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Bibliography on: Human Microbiome

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ESP: PubMed Auto Bibliography 14 Nov 2018 at 01:39 Created: 

Human Microbiome

The human microbiome is the set of all microbes that live on or in humans. Together, a human body and its associated microbiomes constitute a human holobiont. Although a human holobiont is mostly mammal by weight, by cell count it is mostly microbial. The number of microbial genes in the associated microbiomes far outnumber the number of human genes in the human genome. Just as humans (and other multicellular eukaryotes) evolved in the constant presence of gravity, so they also evolved in the constant presence of microbes. Consequently, nearly every aspect of human biology has evolved to deal with, and to take advantage of, the existence of associated microbiota. In some cases, the absence of a "normal microbiome" can cause disease, which can be treated by the transplant of a correct microbiome from a healthy donor. For example, fecal transplants are an effective treatment for chronic diarrhea from over abundant Clostridium difficile bacteria in the gut.

Created with PubMed® Query: "human microbiome" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2018-11-13

Frioux C, Fremy E, Trottier C, et al (2018)

Scalable and exhaustive screening of metabolic functions carried out by microbial consortia.

Bioinformatics (Oxford, England), 34(17):i934-i943.

Motivation: The selection of species exhibiting metabolic behaviors of interest is a challenging step when switching from the investigation of a large microbiota to the study of functions effectiveness. Approaches based on a compartmentalized framework are not scalable. The output of scalable approaches based on a non-compartmentalized modeling may be so large that it has neither been explored nor handled so far.

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

Miscoto source code, instructions for use and examples are available at:

RevDate: 2018-11-13

Yost S, Stashenko P, Choi Y, et al (2018)

Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses.

International journal of oral science, 10(4):32 pii:10.1038/s41368-018-0037-7.

Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.

RevDate: 2018-11-12

Ventura Spagnolo E, Stassi C, Mondello C, et al (2018)

Forensic microbiology applications: A systematic review.

Legal medicine (Tokyo, Japan), 36:73-80 pii:S1344-6223(18)30153-6 [Epub ahead of print].

According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.

RevDate: 2018-11-12

Fonkou MD, Dufour JC, Dubourg G, et al (2018)

Repertoire of bacterial species cultured from the human oral cavity and respiratory tract.

Future microbiology [Epub ahead of print].

While the gut microbiota is currently in the spotlight, the airway microbiome has been recently associated with several pulmonary diseases and carcinogenesis. As there are several biases associated with high-throughput sequencing methods, cultivation techniques are crucial for the investigation of the human microbiome. We thus aimed to build an exhaustive database, including a list of microbes isolated by culture from respiratory specimens, by performing a review of the literature. Herein, we have listed a total of 756 species cultured from the human respiratory tract. This represents 27.23% of the overall bacterial richness captured from human being by culture methods. This repertoire could be valuable for the elucidation of the interactions between the respiratory microbiome and human health.

RevDate: 2018-11-07

Bratburd JR, Keller C, Vivas E, et al (2018)

Gut Microbial and Metabolic Responses to Salmonella enterica Serovar Typhimurium and Candida albicans.

mBio, 9(6): pii:mBio.02032-18.

The gut microbiota confers resistance to pathogens of the intestinal ecosystem, yet the dynamics of pathogen-microbiome interactions and the metabolites involved in this process remain largely unknown. Here, we use gnotobiotic mice infected with the virulent pathogen Salmonella enterica serovar Typhimurium or the opportunistic pathogen Candida albicans in combination with metagenomics and discovery metabolomics to identify changes in the community and metabolome during infection. To isolate the role of the microbiota in response to pathogens, we compared mice monocolonized with the pathogen, uninfected mice "humanized" with a synthetic human microbiome, or infected humanized mice. In Salmonella-infected mice, by 3 days into infection, microbiome community structure and function changed substantially, with a rise in Enterobacteriaceae strains and a reduction in biosynthetic gene cluster potential. In contrast, Candida-infected mice had few microbiome changes. The LC-MS metabolomic fingerprint of the cecum differed between mice monocolonized with either pathogen and humanized infected mice. Specifically, we identified an increase in glutathione disulfide, glutathione cysteine disulfide, inosine 5'-monophosphate, and hydroxybutyrylcarnitine in mice infected with Salmonella in contrast to uninfected mice and mice monocolonized with Salmonella These metabolites potentially play a role in pathogen-induced oxidative stress. These results provide insight into how the microbiota community members interact with each other and with pathogens on a metabolic level.IMPORTANCE The gut microbiota is increasingly recognized for playing a critical role in human health and disease, especially in conferring resistance to both virulent pathogens such as Salmonella, which infects 1.2 million people in the United States every year (E. Scallan, R. M. Hoekstra, F. J. Angulo, R. V. Tauxe, et al., Emerg Infect Dis 17:7-15, 2011,, and opportunistic pathogens like Candida, which causes an estimated 46,000 cases of invasive candidiasis each year in the United States (Centers for Disease Control and Prevention, Antibiotic Resistance Threats in the United States, 2013, 2013). Using a gnotobiotic mouse model, we investigate potential changes in gut microbial community structure and function during infection using metagenomics and metabolomics. We observe that changes in the community and in biosynthetic gene cluster potential occur within 3 days for the virulent Salmonella enterica serovar Typhimurium, but there are minimal changes with a poorly colonizing Candida albicans In addition, the metabolome shifts depending on infection status, including changes in glutathione metabolites in response to Salmonella infection, potentially in response to host oxidative stress.

RevDate: 2018-11-07

Ojo-Okunola A, Nicol M, E du Toit (2018)

Human Breast Milk Bacteriome in Health and Disease.

Nutrients, 10(11): pii:nu10111643.

It is well-known that, beyond nutritional components, human breast milk (HBM) contains a wide variety of non-nutritive bio-factors perfectly suited for the growing infant. In the pre-2000 era, HBM was considered sterile and devoid of micro-organisms. Though HBM was not included as part of the human microbiome project launched in 2007, great strides have been made in studying the bacterial diversity of HBM in both a healthy state and diseased state, and in understanding their role in infant health. HBM provides a vast array of beneficial micro-organisms that play a key role in colonizing the infant's mucosal system, including that of the gut. They also have a role in priming the infant's immune system and supporting its maturation. In this review, we provide an in-depth and updated insight into the immunomodulatory, metabolic, and anti-infective role of HBM bacteriome (bacterial community) and its effect on infant health. We also provide key information from the literature by exploring the possible origin of microbial communities in HBM, the bacterial diversity in this niche and the determinants influencing the HBM bacteriome. Lastly, we investigate the role of the HBM bacteriome in maternal infectious disease (human immunodeficiency virus (HIV) and mastitis)), and cancer. Key gaps in HBM bacterial research are also identified.

RevDate: 2018-11-06

Tirosh O, Conlan S, Deming C, et al (2018)

Expanded skin virome in DOCK8-deficient patients.

Nature medicine pii:10.1038/s41591-018-0211-7 [Epub ahead of print].

Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.

RevDate: 2018-11-05

Woerner AE, Novroski NMM, Wendt FR, et al (2018)

Forensic human identification with targeted microbiome markers using nearest neighbor classification.

Forensic science international. Genetics, 38:130-139 pii:S1872-4973(18)30373-9 [Epub ahead of print].

From the perspective of forensics genetics, the human microbiome is a rich, relatively untapped resource for human identity testing. Since it varies within and among people, and perhaps temporally, the potential forensic applications of the use of the microbiome can exceed that of human identification. However, the same inherent variability in microbial distributions may pose a substantial barrier to forming predictions on an individual as the source of the microbial sample unless stable signatures of the microbiome are identified and targeted. One of the more commonly adopted strategies for microbial human identification relies on quantifying which taxa are present and their respective abundance levels. It remains an open question if such microbial signatures are more individualizing than estimates of the degree of genetic relatedness between microbial samples. This study attempts to address this question by contrasting two prediction strategies. The first approach uses phylogenetic distance to predict the host individual; thus it operates under the premise that microbes within individuals are more closely related than microbes between/among individuals. The second approach uses population genetic measures of diversity at clade-specific markers, serving as a fine-grained assessment of microbial composition and quantification. Both assessments were performed using targeted sequencing of 286 markers from 22 microbial taxa sampled in 51 individuals across three body sites measured in triplicate. Nearest neighbor and reverse nearest neighbor classifiers were constructed based on the pooled data and yielded 71% and 78% accuracy, respectively, when diversity was considered, and performed significantly worse when a phylogenetic distance was used (54% and 63% accuracy, respectively). However, empirical estimates of classification accuracy were 100% when conditioned on a maximum nearest neighbor distance when diversity was used, while identification based on a phylogenetic distance failed to reach saturation. These findings suggest that microbial strain composition is more individualizing than that of a phylogeny, perhaps indicating that microbial composition may be more individualizing than recent common ancestry. One inference that may be drawn from these findings is that host-environment interactions may maintain the targeted microbial profile and that this maintenance may not necessarily be repopulated by intra-individual microbial strains.

RevDate: 2018-11-05

Cogdill AP, Gaudreau PO, Arora R, et al (2018)

The Impact of Intratumoral and Gastrointestinal Microbiota on Systemic Cancer Therapy.

Trends in immunology, 39(11):900-920.

The human microbiome is a complex aggregate of microorganisms, and their genomes exert a number of influences crucial to the metabolic, immunologic, hormonal, and homeostatic function of the host. Recent work, both in preclinical mouse models and human studies, has shed light on the impact of gut and tumor microbiota on responses to systemic anticancer therapeutics. In light of this, strategies to target the microbiome to improve therapeutic responses are underway, including efforts to target gut and intratumoral microbes. Here, we discuss mechanisms by which microbiota may impact systemic and antitumor immunity, in addition to outstanding questions in the field. A deeper understanding of these is critical as we devise putative strategies to target the microbiome.

RevDate: 2018-11-04

Wang Q, Yang F, H Jia (2018)

Mining the Microbiome for Drug Targets.

Methods in enzymology, 610:59-72.

The human microbiome is our "other genome." Implicated in a growing list of complex diseases, for which genomic studies typically explain a portion of the disease susceptibility, the human gut microbiome has been at the spotlight for our understanding of human diseases. As the microbiome is intrinsically more variable than the human genome, it is important to take careful considerations at each step of a study. Here, we put forward our recommendations, which we envision would facilitate identification of true drug targets in the human microbiome in the colon as well as at other body sites.

RevDate: 2018-11-04

Wu BG, LN Segal (2018)

The Lung Microbiome and Its Role in Pneumonia.

Clinics in chest medicine, 39(4):677-689.

The use of next-generation sequencing and multiomic analysis reveals new insights on the identity of microbes in the lower airways blurring the lines between commensals and pathogens. Microbes are not found in isolation; rather they form complex metacommunities where microbe-host and microbe-microbe interactions play important roles on the host susceptibility to pathogens. In addition, the lower airway microbiota exert significant effects on host immune tone. Thus, this review highlights the roles that microbes in the respiratory tract play in the development of pneumonia.

RevDate: 2018-11-03

Junges R, Sturød K, Salvadori G, et al (2018)

Characterization of a signaling system in the oral commensal Streptococcus mitis that mediates interspecies communication with the pathogen Streptococcus pneumoniae.

Applied and environmental microbiology pii:AEM.02297-18 [Epub ahead of print].

Streptococcus mitis is found in the oral cavity and nasopharynx and forms a significant portion of the human microbiome. In this study, in silico analyses indicated the presence of an Rgg/SHP cell-to-cell communication system in S. mitis Although Rgg presented higher similarity to a repressor in Streptococcus pyogenes, auto-inducing assays and an rgg deletion mutant revealed that in S. mitis Rgg acts as an activator. Transcriptome analysis showed that in addition to shp, the system regulates two other downstream genes, comprising a segment of a putative lantibiotic gene cluster that is in a conjugative element locus in different members of the mitis group. Close comparison to a similar lantibiotic gene cluster in Streptococcus pneumoniae indicated that S. mitis lacked the full set of genes. Despite the potential of SHP to trigger a futile cycle of auto-induction, growth was not significantly affected for the rgg mutant under normal or antibiotic stress conditions. The S. mitis SHP was, however, fully functional in promoting cross-species communication and increasing S. pneumoniae surface polysaccharide production, which in this species is regulated by Rgg/SHP. The activity of SHPs produced by both species was detected in co-cultures using a S. mitis reporter strain. In competitive assays, a slight advantage was observed for the rgg mutants. We conclude that the Rgg/SHP system in S. mitis regulates the expression of its own shp, and activates an Rgg/SHP system in S. pneumoniae that regulates surface polysaccharide synthesis. Fundamentally, cross-communication of such systems may have a role during multi-species interactions.IMPORTANCEBacteria secrete signal molecules into the environment which are sensed by other cells when the density reaches a certain threshold. In this study, we describe a communication system in Streptococcus mitis, a commensal species from the oral cavity, which we also found in several species and strains of streptococci from the mitis group. Further, we show that this system can promote cross-communication with S. pneumoniae, a closely-related major human pathogen. Importantly, we show that this cross-communication can take place during co-culture. While the genes regulated in S. mitis are likely part of a futile cycle of activation, the target genes in S. pneumoniae are potentially involved in virulence. The understanding of such complex communication networks can provide important insights into the dynamics of bacterial communities.

RevDate: 2018-11-01

Schooley RT (2018)

The human microbiome: implications for health and disease, including HIV infection.

Topics in antiviral medicine, 26(3):75-78.

Our increased understanding of the human microbiome has brought insight into the role it plays in health and disease, including HIV infection. Studies have shown that the gut microbiome is less diverse in individuals with HIV infection than in noninfected control subjects. Efforts to modify the microbiome to bolster immune reconstitution in people with HIV infection have so far been unsuccessful. The vaginal microbiome affects risk of HIV acquisition, with Lactobacillus dominance being protective compared with vaginosis characterized by larger populations of Gardnerella. The vaginal microbiome might also affect efficacy of topical tenofovir disoproxil fumarate preexposure prophylaxis. This article summarizes a presentation by Robert T. Schooley, MD, at the IAS-USA continuing education program held in San Francisco in May 2018.

RevDate: 2018-10-31

Franzosa EA, McIver LJ, Rahnavard G, et al (2018)

Species-level functional profiling of metagenomes and metatranscriptomes.

Nature methods pii:10.1038/s41592-018-0176-y [Epub ahead of print].

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types.

RevDate: 2018-10-30

Vinberg M, Ottesen NM, Meluken I, et al (2018)

Remitted affective disorders and high familial risk of affective disorders associate with aberrant intestinal microbiota.

Acta psychiatrica Scandinavica [Epub ahead of print].

OBJECTIVE: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk).

METHODS: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region.

RESULTS: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication).

CONCLUSION: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder.

RevDate: 2018-10-30

Pretzl B, Sälzer S, Ehmke B, et al (2018)

Administration of systemic antibiotics during non-surgical periodontal therapy-a consensus report.

Clinical oral investigations pii:10.1007/s00784-018-2727-0 [Epub ahead of print].

AIM: The aim of this meta-review was to evaluate whether there is a meaningful clinical benefit regarding the use of systemic adjunctive antibiotics in the treatment of patients with periodontitis. Additionally, a consensus regarding possible recommendations for future administration of antibiotics should be reached.

METHODS: A structured literature search was performed by two independent investigators focusing on systematic reviews (SR) covering adjunctive systemic antibiosis during non-surgical periodontal therapy. Additionally, recent randomized clinical trials (RCT, July 2015 to July 2017) were searched systematically to update the latest SR. Results were summarized and discussed in a plenary to reach a consensus.

RESULTS: Mostly, systematic reviews and RCTs showed a significant positive effect of adjunctive systematic antibiosis compared to controls. These positive effects gain clinical relevance in patients with severe periodontal disease aged 55 years and younger.

CONCLUSION: Systemic antibiotics as an adjunct to non-surgical periodontal therapy should be sensibly administered and restrictively used. Only certain groups of periodontitis patients show a significant and clinically relevant benefit after intake of systemic antibiosis during periodontal therapy.

CLINICAL RELEVANCE: Avoiding antibiotic resistance and possible side effects on the human microbiome should be a focus of dentists and physicians. Thus, a sensible administration of antibiotics is mandatory. This manuscript suggests guidelines for a reasonable use.

RevDate: 2018-10-27

Shi JY, Huang H, Zhang YN, et al (2018)

BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.

BMC bioinformatics, 19(Suppl 9):281 pii:10.1186/s12859-018-2274-3.

BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.

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

CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).

RevDate: 2018-10-25

Vatanen T, Franzosa EA, Schwager R, et al (2018)

The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.

Nature, 562(7728):589-594.

Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.

RevDate: 2018-10-25

Tackmann J, Arora N, Schmidt TSB, et al (2018)

Ecologically informed microbial biomarkers and accurate classification of mixed and unmixed samples in an extensive cross-study of human body sites.

Microbiome, 6(1):192 pii:10.1186/s40168-018-0565-6.

BACKGROUND: The identification of body site-specific microbial biomarkers and their use for classification tasks have promising applications in medicine, microbial ecology, and forensics. Previous studies have characterized site-specific microbiota and shown that sample origin can be accurately predicted by microbial content. However, these studies were usually restricted to single datasets with consistent experimental methods and conditions, as well as comparatively small sample numbers. The effects of study-specific biases and statistical power on classification performance and biomarker identification thus remain poorly understood. Furthermore, reliable detection in mixtures of different body sites or with noise from environmental contamination has rarely been investigated thus far. Finally, the impact of ecological associations between microbes on biomarker discovery was usually not considered in previous work.

RESULTS: Here we present the analysis of one of the largest cross-study sequencing datasets of microbial communities from human body sites (15,082 samples from 57 publicly available studies). We show that training a Random Forest Classifier on this aggregated dataset increases prediction performance for body sites by 35% compared to a single-study classifier. Using simulated datasets, we further demonstrate that the source of different microbial contributions in mixtures of different body sites or with soil can be detected starting at 1% of the total microbial community. We apply a biomarker selection method that excludes indirect environmental associations driven by microbe-microbe associations, yielding a parsimonious set of highly predictive taxa including novel biomarkers and excluding many previously reported taxa. We find a considerable fraction of unclassified biomarkers ("microbial dark matter") and observe that negatively associated taxa have a surprisingly high impact on classification performance. We further detect a significant enrichment of rod-shaped, motile, and sporulating taxa for feces biomarkers, consistent with a highly competitive environment.

CONCLUSIONS: Our machine learning model shows strong body site classification performance, both in single-source samples and mixtures, making it promising for tasks requiring high accuracy, such as forensic applications. We report a core set of ecologically informed biomarkers, inferred across a wide range of experimental protocols and conditions, providing the most concise, general, and least biased overview of body site-associated microbes to date.

RevDate: 2018-10-24

Benler S, Cobián-Güemes AG, McNair K, et al (2018)

A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.

Microbiome, 6(1):191 pii:10.1186/s40168-018-0573-6.

BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs.

RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively.

CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.

RevDate: 2018-10-23

Chaudhari NM, Gautam A, Gupta VK, et al (2018)

PanGFR-HM: A Dynamic Web Resource for Pan-Genomic and Functional Profiling of Human Microbiome With Comparative Features.

Frontiers in microbiology, 9:2322.

The conglomerate of microorganisms inhabiting various body-sites of human, known as the human microbiome, is one of the key determinants of human health and disease. Comprehensive pan-genomic and functional analysis approach for human microbiome components can enrich our understanding about impact of microbiome on human health. By utilizing this approach we developed PanGFR-HM ( - a novel dynamic web-resource that integrates genomic and functional characteristics of 1293 complete microbial genomes available from Human Microbiome Project. The resource allows users to explore genomic/functional diversity and genome-based phylogenetic relationships between human associated microbial genomes, not provided by any other resource. The key features implemented here include pan-genome and functional analysis of organisms based on taxonomy or body-site, and comparative analysis between groups of organisms. The first feature can also identify probable gene-loss events and significantly over/under represented KEGG/COG categories within pan-genome. The unique second feature can perform comparative genomic, functional and pathways analysis between 4 groups of microbes. The dynamic nature of this resource enables users to define parameters for orthologous clustering and to select any set of organisms for analysis. As an application for comparative feature of PanGFR-HM, we performed a comparative analysis with 67 Lactobacillus genomes isolated from human gut, oral cavity and urogenital tract, and therefore characterized the body-site specific genes, enzymes and pathways. Altogether, PanGFR-HM, being unique in its content and functionality, is expected to provide a platform for microbiome-based comparative functional and evolutionary genomics.

RevDate: 2018-10-23

Chen Z, Yeoh YK, Hui M, et al (2018)

Diversity of macaque microbiota compared to the human counterparts.

Scientific reports, 8(1):15573 pii:10.1038/s41598-018-33950-6.

Studies on the microbial communities in non-human primate hosts provide unique insights in both evolution and function of microbes related to human health and diseases. Using 16S rRNA gene amplicon profiling, we examined the oral, anal and vaginal microbiota in a group of non-captive rhesus macaques (N = 116) and compared the compositions with the healthy communities from Human Microbiome Project. The macaque microbiota was dominated by Bacteroidetes, Firmicutes and Proteobacteria; however, there were marked differences in phylotypes enriched across body sites indicative of strong niche specialization. Compared to human gut microbiota where Bacteroides predominately enriched, the surveyed macaque anal community exhibited increased abundance of Prevotella. In contrast to the conserved human vaginal microbiota extremely dominated by Lactobacillus, the macaque vaginal microbial composition was highly diverse while lactobacilli were rare. A constant decrease of the vaginal microbiota diversity was observed among macaque samples from juvenile, adult without tubectomy, and adult with tubectomy, with the most notable distinction being the enrichment of Halomonas in juvenile and Saccharofermentans in contracepted adults. Both macaque and human oral microbiota were colonized with three most common oral bacterial genera: Streptococcus, Haemophilus and Veillonella, and shared relatively conserved communities to each other. A number of bacteria related to human pathogens were consistently detected in macaques. The findings delineate the range of structure and diversity of microbial communities in a wild macaque population, and enable the application of macaque as an animal model for future characterization of microbes in transmission, genomics and function.

RevDate: 2018-10-22

Ponziani FR, Putignani L, Paroni Sterbini F, et al (2018)

Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis.

Alimentary pharmacology & therapeutics [Epub ahead of print].

BACKGROUND: The cure of hepatitis C virus (HCV) infection may contribute to the reduction of liver fibrosis progression and potentially influence the gut-liver axis.

AIM: To investigate the influence of HCV infection eradication with direct-acting antivirals (DAAs) on the gut microbiota composition as well as on intestinal and systemic inflammatory parameters in patients with cirrhosis.

METHODS: Consecutive patients with HCV-related cirrhosis receiving DAA treatment were included. The gut microbiota composition, intestinal permeability, and inflammation were assessed before treatment and after 1 year. Clinical outcomes such as episodes of decompensation and markers of liver fibrosis were evaluated over a 2-year follow-up period.

RESULTS: The gut microbiota alpha diversity in cirrhotic patients, which was lower than that in healthy subjects, was significantly improved by the cure of HCV infection and a shift in the overall gut microbiota composition was observed compared to baseline. The abundance of potentially pathogenic bacteria (Enterobacteriaceae, Enterococcus, and Staphylococcus) was decreased after treatment. The gut microbiota composition was associated with the inflammatory profile and markers of liver fibrosis. Although a significant reduction in the serum levels of cytokines and chemokines was observed post-DAA treatment, measures of intestinal permeability and inflammation remained unchanged.

CONCLUSIONS: Cure of HCV infection with DAAs in patients with cirrhosis is associated with a modification of the gut microbiota, which correlates with fibrosis and inflammation but does not improve intestinal barrier function.

RevDate: 2018-10-22

Duran-Pinedo AE, Solbiati J, J Frias-Lopez (2018)

The effect of the stress hormone cortisol on the metatranscriptome of the oral microbiome.

NPJ biofilms and microbiomes, 4:25 pii:68.

Imbalances of the microbiome, also referred to as microbial dysbiosis, could lead to a series of different diseases. One factor that has been shown to lead to dysbiosis of the microbiome is exposure to psychological stressors. Throughout evolution microorganisms of the human microbiome have developed systems for sensing host-associated signals such as hormones associated with those stressors, enabling them to recognize essential changes in their environment, thus changing their expression gene profile to fit the needs of the new environment. The most widely accepted theory explaining the ability of hormones to affect the outcome of an infection involves the suppression of the immune system. Commensal microbiota is involved in stressor-induced immunomodulation, but other biological effects are not yet known. Here we present the impact that cortisol had on the community-wide transcriptome of the oral community. We used a metatranscriptomic approach to obtain first insights into the metabolic changes induced by this stress hormone as well as which members of the oral microbiome respond to the presence of cortisol in the environment. Our findings show that the stress hormone cortisol directly induces shifts in the gene expression profiles of the oral microbiome that reproduce results found in the profiles of expression of periodontal disease and its progression.

RevDate: 2018-10-20

Chen B, Wang J, Wang Y, et al (2018)

Oral microbiota dysbiosis and its association with Henoch-Schönlein Purpura in children.

International immunopharmacology, 65:295-302 pii:S1567-5769(18)30864-6 [Epub ahead of print].

BACKGROUND: The pathogenesis of microbes in allergic diseases has been demonstrated and our previous research indicates that microbiota causing gut disorders in children is associated with Henoch-Schönlein Purpura. However, the role of oral microbiota in Henoch-Schönlein Purpura remains unknown.

METHOD: A total of 164 children were enrolled, of which 98 were patients with HSP and 66 were healthy children. Oral swab samples were collected for DNA extraction and 16S rRNA gene sequencing, then analyzed for oral microbiota composition.

RESULTS: Oral microbiota differed between healthy children and those with HSP. Children with HSP exhibited higher oral microbial diversity and richness than the controls. Firmicutes, Proteobacteria, and Bacteroidetes are the dominant phyla in children with HSP. We used linear discriminant analysis (LDA) effect size (LEfSe) algorithm and detected 21 bacterial taxonomic clades showing statistical differences (12 increased and 9 decreased) in children with HSP. The correlation analyses between clinical data and abundance in microbial community indicated that an abundance of Butyrivibrio sp. negatively correlated with the length of hospital stay (LOS). Haemophilus sp. negatively correlated to IgE and IgM but positively correlated to LOS, with decreasing significantly in patients with HSP. Prevotella positively correlated with IgM. Prevotella nanceiensis positively correlated with IgA, and were abundant in children with HSP.

CONCLUSIONS: These results indicate that children with HSP have significantly different oral microbiota compared to healthy children. Although this study does not imply causality, it is helpful to identify the types and pathways of bacteria that can be used to prevent or treat HSP.

RevDate: 2018-10-17

Wyman SK, Avila-Herrera A, Nayfach S, et al (2018)

A most wanted list of conserved microbial protein families with no known domains.

PloS one, 13(10):e0205749 pii:PONE-D-18-08043.

The number and proportion of genes with no known function are growing rapidly. To quantify this phenomenon and provide criteria for prioritizing genes for functional characterization, we developed a bioinformatics pipeline that identifies robustly defined protein families with no annotated domains, ranks these with respect to phylogenetic breadth, and identifies them in metagenomics data. We applied this approach to 271 965 protein families from the SFams database and discovered many with no functional annotation, including >118 000 families lacking any known protein domain. From these, we prioritized 6 668 conserved protein families with at least three sequences from organisms in at least two distinct classes. These Function Unknown Families (FUnkFams) are present in Tara Oceans Expedition and Human Microbiome Project metagenomes, with distributions associated with sampling environment. Our findings highlight the extent of functional novelty in sequence databases and establish an approach for creating a "most wanted" list of genes to prioritize for further characterization.

RevDate: 2018-10-16

Waterhouse M, Hope B, Krause L, et al (2018)

Vitamin D and the gut microbiome: a systematic review of in vivo studies.

European journal of nutrition pii:10.1007/s00394-018-1842-7 [Epub ahead of print].

PURPOSE: Variation in the human microbiome has been linked with a variety of physiological functions, including immune regulation and metabolism and biosynthesis of vitamins, hormones, and neurotransmitters. Evidence for extraskeletal effects of vitamin D has been accruing and it has been suggested that the effect of vitamin D on health is partially mediated through the microbiome. We aimed to critically evaluate the evidence linking vitamin D and the gastrointestinal microbiome.

METHODS: We systematically searched the Embase, Web of Science, PubMed and CINAHL databases, including peer-reviewed publications that reported an association between a measure of vitamin D and the gastrointestinal microbiome in humans or experimental animals.

RESULTS: We included 10 mouse and 14 human studies. Mouse studies compared mice fed diets containing different levels of vitamin D (usually high versus low), or vitamin D receptor knockout or Cyp27B1 knockout with wild-type mice. Five mouse studies reported an increase in Bacteroidetes (or taxa within that phylum) in the low vitamin D diet or gene knockout group. Human studies were predominantly observational; all but two of the included studies found some association between vitamin D and the gut microbiome, but the nature of differences observed varied across studies.

CONCLUSIONS: Despite substantial heterogeneity, we found evidence to support the hypothesis that vitamin D influences the composition of the gastrointestinal microbiome. However, the research is limited, having been conducted either in mice or in mostly small, selected human populations. Future research in larger population-based studies is needed to fully understand the extent to which vitamin D modulates the microbiome.

RevDate: 2018-10-12

Bilen M, Mbogning Fonkou MD, Khelaifia S, et al (2018)

Taxonogenomics description of Parabacteroides timonensis sp. nov. isolated from a human stool sample.

MicrobiologyOpen [Epub ahead of print].

Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236T , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236T through the taxonogenomic approach.

RevDate: 2018-10-10

Balato A, Cacciapuoti S, Di Caprio R, et al (2018)

Human Microbiome: Composition and Role in Inflammatory Skin Diseases.

Archivum immunologiae et therapiae experimentalis pii:10.1007/s00005-018-0528-4 [Epub ahead of print].

This review focuses on recent evidences about human microbiome composition and functions, exploring the potential implication of its impairment in some diffuse and invalidating inflammatory skin diseases, such as atopic dermatitis, psoriasis, hidradenitis suppurativa and acne. We analysed current scientific literature, focusing on the current evidences about gut and skin microbiome composition and the complex dialogue between microbes and the host. Finally, we examined the consequences of this dialogue for health and skin diseases. This review highlights how human microbes interact with different anatomic niches modifying the state of immune activation, skin barrier status, microbe-host and microbe-microbe interactions. It also shows as most of the factors affecting gut and skin microorganisms' activity have demonstrated to be effective also in modulating chronic inflammatory skin diseases. More and more evidences demonstrate that human microbiome plays a key role in human health and diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.

RevDate: 2018-10-09

Bell JS, Spencer JI, Yates RL, et al (2018)

From Nose to Gut - The Role of the Microbiome in Neurological Disease.

Neuropathology and applied neurobiology [Epub ahead of print].

Inflammation and neurodegeneration are key features of many chronic neurological diseases, yet the causative mechanisms underlying these processes are poorly understood. There has been mounting interest in the role of the human microbiome in modulating the inflammatory milieu of the central nervous system in health and disease. To date, most research has focussed on a gut-brain axis, with other mucosal surfaces being relatively neglected. We herein take the novel approach of comprehensively reviewing the roles of the microbiome across several key mucosal interfaces - the nose, mouth, lung, and gut - in health and in Parkinson's disease (PD), Alzheimer's disease (AD) and multiple sclerosis (MS). This review systematically appraises the anatomical and microbiological landscape of each mucosal surface in health and disease before considering relevant mechanisms that may influence the initiation and progression of PD, AD, and MS. The cumulative effects of dysbiosis from the nose to the gut may contribute significantly to neurological disease through a wide variety of mechanisms, including direct translocation of bacteria and their products, and modulation of systemic or central nervous system-specific immunity. This remains an understudied and exciting area for future research and may lead to the development of therapeutic targets for chronic neurological disease. This article is protected by copyright. All rights reserved.

RevDate: 2018-10-09

Macklaim JM, GB Gloor (2018)

From RNA-seq to Biological Inference: Using Compositional Data Analysis in Meta-Transcriptomics.

Methods in molecular biology (Clifton, N.J.), 1849:193-213.

The proper analysis of high-throughput sequencing datasets of mixed microbial communities (meta-transcriptomics) is substantially more complex than for datasets composed of single organisms. Adapting commonly used RNA-seq methods to the analysis of meta-transcriptome datasets can be misleading and not use all the available information in a consistent manner. However, meta-transcriptomic experiments can be investigated in a principled manner using Bayesian probabilistic modeling of the data at a functional level coupled with analysis under a compositional data analysis paradigm. We present a worked example for the differential functional evaluation of mixed-species microbial communities obtained from human clinical samples that were sequenced on an Illumina platform. We demonstrate methods to functionally map reads directly, conduct a compositionally appropriate exploratory data analysis, evaluate differential relative abundance, and finally identify compositionally associated (constant ratio) functions. Using these approaches we have found that meta-transcriptomic functional analyses are highly reproducible and convey significant information regarding the ecosystem.

RevDate: 2018-10-04

Hoggard M, Vesty A, Wong G, et al (2018)

Characterizing the Human Mycobiota: A Comparison of Small Subunit rRNA, ITS1, ITS2, and Large Subunit rRNA Genomic Targets.

Frontiers in microbiology, 9:2208.

Interest in the human microbiome has increased dramatically in the last decade. However, much of this research has focused on bacteria, while the composition and roles of their fungal counterparts remain less understood. Furthermore, a variety of methodological approaches have been applied, and the comparability between studies is unclear. This study compared four primer pairs targeting the small subunit (SSU) rRNA (18S), ITS1, ITS2, and large subunit (LSU) rRNA (26S) genomic regions for their ability to accurately characterize fungal communities typical of the human mycobiota. All four target regions of 21 individual fungal mock community taxa were capable of being amplified adequately and sequenced. Mixed mock community analyses revealed marked variability in the ability of each primer pair to accurately characterize a complex community. ITS target regions outperformed LSU and SSU. Of the ITS regions, ITS1 failed to generate sequences for Yarrowia lipolytica and all three Malassezia species when in a mixed community. These findings were further supported in studies of human sinonasal and mouse fecal samples. Based on these analyses, previous studies using ITS1, SSU, or LSU markers may omit key taxa that are identified by the ITS2 marker. Of methods commonly used in human mycobiota studies to date, we recommend selection of the ITS2 marker. Further investigation of more recently developed fungal primer options will be essential to ultimately determine the optimal methodological approach by which future human mycobiota studies ought to be standardized.

RevDate: 2018-10-03

Romano L, Gualtieri P, Nicoletti F, et al (2018)

Neurodegenerative disorders, gut human microbiome and diet: future research for prevention and supportive therapies.

European review for medical and pharmacological sciences, 22(18):5771-5772.

RevDate: 2018-10-02

Vamanu E (2018)

Complementary functional strategy for modulation of human gut microbiota.

Current pharmaceutical design pii:CPD-EPUB-93334 [Epub ahead of print].

BACKGROUND: Two pathologies commonly associated with gut microbiota dysbiosis are type 2 diabetes and cardiovascular diseases. A disturbance in microbial balance translates into the occurrence of degenerative dysfunctions that are also associated with other pathologies, such as obesity, colon cancer.

METHODS: Thus, the aim of this review was to present the significant findings related to human microbiome modulation via the prebiotic effects of wild edible mushrooms as a complementary strategy to modern treatment.

RESULTS: Since diet and medication are two important causes of microbiome fingerprint modifications, new complementary and alternative methods can include wild edible mushrooms, which serve as functional products, given their properties in modulating the microbial pattern at the colon level. The metagenomic study has enabled the identification of some competitive microbiological and biochemical biomarkers which allow the development of innovative strategies in controlling microbial disbalance from human gut.

CONCLUSION: Certain mushroom species have been approaching and their effects on the microbiota fingerprint of two major target groups are highlighted.

RevDate: 2018-10-02

Perkins RC (2019)

Making the Case for Functional Proteomics.

Methods in molecular biology (Clifton, N.J.), 1871:1-40.

"Making the Case for Functional Proteomics" first differentiates the Functional Proteome from the products of genetic protein expression. Qualitatively, the prevalence of posttranslational modifications (PTMs) virtually insures that individual, functional proteins do not equate to their genetic expression counterparts. Quantitatively, considering the frequency of PTMs and a conservative estimate of the number of functional entities arising from protein interactions, the size of the Functional Proteome exceeds that of the human genome by at least two orders of magnitude. The human genome does not, cannot, map the Functional Proteome. Further, the collective genome of the human microbiome dwarfs the human genome. With these facts established, "Making the Case…" proceeds to examine Functional Proteomics (of which both "gene expression" and "epigenetics" are but parts of a larger whole) within the context of Systems Biology, concluding that functionally related networks comprise the dominant motif for biological activity. Creating just such a network focus is essential in not only expanding basic knowledge but also in applying that knowledge in the pragmatic efforts of drug and biomarker development. Outlines for development of drugs and biomarkers, as well as the realization of precision medicine, within a functional proteomics-based, network motif are provided. The chapter proceeds to asses both the knowledge base and the tools to fully embrace Functional Proteomics. Given the decades-long infatuation with the reductionism of genomics, it is not surprising that both the proteomics knowledge base and tools are assessed as poor to fair. However, even a minor shift in research funding and a renewed challenge to methods developers will rapidly improve the current situation. Adoption of the included "Roadmap" will realistically make the twenty-first century the century of a long-awaited revolution in biology.

RevDate: 2018-10-02

Gonzalez A, Navas-Molina JA, Kosciolek T, et al (2018)

Qiita: rapid, web-enabled microbiome meta-analysis.

Nature methods, 15(10):796-798.

Multi-omic insights into microbiome function and composition typically advance one study at a time. However, in order for relationships across studies to be fully understood, data must be aggregated into meta-analyses. This makes it possible to generate new hypotheses by finding features that are reproducible across biospecimens and data layers. Qiita dramatically accelerates such integration tasks in a web-based microbiome-comparison platform, which we demonstrate with Human Microbiome Project and Integrative Human Microbiome Project (iHMP) data.

RevDate: 2018-10-01

Aziz RK, Hegazy SM, Yasser R, et al (2018)

Drug pharmacomicrobiomics and toxicomicrobiomics: from scattered reports to systematic studies of drug-microbiome interactions.

Expert opinion on drug metabolism & toxicology [Epub ahead of print].

INTRODUCTION: Pharmacomicrobiomics and toxicomicrobiomics study how variations within the human microbiome (the combination of human-associated microbial communities and their genomes) affect drug disposition, action, and toxicity. These emerging fields, interconnecting microbiology, bioinformatics, systems pharmacology, and toxicology, complement pharmacogenomics and toxicogenomics, expanding the scope of precision medicine. Areas covered: This article reviews some of the most recently reported pharmacomicrobiomic and toxicomicrobiomic interactions. Examples include the impact of the human gut microbiota on cardiovascular drugs, natural products, and chemotherapeutic agents, including immune checkpoint inhibitors. Although the gut microbiota has been the most extensively studied, some key drug-microbiome interactions involve vaginal, intratumoral, and environmental bacteria, and are briefly discussed here. Additionally, computational resources, moving the field from cataloguing to predicting interactions, are introduced. Expert opinion: The rapid pace of discovery triggered by the Human Microbiome Project is moving pharmacomicrobiomic research from scattered observations to systematic studies focusing on screening microbiome variants against different drug classes. Better representation of all human populations will improve such studies by avoiding sampling bias, and the integration of multi-omic studies with designed experiments will allow establishing causation. In the near future, pharmacomicrobiomic testing is expected to be a key step in screening novel drugs and designing precision therapeutics.

RevDate: 2018-09-30

Hattori M (2018)

[Ecology and function of human microbiomes.].

Clinical calcium, 28(10):1398-1405.

Hundreds of trillions of bacteria consisting of ~1,000 species reside in various human body sites to form bacterial communities(microbiomes)specific for the sites. In the past decade, the human microbiome research in the world incredibly advanced by development of a culture-independent metagenomic analysis based on next-generation sequencing technologies. Particularly, current studies have revealed that the human gut microbiome is profoundly associated with the host's health and disease.

RevDate: 2018-09-28

Vareki SM, Chanyi RM, Abdur-Rashid K, et al (2018)

Moving on from Metchnikoff: thinking about microbiome therapeutics in cancer.

Ecancermedicalscience, 12:867 pii:can-12-867.

Precision medicine now needs to also consider the microbiome in oncology treatment. Ingested substances, whether they are a carcinogenic or therapeutic agent, will likely come into contact with the microbiota. Even those delivered extra-intestinally can be influenced beyond xenobiotic metabolism by biochemical factors associated with the microbiota or by an immunological predisposition created by the microbiome. We need to undertake one of the largest paradigm shifts to ever occur in medicine, that is, every drug or ingested substance needs to be re-evaluated for its pharmacological effect post-microbiome interaction. The importance of the microbiome with a focus on the treatment of cancer is discussed. In the near future, it may be possible to specifically manipulate the microbial composition within cancer patients to improve the therapeutic potential of existing oncological agents. However, the current tools to do so are limited. Targeted modulation is likely to be achieved by addition, selective enhancement or depletion of specific microbial types. This may include compounds such as narrow spectrum antimicrobial agents or oligosaccharides that will kill or enhance the bacterial growth of distinct members of the microbiota, respectively. This will stimulate a new era in these fields.

RevDate: 2018-09-27

Munson E, KC Carroll (2018)

An Update on the Novel Genera and Species and Revised Taxonomic Status of Bacterial Organisms Described in 2016 and 2017.

Journal of clinical microbiology pii:JCM.01181-18 [Epub ahead of print].

Recognition and acknowledgment of novel bacterial taxonomy and nomenclature revisions can impact clinical practice, disease epidemiology, and routine clinical microbiology laboratory operations. The Journal of Clinical Microbiology (JCM) herein presents its biannual report summarizing such changes published in the years 2016 and 2017, as published and added by the International Journal of Systematic and Evolutionary Microbiology Noteworthy discussion centers around descriptions of novel Corynebacteriaceae and an anaerobic mycolic-acid-producing bacterium in the suborder Corynebacterineae; revisions within the Propionibacterium, Clostridium, Borrelia, and Enterobacter genera; and, a major reorganization of the family EnterobacteriaceaeJCM intends to sustain this series of reports as advancements in molecular genetics, whole genome sequencing, and studies of the human microbiome will continue to produce novel taxa and clearer understandings of bacterial relatedness.

RevDate: 2018-09-26

Nazaroff WW (2018)

Embracing microbes in exposure science.

Journal of exposure science & environmental epidemiology pii:10.1038/s41370-018-0075-4 [Epub ahead of print].

Although defined more broadly, exposure science has mainly focused on exposures to environmental chemicals and related stressors, such as airborne particulate matter. There is an opportunity for exposure science to contribute more substantially to improving public health by devoting more attention to microorganisms as key stressors and agents in exposure. The discovery that pathogenic microbes cause disease in humans precipitated a revolution in public health science and disease prevention. With a continued global urgency to address spread of pathogenic microbes, contributions of microorganisms to both infectious and noninfectious processes merit more attention from the exposure science community. Today, discoveries of the importance of the human microbiome as a determinant of health and disease are precipitating a second revolution. Emerging knowledge creates a major opportunity to expand the scope of exposure science to incorporate the human microbiome as a target and modulator of exposure. A study committee of the National Academies of Sciences, Engineering, and Medicine has defined a research strategy to address health risks that pertain to the interaction of environmental chemicals with the human microbiome. Some aspects of this strategy pose important challenges and opportunities for the exposure science community.

RevDate: 2018-09-25

Zhao Y, Chen B, Li S, et al (2018)

Detection and characterization of bacterial nucleic acids in culture-negative synovial tissue and fluid samples from rheumatoid arthritis or osteoarthritis patients.

Scientific reports, 8(1):14305 pii:10.1038/s41598-018-32675-w.

Human intestinal microbes can mediate development of arthritis - Studies indicate that certain bacterial nucleic acids may exist in synovial fluid (SF) and could be involved in arthritis, although the underlying mechanism remains unclear. To characterize potential SF bacterial nucleic acids, we used 16S rRNA gene amplicon sequencing to assess bacterial nucleic acid communities in 15 synovial tissue (ST) and 110 SF samples from 125 patients with rheumatoid arthritis (RA) and 16 ST and 42 SF samples from 58 patients with osteoarthritis (OA). Our results showed an abundant diversity of bacterial nucleic acids in these clinical samples, including presence of Porphyromonas and Bacteroides in all 183 samples. Agrobacterium, Comamonas, Kocuria, Meiothermus, and Rhodoplanes were more abundant in synovial tissues of rheumatoid arthritis (STRA). Atopobium, Phascolarctobacterium, Rhodotorula mucilaginosa, Bacteroides uniformis, Rothia, Megasphaera, Turicibacter, Leptotrichia, Haemophilus parainfluenzae, Bacteroides fragilis, Porphyromonas, and Streptococcus were more abundant in synovial tissues of osteoarthritis (STOA). Veillonella dispar, Haemophilus parainfluenzae, Prevotella copri and Treponema amylovorum were more abundant in synovial fluid of rheumatoid arthritis (SFRA), while Bacteroides caccae was more abundant in the synovial fluid of osteoarthritis (SFOA). Overall, this study confirms existence of bacterial nucleic acids in SF and ST samples of RA and OA lesions and reveals potential correlations with degree of disease.

RevDate: 2018-09-23

Wang N, Zhu F, Chen L, et al (2018)

Proteomics, metabolomics and metagenomics for type 2 diabetes and its complications.

Life sciences pii:S0024-3205(18)30587-3 [Epub ahead of print].

Type 2 diabetes mellitus (T2DM) is one of the most common diseases of endocrine and metabolic disorders, whose mechanism is still largely unknown. Fortunately, various "omics" tools have been employed to better understand the progression pathologies of T2DM and its complications. More specifically, proteomics, metabolomics and metagenomics have played crucial roles in advancing deeper understanding of the physiological processes and regulatory mechanisms of T2DM, such as regulation of signaling pathways perturbed by glucose levels, intestinal microorganism, and inflammation and so on. By analyzing the dynamic change and modification of proteins, proteomics has become an important tool in biology and medicine. Metabolomic analysis can amplify and quantify metabolites in living organisms to reveal the relative relationship between metabolites and physiological and pathological changes. There are also increasing evidences that the human microbiome, specifically the gastrointestinal microbiome have a potential role in the etiology and pathological outcomes of T2DM and its complications. This article summarized and discussed the recent applications of these "omics" tools in finding biomarkers for T2DM and its complications. We also reviewed employing multiple "omics" to further advance our understanding of this pathology. This review will benefit deeper understanding in new therapeutic and/or diagnostic biological target for the discovery of T2DM and its complications.

RevDate: 2018-09-21

Allaband C, McDonald D, Vázquez-Baeza Y, et al (2018)

Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)31008-5 [Epub ahead of print].

Advances in technical capabilities for reading out complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including inter- and intra-subject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read out the microbiome and its resulting gene products and metabolites. We highlight several common pitfalls for clinicians, including the expectation that an individual's microbiome will be stable, that diet can induce rapid changes that are large compared to the differences among subjects, that everyone has essentially the same core stool microbiome, and that different laboratory and computational methods will yield essentially the same results. We also highlight the current limitations and future promise of these techniques, with the expectation that an understanding of these considerations will help accelerate the path towards routine clinical application of these techniques developed in research settings.

RevDate: 2018-09-21

Kyburz A, Fallegger A, Zhang X, et al (2018)

Trans-maternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T-cells.

The Journal of allergy and clinical immunology pii:S0091-6749(18)31297-1 [Epub ahead of print].

BACKGROUND: The trans-maternal exposure to tobacco, microbes, nutrients and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand, and is inversely associated with allergies and chronic inflammatory conditions on the other.

OBJECTIVE: Here, we investigate the consequences of trans-maternal exposure to H. pylori, in utero and/or during lactation, for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and the development of immune cell populations in the lung and lymphoid organs.

METHODS: We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter infection along with metagenomics analyses, multi-color flow cytometry and bilsufite pyrosequencing to study the effects of H. pylori on allergy severity and immunological and microbiome correlates thereof.

RESULTS: Perinatal exposure to H. pylori extract, or its immunomodulator VacA, confers robust protective effects against allergic airway inflammation not only in the first, but also the second offspring generation, but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T-cells, expansion of Treg subsets expressing CXCR3 or RORγt, and demethylation of the FOXP3 locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H. pylori exposure.

CONCLUSION: We conclude that exposure to H. pylori has consequences not only for the carrier, but also for subsequent generations that may be exploited for interventional purposes.

RevDate: 2018-09-19

Little MS, Ervin SM, Walton WG, et al (2018)

Active Site Flexibility Revealed in Crystal Structures of Parabacteroides merdae β-Glucuronidase from the Human Gut Microbiome.

Protein science : a publication of the Protein Society [Epub ahead of print].

β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo- and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs. This article is protected by copyright. All rights reserved.

RevDate: 2018-09-18

Randolph TW, Zhao S, Copeland W, et al (2018)


The annals of applied statistics, 12(1):540-566.

The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.

RevDate: 2018-09-18

Lin H, He QY, Shi L, et al (2018)

Proteomics and the microbiome: pitfalls and potential.

Expert review of proteomics [Epub ahead of print].

INTRODUCTION: Human symbiotic microbiota are now known to play important roles in human health and disease. Significant progress in our understanding of the human microbiome has been driven by recent technological advances in the fields of genomics, transcriptomics and proteomics. As a complementary method to metagenomics, proteomics is enabling detailed protein profiling of the microbiome to decipher its structure and function and to analyse its relationship with the human body. Faecal proteomics is being increasingly applied to discover and validate potential health and disease biomarkers, and TGA approved instrumentation and a range of clinical assays are being developed that will collectively play key roles in advancing personalized medicine. Areas covered: This review will introduce the complexity of the microbiome and its role in health and disease (in particular the gastrointestinal tract or gut microbiome), discuss current genomic and proteomic methods for studying this system, including the discovery of potential biomarkers, and outline the development of clinically accepted protocols leading to personalized medicine. Expert commentary: Recognition of the important role the microbiome plays in both health and disease is driving current research in this key area. A proteogenomics approach will be essential to unravel the biologies underlying this complex network.

RevDate: 2018-09-15

Zhan X, Xue L, Zheng H, et al (2018)

A small-sample kernel association test for correlated data with application to microbiome association studies.

Genetic epidemiology [Epub ahead of print].

Recent research has highlighted the importance of the human microbiome in many human disease and health conditions. Most current microbiome association analyses focus on unrelated samples; such methods are not appropriate for analysis of data collected from more advanced study designs such as longitudinal and pedigree studies, where outcomes can be correlated. Ignoring such correlations can sometimes lead to suboptimal results or even possibly biased conclusions. Thus, new methods to handle correlated outcome data in microbiome association studies are needed. In this paper, we propose the correlated sequence kernel association test (CSKAT) to address such correlations using the linear mixed model. Specifically, random effects are used to account for the outcome correlations and a variance component test is used to examine the microbiome effect. Compared to existing genetic association tests for longitudinal and family samples, we implement a correction procedure to better calibrate the null distribution of the score test statistic to accommodate the small sample size nature of data collected from a typical microbiome study. Comprehensive simulation studies are conducted to demonstrate the validity and efficiency of our method, and we show that CSKAT achieves a higher power than existing methods while correctly controlling the Type I error rate. We also apply our method to a microbiome data set collected from a UK twin study to illustrate its potential usefulness. A free implementation of our method in R software is available at

RevDate: 2018-09-14

Trinh P, Zaneveld JR, Safranek S, et al (2018)

One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review.

Frontiers in public health, 6:235.

The One Health concept stresses the ecological relationships between human, animal, and environmental health. Much of the One Health literature to date has examined the transfer of pathogens from animals (e.g., emerging zoonoses) and the environment to humans. The recent rapid development of technology to perform high throughput DNA sequencing has expanded this view to include the study of entire microbial communities. Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment. We review recent research studies of such transmission, the molecular and statistical methods being used, and the implications of such microbiome relationships for human health. Our review identified evidence that the environmental microbiome as well as the microbiome of animals in close contact can affect both the human microbiome and human health outcomes. Such microbiome transfer can take place in the household as well as the workplace setting. Urbanization of built environments leads to changes in the environmental microbiome which could be a factor in human health. While affected by environmental exposures, the human microbiome also can modulate the response to environmental factors through effects on metabolic and immune function. Better understanding of these microbiome interactions between humans, animals, and the shared environment will require continued development of improved statistical and ecological modeling approaches. Such enhanced understanding could lead to innovative interventions to prevent and manage a variety of human health and disease states.

RevDate: 2018-09-14

Hill AB, Beitelshees M, Nayerhoda R, et al (2018)

Engineering a Next-Generation Glycoconjugate-Like Streptococcus pneumoniae Vaccine.

ACS infectious diseases [Epub ahead of print].

We detail the development of a next-generation Streptococcus pneumoniae liposomal encapsulation of polysaccharides (LEPS) vaccine, with design characteristics geared toward best-in-class efficacy. The first generation LEPS vaccine, which contained 20 encapsulated pneumococcal capsular polysaccharides (CPSs) and two surface-displayed virulence-associated proteins (GlpO and PncO), enabling prophylactic potency against 70+ serotypes of Streptococcus pneumoniae (the causative agent of pneumococcal disease), was rationally redesigned for advanced clinical readiness and best-in-class coverage. In doing so, the virulent-specific GlpO protein antigen was removed from the final formulation due to off-target immunogenicity toward bacterial species within the human microbiome, while directed protection was maintained by increasing the dose of PncO from 17 to 68 μg. LEPS formulation parameters also readily facilitated an increase in CPS valency (to a total of 24) and systematic variation in protein-liposome attachment mechanisms in anticipation of clinical translation. An additional safety assessment study demonstrated that LEPS does not exhibit appreciable toxicological effects even when administered at ten times the effective dose. In summary, this new design offers the broadest, safest, and most-complete protection while maintaining desirable glycoconjugate-like features, positioning the LEPS vaccine platform for clinical success and a global health impact.

RevDate: 2018-09-13

Ossorio PN, Y Zhou (2018)

Regulating stool for microbiota transplantation.

Gut microbes [Epub ahead of print].

In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.

RevDate: 2018-09-13

Alves LF, Westmann CA, Lovate GL, et al (2018)

Metagenomic Approaches for Understanding New Concepts in Microbial Science.

International journal of genomics, 2018:2312987.

Over the past thirty years, since the dawn of metagenomic studies, a completely new (micro) universe was revealed, with the potential to have profound impacts on many aspects of the society. Remarkably, the study of human microbiome provided a new perspective on a myriad of human traits previously regarded as solely (epi-) genetically encoded, such as disease susceptibility, immunological response, and social and nutritional behaviors. In this context, metagenomics has established a powerful framework for understanding the intricate connections between human societies and microbial communities, ultimately allowing for the optimization of both human health and productivity. Thus, we have shifted from the old concept of microbes as harmful organisms to a broader panorama, in which the signal of the relationship between humans and microbes is flexible and directly dependent on our own decisions and practices. In parallel, metagenomics has also been playing a major role in the prospection of "hidden" genetic features and the development of biotechnological applications, through the discovery of novel genes, enzymes, pathways, and bioactive molecules with completely new or improved biochemical functions. Therefore, this review highlights the major milestones over the last three decades of metagenomics, providing insights into both its potentialities and current challenges.

RevDate: 2018-09-12

Hidalgo-Cantabrana C, Sanozky-Dawes R, R Barrangou (2018)

Insights into the Human Virome Using CRISPR Spacers from Microbiomes.

Viruses, 10(9): pii:v10090479.

Due to recent advances in next-generation sequencing over the past decade, our understanding of the human microbiome and its relationship to health and disease has increased dramatically. Yet, our insights into the human virome, and its interplay with important microbes that impact human health, is relatively limited. Prokaryotic and eukaryotic viruses are present throughout the human body, comprising a large and diverse population which influences several niches and impacts our health at various body sites. The presence of prokaryotic viruses like phages, has been documented at many different body sites, with the human gut being the richest ecological niche. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated proteins constitute the adaptive immune system of bacteria, which prevents attack by invasive nucleic acid. CRISPR-Cas systems function by uptake and integration of foreign genetic element sequences into the CRISPR array, which constitutes a genomic archive of iterative vaccination events. Consequently, CRISPR spacers can be investigated to reconstruct interplay between viruses and bacteria, and metagenomic sequencing data can be exploited to provide insights into host-phage interactions within a niche. Here, we show how the CRISPR spacer content of commensal and pathogenic bacteria can be used to determine the evidence of their phage exposure. This framework opens new opportunities for investigating host-virus dynamics in metagenomic data, and highlights the need to dedicate more efforts for virome sampling and sequencing.

RevDate: 2018-09-12

Hendler R, Y Zhang (2018)

Probiotics in the Treatment of Colorectal Cancer.

Medicines (Basel, Switzerland), 5(3): pii:medicines5030101.

The human microbiome plays many roles in inflammation, drug metabolism, and even the development of cancer that we are only beginning to understand. Colorectal cancer has been a focus for study in this field as its pathogenesis and its response to treatment have both been linked to the functioning of microbiota. This literature review evaluates the animal and human studies that have explored this relationship. By manipulating the microbiome with interventions such as probiotic administration, we may be able to reduce colorectal cancer risk and improve the safety and effectiveness of cancer therapy even though additional clinical research is still necessary.

RevDate: 2018-09-11

Gardner CD, ME Hauser (2017)

Food Revolution.

American journal of lifestyle medicine, 11(5):387-396 pii:10.1177_1559827617696289.

Recent research has found important links between poor dietary choices, a toxic food environment, and high national and global burdens of chronic diseases. These findings serve as an impetus for a Food Revolution. The Gardner Nutrition Studies Research Group, along with a diverse range of collaborators, has been focusing on solution-oriented research to help find answers to the problems that plague the current food system. Research topics include (1) a recently completed weight loss diet study contrasting Healthy Low-Fat to Healthy Low-Carbohydrate diets among 609 overweight and obese adults; (2) a quasi-experimental study conducted among Stanford undergraduates that examined social and environmental, rather than health-focused, motivations for dietary change; (3) links between dietary fiber, the human microbiome, and immune function; and (4) ongoing collaborations with university chefs to create unapologetically delicious food for campus dining halls that is also healthy and environmentally sustainable. Most of these approaches emphasize plant-based diets. The decreased consumption of animal products has created some concern over the ability of one to obtain adequate protein intake. Evidence is presented that adequate protein is easily obtainable from vegetarian, vegan, and other diets that contain significantly less meat and fewer animal foods than the standard American diet.

RevDate: 2018-09-10

Xia Y, J Sun (2017)

Hypothesis Testing and Statistical Analysis of Microbiome.

Genes & diseases, 4(3):138-148.

After the initiation of Human Microbiome Project in 2008, various biostatistic and bioinformatic tools for data analysis and computational methods have been developed and applied to microbiome studies. In this review and perspective, we discuss the research and statistical hypotheses in gut microbiome studies, focusing on mechanistic concepts that underlie the complex relationships among host, microbiome, and environment. We review the current available statistic tools and highlight recent progress of newly developed statistical methods and models. Given the current challenges and limitations in biostatistic approaches and tools, we discuss the future direction in developing statistical methods and models for the microbiome studies.

RevDate: 2018-09-09

Dong TS, A Gupta (2018)

Influence of Early Life, Diet, and the Environment on the Microbiome.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(18)30946-7 [Epub ahead of print].

Advances in sequencing technology and bioinformatics have greatly enhanced our ability to understand the human microbiome. Over the last decade, a growing body of literature has linked nutrition and the environment to the microbiome and is now thought to be an important contributor to overall health. This paper reviews the literature from the past 10 years to highlight the influence of environmental factors such as diet, early life adversity and stress in shaping and modifying our microbiome towards health and disease. The review shows that many factors such as the mode of delivery, breast milk, stress, diet and medications can greatly influence the development of our gut microbiome and potentially make us more prone to certain diseases. By incorporating environmental factors into models that study the microbiome in the setting of health and disease, may provide a better understanding of disease and potentially new areas of treatment. To highlight this, we will additionally explore the role of the environment and the microbiome in the development of obesity and functional bowel disorders.

RevDate: 2018-09-08

Sharma A, JA Gilbert (2018)

Microbial exposure and human health.

Current opinion in microbiology, 44:79-87 pii:S1369-5274(18)30053-5 [Epub ahead of print].

The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.

RevDate: 2018-09-07

Di Francesco L, Di Girolamo F, Mennini M, et al (2018)

A MALDI-TOF MS Approach for Mammalian, Human, and Formula Milks' Profiling.

Nutrients, 10(9): pii:nu10091238.

Human milk composition is dynamic, and substitute formulae are intended to mimic its protein content. The purpose of this study was to investigate the potentiality of matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), followed by multivariate data analyses as a tool to analyze the peptide profiles of mammalian, human, and formula milks. Breast milk samples from women at different lactation stages (2 (n = 5), 30 (n = 6), 60 (n = 5), and 90 (n = 4) days postpartum), and milk from donkeys (n = 4), cows (n = 4), buffaloes (n = 7), goats (n = 4), ewes (n = 5), and camels (n = 2) were collected. Different brands (n = 4) of infant formulae were also analyzed. Protein content (<30 kDa) was analyzed by MS, and data were exported for statistical elaborations. The mass spectra for each milk closely clustered together, whereas different milk samples resulted in well-separated mass spectra. Human samples formed a cluster in which colostrum constituted a well-defined subcluster. None of the milk formulae correlated with animal or human milk, although they were specifically characterized and correlated well with each other. These findings propose MALDI-TOF MS milk profiling as an analytical tool to discriminate, in a blinded way, different milk types. As each formula has a distinct specificity, shifting a baby from one to another formula implies a specific proteomic exposure. These profiles may assist in milk proteomics for easiness of use and minimization of costs, suggesting that the MALDI-TOF MS pipelines may be useful for not only milk adulteration assessments but also for the characterization of banked milk specimens in pediatric clinical settings.

RevDate: 2018-09-05

Zhu X, Wang J, Reyes-Gibby C, et al (2017)

Correction to: Processing and Analyzing Human Microbiome Data.

Methods in molecular biology (Clifton, N.J.), 1666:E1.

The original version of this chapter was inadvertently published without including the dbGaP acknowledgment. The updated chapter now contains that information.

RevDate: 2018-09-05

Strouse C, Mangalam A, J Zhang (2018)

Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.

Gut microbes [Epub ahead of print].

The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.

RevDate: 2018-09-05

Neil JA, K Cadwell (2018)

The Intestinal Virome and Immunity.

Journal of immunology (Baltimore, Md. : 1950), 201(6):1615-1624.

The composition of the human microbiome is considered a major source of interindividual variation in immunity and, by extension, susceptibility to diseases. Intestinal bacteria have been the major focus of research. However, diverse communities of viruses that infect microbes and the animal host cohabitate the gastrointestinal tract and collectively constitute the gut virome. Although viruses are typically investigated as pathogens, recent studies highlight a relationship between the host and animal viruses in the gut that is more akin to host-microbiome interactions and includes both beneficial and detrimental outcomes for the host. These viruses are likely sources of immune variation, both locally and extraintestinally. In this review, we describe the components of the gut virome, in particular mammalian viruses, and their ability to modulate host responses during homeostasis and disease.

RevDate: 2018-09-04

Riscuta G, Xi D, Pierre-Victor D, et al (2018)

Diet, Microbiome, and Epigenetics in the Era of Precision Medicine.

Methods in molecular biology (Clifton, N.J.), 1856:141-156.

Precision medicine is a revolutionary approach to disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. The US National Institutes of Health has recently launched The All of Us Research Program (2016) to extend precision medicine to all diseases by building a national research cohort of one million or more US participants. This review is limited to how the human microbiome factors into precision medicine from the applied aspect of preventing and managing cancer. The Precision Medicine Initiative was established in an effort to address particular characteristics of each person with the aim to increase the effectiveness of medical interventions in terms of prevention and treatment of multiple diseases including cancer. Many factors contribute to the response to an intervention. The microbiome and microbially produced metabolites are capable of epigenetic modulation of gene activity, and can influence the response through these mechanisms. The fact that diet has an impact on microbiome implies that it will also affect the epigenetic mechanisms involving microbiota. In this chapter, we review some major epigenetic mechanisms, notably DNA methylation, chromatin remodeling and histone modification, and noncoding RNA, implicated in cancer prevention and treatment. Several examples of how microbially produced metabolites from food influence cancer risk and treatment response through epigenetic mechanisms will be discussed. Some challenges include the limited understanding of how diet shapes the microbiome and how to best evaluate those changes since both, diet and the microbiota, exhibit daily and seasonal variations. Ongoing research seeks to understand the relationship between the human microbiome and multiple diseases including cancer.

RevDate: 2018-09-04

Lee JYH, Monk IR, Gonçalves da Silva A, et al (2018)

Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.

Nature microbiology pii:10.1038/s41564-018-0230-7 [Epub ahead of print].

Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.

RevDate: 2018-09-03

Meng S, Chen B, Yang J, et al (2018)

Study of Microbiomes in Aseptically Collected Samples of Human Breast Tissue Using Needle Biopsy and the Potential Role of in situ Tissue Microbiomes for Promoting Malignancy.

Frontiers in oncology, 8:318.

Mounting evidence suggests that changes in microbiome are linked to development of cancer and its aggressiveness. Microbiome profiles in human breast tissue previously presumed to be sterile, have recently been characterized using high-throughput technologies. Recent findings of microbiome variation between benign and malignant disease provides a rationale for exploring microbiomes associated with cancer during tumor progression. We assessed microbiomes of aseptically collected human breast tissue samples in this study, using needle biopsy from patients with benign and malignant tumors of different histological grading, using 16S rRNA gene amplicon sequencing. This is consistent with previous studies, and our results identified distinct microbiome profiles in breast tissues from women with cancer as compared to women with benign breast disease in Chinese cohorts. The enriched microbial biomarkers in malignant tissue included genus Propionicimonas and families Micrococcaceae, Caulobacteraceae, Rhodobacteraceae, Nocardioidaceae, Methylobacteriaceae, which appeared to be ethno-specific. Further, we compared microbiome profiles in malignant tissues of three different histological grades. The relative abundance of family Bacteroidaceae decreased and that of genus Agrococcus increased with the development of malignancy. KEGG pathways inferred by PICRUSt showed that biotin and glycerophospholipid metabolism had significant differences in all three grades. Glycerophospholipid and ribosome biogenesis increased in grade III tissue as compared to grades I and II. Flavonoid biosynthesis significantly decreased in grade III tissue. The specific correlation of these potential microbial biomarkers and indicated pathways with advanced disease could have broad implications in the diagnosis and staging of breast cancer. Further large-cohort investigation of the breast cancer microbiome and its potential mechanism in breast cancer development are essential.

RevDate: 2018-08-31

Willis-Owen SAG, Cookson WOC, MF Moffatt (2018)

The Genetics and Genomics of Asthma.

Annual review of genomics and human genetics, 19:223-246.

Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.

RevDate: 2018-08-31

Chanyi RM (2018)

The complete microbiologist, Dr. Terry Beveridge.

Canadian journal of microbiology, 64(9):643.

RevDate: 2018-08-30

Skelly E, Kapellas K, Cooper A, et al (2018)

Consequences of colonialism: A microbial perspective to contemporary Indigenous health.

American journal of physical anthropology [Epub ahead of print].

Nearly all Indigenous populations today suffer from worse health than their non-Indigenous counterparts, and despite interventions against known factors, this health "gap" has not improved. The human microbiome-the beneficial, diverse microbial communities that live on and within the human body-is a crucial component in developing and maintaining normal physiological health. Disrupting this ecosystem has repercussions for microbial functionality, and thus, human health. In this article, we propose that modern-day Indigenous population health may suffer from disrupted microbial ecosystems as a consequence of historical colonialism. Colonialism may have interrupted the established relationships between the environment, traditional lifeways, and microbiomes, altering the Indigenous microbiome with detrimental health consequences.

RevDate: 2018-08-29

Ma ZS (2018)

Sketching the Human Microbiome Biogeography with DAR (Diversity-Area Relationship) Profiles.

Microbial ecology pii:10.1007/s00248-018-1245-6 [Epub ahead of print].

SAR (species area relationship) is a classic ecological theory that has been extensively investigated and applied in the studies of global biogeography and biodiversity conservation in macro-ecology. It has also found important applications in microbial ecology in recent years thanks to the breakthroughs in metagenomic sequencing technology. Nevertheless, SAR has a serious limitation for practical applications-ignoring the species abundance and treating all species as equally abundant. This study aims to explore the biogeography discoveries of human microbiome over 18 sites of 5 major microbiome habitats, establish the baseline DAR (diversity-area scaling relationship) parameters, and perform comparisons with the classic SAR. The extension from SAR to DAR by adopting the Hill numbers as diversity measures not only overcomes the previously mentioned flaw of SAR but also allows for obtaining a series of important findings on the human microbiome biodiversity and biogeography. Specifically, two types of DAR models were built, the traditional power law (PL) and power law with exponential cutoff (PLEC), using comprehensive datasets from the HMP (human microbiome project). Furthermore, the biogeography "maps" for 18 human microbiome sites using their DAR profiles for assessing and predicting the diversity scaling across individuals, PDO profiles (pair-wise diversity overlap) for measuring diversity overlap (similarity), and MAD profile (for predicting the maximal accrual diversity in a population) were sketched out. The baseline biogeography maps for the healthy human microbiome diversity can offer guidelines for conserving human microbiome diversity and investigating the health implications of the human microbiome diversity and heterogeneity.

RevDate: 2018-08-29

Westerik N, Reid G, Sybesma W, et al (2018)

The Probiotic Lactobacillus rhamnosus for Alleviation of Helicobacter pylori-Associated Gastric Pathology in East Africa.

Frontiers in microbiology, 9:1873.

The probiotic Lactobacillus rhamnosus GG (LGG) can play a role in establishing a harmless relationship with Helicobacter pylori and reduce gastric pathology in East African populations. H. pylori has the ability to inhabit the surface of the mucous layer of the human stomach and duodenum. In the developing world, an estimated 51% of the population is carrier of H. pylori, while in some Western countries these numbers dropped below 20%, which is probably associated with improved sanitation and smaller family sizes. Colonization by H. pylori can be followed by inflammation of the gastric mucus layer, and is a risk factor in the development of atrophic gastritis, peptic ulcers and gastric cancer. Notwithstanding the higher prevalence of H. pylori carriers in developing countries, no equal overall increase in gastric pathology is found. This has been attributed to a less pro-inflammatory immune response to H. pylori in African compared to Caucasian populations. In addition, a relatively low exposure to other risk factors in certain African populations may play a role, including the use of non-steroidal anti-inflammatory drugs, smoking, and diets without certain protective factors. A novel approach to the reduction of H. pylori associated gastric pathology is found in the administration of the probiotic bacterium Lactobacillus rhamnosus yoba 2012 (LRY), the generic variant of LGG. This gastro-intestinal isolate inhibits H. pylori by competition for substrate and binding sites as well as production of antimicrobial compounds such as lactic acid. In addition, it attenuates the host's H. pylori-induced apoptosis and inflammation responses and stimulates angiogenesis in the gastric and duodenal epithelium. The probiotic LRY is not able to eradicate H. pylori completely, but its co-supplementation in antibiotic eradication therapy has been shown to relieve side effects of this therapy. In Uganda, unlike other African countries, gastric pathology is relatively common, presumably resulting from the lack of dietary protective factors in the traditional diet. Supplementation with LRY through local production of probiotic yogurt, could be a solution to establish a harmless relationship with H. pylori and reduce gastric pathology and subsequent eradication therapy treatment.

RevDate: 2018-08-29

Kho ZY, SK Lal (2018)

The Human Gut Microbiome - A Potential Controller of Wellness and Disease.

Frontiers in microbiology, 9:1835.

Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.

RevDate: 2018-08-28

Xu W, Luo Z, Alekseyenko AV, et al (2018)

Distinct systemic microbiome and microbial translocation are associated with plasma level of anti-CD4 autoantibody in HIV infection.

Scientific reports, 8(1):12863 pii:10.1038/s41598-018-31116-y.

Microbial signals have been linked to autoantibody induction. Recently, we found that purified anti-CD4 autoantibodies from the plasma of chronic HIV-1-infected patients under viral-suppressed antiretroviral therapy (ART) play a pathologic role in poor CD4+ T cell recovery. The purpose of the study was to investigate the association of systemic microbiome and anti-CD4 autoantibody production in HIV. Plasma microbiome from 12 healthy controls and 22 HIV-infected subjects under viral-suppressed ART were analyzed by MiSeq sequencing. Plasma level of autoantibodies and microbial translocation (LPS, total bacterial 16S rDNA, soluble CD14, and LPS binding protein) were analyzed by ELISA, limulus amebocyte assay, and qPCR. We found that plasma level of anti-CD4 IgGs but not anti-CD8 IgGs was increased in HIV+ subjects compared to healthy controls. HIV+ subjects with plasma anti-CD4 IgG > 50 ng/mL (high) had reduced microbial diversity compared to HIV+ subjects with anti-CD4 IgG ≤ 50 ng/mL (low). Moreover, plasma anti-CD4 IgG level was associated with elevated microbial translocation and reduced microbial diversity in HIV+ subjects. The Alphaproteobacteria class was significantly enriched in HIV+ subjects with low anti-CD4 IgG compared to patients with high anti-CD4 IgG even after controlling for false discovery rate (FDR). The microbial components were different from the phylum to genus level in HIV+ subjects with high anti-CD4 IgGs compared to the other two groups, but these differences were not significant after controlling for FDR. These results suggest that systemic microbial translocation and microbiome may associate with anti-CD4 autoantibody production in ART-treated HIV disease.

RevDate: 2018-08-27

Suda W, Ogata Y, S Nishijima (2018)

[Analysis of human microbiome using NGS.].

Clinical calcium, 28(9):1274-1281.

Recently, next generation sequencers(NGS)became prevalent and enable us possible to comprehensively analyze the entire human microbiome community structures including difficult-to-culture microbes. In this review, we introduce the NGS-based analytical methods of human microbiome, called "meta-16S analysis" and "metagenomic analysis", then show several fundamental data basing these analyses. Furthermore, we also introduce the importance of database improvement used for analysis and the DNA preparation method from human samples.

RevDate: 2018-08-25

Friedman ES, Li Y, Shen TD, et al (2018)

FXR-Dependent Modulation of the Human Small Intestinal Microbiome by the Bile Acid Derivative Obeticholic Acid.

Gastroenterology pii:S0016-5085(18)34887-X [Epub ahead of print].

BACKGROUND & AIMS: Intestinal bacteria can modify the composition of bile acids and bile acids, which are regulated by the farnesoid X receptor (FXR), affect the survival and growth of gut bacteria. We studied the effects of obeticholic acid (OCA), a bile acid analog and FXR agonist, on the intestinal microbiomes of humans and mice.

METHODS: We performed a phase 1 study in 24 healthy volunteers given OCA (5 mg, 10 mg, or 25 mg per day, for 17 days). Fecal and plasma specimens were collected at baseline (day 0) and on days 17 (end of dosing) and 37 (end of study). The fecal specimens were analyzed by shotgun metagenomic sequencing. A Uniref90 high stringency genomic analysis was used to assign specific genes to the taxonomic signature of bacteria whose abundance was associated with OCA. Male C57BL/6 mice were gavaged daily with water, vehicle, or OCA (10 mg/kg) for 2 weeks. Small intestine luminal contents were collected by flushing with saline and fecal pellets were collected at baseline and day 14. Mouse samples were analyzed by 16S tagged sequencing. Culture experiments were performed to determine taxonomic-specific effects of bile acids and OCA on bacterial growth.

RESULTS: Suppression of endogenous bile acid synthesis by OCA in subjects led to a reversible induction of Gram-positive bacteria that are found in the small intestine and are components of diet and the oral microbiota. We found that bile acids reduced proliferation of these bacteria in minimum inhibitory concentration assays. In these organisms, there was an increase in the representation of microbial genomic pathways involved in DNA synthesis and amino acid metabolism with OCA treatment of subjects. Consistent with these findings, mice fed OCA had reduced endogenous bile acid levels and an increased proportion of Firmicutes, specifically in the small intestine, compared to mice fed water or vehicle.

CONCLUSIONS: In studying the effects of OCA in humans and mice, we found evidence for interactions between bile acids and features of the small intestinal microbiome. These findings indicate that FXR activation alters the intestinal microbiota and could provide opportunities for microbiome biomarker discovery or new approaches to engineering the human microbiome.


RevDate: 2018-08-23

Hoen AG, Madan JC, Li Z, et al (2018)

Sex-specific associations of infants' gut microbiome with arsenic exposure in a US population.

Scientific reports, 8(1):12627 pii:10.1038/s41598-018-30581-9.

Arsenic is a ubiquitous environmental toxicant with antimicrobial properties that can be found in food and drinking water. The influence of arsenic exposure on the composition of the human microbiome in US populations remains unknown, particularly during the vulnerable infant period. We investigated the relationship between arsenic exposure and gut microbiome composition in 204 infants prospectively followed as part of the New Hampshire Birth Cohort Study. Infant urine was analyzed for total arsenic concentration using inductively coupled plasma mass spectrometry. Stool microbiome composition was determined using sequencing of the bacterial 16S rRNA gene. Infant urinary arsenic related to gut microbiome composition at 6 weeks of life (p = 0.05, adjusted for infant feeding type and urine specific gravity). Eight genera, six within the phylum Firmicutes, were enriched with higher arsenic exposure. Fifteen genera were negatively associated with urinary arsenic concentration, including Bacteroides and Bifidobacterium. Upon stratification by both sex and feeding method, we found detectable associations among formula-fed males (p = 0.008), but not other groups (p > 0.05 for formula-fed females and for breastfed males and females). Our findings from a US population indicate that even moderate arsenic exposure may have meaningful, sex-specific effects on the gut microbiome during a critical window of infant development.

RevDate: 2018-08-22

Ma Z, Li L, W Li (2018)

Assessing and Interpreting the Within-Body Biogeography of Human Microbiome Diversity.

Frontiers in microbiology, 9:1619.

A human body hosts a relatively independent microbiome including five major regional biomes (i.e., airway, oral, gut, skin, and urogenital). Each of them may possess different regional characteristics with important implications to our health and diseases (i.e., so-termed microbiome associated diseases). Nevertheless, these regional microbiomes are connected with each other through diffusions and migrations. Here, we investigate the within-body (intra-individual) distribution feature of microbiome diversity via diversity area relationship (DAR) modeling, which, to the best of our knowledge, has not been systematically studied previously. We utilized the Hill numbers for measuring alpha and beta-diversities and built 1,200 within-body DAR models with to date the most comprehensive human microbiome datasets of 18 sites from the human microbiome project (HMP) cohort. We established the intra-DAR profile (z-q pattern: the diversity scaling parameter z of the power law (PL) at diversity order q = 0-3), intra-PDO (pair-wise diversity overlap) profile (g-q), and intra-MAD (maximal accrual diversity) profile (Dmax-q) for the within-body biogeography of the human microbiome. These profiles constitute the "maps" of the within-body biogeography, and offer important insights on the within-body distribution of the human microbiome. Furthermore, we investigated the heterogeneity among individuals in their biogeography parameters and found that there is not an "average Joe" that can represent majority of individuals in a cohort or population. For example, we found that most individuals in the HMP cohort have relatively lower maximal accrual diversity (MAD) or in the "long tail" of the so-termed power law distribution. In the meantime, there are a small number of individuals in the cohort who possess disproportionally higher MAD values. These findings may have important implications for personalized medicine of the human microbiome associated diseases in practice, besides their theoretical significance in microbiome research such as establishing the baseline for the conservation of human microbiome.

RevDate: 2018-08-21

Heerema-McKenney A (2018)

Defense and infection of the human placenta.

APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 126(7):570-588.

The placenta functions as a shield against infection of the fetus. The innate and adaptive immune defenses of the developing fetus are poorly equipped to fight infections. Infection by bacteria, viruses, and protozoa may cause infertility, spontaneous abortion, stillbirth, growth retardation, anomalies of development, premature delivery, neonatal morbidity, and mortality. However, appreciation of the human microbiome and host cell-microbe interactions must be taken into consideration as we try to determine what interactions are pathologic. Infection is typically recognized histologically by the presence of inflammation. Yet, several factors make comparison of the placenta to other human organs difficult. The placenta comprises tissues from two persons, complicating the role of the immune system. The placenta is a temporary organ. It must be eventually expelled; the processes leading to partuition involve maternal inflammation. What is normal or pathologic may be a function of timing or extent of the process. We now must consider whether bacteria, and even some viruses, are useful commensals or pathogens. Still, recognizing infection of the placenta is one of the most important contributions placental pathologic examination can give to care of the mother and neonate. This review provides a brief overview of placental defense against infection, consideration of the placental microbiome, routes of infection, and the histopathology of amniotic fluid infection and TORCH infections.

RevDate: 2018-08-21

Lin J, Kimura BY, Oikarinen S, et al (2018)

Bioinformatics Assembling and Assessment of Novel Coxsackievirus B1 Genome.

Methods in molecular biology (Clifton, N.J.), 1838:261-272.

The human microbiome project via application of metagenomic next-generation sequencing techniques has found surprising large and diverse amounts of microbial sequences across different body sites. There is a wave of investigators studying autoimmune related diseases designing from birth case and control studies to elucidate microbial associations and potential direct triggers. Sequencing analysis, considered big data as it typically includes millions of reads, is challenging but particularly demanding and complex is virome profiling due to its lack of pan-viral genomic signature. Impressively thousands of virus complete genomes have been deposited and these high-quality references are core components of virus profiling pipelines and databases. Still it is commonly known that most viral sequences do not map to known viruses. Moreover human viruses, particularly RNA groups, are notoriously heterogeneous due to high mutation rates. Here, we present the related assembling challenges and a series of bioinformatics steps that were applied in the construction of the complete consensus genome of a novel clinical isolate of Coxsackievirus B1. We further demonstrate our effort in calling mutations between prototype Coxsackievirus B1 sequence from GenBank and serial clinical isolate genome grown in cell culture.

RevDate: 2018-08-20

Dubourg G, Baron S, Cadoret F, et al (2018)

From Culturomics to Clinical Microbiology and Forward.

Emerging infectious diseases, 24(9):1683-1690.

Culturomics has permitted discovery of hundreds of new bacterial species isolated from the human microbiome. Profiles generated by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry have been added to the mass spectrometer database used in clinical microbiology laboratories. We retrospectively collected raw data from MALDI-TOF mass spectrometry used routinely in our laboratory in Marseille, France, during January 2012-March 2018 and analyzed 16S rDNA sequencing results from misidentified strains. During the study period, 744 species were identified from clinical specimens, of which 21 were species first isolated from culturomics. This collection involved 105 clinical specimens, accounting for 98 patients. In 64 cases, isolation of the bacteria was considered clinically relevant. MALDI-TOF mass spectrometry was able to identify the species in 95.2% of the 105 specimens. While contributing to the extension of the bacterial repertoire associated with humans, culturomics studies also enlarge the spectrum of prokaryotes involved in infectious diseases.

RevDate: 2018-08-16

Bisanz JE, Spanogiannopoulos P, Pieper LM, et al (2018)

How to determine the role of the microbiome in drug disposition.

Drug metabolism and disposition: the biological fate of chemicals pii:dmd.118.083402 [Epub ahead of print].

With a paradigm shift occurring in health care towards personalized and precision medicine, understanding the numerous environmental factors that impact drug disposition is of paramount importance. The highly diverse and variant nature of the human microbiome is now recognized as a factor driving inter-individual variation in therapeutic outcomes. The purpose of this review is to provide a practical guide on methodology that can be applied to study the effects of microbes on the absorption, distribution, metabolism, and excretion of drugs. We also highlight recent examples of how these methods have been successfully applied to help build the basis for researching the intersection of microbiome and pharmacology. While in vitro and in vivo preclinical models are highlighted, these methods are also relevant in late-phase drug development or even as a part of routine after-market surveillance. These approaches will aid in filling major knowledge gaps for both current and upcoming therapeutics with the long-term goal of achieving a new type of knowledge-based medicine that integrates data on the host and the microbiome.

RevDate: 2018-08-16

Fernández MF, Reina-Pérez I, Astorga JM, et al (2018)

Breast Cancer and Its Relationship with the Microbiota.

International journal of environmental research and public health, 15(8): pii:ijerph15081747.

The microorganisms that live symbiotically in human beings are increasingly recognized as important players in health and disease. The largest collection of these microorganisms is found in the gastrointestinal tract. Microbial composition reflects both genetic and lifestyle variables of the host. This microbiota is in a dynamic balance with the host, exerting local and distant effects. Microbial perturbation (dysbiosis) could contribute to the risk of developing health problems. Various bacterial genes capable of producing estrogen-metabolizing enzymes have been identified. Accordingly, gut microbiota is capable of modulating estrogen serum levels. Conversely, estrogen-like compounds may promote the proliferation of certain species of bacteria. Therefore, a crosstalk between microbiota and both endogenous hormones and estrogen-like compounds might synergize to provide protection from disease but also to increase the risk of developing hormone-related diseases. Recent research suggests that the microbiota of women with breast cancer differs from that of healthy women, indicating that certain bacteria may be associated with cancer development and with different responses to therapy. In this review, we discuss recent knowledge about the microbiome and breast cancer, identifying specific characteristics of the human microbiome that may serve to develop novel approaches for risk assessment, prevention and treatment for this disease.

RevDate: 2018-08-15

Bučević Popović V, Šitum M, Chow CT, et al (2018)

The urinary microbiome associated with bladder cancer.

Scientific reports, 8(1):12157 pii:10.1038/s41598-018-29054-w.

Recent findings suggest that human microbiome can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from 12 male patients diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were analysed using 16S sequencing. Our results show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between groups, we could identify operational taxonomic units (OTUs) that were more abundant in either group. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and Corynebacterium were more abundant in healthy urines. However, due to the limited number of participants additional studies are needed to determine if urinary microbiome is associated with bladder cancer.

RevDate: 2018-08-12

Bastiaanssen TFS, Cowan CSM, Claesson MJ, et al (2018)

Making Sense of… the Microbiome in Psychiatry.

The international journal of neuropsychopharmacology pii:5067516 [Epub ahead of print].

Microorganisms can be found almost anywhere, including in and on the human body. The collection of microorganisms associated with a certain location is called a microbiota with its collective genetic material referred to as the microbiome. The largest population of microorganisms on the human body resides in the gastrointestinal tract thus it is not surprising that most investigated human microbiome is the human gut microbiome. On average, the gut hosts microbes from more than 60 genera and contains more cells than the human body. The human gut microbiome has been shown to influence many aspects of host health including more recently the brain.Several modes of interaction between the gut and the brain have been discovered, including via the synthesis of metabolites and neurotransmitters, activation of the vagus nerve and activation of the immune system. A growing body of work is implicating the microbiome in a variety of psychological processes and neuropsychiatric disorders. These include mood and anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder and schizophrenia, and even neurodegenerative disorders such as Alzheimer's and Parkinson's Disease. Moreover, it is probable that most psychotropic medications have an impact on the microbiome.Here, an overview will be provided for the bidirectional role of the microbiome in brain health, age-associated cognitive decline, neurological and psychiatric disorders. Furthermore, a primer on the common microbiological and bioinformatics techniques used to interrogate the microbiome will be provided. This review is meant to equip the reader with a primer to this exciting research area which is permeating all areas of biological psychiatry research.

RevDate: 2018-08-12

Kroon SJ, Ravel J, WM Huston (2018)

Cervicovaginal microbiota, women's health, and reproductive outcomes.

Fertility and sterility, 110(3):327-336.

The human microbiome project has shown a remarkable diversity of microbial ecology within the human body. The vaginal microbiota is unique in that in many women it is most often dominated by Lactobacillus species. However, in some women it lacks Lactobacillus spp. and is comprised of a wide array of strict and facultative anaerobes, a state that broadly correlates with increased risk for infection, disease, and poor reproductive and obstetric outcomes. Interestingly, the level of protection against infection can also vary by species and strains of Lactobacillus, and some species although dominant are not always optimal. This factors into the risk of contracting sexually transmitted infections and possibly influences the occurrence of resultant adverse reproductive outcomes such as tubal factor infertility. The composition and function of the vaginal microbiota appear to play an important role in pregnancy and fertility treatment outcomes and future research in this field will shed further translational mechanistic understanding onto the interplay of the vaginal microbiota with women's health and reproduction.

RevDate: 2018-08-09

Zhang XS, Li J, Krautkramer KA, et al (2018)

Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity.

eLife, 7: pii:37816.

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

RevDate: 2018-08-07

Shrivastava A, Patel VK, Tang Y, et al (2018)

Cargo transport shapes the spatial organization of a microbial community.

Proceedings of the National Academy of Sciences of the United States of America pii:1808966115 [Epub ahead of print].

The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella. Genomic analysis suggests that gliding bacteria are present in human microbial communities. We focus on Capnocytophaga gingivalis, which is present in abundance in the human oral microbiome. Tracking of fluorescently labeled single cells and of gas bubbles carried by fluid flow shows that swarms of C. gingivalis are layered, with cells in the upper layers moving more rapidly than those in the lower layers. Thus, cells also glide on top of one another. Cells of nonmotile bacterial species attach to the surface of C. gingivalis and are propelled as cargo. The cargo cell moves along the length of a C. gingivalis cell, looping from one pole to the other. Multicolor fluorescent spectral imaging of cells of different live but nonmotile bacterial species reveals their long-range transport in a polymicrobial community. A swarm of C. gingivalis transports some nonmotile bacterial species more efficiently than others and helps to shape the spatial organization of a polymicrobial community.

RevDate: 2018-08-06

Yao L, Seaton SC, Ndousse-Fetter S, et al (2018)

A selective gut bacterial bile salt hydrolase alters host metabolism.

eLife, 7: pii:37182.

The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.

RevDate: 2018-08-05

Martin TC, Visconti A, Spector TD, et al (2018)

Conducting metagenomic studies in microbiology and clinical research.

Applied microbiology and biotechnology pii:10.1007/s00253-018-9209-9 [Epub ahead of print].

Owing to the increased cost-effectiveness of high-throughput technologies, the number of studies focusing on the human microbiome and its connections to human health and disease has recently surged. However, best practices in microbiology and clinical research have yet to be clearly established. Here, we present an overview of the challenges and opportunities involved in conducting a metagenomic study, with a particular focus on data processing and analytical methods.

RevDate: 2018-08-03

Bicknell B, Liebert A, Johnstone D, et al (2018)

Photobiomodulation of the microbiome: implications for metabolic and inflammatory diseases.

Lasers in medical science pii:10.1007/s10103-018-2594-6 [Epub ahead of print].

The human microbiome is intimately associated with human health, with a role in obesity, metabolic diseases such as type 2 diabetes, and divergent diseases such as cardiovascular and neurodegenerative diseases. The microbiome can be changed by diet, probiotics, and faecal transplants, which has flow-on effects to health outcomes. Photobiomodulation has a therapeutic effect on inflammation and neurological disorders (amongst others) and has been reported to influence metabolic disorders and obesity. The aim of this study was to examine the possibility that PBM could influence the microbiome of mice. Mice had their abdomen irradiated with red (660 nm) or infrared (808 nm) low-level laser, either as single or multiple doses, over a 2-week period. Genomic DNA extracted from faecal pellets was pyrosequenced for the 16S rRNA gene. There was a significant (p < 0.05) difference in microbial diversity between PBM- and sham-treated mice. One genus of bacterium (Allobaculum) significantly increased (p < 0.001) after infrared (but not red light) PBM by day 14. Despite being a preliminary trial with small experimental numbers, we have demonstrated for the first time that PBM can alter microbiome diversity in healthy mice and increase numbers of Allobaculum, a bacterium associated with a healthy microbiome. This change is most probably a result of PBMt affecting the host, which in turn influenced the microbiome. If this is confirmed in humans, the possibility exists for PBMt to be used as an adjunct therapy in treatment of obesity and other lifestyle-related disorders, as well as cardiovascular and neurodegenerative diseases. The clinical implications of altering the microbiome using PBM warrants further investigation.

RevDate: 2018-08-02

Hanssen EN, Liland KH, Gill P, et al (2018)

Optimizing body fluid recognition from microbial taxonomic profiles.

Forensic science international. Genetics, 37:13-20 pii:S1872-4973(18)30174-1 [Epub ahead of print].

In forensics the DNA-profile is used to identify the person who left a biological trace, but information on body fluid can also be essential in the evidence evaluation process. Microbial composition data could potentially be used for body fluid recognition as an improved alternative to the currently used presumptive tests. We have developed a customized workflow for interpretation of bacterial 16S sequence data based on a model composed of Partial Least Squares (PLS) in combination with Linear Discriminant Analysis (LDA). Large data sets from the Human Microbiome Project (HMP) and the American Gut Project (AGP) were used to test different settings in order to optimize performance. From the initial cross-validation of body fluid recognition within the HMP data, the optimal overall accuracy was close to 98%. Sensitivity values for the fecal and oral samples were ≥0.99, followed by the vaginal samples with 0.98 and the skin and nasal samples with 0.96 and 0.81 respectively. Specificity values were high for all 5 categories, mostly >0.99. This optimal performance was achieved by using the following settings: Taxonomic profiles based on operational taxonomic units (OTUs) with 0.98 identity (OTU98), Aitchisons simplex transform with C = 1 pseudo-count and no regularization (r = 1) in the PLS step. Variable selection did not improve the performance further. To test for robustness across sequencing platforms, we also trained the classifier on HMP data and tested on the AGP data set. In this case, the standard OTU based approach showed moderately decline in accuracy. However, by using taxonomic profiles made by direct assignment of reads to a genus, we were able to nearly maintain the high accuracy levels. The optimal combination of settings was still used, except the taxonomic level being genus instead of OTU98. The performance may be improved even further by using higher resolution taxonomic bins.

RevDate: 2018-08-02

Mert I, Walther-Antonio M, A Mariani (2018)

Case for a role of the microbiome in gynecologic cancers: Clinician's perspective.

The journal of obstetrics and gynaecology research [Epub ahead of print].

In this review, we aimed to provide insight into the microbiome and its association with endometrial and ovarian cancer and their risk factors. We reviewed the literature focusing on the relationship between the microbiome and cancer, as well as the relationship between gynecologic diseases and cancers. The human body contains different kinds of microorganisms in various body parts, which is termed the microbiome. The number of microorganisms that live in and on the human body is greater than that of the human germ and somatic cells by 10-fold. The relationship between a human and their microbiome is complex; it is also one of the most important components of homeostasis. Impairment of microbiome-host homeostasis has been associated with obesity, several cancers, preterm labor, inflammatory and allergic conditions and neurodevelopmental disorders. Direct and strong causal relationships have been established for several cancers and microorganisms, such as gastric lymphoma and Helicobacter pylori infection. Interestingly, eradication of the infectious agents has also been shown to be therapeutic. The association between cancer and the microbiome, however, is more complicated than a 1 bacteria-1 cancer model, and a shift in a healthy microbiome can result in various cancers via inflammation, change in microenvironment or DNA-damaging toxins. The human microbiome is an integral part of homeostasis. Understanding the mechanisms that cause dysbiosis will enable us to elucidate the pathways that result in malignancy and investigate new treatment modalities.

RevDate: 2018-08-01

Costa AN, Costa FMD, Campos SV, et al (2018)

The pulmonary microbiome: challenges of a new paradigm.

Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia pii:S1806-37132018005004101 [Epub ahead of print].

The study of the human microbiome-and, more recently, that of the respiratory system-by means of sophisticated molecular biology techniques, has revealed the immense diversity of microbial colonization in humans, in human health, and in various diseases. Apparently, contrary to what has been believed, there can be nonpathogenic colonization of the lungs by microorganisms such as bacteria, fungi, and viruses. Although this physiological lung microbiome presents low colony density, it presents high diversity. However, some pathological conditions lead to a loss of that diversity, with increasing concentrations of some bacterial genera, to the detriment of others. Although we possess qualitative knowledge of the bacteria present in the lungs in different states of health or disease, that knowledge has advanced to an understanding of the interaction of this microbiota with the local and systemic immune systems, through which it modulates the immune response. Given this intrinsic relationship between the microbiota and the lungs, studies have put forth new concepts about the pathophysiological mechanisms of homeostasis in the respiratory system and the potential dysbiosis in some diseases, such as cystic fibrosis, COPD, asthma, and interstitial lung disease. This departure from the paradigm regarding knowledge of the lung microbiota has made it imperative to improve understanding of the role of the microbiome, in order to identify possible therapeutic targets and to develop innovative clinical approaches. Through this new leap of knowledge, the results of preliminary studies could translate to benefits for our patients.

RevDate: 2018-07-30

Greco V, Piras C, Pieroni L, et al (2018)

Applications of MALDI-TOF mass spectrometry in clinical proteomics.

Expert review of proteomics [Epub ahead of print].

INTRODUCTION: The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.

RevDate: 2018-07-30

Rosa CP, Brancaglion GA, Miyauchi-Tavares TM, et al (2018)

Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions.

Life sciences, 207:480-491.

The gastrointestinal tract has become a focus of study recently. The crosstalk between microbiota, especially bacteria, and the intestinal mucosa has to be accurately balanced in order to maintain physiological homeostasis in the human body. This dynamic interaction results in different levels of short-chain fatty acids (SCFAs), IgA, and T cell lymphocyte subsets, which could lead the human body towards health or disease. The disruption of this microbiome characterises gut dysbiosis. Antibiotics are usually prescribed to fight against bacterial infection. They can also modulate the human microbiome, since it acts directly over organisational taxonomic units (OTUs) when taken orally. As a result, these pharmaceuticals enable gut dysbiosis and its systemic effects due to microbiome disturbance. Here, current data have been gathered from mice model experiments and epidemiological studies in an antibiotic-centred perspective. The presented data suggest the importance of translational studies in a murine model focusing on GIT homeostasis with bacterial groups since any changes to the GIT-microbiota have systemic repercussions in human health and disease.

RevDate: 2018-07-27

Frey AM, Ansbro K, Kamble NS, et al (2018)

Characterisation and pure culture of putative health-associated oral bacterium BU063 (Tannerella sp. HOT-286) reveals presence of a potentially novel glycosylated S-layer.

FEMS microbiology letters pii:5056158 [Epub ahead of print].

Tannerella HOT-286 (phylotype BU063) is a recently identified novel filamentous Gram-negative anaerobic oral bacterium cultured for the first time recently in co-culture with Propionibacterium acnes. In contrast to the related periodontal disease associated pathobiont Tannerella forsythia it is considered a putative health-associated bacterium. In this paper we identified that this organism could be grown in pure culture if N-acetyl muramic acid (NAM) was provided in the media, although surprisingly the genetic basis of this phenomenon is not likely to be due to a lack of NAM synthesis genes. During further microbiological investigations we showed for the first time that Tannerella HOT-286 possesses a prominent extracellular S-layer with a novel morphology putatively made up of two proteins modified with an unknown glycan. This data furthers our knowledge of this poorly understood organism and genus that is an important part of the oral and human microbiome.

RevDate: 2018-07-27

Laing B, Barnett MPG, Marlow G, et al (2018)

An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.

Expert review of gastroenterology & hepatology [Epub ahead of print].

INTRODUCTION: The human microbiome plays a critical role in human health, having both metabolic, protective and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breast feeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective and trophic functions of the microbiome and influences through the lifespan from post- partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalised to the individual.

RevDate: 2018-07-25

Westerik N, Kort R, Sybesma W, et al (2018)

Lactobacillus rhamnosus Probiotic Food as a Tool for Empowerment Across the Value Chain in Africa.

Frontiers in microbiology, 9:1501.

Perhaps by serendipity, but Lactobacillus rhamnosus has emerged from the 1980s as the most researched probiotic species. The many attributes of the two main probiotic strains of the species, L. rhamnosus GG and GR-1, have made them suitable for applications to developing countries in Africa and beyond. Their use with a Streptococcus thermophilus starter strain C106, in the fermentation of milk, millet, and juices has provided a means to reach over 250,000 consumers of the first probiotic food on the continent. The social and economical implications for this translational research are significant, and especially pertinent for people living in poverty, with malnutrition and exposure to environmental toxins and infectious diseases including HIV and malaria. This example of probiotic applications illustrates the power of microbes in positively impacting the lives of women, men, and children, right across the food value chain.

RevDate: 2018-07-18

Proal AD, TG Marshall (2018)

Re-framing the theory of autoimmunity in the era of the microbiome: persistent pathogens, autoantibodies, and molecular mimicry.

Discovery medicine, 25(140):299-308.

The theory of autoimmunity was developed at a time when the human body was regarded as largely sterile. Antibodies in patients with chronic inflammatory disease could consequently not be tied to persistent human pathogens. The concept of the "autoantibody" was created to reconcile this phenomenon. Today, however, the discovery of the human microbiome has revolutionized our understanding of human biology. Humans are superorganisms that harbor trillions of persistent microbial cells. Indeed, vast human microbiomes have been detected in human tissue and blood. These microbial ecosystems harbor thousands of newly identified bacteria, viruses, and other microorganisms -- most of which can act as pathogens under conditions of immunosuppression. The theory of autoimmunity must be revised to account for the human microbiome. Here, we propose a model in which "autoantibodies" are created in response to chronic, persistent microbiome pathogens. The structural homology (molecular mimicry) between pathogen and host proteins can result in "collateral damage" to surrounding human tissue. This calls for a paradigm shift in autoimmune disease treatment. Immunosuppressive medications palliate inflammatory symptoms at the expense of microbiome health and balance. In contrast, treatments that support the immune system in autoimmune disease could allow patients to target pathogens at the root of the disease process.

RevDate: 2018-07-18

Wang AY, Thuy-Boun PS, Stupp GS, et al (2018)

Triflic acid treatment enables LC-MS/MS analysis of insoluble bacterial biomass.

Journal of proteome research [Epub ahead of print].

The lysis and extraction of soluble bacterial proteins from cells is a common practice for proteomics analyses, but insoluble bacterial biomasses are often left behind. Here, we show that with triflic acid treatment, the insoluble bacterial biomass of Gram- and Gram+ bacteria can be rendered soluble. We use LC-MS/MS shotgun proteomics to show that bacterial proteins in the soluble and insoluble post-lysis fractions differ significantly. Additionally, in the case of Gram- Pseudomonas aeruginosa, triflic acid treatment enriches for cell envelope-associated proteins. Finally, we apply triflic acid to a human microbiome sample to show that this treatment is robust and enables the identification of a new, complementary subset of proteins from a complex microbial mixture.


ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

ESP Support

In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

ESP Rationale

Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

ESP Goal

In reading the early works of classical genetics, one is drawn, almost inexorably, into ever more complex models, until molecular explanations begin to seem both necessary and natural. At that point, the tools for understanding genome research are at hand. Assisting readers reach this point was the original goal of The Electronic Scholarly Publishing Project.

ESP Usage

Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

ESP Content

When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

ESP Help

Early support from the DOE component of the Human Genome Project was critically important for getting the ESP project on a firm foundation. Since that funding ended (nearly 20 years ago), the project has been operated as a purely volunteer effort. Anyone wishing to assist in these efforts should send an email to Robbins.

ESP Plans

With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

Electronic Scholarly Publishing
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E-mail: RJR8222 @

Papers in Classical Genetics

The ESP began as an effort to share a handful of key papers from the early days of classical genetics. Now the collection has grown to include hundreds of papers, in full-text format.

Digital Books

Along with papers on classical genetics, ESP offers a collection of full-text digital books, including many works by Darwin (and even a collection of poetry — Chicago Poems by Carl Sandburg).


ESP now offers a much improved and expanded collection of timelines, designed to give the user choice over subject matter and dates.


Biographical information about many key scientists.

Selected Bibliographies

Bibliographies on several topics of potential interest to the ESP community are now being automatically maintained and generated on the ESP site.

ESP Picks from Around the Web (updated 07 JUL 2018 )