scholarly journals Genome Sequence of Christensenella minuta DSM 22607T

2017 ◽  
Vol 5 (2) ◽  
Author(s):  
Bruce A. Rosa ◽  
Kymberlie Hallsworth-Pepin ◽  
John Martin ◽  
Aye Wollam ◽  
Makedonka Mitreva
Keyword(s):  
Genome Sequence ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Biological Mechanism ◽  
Valuable Resource ◽  
Human Gut ◽  
Content Type ◽  
Human Gut Microbiome

ABSTRACT Obesity influences and is influenced by the human gut microbiome. Here, we present the genome of Christensenella minuta, a highly heritable bacterial species which has been found to be strongly associated with obesity through an unknown biological mechanism. This novel genome provides a valuable resource for future obesity therapeutic studies.

scholarly journals Complete Genome Sequence of Phascolarctobacterium faecium JCM 30894, a Succinate-Utilizing Bacterium Isolated from Human Feces

2019 ◽  
Vol 8 (3) ◽  
Author(s):  
Yusuke Ogata ◽  
Wataru Suda ◽  
Nao Ikeyama ◽  
Masahira Hattori ◽  
Moriya Ohkuma ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Genome Analysis ◽  
Gut Microbiome ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Human Feces ◽  
Human Gut ◽  
Content Type ◽  
Human Gut Microbiome

Phascolarctobacterium faecium is an anaerobic microbe known as a member of the human gut microbiome. Here, we report the complete genome sequence of Phascolarctobacterium faecium JCM 30894 and the elucidation of the mechanism for utilization of succinate by this bacterium based on the genome analysis.

scholarly journals Systematic mapping of drug metabolism by the human gut microbiome

2019 ◽  
Author(s):  
Pranatchareeya Chankhamjon ◽  
Bahar Javdan ◽  
Jaime Lopez ◽  
Raphaella Hull ◽  
Seema Chatterjee ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Small Molecules ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Drug Bioavailability ◽  
Oral Drugs ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
Comprehensive Framework

ABSTRACTThe human gut microbiome harbors hundreds of bacterial species with diverse biochemical capabilities, making it one of nature’s highest density, highest diversity bioreactors. Several drugs have been previously shown to be directly metabolized by the gut microbiome, but the extent of this phenomenon has not been systematically explored. Here, we develop a systematic screen for mapping the ability of the complex human gut microbiome to biochemically transform small molecules (MDM-Screen), and apply it to a library of 575 clinically used oral drugs. We show that 13% of the analyzed drugs, spanning 28 pharmacological classes, are metabolized by a single microbiome sample. In a proof-of-principle example, we show that microbiome-derived metabolism occursin vivo, identify the genes responsible for it, and provide a possible link between its consequences and clinically observed features of drug bioavailability and toxicity. Our findings reveal a previously underappreciated role for the gut microbiome in drug metabolism, and provide a comprehensive framework for characterizing this important class of drug-microbiome interactions.

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 Developing a Bacteroides System for Function-Based Screening of DNA from the Human Gut Microbiome

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Kathy N. Lam ◽  
Eric C. Martens ◽  
Trevor C. Charles
Keyword(s):  
Gene Function ◽  
Gut Microbiome ◽  
Environmental Dna ◽  
Functional Metagenomics ◽  
Human Gut ◽  
Metagenomic Dna ◽  
Content Type ◽  
Human Gut Microbiome ◽  
Surrogate Host ◽  
Functional Screens

ABSTRACT Functional metagenomics is a powerful method that allows the isolation of genes whose role may not have been predicted from DNA sequence. In this approach, first, environmental DNA is cloned to generate metagenomic libraries that are maintained in Escherichia coli , and second, the cloned DNA is screened for activities of interest. Typically, functional screens are carried out using E. coli as a surrogate host, although there likely exist barriers to gene expression, such as lack of recognition of native promoters. Here, we describe efforts to develop Bacteroides thetaiotaomicron as a surrogate host for screening metagenomic DNA from the human gut. We construct a B. thetaiotaomicron -compatible fosmid cloning vector, generate a fosmid clone library using DNA from the human gut, and show successful functional complementation of a B. thetaiotaomicron glycan utilization mutant. Though we were unable to retrieve the physical fosmid after complementation, we used genome sequencing to identify the complementing genes derived from the human gut microbiome. Our results demonstrate that the use of B. thetaiotaomicron to express metagenomic DNA is promising, but they also exemplify the challenges that can be encountered in the development of new surrogate hosts for functional screening. IMPORTANCE Human gut microbiome research has been supported by advances in DNA sequencing that make it possible to obtain gigabases of sequence data from metagenomes but is limited by a lack of knowledge of gene function that leads to incomplete annotation of these data sets. There is a need for the development of methods that can provide experimental data regarding microbial gene function. Functional metagenomics is one such method, but functional screens are often carried out using hosts that may not be able to express the bulk of the environmental DNA being screened. We expand the range of current screening hosts and demonstrate that human gut-derived metagenomic libraries can be introduced into the gut microbe Bacteroides thetaiotaomicron to identify genes based on activity screening. Our results support the continuing development of genetically tractable systems to obtain information about gene function.

scholarly journals Microbe-seq: high-throughput, single-microbe genomics with strain resolution, applied to a human gut microbiome

2020 ◽  
Author(s):  
Wenshan Zheng ◽  
Shijie Zhao ◽  
Yehang Yin ◽  
Huidan Zhang ◽  
David M. Needham ◽  
...  
Keyword(s):  
Microbial Communities ◽  
High Throughput ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Microbial Interactions ◽  
Single Individual ◽  
Human Gut ◽  
Single Strain ◽  
Human Gut Microbiome

AbstractWe present Microbe-seq, a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.

scholarly journals Comparative Genomics Guides Elucidation of Vitamin B12 Biosynthesis in Novel Human-Associated Akkermansia Strains

2019 ◽  
Vol 86 (3) ◽  
Author(s):  
Nina Kirmiz ◽  
Kadir Galindo ◽  
Karissa L. Cross ◽  
Estefani Luna ◽  
Nicholas Rhoades ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Species Level ◽  
Vitamin B ◽  
Human Gut ◽  
Content Type ◽  
Human Host ◽  
Akkermansia Muciniphila ◽  
Human Gut Microbiome ◽  
Physiological Diversity ◽  
Bacterial Lineage

ABSTRACT Akkermansia muciniphila is a mucin-degrading bacterium found in the gut of most humans and is considered a “next-generation probiotic.” However, knowledge of the genomic and physiological diversity of human-associated Akkermansia sp. strains is limited. Here, we reconstructed 35 metagenome-assembled genomes and combined them with 40 publicly available genomes for comparative genomic analysis. We identified at least four species-level phylogroups (AmI to AmIV), with distinct functional potentials. Most notably, we identified genes for cobalamin (vitamin B12) biosynthesis within the AmII and AmIII phylogroups. To verify these predictions, 10 Akkermansia strains were isolated from adults and screened for vitamin B12 biosynthesis genes via PCR. Two AmII strains were positive for the presence of cobalamin biosynthesis genes, while all 9 AmI strains tested were negative. To demonstrate vitamin B12 biosynthesis, we measured the production of acetate, succinate, and propionate in the presence and absence of vitamin supplementation in representative strains of the AmI and AmII phylogroups, since cobalamin is an essential cofactor in propionate metabolism. Results showed that the AmII strain produced acetate and propionate in the absence of supplementation, which is indicative of vitamin B12 biosynthesis. In contrast, acetate and succinate were the main fermentation products for the AmI strains when vitamin B12 was not supplied in the culture medium. Lastly, two bioassays were used to confirm vitamin B12 production by the AmII phylogroup. This novel physiological trait of human-associated Akkermansia strains may affect how these bacteria interact with the human host and other members of the human gut microbiome. IMPORTANCE There is significant interest in the therapeutic and probiotic potential of the common gut bacterium Akkermansia muciniphila. However, knowledge of both the genomic and physiological diversity of this bacterial lineage is limited. Using a combination of genomic, molecular biological, and traditional microbiological approaches, we identified at least four species-level phylogroups with differing functional potentials that affect how these bacteria interact with both their human host and other members of the human gut microbiome. Specifically, we identified and isolated Akkermansia strains that were able to synthesize vitamin B12. The ability to synthesize this important cofactor broadens the physiological capabilities of human-associated Akkermansia strains, fundamentally altering our understanding of how this important bacterial lineage may affect human health.

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 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 Genetic Manipulation of Wild Human Gut Bacteroides

2019 ◽  
Vol 202 (3) ◽  
Author(s):  
Natasha A. Bencivenga-Barry ◽  
Bentley Lim ◽  
Carmen M. Herrera ◽  
M. Stephen Trent ◽  
Andrew L. Goodman
Keyword(s):  
Gut Microbiome ◽  
Genetic Manipulation ◽  
Defined Medium ◽  
Model Organisms ◽  
Human Gut ◽  
Content Type ◽  
Inducible Promoters ◽  
Human Gut Microbiome ◽  
Antimicrobial Peptide Resistance ◽  
Defined Culture

ABSTRACT Bacteroides is one of the most prominent genera in the human gut microbiome, and study of this bacterial group provides insights into gut microbial ecology and pathogenesis. In this report, we introduce a negative selection system for rapid and efficient allelic exchange in wild Bacteroides species that does not require any alterations to the genetic background or a nutritionally defined culture medium. In this approach, dual antibacterial effectors normally delivered via type VI secretion are targeted to the bacterial periplasm under the control of tightly regulated anhydrotetracycline (aTC)-inducible promoters. Introduction of aTC selects for recombination events producing the desired genetic modification, and the dual effector design allows for broad applicability across strains that may have immunity to one counterselection effector. We demonstrate the utility of this approach across 21 human gut Bacteroides isolates representing diverse species, including strains isolated directly from human donors. We use this system to establish that antimicrobial peptide resistance in Bacteroides vulgatus is determined by the product of a gene that is not included in the genomes of previously genetically tractable members of the human gut microbiome. IMPORTANCE Human gut Bacteroides species exhibit strain-level differences in their physiology, ecology, and impact on human health and disease. However, existing approaches for genetic manipulation generally require construction of genetically modified parental strains for each microbe of interest or defined medium formulations. In this report, we introduce a robust and efficient strategy for targeted genetic manipulation of diverse wild-type Bacteroides species from the human gut. This system enables genetic investigation of members of human and animal microbiomes beyond existing model organisms.

scholarly journals MRGM: a mouse reference gut microbiome reveals a large functional discrepancy for gut bacteria of the same genus between mice and humans

2021 ◽  
Author(s):  
Nayeon Kim ◽  
Chan Yeong Kim ◽  
Summo Yang ◽  
Dongjin Park ◽  
Sang-Jun Ha ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Bacterial Species ◽  
Drug Effects ◽  
Core Gene ◽  
Metagenomic Sequencing ◽  
Human Gut ◽  
Classification Rate ◽  
Human Gut Microbiome ◽  
Dietary Components

The gut microbiome is associated with human diseases and interacts with dietary components and drugs. In vivo mouse models may be effective for studying diet and drug effects on the gut microbiome. We constructed a mouse reference gut microbiome (MRGM, https://www.mbiomenet.org/MRGM/) that includes newly-assembled genomes from 878 metagenomes. Leveraging samples with ultra-deep metagenomic sequencing (>130 million read pairs), we demonstrated quality improvement in assembled genomes for mouse gut microbes as sequencing depth increased. MRGM provides a catalog of 46,267 non-redundant genomes with ≥70% completeness and ≤5% contamination comprising 1,689 representative bacterial species and 15.2 million non-redundant proteins. Importantly, MRGM significantly improved the taxonomic classification rate of sequencing reads from mouse fecal samples compared to previous databases. Using MRGM, we determined that reliable low-abundance taxa profiles of the mouse gut microbiome require sequencing >10 million reads. Despite the high overall functional similarity of the mouse and human gut microbiomes, only ~10% of MRGM species are shared with the human gut microbiome. Although ~80% of MRGM genera are present in the human gut microbiome, ~70% of the shared genera have <40% of core gene content for the respective genus with human counterparts. These suggest that although metabolic processes of the human gut microbiome largely occur in the mouse gut microbiome, functional translations between them according to genus-level taxonomic commonality require caution.

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