Xenobiotics shape the physiology and gene expression of the active human gut microbiome
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The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider interindividual variations in the active human gut microbiome.
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Exposure to a panel of host-targeted drugs including digoxin and sulfasalazine induces subtle changes in community structure but more marked changes in the genes expressed by the gut microbiome, including genes involved in xenobiotic metabolism.
“Exposure in incubation experiments to a panel of hosttargeted drugs, including digoxin and sulfasalazine, induces subtle changes in community structure, but more marked changes in the genes expressed by the gut microbiome, including those genes involved in xenobiotic metabolism (Maurice et al., 2013).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Maurice et al., 2013
One major function of the gut microbiota is metabolism of dietary components leading to the generation of active metabolites that directly regulate human physiology including gut barrier function.
“One of the major functions of the gut microbiota is metabolism of dietary components leading to the generation of active metabolites that directly regulate human physiology including gut barrier function.21”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [21]
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- Authors
- Maurice, C. F., Haiser, H. J., & Turnbaugh, P. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Turnbaugh, Peter James
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 152
- Issue
- 1-2
- Pages
- 39-50
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3552296
- OpenAlex
- W2063856799
- Cited by
- 811
- References
- 68
- Citations by year
- 2026: 22 · 2025: 37 · 2024: 48 · 2023: 42 · 2022: 51 · 2021: 75 · 2020: 79 · 2019: 69 · 2018: 100 · 2017: 62 · 2016: 66 · 2015: 60 · 2014: 58 · 2013: 42
- FWCI
- 33.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Canadian Institutes of Health Research (112991_1)
- National Institute of General Medical Sciences (P50GM068763)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, xenobiotics, Firmicutes, antibiotic resistance, drug metabolism, stress response, microbial gene expression, metatranscriptomics, 16S rRNA gene sequencing, flow cytometry, personalized medicine, interindividual variability
- MeSH terms
- Anti-Bacterial Agents, Feces, Gram-Positive Bacteria, Humans, Xenobiotics, Gene Expression Profiling, Gastrointestinal Tract, Metagenome, Metagenomics
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