon runner before and after competing in the Western States Endurance Run (WSER), a 163 km mountain footrace. Anthropometrics and body composition were assessed and the ultramarathoner's submaximal and maximal performance profiles were evaluated. Gut microbiome analyses were performed at four time-points: 21 weeks and 2 weeks before and 2 hours and 10 days after WSER. Aerobic power (VO2 max) was 4.24 L/min (66.7 ml kg-1 min-1), and running economy (51.1 ml kg-1 min-1 at 268 m/min) and lactate threshold (~83% VO2 max) values were comparable to that of highly trained distance runners. Two hours post-race, considerable changes in the ultrarunners' gut microbiome were observed. Alpha diversity (Shannon Diversity Index) increased from 2.73 to 2.80 and phylum-level bacterial composition (Firmicutes/Bacteroidetes ratio) rose from 4.4 to 14.2. Underlying these macro-level microbial alterations were demonstrable increases in select bacterial genera such as Veillonella (+14,229%) and Streptococcus (+438%) concomitant with reductions in Alloprevotella (-79%) and Subdolingranulum (-50%). To our knowledge, this case study shows the most rapid and pronounced shifts in human gut microbiome composition after acute exercise in the human literature. These findings provide yet another example of how exercise can be a powerful modulator of human health.}, }
@article {pmid31870912, year = {2020}, author = {Ly, LK and Rowles, JL and Paul, HM and Alves, JMP and Yemm, C and Wolf, PM and Devendran, S and Hudson, ME and Morris, DJ and Erdman, JW and Ridlon, JM}, title = {Bacterial steroid-17,20-desmolase is a taxonomically rare enzymatic pathway that converts prednisone to 1,4-androstanediene-3,11,17-trione, a metabolite that causes proliferation of prostate cancer cells.}, journal = {The Journal of steroid biochemistry and molecular biology}, volume = {199}, number = {}, pages = {105567}, pmid = {31870912}, issn = {1879-1220}, support = {T32 CA057699/CA/NCI NIH HHS/United States ; }, mesh = {Adrenal Glands/metabolism ; Androgens/metabolism ; Androstadienes/*metabolism ; Cell Line, Tumor ; Cell Proliferation/genetics ; Clostridiales/enzymology ; Glucocorticoids/*metabolism ; Humans ; Hydrocortisone/metabolism ; Male ; Metabolic Networks and Pathways/genetics ; Phylogeny ; Prednisolone/metabolism ; Prednisone/metabolism ; Propionibacteriaceae/enzymology ; Prostatic Neoplasms/enzymology/genetics/*metabolism/pathology ; Steroid 17-alpha-Hydroxylase/genetics/*metabolism ; }, abstract = {The adrenal gland has traditionally been viewed as a source of "weak androgens"; however, emerging evidence indicates 11-oxy-androgens of adrenal origin are metabolized in peripheral tissues to potent androgens. Also emerging is the role of gut bacteria in the conversion of C21 glucocorticoids to 11-oxygenated C19 androgens. Clostridium scindens ATCC 35,704 is a gut microbe capable of converting cortisol into 11-oxy-androgens by cleaving the side-chain. The desA and desB genes encode steroid-17,20-desmolase. Our prior study indicated that the urinary tract bacterium, Propionimicrobium lymphophilum ACS-093-V-SCH5 encodes desAB and converts cortisol to 11β-hydroxyandrostenedione. We wanted to determine how widespread this function occurs in the human microbiome. Phylogenetic and sequence similarity network analyses indicated that the steroid-17,20-desmolase pathway is taxonomically rare and located in gut and urogenital microbiomes. Two microbes from each of these niches, C. scindens and Propionimicrobium lymphophilum, respectively, were screened for activity against endogenous (cortisol, cortisone, and allotetrahydrocortisol) and exogenous (prednisone, prednisolone, dexamethasone, and 9-fluorocortisol) glucocorticoids. LC/MS analysis showed that both microbes were able to side-chain cleave all glucocorticoids, forming 11-oxy-androgens. Pure recombinant DesAB from C. scindens showed the highest activity against prednisone, a commonly prescribed glucocorticoid. In addition, 0.1 nM 1,4-androstadiene-3,11,17-trione, bacterial side-chain cleavage product of prednisone, showed significant proliferation relative to vehicle in androgen-dependent growth LNCaP prostate cancer cells after 24 h (2.3 fold; P < 0.01) and 72 h (1.6 fold; P < 0.01). Taken together, DesAB-expressing microbes may be an overlooked source of androgens in the body, potentially contributing to various disease states, such as prostate cancer.}, }
@article {pmid31866425, year = {2020}, author = {Liu, Q and Liu, Q and Meng, H and Lv, H and Liu, Y and Liu, J and Wang, H and He, L and Qin, J and Wang, Y and Dai, Y and Otto, M and Li, M}, title = {Staphylococcus epidermidis Contributes to Healthy Maturation of the Nasal Microbiome by Stimulating Antimicrobial Peptide Production.}, journal = {Cell host & microbe}, volume = {27}, number = {1}, pages = {68-78.e5}, doi = {10.1016/j.chom.2019.11.003}, pmid = {31866425}, issn = {1934-6069}, support = {ZIA AI000904/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged, 80 and over ; Antimicrobial Cationic Peptides/*biosynthesis ; Biofilms/growth & development ; Cell Line ; Child ; Child, Preschool ; Epidermal Cells ; Female ; High-Throughput Nucleotide Sequencing ; Host Microbial Interactions ; Humans ; Immunity, Innate ; Male ; Metagenomics ; Microbiota/*immunology ; Nasal Cavity/*microbiology ; RNA, Ribosomal, 16S ; *Staphylococcus epidermidis/isolation & purification/metabolism ; Symbiosis ; Young Adult ; }, abstract = {The composition of the human microbiome profoundly impacts human well-being. However, the mechanisms underlying microbiome maturation are poorly understood. The nasal microbiome is of particular importance as a source of many respiratory infections. Here, we performed a large sequencing and culture-based analysis of the human nasal microbiota from different age groups. We observed a significant decline of pathogenic bacteria before adulthood, with an increase of the commensal Staphylococcus epidermidis. In seniors, this effect was partially reversed. In vitro, many S. epidermidis isolates stimulated nasal epithelia to produce antimicrobial peptides, killing pathogenic competitors, while S. epidermidis itself proved highly resistant owing to its exceptional capacity to form biofilms. Furthermore, S. epidermidis isolates with high antimicrobial peptide-inducing and biofilm-forming capacities outcompeted pathogenic bacteria during nasal colonization in vivo. Our study identifies a pivotal role of S. epidermidis in healthy maturation of the nasal microbiome, which is achieved at least in part by symbiotic cooperation with innate host defense.}, }
@article {pmid31861722, year = {2019}, author = {Deering, KE and Devine, A and O'Sullivan, TA and Lo, J and Boyce, MC and Christophersen, CT}, title = {Characterizing the Composition of the Pediatric Gut Microbiome: A Systematic Review.}, journal = {Nutrients}, volume = {12}, number = {1}, pages = {}, pmid = {31861722}, issn = {2072-6643}, support = {NA//Edith Cowan University/ ; }, mesh = {Bacteria/classification/*genetics ; Child ; Diet ; *Gastrointestinal Microbiome ; Humans ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {The consortium of trillions of microorganisms that live inside the human gut are integral to health. Little has been done to collate and characterize the microbiome of children. A systematic review was undertaken to address this gap (PROSPERO ID: CRD42018109599). MEDLINE and EMBASE were searched using the keywords: "healthy preadolescent children" and "gut microbiome" to 31 August 2018. Of the 815 journal articles, 42 met the inclusion criteria. The primary outcome was the relative abundance of bacteria at the phylum, family, and genus taxonomic ranks. α-diversity, short chain fatty acid concentrations, diet, 16S rRNA sequencing region, and geographical location were documented. The preadolescent gut microbiome is dominated at the phylum level by Firmicutes (weighted overall average relative abundance = 51.1%) and Bacteroidetes (36.0%); genus level by Bacteroides (16.0%), Prevotella (8.69%), Faecalibacterium (7.51%), and Bifidobacterium (5.47%). Geographic location and 16S rRNA sequencing region were independently associated with microbial proportions. There was limited consensus between studies that reported α-diversity and short chain fatty acids. Broadly speaking, participants from non-Western locations, who were less likely to follow a Westernized dietary pattern, had higher α-diversity and SCFA concentrations. Confirmatory studies will increase the understanding of the composition and functional capacity of the preadolescent gut microbiome.}, }
@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 ; DEB-1925761//NSF | BIO | Division of Environmental Biology (DEB)/International ; N00014-19-1-2313//United States Department of Defense | United States Navy | Office of Naval Research (ONR)/International ; }, mesh = {Animals ; Capital Financing ; Communication ; Humans ; Interdisciplinary Research/economics/*organization & administration/*trends ; *Microbiota ; }, }
@article {pmid31850811, year = {2019}, author = {Lo Presti, A and Del Chierico, F and Altomare, A and Zorzi, F and Cella, E and Putignani, L and Guarino, MPL and Monteleone, G and Cicala, M and Angeletti, S and Ciccozzi, M}, title = {Exploring the genetic diversity of the 16S rRNA gene of Akkermansia muciniphila in IBD and IBS.}, journal = {Future microbiology}, volume = {14}, number = {}, pages = {1497-1509}, doi = {10.2217/fmb-2019-0175}, pmid = {31850811}, issn = {1746-0921}, mesh = {Adult ; Akkermansia ; Evolution, Molecular ; Feces/microbiology ; Gastrointestinal Microbiome ; *Genetic Variation ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Irritable Bowel Syndrome/*microbiology ; Middle Aged ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/*genetics ; Verrucomicrobia/*genetics ; }, abstract = {Aim: The human gastrointestinal tract harbors diverse, abundant microbiota and Akkermansia muciniphila is involved in this community. The aim of this study is to characterize 16 new A. muciniphila 16S ribosomal RNA sequences selected from a metagenomic database from stools of patients with irritable bowel syndrome (IBS), inflammatory bowel diseases and control (CTRLs) subjects by a phylogenetic approach. Materials & methods: A phylogenetic approach was used to study the genetic diversity and SNPs in 16 A. muciniphila 16S ribosomal RNA sequences from stools of 107 individuals, 36 of which were patients affected by IBS, 30 by inflammatory bowel disease and 41 were CTRLs. Results: Phylogenetic analysis confirmed the subdivision into different supported clusters. An increase of variability in IBS has been identified. Conclusion: The genetic variation combined to the relative abundance, contribute to the protective role of A. muciniphila. Phylogenesis represent an additional approach to investigate genetic variability.}, }
@article {pmid31850333, year = {2019}, author = {Song, N and Liu, X and Feng, Q and Xu, M and Lan, X and Li, M and Liu, R and Li, C and Dong, T and Wang, D and Liu, S}, title = {Whole Body Vibration Triggers a Change in the Mutual Shaping State of Intestinal Microbiota and Body's Immunity.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {7}, number = {}, pages = {377}, pmid = {31850333}, issn = {2296-4185}, abstract = {Whole body vibration (WBV) is a non-invasive physical therapy that has recently been included in the hospital's patient rehabilitation training catalog, but its health effects have not been sufficiently studied. In the present study, to examine the possible effects of WBV on immune cell differentiation, the IFN, IL-4,-17, F4/80 and CD3,-4,-8,-11b,-11c,-19 markers were used to characterizing the cells in mouse spleen. The results showed that the CD4 and CD25 positive lymphocytes in the spleen were significantly increased in the WBV group, and the population of Treg cells was enhanced significantly in response to WBV. Since the differentiation in immune cells is usually associated with microbiota, therefore the intestinal flora was characterized in mice and human individuals. The results indicated that WBV significantly reduced the α-diversity of mouse intestinal microbiota. Moreover, the principal coordinate analysis (PCoA) results indicated that the β-diversities of both mice and human fecal microbiota increased after WBV. Analysis of the bacterial composition indicated that the contents of a variety of bacteria changed in mice upon the stimulation of vibration, such as Lactobacillus animalis in mice, and Lactobacillus paraplantarum and Lactobacillus sanfranciscensis in human. The succeeding correlation analysis revealed that some bacteria with significant content variations were correlated to the regulatory T cell differentiation in mice and physical characteristics in human. Our research will provide the basis for future non-invasive treatment of microbial and immune related diseases.}, }
@article {pmid31849833, year = {2019}, author = {Sutton, TDS and Hill, C}, title = {Gut Bacteriophage: Current Understanding and Challenges.}, journal = {Frontiers in endocrinology}, volume = {10}, number = {}, pages = {784}, pmid = {31849833}, issn = {1664-2392}, abstract = {The gut microbiome is widely accepted to have a significant impact on human health yet, despite years of research on this complex ecosystem, the contributions of different forces driving microbial population structure remain to be fully elucidated. The viral component of the human gut microbiome is dominated by bacteriophage, which are known to play crucial roles in shaping microbial composition, driving bacterial diversity, and facilitating horizontal gene transfer. Bacteriophage are also one of the most poorly understood components of the human gut microbiome, with the vast majority of viral sequences sharing little to no homology to reference databases. If we are to understand the dynamics of bacteriophage populations, their interaction with the human microbiome and ultimately their influence on human health, we will depend heavily on sequence based approaches and in silico tools. This is complicated by the fact that, as with any research field in its infancy, methods of analyses vary and this can impede our ability to compare the outputs of different studies. Here, we discuss the major findings to date regarding the human virome and reflect on our current understanding of how gut bacteriophage shape the microbiome. We consider whether or not the virome field is built on unstable foundations and if so, how can we provide a solid basis for future experimentation. The virome is a challenging yet crucial piece of the human microbiome puzzle. In order to develop our understanding, we will discuss the need to underpin future studies with robust research methods and suggest some solutions to existing challenges.}, }
@article {pmid31848308, year = {2019}, author = {Wang, C and Li, P and Yan, Q and Chen, L and Li, T and Zhang, W and Li, H and Chen, C and Han, X and Zhang, S and Xu, M and Li, B and Zhang, X and Ni, H and Ma, Y and Dong, B and Li, S and Liu, S}, title = {Characterization of the Pig Gut Microbiome and Antibiotic Resistome in Industrialized Feedlots in China.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31848308}, issn = {2379-5077}, abstract = {To characterize the diversity and richness and explore the function and structure of swine gut microbiome and resistome in common pig-farming feedlots, we sampled and metagenomic sequenced the feces of pigs from four different industrialized feedlots located in four distant provinces across China. Surprisingly, more than half of the nonredundant genes (1,937,648, 54.3%) in the current catalogue were newly found compared with the previously published reference gene catalogue (RGC) of the pig gut microbiome. Additionally, 16 high-completeness draft genomes were obtained by analyzing the dominant species on each feedlot. Notably, seven of these species often appeared in the human body sites. Despite a smaller number of nonredundant genes, our study identified more antibiotic resistance genes than those available in the RGC. Tetracycline, aminoglycoside, and multidrug resistance genes accounted for nearly 70% of the relative abundance in the current catalogue. Slightly higher sharing ratios were shown between the industrialized feedlot pig gut microbiomes and human gut microbiomes than that between the RGC and human counterpart (14.7% versus 12.6% in genes and 94.1% versus 87.7% in functional groups, respectively). Furthermore, a remarkably high number of the antibiotic resistance proteins (n =141) were identified to be shared by the pig, human, and mouse resistome, indicating the potential for horizontal transfer of resistance genes. Of the antibiotic resistance proteins shared by pigs and humans, 50 proteins were related to tetracycline resistance, and 49 were related to aminoglycoside resistance.IMPORTANCE The gut microbiota is believed to be closely related to many important physical functions in the host. Comprehensive data on mammalian gut metagenomes has facilitated research on host-microbiome interaction mechanisms, but less is known about pig gut microbiome, especially the gut microbiome in industrialized feedlot pigs, compared with human microbiome. On the other hand, pig production, as an important source of food, is believed to exacerbate the antibiotic resistance in humans due to the abuse of antibiotics in pig production in various parts of the world. This study delineates an intricate picture of swine gut microbiome and antibiotic resistome in industrialized feedlots and may provide insight for the pig producing industry.}, }
@article {pmid31848304, year = {2019}, author = {Wang, Y and Randolph, TW and Shojaie, A and Ma, J}, title = {The Generalized Matrix Decomposition Biplot and Its Application to Microbiome Data.}, journal = {mSystems}, volume = {4}, number = {6}, pages = {}, pmid = {31848304}, issn = {2379-5077}, support = {R01 CA192222/CA/NCI NIH HHS/United States ; R01 GM114029/GM/NIGMS NIH HHS/United States ; R01 GM129512/GM/NIGMS NIH HHS/United States ; S10 OD020069/OD/NIH HHS/United States ; }, abstract = {Exploratory analysis of human microbiome data is often based on dimension-reduced graphical displays derived from similarities based on non-Euclidean distances, such as UniFrac or Bray-Curtis. However, a display of this type, often referred to as the principal-coordinate analysis (PCoA) plot, does not reveal which taxa are related to the observed clustering because the configuration of samples is not based on a coordinate system in which both the samples and variables can be represented. The reason is that the PCoA plot is based on the eigen-decomposition of a similarity matrix and not the singular value decomposition (SVD) of the sample-by-abundance matrix. We propose a novel biplot that is based on an extension of the SVD, called the generalized matrix decomposition biplot (GMD-biplot), which involves an arbitrary matrix of similarities and the original matrix of variable measures, such as taxon abundances. As in a traditional biplot, points represent the samples, and arrows represent the variables. The proposed GMD-biplot is illustrated by analyzing multiple real and simulated data sets which demonstrate that the GMD-biplot provides improved clustering capability and a more meaningful relationship between the arrows and points.IMPORTANCE Biplots that simultaneously display the sample clustering and the important taxa have gained popularity in the exploratory analysis of human microbiome data. Traditional biplots, assuming Euclidean distances between samples, are not appropriate for microbiome data, when non-Euclidean distances are used to characterize dissimilarities among microbial communities. Thus, incorporating information from non-Euclidean distances into a biplot becomes useful for graphical displays of microbiome data. The proposed GMD-biplot accounts for any arbitrary non-Euclidean distances and provides a robust and computationally efficient approach for graphical visualization of microbiome data. In addition, the proposed GMD-biplot displays both the samples and taxa with respect to the same coordinate system, which further allows the configuration of future samples.}, }
@article {pmid31847455, year = {2019}, author = {Parida, S and Sharma, D}, title = {The Microbiome-Estrogen Connection and Breast Cancer Risk.}, journal = {Cells}, volume = {8}, number = {12}, pages = {}, pmid = {31847455}, issn = {2073-4409}, support = {R01 CA204555/CA/NCI NIH HHS/United States ; }, mesh = {Adiposity/physiology ; Breast Neoplasms/metabolism/*microbiology ; Dysbiosis/metabolism ; Estrogens/*metabolism ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Microbiota/*physiology ; Obesity/microbiology/physiopathology ; Risk Factors ; }, abstract = {The microbiome is undoubtedly the second genome of the human body and has diverse roles in health and disease. However, translational progress is limited due to the vastness of the microbiome, which accounts for over 3.3 million genes, whose functions are still unclear. Numerous studies in the past decade have demonstrated how microbiome impacts various organ-specific cancers by altering the energy balance of the body, increasing adiposity, synthesizing genotoxins and small signaling molecules, and priming and regulating immune response and metabolism of indigestible dietary components, xenobiotics, and pharmaceuticals. In relation to breast cancer, one of the most prominent roles of the human microbiome is the regulation of steroid hormone metabolism since endogenous estrogens are the most important risk factor in breast cancer development especially in postmenopausal women. Intestinal microbes encode enzymes capable of deconjugating conjugated estrogen metabolites marked for excretion, pushing them back into the enterohepatic circulation in a biologically active form. In addition, the intestinal microbes also break down otherwise indigestible dietary polyphenols to synthesize estrogen-like compounds or estrogen mimics that exhibit varied estrogenic potency. The present account discusses the potential role of gastrointestinal microbiome in breast cancer development by mediating metabolism of steroid hormones and synthesis of biologically active estrogen mimics.}, }
@article {pmid31844880, year = {2019}, author = {Jiang, S and Xiao, G and Koh, AY and Kim, J and Li, Q and Zhan, X}, title = {A Bayesian zero-inflated negative binomial regression model for the integrative analysis of microbiome data.}, journal = {Biostatistics (Oxford, England)}, volume = {}, number = {}, pages = {}, doi = {10.1093/biostatistics/kxz050}, pmid = {31844880}, issn = {1468-4357}, abstract = {Microbiome omics approaches can reveal intriguing relationships between the human microbiome and certain disease states. Along with identification of specific bacteria taxa associated with diseases, recent scientific advancements provide mounting evidence that metabolism, genetics, and environmental factors can all modulate these microbial effects. However, the current methods for integrating microbiome data and other covariates are severely lacking. Hence, we present an integrative Bayesian zero-inflated negative binomial regression model that can both distinguish differentially abundant taxa with distinct phenotypes and quantify covariate-taxa effects. Our model demonstrates good performance using simulated data. Furthermore, we successfully integrated microbiome taxonomies and metabolomics in two real microbiome datasets to provide biologically interpretable findings. In all, we proposed a novel integrative Bayesian regression model that features bacterial differential abundance analysis and microbiome-covariate effects quantifications, which makes it suitable for general microbiome studies.}, }
@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 {pmid31828607, year = {2020}, author = {Berkes, E and Liao, YH and Neef, D and Grandalski, M and Monsul, N}, title = {Potentiated In Vitro Probiotic Activities of Lactobacillus fermentum LfQi6 Biofilm Biomass Versus Planktonic Culture.}, journal = {Probiotics and antimicrobial proteins}, volume = {12}, number = {3}, pages = {1097-1114}, doi = {10.1007/s12602-019-09624-8}, pmid = {31828607}, issn = {1867-1314}, abstract = {In this study, we describe enhanced in vitro probiotic activities of preformed biofilms versus planktonic cultures of Lactobacillus fermentum LfQi6 (LfQi6), a lactic acid bacterium (LAB) isolated from the human microbiome. These evaluations are used to help predict host in vivo probiotic benefits and therefore indicate that LfQi6 may provide significant probiotic benefits in the human host when administered as preformed biofilms rather than as planktonic cultures. Specifically, LfQi6 biofilms demonstrated improved in vitro performance versus LfQi6 planktonic cultures for host gastrointestinal survival and engraftment, strain-specific antimicrobial and anti-biofilm activity against clinically significant pathogens, concurrent promotion of beneficial gastrointestinal commensal biofilms, beneficial commensal enzyme activities, and host cellular-protective glutathione antioxidant activity. Evaluation of LfQi6 according to the European Food Safety Authority (EFSA 2007, 2012, 2015) Guidelines and Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Evaluation of Probiotics in Food (FAO/WHO, 2002) demonstrates strain safety. In summary, in vitro evaluation of Lact. fermentum LfQi6 demonstrates significant evidence for strain-specific probiotic characteristics and safety. Moreover, strain-specific as well as biofilm-phenotype-specific benefits demonstrated in vitro furthermore suggest that in vivo use of LfQi6 biofilm biomass may be of greater benefit to the human host than the use of standard planktonic cultures. This concept - potentiating probiotic benefits through the use of preformed commensal biofilms - is novel and may serve to further broaden the application of microbial biofilms to human health.}, }
@article {pmid31827811, year = {2019}, author = {Rapp, R}, title = {On mycohuman performances: fungi in current artistic research.}, journal = {Fungal biology and biotechnology}, volume = {6}, number = {}, pages = {22}, doi = {10.1186/s40694-019-0085-6}, pmid = {31827811}, issn = {2054-3085}, abstract = {This review reflects several artists and their artistic research in the field of hybrid art, bio art, or science art, working with Fungi as both subject matter and medium. The work of Saša Spačal, Tarsh Bates and Theresa Schubert is not representational in the manner of traditional fine art, but works rather through performative, multidisciplinary and research-based strategies to produce artwork through fungal material as such. My research results are based on the series "Nonhuman subjectivities" and "Nonhuman agents" that Christian de Lutz and I conceived and realized at Art Laboratory Berlin (2016-18) in various formats-exhibitions, workshops, lectures and a conference. The work of Saša Spačal and her colleagues involves creating interactive situations of symbiosis between the fungal and the human. An example of this is Myconnect, in which a biofeedback loop is related between the human participant and Oyster mushroom mycelia through a special encounter, which is mediated by non-linguistic forms of awareness and exchange-sonic, electronic and metabolic. Tarsh Bates' work with Candida albicans and Candida parapsilosis refers to a complex and intimate relation between the human and yeasts that form part of the human microbiome. Bates considers the relationship between humans and yeast as "CandidaHomo Ecologies" and sees both partners as equals. She explores this relationship through her work The Surface dynamics of adhesion, examines it from historical and metabolic levels through an installation that includes the live yeast growing on agar mixed with the artist's own blood. Theresa Schubert's installations and site-specific interventions treat living organisms, especially Fungi, as collaborators and co-creators. Her work Growing Geometries-Tattooing Mushrooms follows the morphological development of fungal fruiting bodies through the intervention of a tattoo. Her performative forest walks, especially the Forestal Psyche and also new actions for the "Mind the Fungi" project, engage the public in an intimate and multi sensory encounter with Fungi and their surrounding environment.}, }
@article {pmid31824656, year = {2019}, author = {Barton, W and O'Sullivan, O and Cotter, PD}, title = {Metabolic phenotyping of the human microbiome.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, pmid = {31824656}, issn = {2046-1402}, mesh = {Humans ; Metabolomics ; *Microbiota ; }, abstract = {The human microbiome has been identified as having a key role in health and numerous diseases. Trillions of microbial cells and viral particles comprise the microbiome, each representing modifiable working elements of an intricate bioactive ecosystem. The significance of the human microbiome as it relates to human biology has progressed through culture-dependent (for example, media-based methods) and, more recently, molecular (for example, genetic sequencing and metabolomic analysis) techniques. The latter have become increasingly popular and evolved from being used for taxonomic identification of microbiota to elucidation of functional capacity (sequencing) and metabolic activity (metabolomics). This review summarises key elements of the human microbiome and its metabolic capabilities within the context of health and disease.}, }
@article {pmid31824493, year = {2019}, author = {Michel-Todó, L and Reche, PA and Bigey, P and Pinazo, MJ and Gascón, J and Alonso-Padilla, J}, title = {In silico Design of an Epitope-Based Vaccine Ensemble for Chagas Disease.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2698}, pmid = {31824493}, issn = {1664-3224}, mesh = {Antigens, Protozoan/*immunology ; Chagas Disease/immunology/*prevention & control ; Computer Simulation ; Drug Design ; Epitopes, B-Lymphocyte/*immunology ; Epitopes, T-Lymphocyte/*immunology ; Humans ; Protozoan Vaccines/*immunology ; }, abstract = {Trypanosoma cruzi infection causes Chagas disease, which affects 7 million people worldwide. Two drugs are available to treat it: benznidazole and nifurtimox. Although both are efficacious against the acute stage of the disease, this is usually asymptomatic and goes undiagnosed and untreated. Diagnosis is achieved at the chronic stage, when life-threatening heart and/or gut tissue disruptions occur in ~30% of those chronically infected. By then, the drugs' efficacy is reduced, but not their associated high toxicity. Given current deficiencies in diagnosis and treatment, a vaccine to prevent infection and/or the development of symptoms would be a breakthrough in the management of the disease. Current vaccine candidates are mostly based on the delivery of single antigens or a few different antigens. Nevertheless, due to the high biological complexity of the parasite, targeting as many antigens as possible would be desirable. In this regard, an epitope-based vaccine design could be a well-suited approach. With this aim, we have gone through publicly available databases to identify T. cruzi epitopes from several antigens. By means of a computer-aided strategy, we have prioritized a set of epitopes based on sequence conservation criteria, projected population coverage of Latin American population, and biological features of their antigens of origin. Fruit of this analysis, we provide a selection of CD8+ T cell, CD4+ T cell, and B cell epitopes that have <70% identity to human or human microbiome protein sequences and represent the basis toward the development of an epitope-based vaccine against T. cruzi.}, }
@article {pmid31824463, year = {2019}, author = {Freitag, TL and Hartikainen, A and Jouhten, H and Sahl, C and Meri, S and Anttila, VJ and Mattila, E and Arkkila, P and Jalanka, J and Satokari, R}, title = {Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2685}, pmid = {31824463}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.}, }
@article {pmid31821833, year = {2020}, author = {Golofast, B and Vales, K}, title = {The connection between microbiome and schizophrenia.}, journal = {Neuroscience and biobehavioral reviews}, volume = {108}, number = {}, pages = {712-731}, doi = {10.1016/j.neubiorev.2019.12.011}, pmid = {31821833}, issn = {1873-7528}, mesh = {Animals ; Cesarean Section/*adverse effects ; *Dysbiosis/etiology/immunology/microbiology ; Female ; Humans ; *Inflammation/diet therapy/immunology/microbiology ; *Microbiota/immunology ; Pregnancy ; *Prenatal Exposure Delayed Effects/immunology/microbiology ; Probiotics/*therapeutic use ; *Schizophrenia/diet therapy/immunology/microbiology ; }, abstract = {There has been an accumulation of knowledge about the human microbiome, some detailed investigations of the gastrointestinal microbiota and its functions, and the highlighting of complex interactions between the gut, the gut microbiota, and the central nervous system. That assumes the involvement of the microbiome in the pathogenesis of various CNS diseases, including schizophrenia. Given this information and the fact, that the gut microbiota is sensitive to internal and environmental influences, we have speculated that among the factors that influence the formation and composition of gut microbiota during life, possible key elements in the schizophrenia development chain are hidden where gut microbiota is a linking component. This article aims to describe and understand the developmental relationships between intestinal microbiota and the risk of developing schizophrenia.}, }
@article {pmid31812808, year = {2019}, author = {Hall, CV and Lord, A and Betzel, R and Zakrzewski, M and Simms, LA and Zalesky, A and Radford-Smith, G and Cocchi, L}, title = {Co-existence of Network Architectures Supporting the Human Gut Microbiome.}, journal = {iScience}, volume = {22}, number = {}, pages = {380-391}, doi = {10.1016/j.isci.2019.11.032}, pmid = {31812808}, issn = {2589-0042}, abstract = {Microbial organisms of the human gut microbiome do not exist in isolation but form complex and diverse interactions to maintain health and reduce risk of disease development. The organization of the gut microbiome is assumed to be a singular assortative network, where interactions between operational taxonomic units (OTUs) can readily be clustered into segregated and distinct communities. Here, we leverage recent methodological advances in network modeling to assess whether communities in the human microbiome exhibit a single network structure or whether co-existing mesoscale network architectures are present. We found evidence for core-periphery structures in the microbiome, supported by strong, assortative community interactions. This complex architecture, coupled with previously reported functional roles of OTUs, provides a nuanced understanding of how the microbiome simultaneously promotes high microbial diversity and maintains functional redundancy.}, }
@article {pmid31812180, year = {2019}, author = {Borbet, TC and Zhang, X and Müller, A and Blaser, MJ}, title = {The role of the changing human microbiome in the asthma pandemic.}, journal = {The Journal of allergy and clinical immunology}, volume = {144}, number = {6}, pages = {1457-1466}, pmid = {31812180}, issn = {1097-6825}, support = {U01 AI122285/AI/NIAID NIH HHS/United States ; TL1 TR001447/TR/NCATS NIH HHS/United States ; }, mesh = {Allergens/immunology ; *Asthma/epidemiology/immunology/microbiology ; Disease Susceptibility/immunology/microbiology ; Helicobacter pylori/immunology ; Humans ; Microbiota/*immunology ; Pandemics ; Risk Factors ; }, abstract = {Asthma and allergy incidence continue to increase globally. We have made significant strides in treating disease, but it is becoming more apparent that we need to advance our knowledge into the origins of asthmatic disease. Much recent work has indicated that microbiome composition influences immune regulation and that multiple health care factors have driven a loss in microbiome diversity in modern human populations. Evidence is growing of microbiota-driven influences on immune development, asthma susceptibility, and asthma pathogenesis. The focus of this review is to highlight the strides the field has made in characterizing the constituents of the human gastrointestinal microbiota, such as Helicobacter pylori, other members of the neonatal intestinal microbiota, and microbial peptides and metabolites that influence host immunity and immune response to allergens. As we delve further into this field of research, the goal will be to find actionable and clinical interventions to identify at-risk populations earlier to prevent disease onset. Manipulation of the host microbial community during infancy might be an especially promising approach.}, }
@article {pmid31812098, year = {2020}, author = {Neckovic, A and van Oorschot, RAH and Szkuta, B and Durdle, A}, title = {Investigation of direct and indirect transfer of microbiomes between individuals.}, journal = {Forensic science international. Genetics}, volume = {45}, number = {}, pages = {102212}, doi = {10.1016/j.fsigen.2019.102212}, pmid = {31812098}, issn = {1878-0326}, abstract = {The human microbiome encompasses the fungi, bacteria and viruses that live on, within, and immediately surrounding the body. Microbiomes have potential utility in forensic science as an evidentiary tool to link or exclude persons of interest associated with criminal activities. Research has shown the microbiome is individualised, and that personal microbial signatures can be recovered from surfaces such as phones, shoes and fabrics. Before the human microbiome may be used as an investigative tool, further research is required to investigate the utility and potential limitations surrounding microbial profiling. This includes the detectability of microbial transfer between individuals or items, the associated risks (such as contamination events) and the applicability of microbial profiling for forensic purposes. This research aimed to identify whether an individual's distinguishable microbiome could be transferred to another individual and onto substrates, and vice versa. Paper, cotton, and glass surfaces were chosen to represent a range of substrate matrices. The study involved six participants placed into three pairs; participants took part in two modes of transfer. Transfer Mode 1 involved the pair shaking hands, followed by rubbing a substrate in their right hand. Transfer Mode 2 involved individuals rubbing a substrate in their left hand, swapping substrates with their partner and then rubbing the swapped substrate in their left hand. 16S rRNA sequencing was performed on the extracted microbial DNA from participant and substrate samples. Quantitative Insights into Microbial Ecology 2 (QIIME 2) was used for sequence quality control and beta (between-sample) diversity analyses and taxonomic assignment. Principal Coordinate Analysis (PCoA) based on Jaccard distances was visualised through Emperor software to determine the phylogenetic similarity of bacterial communities between participants and among participant pairs. Statistical testing through PERMANOVA revealed significant differences in the Jaccard distances between each participant pair (P < 0.001), highlighting not only the potential distinguishability of skin microbiomes among individuals, but also the clustering effect observed between participant pairs due to the potential transfer of hand-associated microbiomes between individuals. The study demonstrated that transfer of the human skin microbiome had occurred between all participant pairs, regardless of substrate type or mode of transfer.}, }
@article {pmid31802114, year = {2020}, author = {Barrera-Vázquez, OS and Gomez-Verjan, JC}, title = {The Unexplored World of Human Virome, Mycobiome, and Archaeome in Aging.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {75}, number = {10}, pages = {1834-1837}, doi = {10.1093/gerona/glz274}, pmid = {31802114}, issn = {1758-535X}, abstract = {In the last decades, improvements in different aspects of sanitation, medical care, and nutrition, among others, have permitted an increase in the average lifespan of human population around the world. These advances have stimulated an increased interest in the study of the aging process and age-sensitive characteristics, such as the microbial community that colonizes the human body (microbiome). The human microbiome is composed of bacteria (bacteriome), archaea (archaeome), fungi (mycobiome), and viruses (virome). To date, research has mainly been centered on the composition of the bacteriome, with other members remain poorly studied. Interestingly, changes in the composition of the microbiome have been implicated in aging and age-related diseases. Therefore, in the present perspective, we suggest expanding the scope to research to include the role and the possible associations that the other members of the microbiome could have in the aging organism. An expanded view of the microbiome would increase our knowledge of the physiology of aging and may be particularly valuable for the treatment and diagnosis of age-related diseases.}, }
@article {pmid31795231, year = {2019}, author = {Leon-Velarde, CG and Jun, JW and Skurnik, M}, title = {Yersinia Phages and Food Safety.}, journal = {Viruses}, volume = {11}, number = {12}, pages = {}, pmid = {31795231}, issn = {1999-4915}, mesh = {Animals ; Bacteriophages/*physiology ; *Food Microbiology ; *Food Safety ; Humans ; Yersinia Infections/*microbiology ; Yersinia enterocolitica/isolation & purification/*virology ; }, abstract = {One of the human- and animal-pathogenic species in genus Yersinia is Yersinia enterocolitica, a food-borne zoonotic pathogen that causes enteric infections, mesenteric lymphadenitis, and sometimes sequelae such as reactive arthritis and erythema nodosum. Y. enterocolitica is able to proliferate at 4 C, making it dangerous if contaminated food products are stored under refrigeration. The most common source of Y. enterocolitica is raw pork meat. Microbiological detection of the bacteria from food products is hampered by its slow growth rate as other bacteria overgrow it. Bacteriophages can be exploited in several ways to increase food safety with regards to contamination by Y. enterocolitica. For example, Yersinia phages could be useful in keeping the contamination of food products under control, or, alternatively, the specificity of the phages could be exploited in developing rapid and sensitive diagnostic tools for the identification of the bacteria in food products. In this review, we will discuss the present state of the research on these topics.}, }
@article {pmid31790791, year = {2020}, author = {Ahmed, N and Daniel, B and Varghese, J and Evangeline, R and Jose, T}, title = {Oropharyngeal microbiome of an HIV-positive patient.}, journal = {Microbial pathogenesis}, volume = {139}, number = {}, pages = {103805}, doi = {10.1016/j.micpath.2019.103805}, pmid = {31790791}, issn = {1096-1208}, mesh = {Bacteroides/isolation & purification/metabolism ; Clostridium/isolation & purification/metabolism ; DNA, Bacterial/genetics/isolation & purification ; Enterococcus/isolation & purification/metabolism ; Gastrointestinal Microbiome ; HIV Infections/*microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; *Microbiota ; Micrococcus/isolation & purification/metabolism ; Oropharynx/*microbiology ; Pharynx/microbiology ; Phylogeny ; Prevotella/isolation & purification/metabolism ; Proteus/isolation & purification/metabolism ; RNA, Ribosomal, 16S/genetics/isolation & purification ; Respiratory System/metabolism/microbiology ; Respiratory Tract Infections/microbiology ; Sequence Analysis, DNA ; }, abstract = {Studies on understanding the human microbiome continue to grow rapidly; nonetheless, reports on alterations in the microbiome post HIV infection are limited. Human microbiome is an aggregate of bacteria, fungi, viruses and archaea that have co-evolved with humans. These microbes have important roles in immune modulation, vitamin synthesis, metabolism etc. The human pharyngeal microbiome, which resides in the junction between digestive and respiratory tracts, might have a key role in the prevention of respiratory tract infections, akin to the actions of the intestinal microbiome against enteric infections. The respiratory tract is constantly exposed to various environmental and endogenous microbes; however, unlike other similar mucosal surfaces, there has been limited investigation of the microbiome of the respiratory tract. HIV infection is associated with alterations in the respiratory microbiome. The aim of this study was to use next-generation sequencing to determine the composition of the oropharyngeal microbiome in a HIV-positive individual. The bacterial composition was determined by illumina sequencing using MiSeq of partial 16S rRNA genes (V3-V4). A total of 3, 57,926 reads were analyzed. Overall, the genera Proteus, Enterococcus, Bacteroides, Prevotella and Clostridium were most prevalent bacterial populations in the oropharynx of an HIV positive patient.}, }
@article {pmid31782749, year = {2019}, author = {Quagliariello, A and Di Paola, M and De Fanti, S and Gnecchi-Ruscone, GA and Martinez-Priego, L and Pérez-Villaroya, D and Sherpa, MG and Sherpa, PT and Marinelli, G and Natali, L and Di Marcello, M and Peluzzi, D and Di Cosimo, P and D'Auria, G and Pettener, D and Sazzini, M and Luiselli, D and De Filippo, C}, title = {Gut microbiota composition in Himalayan and Andean populations and its relationship with diet, lifestyle and adaptation to the high-altitude environment.}, journal = {Journal of anthropological sciences = Rivista di antropologia : JASS}, volume = {96}, number = {}, pages = {189-208}, doi = {10.4436/JASS.97007}, pmid = {31782749}, issn = {2037-0644}, mesh = {Adaptation, Physiological/*physiology ; Adult ; Altitude ; Biological Evolution ; Bolivia/ethnology ; Diet/*statistics & numerical data ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Life Style/*ethnology ; Male ; Mountaineering/*physiology ; Nepal/ethnology ; Young Adult ; }, abstract = {Human populations living at high altitude evolved a number of biological adjustments to cope with a challenging environment characterised especially by reduced oxygen availability and limited nutritional resources. This condition may also affect their gut microbiota composition. Here, we explored the impact of exposure to such selective pressures on human gut microbiota by considering different ethnic groups living at variable degrees of altitude: the high-altitude Sherpa and low-altitude Tamang populations from Nepal, the high-altitude Aymara population from Bolivia, as well as a low-altitude cohort of European ancestry, used as control. We thus observed microbial profiles common to the Sherpa and Aymara, but absent in the low-altitude cohorts, which may contribute to the achievement of adaptation to high-altitude lifestyle and nutritional conditions. The collected evidences suggest that microbial signatures associated to these rural populations may enhance metabolic functions able to supply essential compounds useful for the host to cope with high altitude-related physiological changes and energy demand. Therefore, these results add another valuable piece of the puzzle to the understanding of the beneficial effects of symbiosis between microbes and their human host even from an evolutionary perspective.}, }
@article {pmid31781817, year = {2020}, author = {Bajerski, F and Bürger, A and Glasmacher, B and Keller, ERJ and Müller, K and Mühldorfer, K and Nagel, M and Rüdel, H and Müller, T and Schenkel, J and Overmann, J}, title = {Factors determining microbial colonization of liquid nitrogen storage tanks used for archiving biological samples.}, journal = {Applied microbiology and biotechnology}, volume = {104}, number = {1}, pages = {131-144}, pmid = {31781817}, issn = {1432-0614}, support = {GDK//GDK Gemeinschaft Deutscher Kryobanken/ ; FP7-HEALTH-F4-2010-261492//Helmholtz-Gemeinschaft/ ; ExNet-0041-Phase2-3//Helmholtz-Gemeinschaft/ ; }, mesh = {Bacteria/genetics ; Bacterial Load ; Biological Specimen Banks/*standards ; Cryopreservation/*instrumentation ; DNA, Bacterial/genetics ; *Equipment Contamination ; Fungi/genetics ; Humans ; Ice ; Limit of Detection ; *Nitrogen ; RNA, Ribosomal, 16S ; }, abstract = {The availability of bioresources is a precondition for life science research, medical applications, and diagnostics, but requires a dedicated quality management to guarantee reliable and safe storage. Anecdotal reports of bacterial isolates and sample contamination indicate that organisms may persist in liquid nitrogen (LN) storage tanks. To evaluate the safety status of cryocollections, we systematically screened organisms in the LN phase and in ice layers covering inner surfaces of storage tanks maintained in different biobanking facilities. We applied a culture-independent approach combining cell detection by epifluorescence microscopy with the amplification of group-specific marker genes and high-throughput sequencing of bacterial ribosomal genes. In the LN phase, neither cells nor bacterial 16S rRNA gene copy numbers were detectable (detection limit, 102 cells per ml, 103 gene copies per ml). In several cases, small numbers of bacteria of up to 104 cells per ml and up to 106 gene copies per ml, as well as Mycoplasma, or fungi were detected in the ice phase formed underneath the lids or accumulated at the bottom. The bacteria most likely originated from the stored materials themselves (Elizabethingia, Janthibacterium), the technical environment (Pseudomonas, Acinetobacter, Methylobacterium), or the human microbiome (Bacteroides, Streptococcus, Staphylococcus). In single cases, bacteria, Mycoplasma, fungi, and human cells were detected in the debris at the bottom of the storage tanks. In conclusion, the limited microbial load of the ice phase and in the debris of storage tanks can be effectively avoided by minimizing ice formation and by employing hermetically sealed sample containers.}, }
@article {pmid31780826, year = {2019}, author = {Tang, L}, title = {Exploring the chemical space of the human microbiome.}, journal = {Nature methods}, volume = {16}, number = {12}, pages = {1201}, doi = {10.1038/s41592-019-0671-9}, pmid = {31780826}, issn = {1548-7105}, mesh = {Humans ; Metagenome ; *Microbiota ; }, }
@article {pmid31780057, year = {2020}, author = {Garud, NR and Pollard, KS}, title = {Population Genetics in the Human Microbiome.}, journal = {Trends in genetics : TIG}, volume = {36}, number = {1}, pages = {53-67}, doi = {10.1016/j.tig.2019.10.010}, pmid = {31780057}, issn = {0168-9525}, abstract = {While the human microbiome's structure and function have been extensively studied, its within-species genetic diversity is less well understood. However, genetic mutations in the microbiome can confer biomedically relevant traits, such as the ability to extract nutrients from food, metabolize drugs, evade antibiotics, and communicate with the host immune system. The population genetic processes by which these traits evolve are complex, in part due to interacting ecological and evolutionary forces in the microbiome. Advances in metagenomic sequencing, coupled with bioinformatics tools and population genetic models, facilitate quantification of microbiome genetic variation and inferences about how this diversity arises, evolves, and correlates with traits of both microbes and hosts. In this review, we explore the population genetic forces (mutation, recombination, drift, and selection) that shape microbiome genetic diversity within and between hosts, as well as efforts towards predictive models that leverage microbiome genetics.}, }
@article {pmid31775543, year = {2020}, author = {Poon, WL and Lee, JC and Leung, KS and Alenius, H and El-Nezami, H and Karisola, P}, title = {Nanosized silver, but not titanium dioxide or zinc oxide, enhances oxidative stress and inflammatory response by inducing 5-HETE activation in THP-1 cells.}, journal = {Nanotoxicology}, volume = {14}, number = {4}, pages = {453-467}, doi = {10.1080/17435390.2019.1687776}, pmid = {31775543}, issn = {1743-5404}, mesh = {Antioxidants/metabolism ; Glutathione/metabolism ; Humans ; Hydroxyeicosatetraenoic Acids/*metabolism ; Inflammation ; Metal Nanoparticles/*toxicity ; Mitochondria/drug effects/metabolism ; Oxidative Stress/*drug effects/immunology ; Silver/*toxicity ; THP-1 Cells ; Titanium/*toxicity ; Zinc Oxide/*toxicity ; }, abstract = {Bioactive, oxygenated metabolites of polyunsaturated fatty acids (PUFAs) are important indicators of inflammation and oxidative stress but almost nothing is known about their interactions with nanomaterials (NMs). To investigate the effects of nano-sized materials (n-TiO2, n-ZnO, n-Ag) and their bulk-sized or ionic (b-TiO2, b-ZnO, i-Ag) counterpart, we studied the status of oxidative stress and PUFA metabolism in THP-1 cells at low-toxic concentrations (<15% cytotoxicity) 6 h or 24 h after the particle exposures by LC/MS and microarray. N-Ag had a significant and sustained impact on cellular antioxidant defense, seen as incremental synthesis and accumulation of glutathione (GSH) in the cell, and reduction of superoxide dismutase (SOD) activity. The cellular particle doses were largely dependent on exposure duration and particle dissolution, and active transporter mechanisms controlled the concentration of Zn in cytosol. Even at these sub-toxic concentrations, n-Ag was able to induce statistically significant elevation in the 5-HETE: arachidonic acid ratio at 24 h, which suggests association to oxidative stress and induction of pro-inflammatory responses. This was supported by the enhanced gene expression of chemotaxis-related genes. Overall, THP-1 cells internalized all tested particles, but only n-Ag led to low level of oxidative stress through ROS production and antioxidant balance disruption. N-Ag stimulated arachidonic acid oxidation to form 5-HETE which further magnified the inflammatory responses by enhancing the production of mitochondrial superoxide and leukocyte chemokines. Since the sustained n-Ag uptake was detected, the effects may last long and function as a trigger for the low-grade inflammation playing role in the chronic inflammatory diseases.}, }
@article {pmid31753125, year = {2019}, author = {Croitoru, DO and Piguet, V}, title = {A Mother's Touch: Emerging Roles in Development of the Cutaneous Microbiome.}, journal = {The Journal of investigative dermatology}, volume = {139}, number = {12}, pages = {2414-2416}, doi = {10.1016/j.jid.2019.06.144}, pmid = {31753125}, issn = {1523-1747}, mesh = {Child ; Female ; Humans ; Infant ; *Microbiota ; *Mothers ; Skin ; Touch ; }, abstract = {Skin-associated bacteria constitute a large proportion of the human microbiome and influence host immunity. The healthy cutaneous microbiome adopts site-specific composition, weeks to months postpartum. Zhu et al. (2019) expand the scope of pediatric data, tracking infant skin microflora changes by site, through childhood, and establish new associations with delivery mode and maternal microbiome.}, }
@article {pmid31752095, year = {2019}, author = {Ristori, MV and Quagliariello, A and Reddel, S and Ianiro, G and Vicari, S and Gasbarrini, A and Putignani, L}, title = {Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions.}, journal = {Nutrients}, volume = {11}, number = {11}, pages = {}, pmid = {31752095}, issn = {2072-6643}, mesh = {Autism Spectrum Disorder/*complications/*diet therapy ; Child ; *Child Nutritional Physiological Phenomena ; Child, Preschool ; Diet/classification ; Fatty Acids, Volatile/metabolism ; Food Preferences ; Gastrointestinal Diseases/*complications/*microbiology ; *Gastrointestinal Microbiome ; Humans ; Neurotransmitter Agents/metabolism ; Nutritional Status ; Serotonin/metabolism ; }, abstract = {Autism spectrum disorder (ASD) is a complex behavioral syndrome that is characterized by speech and language disorders, intellectual impairment, learning and motor dysfunctions. Several genetic and environmental factors are suspected to affect the ASD phenotype including air pollution, exposure to pesticides, maternal infections, inflammatory conditions, dietary factors or consumption of antibiotics during pregnancy. Many children with ASD shows abnormalities in gastrointestinal (GI) physiology, including increased intestinal permeability, overall microbiota alterations, and gut infection. Moreover, they are "picky eaters" and the existence of specific sensory patterns in ASD patients could represent one of the main aspects in hampering feeding. GI disorders are associated with an altered composition of the gut microbiota. Gut microbiome is able to communicate with brain activities through microbiota-derived signaling molecules, immune mediators, gut hormones as well as vagal and spinal afferent neurons. Since the diet induces changes in the intestinal microbiota and in the production of molecules, such as the SCFA, we wanted to investigate the role that nutritional intervention can have on GI microbiota composition and thus on its influence on behavior, GI symptoms and microbiota composition and report which are the beneficial effect on ASD conditions.}, }
@article {pmid31744921, year = {2019}, author = {Estrela, AB and Nakashige, TG and Lemetre, C and Woodworth, ID and Weisman, JL and Cohen, LJ and Brady, SF}, title = {Functional Multigenomic Screening of Human-Associated Bacteria for NF-κB-Inducing Bioactive Effectors.}, journal = {mBio}, volume = {10}, number = {6}, pages = {}, pmid = {31744921}, issn = {2150-7511}, support = {R01 AT009562/AT/NCCIH NIH HHS/United States ; }, mesh = {Bacteria/*genetics ; Bacterial Infections/*metabolism/*microbiology ; Gene Expression Regulation, Bacterial ; Gene Library ; *Genome, Bacterial ; Humans ; *Metagenomics/methods ; Microbiota ; NF-kappa B/*metabolism ; Operon ; Phylogeny ; }, abstract = {The effect of the microbiota on its human host is driven, at least in part, by small-molecule and protein effectors it produces. Here, we report on the use of functional multigenomic screening to identify microbiota-encoded effectors. In this study, genomic DNA from 116 human-associated bacteria was cloned en masse, and the resulting multigenomic library was screened using a nuclear factor-κB reporter (NF-κB) assay. Functional multigenomics builds on the concept of functional metagenomics but takes advantage of increasing advances in cultivating and sequencing human-associated bacteria. Effector genes found to confer NF-κB-inducing activity to Escherichia coli encode proteins in four general categories: cell wall hydrolases, membrane transporters, lipopolysaccharide biosynthetic enzymes, and proteins of unknown function. The compact nature of multigenomic libraries, which results from the ability to normalize input DNA ratios, should simplify screening of libraries using diverse heterologous hosts and reporter assays, increasing the rate of discovery of novel effector genes.IMPORTANCE Human-associated bacteria are thought to encode bioactive small molecules and proteins that play an intimate role in human health and disease. Here, we report on the creation and functional screening of a multigenomic library constructed using genomic DNA from 116 bacteria found at diverse sites across the human body. Individual clones were screened for genes capable of conferring NF-κB-inducing activity to Escherichia coli NF-κB is a useful reporter for a range of cellular processes related to immunity, pathogenesis, and inflammation. Compared to the screening of metagenomic libraries, the ability to normalize input DNA ratios when constructing a multigenomic library should facilitate the more efficient examination of commensal bacteria for diverse bioactivities. Multigenomic screening takes advantage of the growing available resources in culturing and sequencing the human microbiota and generates starting points for more in-depth studies on the mechanisms by which commensal bacteria interact with their human host.}, }
@article {pmid31744351, year = {2019}, author = {Bender, JM and Li, F and Purswani, H and Capretz, T and Cerini, C and Zabih, S and Hung, L and Francis, N and Chin, S and Pannaraj, PS and Aldrovandi, G}, title = {Early exposure to antibiotics in the neonatal intensive care unit alters the taxonomic and functional infant gut microbiome.}, journal = {The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians}, volume = {}, number = {}, pages = {1-9}, pmid = {31744351}, issn = {1476-4954}, support = {K12 HD052954/HD/NICHD NIH HHS/United States ; }, abstract = {Introduction: The infant gut microbiome is thought to play a key role in developing metabolic and immunologic pathways. Antibiotics have been shown to disrupt the human microbiome, but the impact they have on infants during this key window of development remains poorly understood. Through this study, we further characterize the effect antibiotics have on the gut microbiome of infants by looking at metagenomic sequencing data over time.Materials and methods: Stool samples were collected on infants from a large tertiary care neonatal intensive care unit. After DNA extraction, metagenomics libraries were generated and sequenced. Taxonomic and functional analyses were then performed. Further directed specimen sequencing for fungal species was also performed.Results: A total of 51 stool samples from 25 infants were analyzed: seven infants were on antibiotics during at least one of their collection time points. Antibiotics given at birth altered the microbiome (PERMANOVA R2 = 0.044, p = .002) but later courses did not (R2 = 0.023, p = .114). Longitudinal samples collected while off antibiotics were more similar than those collected during a transition on or off antibiotics (mean Bray-Curtis distance 0.29 vs. 0.63, Wilcoxon p = .06). Functional analysis revealed four microbial pathways that were disrupted by antibiotics given at-birth (p < .1, folate synthesis, glycerolipid metabolism, fatty acid biosynthesis, and glycolysis). No functional changes associated with current antibiotic use were identified. In a limited sample set, we saw little evidence of fungal involvement in the overall infant microbiome.Conclusion: Through this study, we have further characterized the role antibiotics have in the development of the infant microbiome. Antibiotics given at birth were associated with alterations in the microbiome and had significant impact on the functional pathways involved in folate synthesis and multiple metabolic pathways. Later courses of antibiotics led to stochastic dysbiosis and a significant decrease in Escherichia coli. Further characterization of the infant mycobiome is still needed.}, }
@article {pmid31739448, year = {2019}, author = {Mohanraj, U and Wan, X and Spruit, CM and Skurnik, M and Pajunen, MI}, title = {A Toxicity Screening Approach to Identify Bacteriophage-Encoded Anti-Microbial Proteins.}, journal = {Viruses}, volume = {11}, number = {11}, pages = {}, pmid = {3173944