scholarly journals Polyphenol utilization proteins in human gut microbiome

2021 ◽  
Author(s):  
Bo Zheng ◽  
Yinchao He ◽  
Pengxiang Zhang ◽  
Yi-Xin Huo ◽  
Yanbin Yin
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Sequence Similarity ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Human Populations ◽  
Human Gut ◽  
Systematic Classification ◽  
Dietary Polyphenols ◽  
Human Gut Microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

scholarly journals Putative mobilized colistin resistance genes in the human gut microbiome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bruno G. N. Andrade ◽  
Tobias Goris ◽  
Haithem Afli ◽  
Felipe H. Coutinho ◽  
Alberto M. R. Dávila ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Future Research ◽  
Human Populations ◽  
Bacterial Strains ◽  
Colistin Resistance ◽  
Human Gut ◽  
Human Gut Microbiome

Abstract Background The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes. Results A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings. Conclusion This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.

scholarly journals A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

2019 ◽  
Author(s):  
Alexandre Almeida ◽  
Stephen Nayfach ◽  
Miguel Boland ◽  
Francesco Strozzi ◽  
Martin Beracochea ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Functional Characterization ◽  
Genomic Variation ◽  
Human Populations ◽  
Single Nucleotide Variants ◽  
Human Gut ◽  
Large Reservoir ◽  
Functional Annotations ◽  
Human Gut Microbiome ◽  
Gene Catalogue

AbstractComprehensive reference data is essential for accurate taxonomic and functional characterization of the human gut microbiome. Here we present the Unified Human Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 million protein sequences used to generate the Unified Human Gastrointestinal Protein (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome remains to be fully explored, with over 70% of the UHGG species lacking cultured representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-species genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which were specific to individual human populations. These freely available genomic resources should greatly facilitate investigations into the human gut microbiome.

scholarly journals Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species

2021 ◽  
Author(s):  
Moses Stamboulian ◽  
Jamie Canderan ◽  
Yuzhen Ye
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
De Novo ◽  
Bacterial Species ◽  
Individual Species ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Microbial Species ◽  
Microbial Organisms

AbstractHost-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a powerful technique to study microbiome functional activity by characterizing the complex and dynamic composition of microbial proteins. We conducted a large-scale survey of human gut microbiome metaproteomic data to identify generalist species that are ubiquitously expressed across all samples and specialists that are highly expressed in a small subset of samples associated with a certain phenotype. We were able to utilize the metaproteomic mass spectrometry data to reveal the protein landscapes of these species, which enables the characterization of the expression levels of proteins of different functions and underlying regulatory mechanisms, such as operons. Finally, we were able to recover a large number of open reading frames (ORFs) with spectral support, which were missed by de novo protein-coding gene predictors. We showed that a majority of the rescued ORFs overlapped with de novo predicted proteincoding genes, but on opposite strands or on different frames. Together, these demonstrate applications of metaproteomics for the characterization of important gut bacterial species. Results are available for public access at https://omics.informatics.indiana.edu/GutBac.Author summaryMany reference genomes for studying human gut microbiome are available, but knowledge about how microbial organisms work is limited. Identification of proteins at individual species or community level provides direct insight into the functionality of microbial organisms. By analyzing more than a thousand metaproteomics datasets, we examined protein landscapes of more than two thousands of microbial species that may be important to human health and diseases. This work demonstrated new applications of metaproteomic datasets for studying individual genomes. We made the analysis results available through the GutBac website, which we believe will become a resource for studying microbial species important for human health and diseases.

scholarly journals Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference

2019 ◽  
Vol 244 (6) ◽  
pp. 445-458 ◽  
Author(s):  
Anders B Dohlman ◽  
Xiling Shen
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Network Inference ◽  
Therapeutic Strategies ◽  
Microbial Interactions ◽  
Interaction Networks ◽  
Human Gut ◽  
Statistical Tools ◽  
Human Gut Microbiome ◽  
Network Analyses

Advances in high-throughput sequencing have ushered in a new era of research into the gut microbiome and its role in human health and disease. However, due to the unique characteristics of microbiome survey data, their use for the detection of ecological interaction networks remains a considerable challenge, and a field of active methodological development. In this review, we discuss the landscape of existing statistical and experimental methods for detecting and characterizing microbial interactions, as well as the role that host and environmental metabolic signals play in mediating the behavior of these networks. Numerous statistical tools for microbiome network inference have been developed. Yet due to tool-specific biases, the networks identified by these methods are often discordant, motivating a need for the development of more general tools, the use of ensemble approaches, and the incorporation of prior knowledge into prediction. By elucidating the complex dynamics of the microbial interactome, we will enhance our understanding of the microbiome’s role in disease, more precisely predict the microbiome’s response to perturbation, and inform the development of future therapeutic strategies for microbiome-related disease. Impact statement This review provides a comprehensive description of experimental and statistical tools used for network analyses of the human gut microbiome. Understanding the system dynamics of microbial interactions may lead to the improvement of therapeutic approaches for managing microbiome-associated diseases. Microbiome network inference tools have been developed and applied to both cross-sectional and longitudinal experimental designs, as well as to multi-omic datasets, with the goal of untangling the complex web of microbe-host, microbe-environmental, and metabolism-mediated microbial interactions. The characterization of these interaction networks may lead to a better understanding of the systems dynamics of the human gut microbiome, augmenting our knowledge of the microbiome’s role in human health, and guiding the optimization of effective, precise, and rational therapeutic strategies for managing microbiome-associated disease.

scholarly journals A robust statistical framework for reconstructing genomes from metagenomic data

2014 ◽  
Author(s):  
Dongwan Don Kang ◽  
Jeff Froula ◽  
Rob Egan ◽  
Zhong Wang
Keyword(s):  
Gut Microbiome ◽  
Metagenomic Data ◽  
Metagenomic Dataset ◽  
Human Gut ◽  
Sequence Composition ◽  
Human Gut Microbiome ◽  
Statistical Framework ◽  
Large Complex ◽  
Probabilistic Distances ◽  
Unidentified Species

We present software that reconstructs genomes from shotgun metagenomic sequences using a reference-independent approach. This method permits the identification of OTUs in large complex communities where many species are unknown. Binning reduces the complexity of a metagenomic dataset enabling many downstream analyses previously unavailable. In this study we developed MetaBAT, a robust statistical framework that integrates probabilistic distances of genome abundance with sequence composition for automatic binning. Applying MetaBAT to a human gut microbiome dataset identified 173 highly specific genomes bins including many representing previously unidentified species.

scholarly journals Bacterial associations in the healthy human gut microbiome across populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark Loftus ◽  
Sayf Al-Deen Hassouneh ◽  
Shibu Yooseph
Keyword(s):  
Gut Microbiome ◽  
Sequence Data ◽  
Bacterial Species ◽  
Human Populations ◽  
Human Gut ◽  
Healthy Human ◽  
Human Gut Microbiome ◽  
Genome Shotgun Sequence ◽  
Bacterial Associations ◽  
And Function

AbstractIn a microbial community, associations between constituent members play an important role in determining the overall structure and function of the community. The human gut microbiome is believed to play an integral role in host health and disease. To understand the nature of bacterial associations at the species level in healthy human gut microbiomes, we analyzed previously published collections of whole-genome shotgun sequence data, totaling over 1.6 Tbp, generated from 606 fecal samples obtained from four different healthy human populations. Using a Random Forest Classifier, we identified 202 signature bacterial species that were prevalent in these populations and whose relative abundances could be used to accurately distinguish between the populations. Bacterial association networks were constructed with these signature species using an approach based on the graphical lasso. Network analysis revealed conserved bacterial associations across populations and a dominance of positive associations over negative associations, with this dominance being driven by associations between species that are closely related either taxonomically or functionally. Bacterial species that form network modules, and species that constitute hubs and bottlenecks, were also identified. Functional analysis using protein families suggests that much of the taxonomic variation across human populations does not foment substantial functional or structural differences.

scholarly journals The gut mycobiome: a novel player in chronic liver diseases

2020 ◽  
Author(s):  
Lu Jiang ◽  
Peter Stärkel ◽  
Jian-Gao Fan ◽  
Derrick Eugene Fouts ◽  
Petra Bacher ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Therapeutic Targets ◽  
Chronic Liver Diseases ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
The Impact ◽  
Potential Use

Abstract The human gut microbiome (bacteria, fungi, viruses, and archaea) is a complex and diverse ecosystem. It plays an important role in human health, but is involved in several intestinal and extraintestinal diseases. Most research to date has focused on the role of bacteria, while studies focusing on fungi (also referred to as “mycobiome” or “fungome”) are still in its infancy. In this review, we focus on the existing literature available about the gut mycobiome with an emphasis on compositional mycobiome changes associated with liver diseases, the impact on pathogenesis of disease, and its potential use as therapeutic targets. We also provide insights into current methodologies of studying mycobiome, and we highlight the interkingdom interactions in the context of disease and how they affect health of the host. Herein, by focusing on the gut mycobiome, this review provides novel insights and directions for liver research.

scholarly journals Establishing What Constitutes a Healthy Human Gut Microbiome: State of the Science, Regulatory Considerations, and Future Directions

2019 ◽  
Vol 149 (11) ◽  
pp. 1882-1895 ◽  
Author(s):  
Michael I McBurney ◽  
Cindy Davis ◽  
Claire M Fraser ◽  
Barbara O Schneeman ◽  
Curtis Huttenhower ◽  
...  
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Interindividual Variation ◽  
Sufficient Evidence ◽  
Human Gut ◽  
Future Studies ◽  
Human Gut Microbiome ◽  
Host Health ◽  
Short And Long Term

ABSTRACTOn December 17, 2018, the North American branch of the International Life Sciences Institute (ILSI North America) convened a workshop “Can We Begin to Define a Healthy Gut Microbiome Through Quantifiable Characteristics?” with >40 invited academic, government, and industry experts in Washington, DC. The workshop objectives were to 1) develop a collective expert assessment of the state of the evidence on the human gut microbiome and associated human health benefits, 2) see if there was sufficient evidence to establish measurable gut microbiome characteristics that could serve as indicators of “health,” 3) identify short- and long-term research needs to fully characterize healthy gut microbiome–host relationships, and 4) publish the findings. Conclusions were as follows: 1) mechanistic links of specific changes in gut microbiome structure with function or markers of human health are not yet established; 2) it is not established if dysbiosis is a cause, consequence, or both of changes in human gut epithelial function and disease; 3) microbiome communities are highly individualized, show a high degree of interindividual variation to perturbation, and tend to be stable over years; 4) the complexity of microbiome-host interactions requires a comprehensive, multidisciplinary research agenda to elucidate relationships between gut microbiome and host health; 5) biomarkers and/or surrogate indicators of host function and pathogenic processes based on the microbiome need to be determined and validated, along with normal ranges, using approaches similar to those used to establish biomarkers and/or surrogate indicators based on host metabolic phenotypes; 6) future studies measuring responses to an exposure or intervention need to combine validated microbiome-related biomarkers and/or surrogate indicators with multiomics characterization of the microbiome; and 7) because static genetic sampling misses important short- and long-term microbiome-related dynamic changes to host health, future studies must be powered to account for inter- and intraindividual variation and should use repeated measures within individuals.

scholarly journals The capacity to produce hydrogen sulfide (H2S) via cysteine degradation is ubiquitous in the human gut microbiome

2021 ◽  
Author(s):  
Domenick J Braccia ◽  
Xiaofang Jiang ◽  
Mihai Pop ◽  
Brantley Hall
Keyword(s):  
Hydrogen Sulfide ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Therapeutic Interventions ◽  
Metagenomic Data ◽  
Human Gut ◽  
Gut Microbes ◽  
Human Gut Microbiome ◽  
Degrading Bacteria ◽  
H2s Production

As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in gut microbes. To better understand the potential for H2S production via cysteine degradation by the human gut microbiome, we performed a comprehensive search for genes encoding cysteine-degrading genes in 4,644 bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalogue. We identified 407 gut bacterial species as putative cysteine degrading bacteria, 328 of which have not been previously implicated in H2S production. We identified the presence of at least one putative cysteine degrading bacteria in metagenomic data of 100% of 6,644 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomics data of 100% of 59 samples. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate reducing bacteria (p<2.2e-16). Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.

scholarly journals Acquired interbacterial defense systems protect against interspecies antagonism in the human gut microbiome

2018 ◽  
Author(s):  
Benjamin D. Ross ◽  
Adrian J. Verster ◽  
Matthew C. Radey ◽  
Danica T. Schmidtke ◽  
Christopher E. Pope ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Gene Clusters ◽  
Protective Capacity ◽  
Human Gut ◽  
Microbiome Composition ◽  
Toxin Resistance ◽  
Human Gut Microbiome ◽  
Bacterial Antagonism ◽  
The Impact

AbstractThe impact of direct interactions between co-resident microbes on microbiome composition is not well understood. Here we report the occurrence of acquired interbacterial defense (AID) gene clusters in bacterial residents of the human gut microbiome. These clusters encode arrays of immunity genes that protect against type VI secretion toxin-mediated intra- and inter-species bacterial antagonism. Moreover, the clusters reside on mobile elements and we demonstrate that their transfer is sufficient to confer toxin resistance in vitro and in gnotobiotic mice. Finally, we identify and validate the protective capacity of a recombinase-associated AID subtype (rAID-1) present broadly in Bacteroidales genomes. These rAID-1 gene clusters have a structure suggestive of active gene acquisition and include predicted immunity factors of toxins deriving from diverse organisms. Our data suggest that neutralization of contact-dependent interbacterial antagonism via AID systems shapes human gut microbiome ecology.

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