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 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 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.

scholarly journals Bioactive small molecules produced by the human gut microbiome modulate Vibrio cholerae sessile and planktonic lifestyles

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1-19
Author(s):  
Heidi Pauer ◽  
Felipe Lopes Teixeira ◽  
Avery V. Robinson ◽  
Thiago E. Parente ◽  
Marília A. F. De Melo ◽  
...  
Keyword(s):  
Small Molecules ◽  
Vibrio Cholerae ◽  
Gut Microbiome ◽  
Human Gut ◽  
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 Concentrated Raw Fibers Enhance the Fiber-Degrading Capacity of a Synthetic Human Gut Microbiome

2021 ◽  
Author(s):  
Alexander Steimle ◽  
Mareike Neumann ◽  
Erica Grant ◽  
Jonathan D Turner ◽  
Mahesh S Desai
Keyword(s):  
Gut Microbiome ◽  
A Priori ◽  
Human Gut ◽  
In Vivo Models ◽  
Human Gut Microbiome ◽  
Different Strains ◽  
Alpha Glucosidase ◽  
Prebiotic Fibers

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)&mdash;containing fibers from pea, oat, psyllium, wheat and apple&mdash;on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading &alpha;-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

scholarly journals Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome

2017 ◽  
Author(s):  
Emily K. Mallory ◽  
Ambika Acharya ◽  
Stefano E. Rensi ◽  
Peter J. Turnbaugh ◽  
Roselie A. Bright ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Chemical Reaction ◽  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome

scholarly journals Personalized Mapping of Drug Metabolism by the Human Gut Microbiome

Cell ◽  
2020 ◽  
Vol 181 (7) ◽  
pp. 1661-1679.e22 ◽  
Author(s):  
Bahar Javdan ◽  
Jaime G. Lopez ◽  
Pranatchareeya Chankhamjon ◽  
Ying-Chiang J. Lee ◽  
Raphaella Hull ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Gut Microbiome ◽  
Human Gut ◽  
Human Gut Microbiome

scholarly journals Concentrated Raw Fibers Enhance the Fiber-Degrading Capacity of a Synthetic Human Gut Microbiome

2021 ◽  
Vol 22 (13) ◽  
pp. 6855
Author(s):  
Alex Steimle ◽  
Mareike Neumann ◽  
Erica T. Grant ◽  
Jonathan D. Turner ◽  
Mahesh S. Desai
Keyword(s):  
Gut Microbiome ◽  
A Priori ◽  
Human Gut ◽  
General Increase ◽  
In Vivo Models ◽  
Human Gut Microbiome ◽  
Different Strains ◽  
Prebiotic Fibers

The consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing a 14-member synthetic human gut microbiome (SM) in vivo, characterized a priori for their ability to metabolize a collection of fibers in vitro. This SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of dietary concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders, namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

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