The gut microbiota contributes to diverse aspects of host physiology, ranging from immunomodulation to drug metabolism. Changes in the gut microbiota composition are associated with various diseases as well as with the response to medications. It is therefore important to understand how different lifestyle and environmental factors shape gut microbiota composition. Beyond the commonly considered factor of diet, small-molecule drugs have recently been identified as major effectors of the microbiota composition. Other xenobiotics, such as environmental or chemical pollutants, can also impact gut bacterial communities. Here, we review the mechanisms of interactions between gut bacteria and antibiotics, host-targeted drugs, natural food compounds, food additives and environmental pollutants. While xenobiotics can impact bacterial growth and metabolism, bacteria in turn can bioaccumulate or chemically modify these compounds. These reciprocal interactions can manifest in complex xenobiotic–microbiota–host relationships. Our Review highlights the need to study mechanisms underlying interactions with pollutants and food additives towards deciphering the dynamics and evolution of the gut microbiota.
Your institute does not have access to this article
Subscribe to Journal
Get full journal access for 1 year
only 7,71 € per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Sender, R., Fuchs, S. & Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14, e1002533 (2016).
Li, J. H. et al. An integrated catalog of reference genes in the human gut microbiome. Nat. Biotechnol. 32, 834–841 (2014).
Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19, 55–71 (2021).
Fung, T. C., Olson, C. A. & Hsiao, E. Y. Interactions between the microbiota, immune and nervous systems in health and disease. Nat. Neurosci. 20, 145–155 (2017).
Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).
Kamada, N., Chen, G. Y., Inohara, N. & Núñez, G. Control of pathogens and pathobionts by the gut microbiota. Nat. Immunol. 14, 685–690 (2013).
Franzosa, E. A. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat. Microbiol. 4, 293–305 (2019).
Rajagopala, S. V. et al. The human microbiome and cancer. Cancer Prev. Res. 10, 226–234 (2017).
Cryan, J. F., O’Riordan, K. J., Sandhu, K., Peterson, V. & Dinan, T. G. The gut microbiome in neurological disorders. Lancet Neurol. 19, 179–194 (2020).
Baquero, F. & Nombela, C. The microbiome as a human organ. Clin. Microbiol. Infect. 18, 2–4 (2012).
Krautkramer, K. A., Fan, J. & Bäckhed, F. Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Microbiol. 19, 77–94 (2021).
Lee-Sarwar, K. A., Lasky-Su, J., Kelly, R. S., Litonjua, A. A. & Weiss, S. T. Metabolome–microbiome crosstalk and human disease. Metabolites 10, 181 (2020).
Zierer, J. et al. The fecal metabolome as a functional readout of the gut microbiome. Nat. Genet. 50, 790–795 (2018).
Shuo Han, W. V. T. et al. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature 595, 415–420 (2021). Microbiome-focused in vitro metabolomics pipeline to systematically characterize bacterial metabolism, which is essential for mechanistic understanding of microbial metabolic potential.
Vujkovic-Cvijin, I. et al. Host variables confound gut microbiota studies of human disease. Nature 587, 448–454 (2020).
Hughes, D. A. et al. Genome-wide associations of human gut microbiome variation and implications for causal inference analyses. Nat. Microbiol. 5, 1079 (2020).
Abdelsalam, N. A., Ramadan, A. T., ElRakaiby, M. T. & Aziz, R. K. Toxicomicrobiomics: the human microbiome vs. pharmaceutical, dietary, and environmental xenobiotics. Front. Pharmacol. 11, 390 (2020).
Kolodziejczyk, A. A., Zheng, D. & Elinav, E. Diet–microbiota interactions and personalized nutrition. Nat. Rev. Microbiol. 17, 742–753 (2019).
Gacesa, R. et al. The Dutch Microbiome Project defines factors that shape the healthy gut microbiome. BioRxiv https://doi.org/10.1101/2020.11.27.401125 (2020).
Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210 (2018). Genotype and microbiome examination of 1,046 healthy individuals disentangling genetic and environmental influences on the composition of the gut microbiota.
Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).
Forslund, K. et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528, 262–266 (2015).
Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium eggerthella lenta. Science 341, 295–298 (2013).
Lindenbaum, J., Rund, D. G., Butler, V. P., Tse-Eng, D. & Saha, J. R. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N. Engl. J. Med. 305, 789–794 (1981).
Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J. & Balskus, E. P. Discovery and inhibition of an interspecies gut bacterial pathway for levodopa metabolism. Science 364, eaau6323 (2019). Gnotobiotic mouse models and in vitro screens allowed to identify an interspecies pathway for gut bacterial levodopa metabolism, characterize responsible genes and suggest a chemical strategy to successfully inhibit bacterial drug metabolism in vivo.
Pristner, M. & Warth, B. Drug-exposome interactions: the next frontier in precision medicine. Trends Pharmacol. Sci. 41, 994–1005 (2020).
Chiu, K., Warner, G., Nowak, R. A., Flaws, J. A. & Mei, W. The impact of environmental chemicals on the gut microbiome. Toxicol. Sci. 176, 253–284 (2020).
Mao, Q. X. et al. The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome. Environ. Health Glob. 17, 50 (2018).
Reygner, J. et al. Inulin supplementation lowered the metabolic defects of prolonged exposure to chlorpyrifos from gestation to young adult stage in offspring rats. PLoS ONE 11, e0164614 (2016).
Yuan, X. L. et al. Gut microbiota: an underestimated and unintended recipient for pesticide-induced toxicity. Chemosphere 227, 425–434 (2019).
Li, X. et al. Heavy metal exposure causes changes in the metabolic health-associated gut microbiome and metabolites. Environ. Int. 126, 454–467 (2019).
Zhai, Q. X. et al. Effects of subchronic oral toxic metal exposure on the intestinal microbiota of mice. Sci. Bull. 62, 831–840 (2017).
Xue, B. et al. Low-concentration of dichloroacetonitrile (DCAN) in drinking water perturbs the health-associated gut microbiome and metabolic profile in rats. Chemosphere 258, 127067 (2020).
Zhu, J. Q. et al. Consumption of drinking water N-nitrosamines mixture alters gut microbiome and increases the obesity risk in young male rats. Environ. Pollut. 248, 388–396 (2019).
Coryell, M., McAlpine, M., Pinkham, N. V., McDermott, T. R. & Walk, S. T. The gut microbiome is required for full protection against acute arsenic toxicity in mouse models. Nat. Commun. 9, 5424 (2018).
Ilett, K. F., Tee, L. B. G., Reeves, P. T. & Minchin, R. F. Mebolism of drugs and other xenobiotics in the gut lumen and wall. Pharmacol. Ther. 46, 67–93 (1990).
Harishankar, M. K., Sasikala, C. & Ramya, M. Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos. 3 Biotech. 3, 137–142 (2013).
Xu, H., Heinze, T. M., Paine, D. D., Cerniglia, C. E. & Chen, H. Sudan azo dyes and Para Red degradation by prevalent bacteria of the human gastrointestinal tract. Anaerobe 16, 114–119 (2010).
Koppel, N., Rekdal, V. M. & Balskus, E. P. Chemical transformation of xenobiotics by the human gut microbiota. Science 356, eaag2770 (2017).
Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 363, eaat9931 (2019).
Roberts, M. S., Magnusson, B. M., Burczynski, F. J. & Weiss, M. Enterohepatic Circulation. Clin. Pharmacokinetics 41, 751–790 (2002).
Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R. & Goodman, A. L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570, 462–467 (2019). Systematic screen demonstrating that 176 human-targeted drugs can be biotransformed by gut bacterial strains and identifying responsible bacterial gene products.
Javdan, B. et al. Personalized mapping of drug metabolism by the human gut microbiome. Cell 181, 1661–1679.e22 (2020). Systematic screen of 438 drugs showing biotransformation of 57 human-targeted drugs by faecal microbial communities.
Zimmermann, M., Patil, K. R., Typas, A. & Maier, L. Towards a mechanistic understanding of reciprocal drug–microbiome interactions. Molecular Syst. Biol. 17, e10116 (2021).
Maurice, C. F., Haiser, H. J. & Turnbaugh, P. J. Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152, 39–50 (2013).
Li, L. et al. RapidAIM: a culture- and metaproteomics-based rapid assay of individual microbiome responses to drugs. Microbiome 8, 33 (2020).
Haak, B. W. et al. Long-term impact of oral vancomycin, ciprofloxacin and metronidazole on the gut microbiota in healthy humans. J. Antimicrob. Chemother. 74, 782–786 (2019).
Rashid, M.-U. et al. Determining the long-term effect of antibiotic administration on the human normal intestinal microbiota using culture and pyrosequencing methods. Clin. Infect. Dis. 60, S77–S84 (2015).
Suez, J. et al. Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 174, 1406–1423.e16 (2018).
Modi, S. R., Collins, J. J. & Relman, D. A. Antibiotics and the gut microbiota. J. Clin. Investig. 124, 4212–4218 (2014).
Theriot, C. M. et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5, 3114 (2014).
Kachrimanidou, M. & Tsintarakis, E. Insights into the role of human gut microbiota in clostridioides difficile infection. Microorganisms 8, 200 (2020).
Palleja, A. et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat. Microbiol. 3, 1255–1265 (2018).
Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850–858 (2017).
Vich Vila, A. et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 11, 362 (2020).
Seeman, M. V. The gut microbiome and antipsychotic treatment response. Behav. Brain Res. 396, 112886 (2021).
Vieira-Silva, S. et al. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature 581, 310–315 (2020).
Weersma, R. K., Zhernakova, A. & Fu, J. Interaction between drugs and the gut microbiome. Gut 69, 1510–1519 (2020).
David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).
Pérez-Burillo, S., Hinojosa-Nogueira, D., Pastoriza, S. & Rufián-Henares, J. A. Plant extracts as natural modulators of gut microbiota community structure and functionality. Heliyon 6, e05474 (2020).
Peterson, C. T. et al. Effects of turmeric and curcumin dietary supplementation on human gut microbiota: a double-blind, randomized, placebo-controlled pilot study. J. Evid. Based. Integr. Med. https://doi.org/10.1177/2515690X18790725 (2018).
Sun, H. et al. The modulatory effect of polyphenols from green tea, oolong tea and black tea on human intestinal microbiota in vitro. J. Food Sci. Technol. 55, 399–407 (2018).
Bian, X. et al. Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions. Food Chem. Toxicol. 107, 530–539 (2017).
Rodriguez-Palacios, A. et al. The artificial sweetener Splenda promotes gut proteobacteria, dysbiosis, and myeloperoxidase reactivity in Crohn’s disease-like ileitis. Inflamm. Bowel Dis. 24, 1005–1020 (2018).
Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181–186 (2014). Gnotobiotic mouse model demonstrating the effects of artificial sweeteners on the development of glucose intolerance mediated by the changes in microbiota composition and metabolism.
Wang, Q.-P., Browman, D., Herzog, H. & Neely, G. G. Non-nutritive sweeteners possess a bacteriostatic effect and alter gut microbiota in mice. PLoS One 13, e0199080 (2018).
Chassaing, B. et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 519, 92–96 (2015). Gnotobiotic mouse model demonstrating the effects of processed food components on inflammation and metabolic-syndrome like symptoms mediated by the changes in microbiota composition.
Viennois, E., Merlin, D., Gewirtz, A. T. & Chassaing, B. Dietary emulsifier-induced low-grade inflammation promotes colon carcinogenesis. Cancer Res. 77, 27–40 (2017).
Chassaing, B., Van De Wiele, T., De Bodt, J., Marzorati, M. & Gewirtz, A. T. Dietary emulsifiers directly alter human microbiota composition and gene expression ex vivo potentiating intestinal inflammation. Gut 66, 1414–1427 (2017).
European Commission. Contaminants https://ec.europa.eu/food/safety/chemical_safety/contaminants_en (2021).
European Food Safety Authority (EFSA); Medina-Pastor, P. & Triacchini, G. The 2018 European Union report on pesticide residues in food. EFSA J. 18, e06057 (2020).
FDA. Pesticide Residue Monitoring Program Fiscal Year 2018 Pesticide Report 46 (2020).
Department for Environment Food & Rural Affairs. The Expert Committee on Pesticide Residues in Food (PRiF) Annual Report 2020 (2021).
Mesnage, R. et al. Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins. bioRxiv https://doi.org/10.1101/2021.06.16.448511 (2021). Metabolomic analysis of urine samples highlighting exposure to a variety of pesticides.
Velmurugan, G. et al. Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis. Genome Biol. 18, 8 (2017).
Aitbali, Y. et al. Glyphosate based-herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice. Neurotoxicol Teratol. 67, 44–49 (2018).
Mesnage, R. et al. Use of shotgun metagenomics and metabolomics to evaluate the impact of glyphosate or roundup MON 52276 on the gut microbiota and serum metabolome of sprague-dawley rats. Environ. Health Perspect. 129, 017005 (2021).
Gushgari, A. J. & Halden, R. U. Critical review of major sources of human exposure to N-nitrosamines. Chemosphere 210, 1124–1136 (2018).
Bharate, S. S. Critical analysis of drug product recalls due to nitrosamine impurities. J. Med. Chem. 64, 2923–2936 (2021).
FDA. Information about Nitrosamine Impurities in Medications https://www.fda.gov/drugs/drug-safety-and-availability/information-about-nitrosamine-impurities-medications#:~:text=Nitrosamine%20impurities%20may%20increase%20the,an%20increased%20risk%20of%20cancer (2021).
Ha, W. S., Kim, C. K., Song, S. H. & Kang, C. B. Study on mechanism of multistep hepatotumorigenesis in rat: development of hepatotumorigenesis. J. Vet. Sci. 2, 53–58 (2001).
Lijinsky, W. & Reuber, M. D. Dose-response study with N-nitrosodiethanolamine in F344 rats. Food Chem. Toxicol. 22, 23–26 (1984).
Alshannaq, A. & Yu, J. H. Occurrence, toxicity, and analysis of major mycotoxins in food. Int. J. Environ. Res. Public Health 14, 632 (2017).
Eskola, M. et al. Worldwide contamination of food-crops with mycotoxins: Validity of the widely cited ‘FAO estimate’ of 25%. Crit. Rev. Food Sci. Nutr. 60, 2773–2789 (2020).
Guo, M. et al. Combination of metagenomics and culture-based methods to study the interaction between ochratoxin A and gut microbiota. Toxicol. Sci. 141, 314–323 (2014).
Vignal, C. et al. Chronic ingestion of deoxynivalenol at human dietary levels impairs intestinal homeostasis and gut microbiota in mice. Arch. Toxicol. 92, 2327–2338 (2018).
Giambò, F. et al. Influence of toxic metal exposure on the gut microbiota (Review). World Acad. Sci. J. https://doi.org/10.3892/wasj.2021.90 (2021).
Zackular, J. P. et al. Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. Nat. Med. 22, 1330–1334 (2016).
EFSA. Report for 2018 on the results from the monitoring of veterinary medicinal product residues and other substances in live animals and animal products. EFSA https://doi.org/10.2903/sp.efsa.2020.en-1775 (2020).
Roca-Saavedra, P. et al. Food additives, contaminants and other minor components: effects on human gut microbiota-a review. J. Physiol. Biochem. 74, 69–83 (2018).
Maier, L. et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature 555, 623–628 (2018). Systematic growth screen of 40 bacterial strains against 1,197 drugs showing growth inhibitory effects of host-targeted drugs.
Cabreiro, F. et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228–239 (2013). Experimental study in worm model that demonstrates the effect of metformin on the host mediated by changes in native microbial metabolism affected by the drug.
Grimsey, E. M. et al. Chlorpromazine and amitriptyline are substrates and inhibitors of the AcrB multidrug efflux pump. mBio 11, e00465–20 (2020).
Lu, Q.-Y. et al. Prebiotic potential and chemical composition of seven culinary spice extracts. J. Food Sci. 82, 1807–1813 (2017).
Pan, H., Feng, J., He, G.-X., Cerniglia, C. E. & Chen, H. Evaluation of impact of exposure of Sudan azo dyes and their metabolites on human intestinal bacteria. Anaerobe 18, 445–453 (2012).
Crudo, F. et al. In vitro interactions of Alternaria mycotoxins, an emerging class of food contaminants, with the gut microbiota: a bidirectional relationship. Arch. Toxicol. 95, 2533–2549 (2021).
Tian, Y. et al. Metabolic impact of persistent organic pollutants on gut microbiota. Gut Microbes 12, 1848209 (2020).
Klünemann, M. et al. Bioaccumulation of therapeutic drugs by human gut bacteria. Nature 597, 533–538 (2021). Mechanistic study demonstrating bioaccumulation of human-targeted drugs by gut bacteria.
Frame, L. A., Costa, E. & Jackson, S. A. Current explorations of nutrition and the gut microbiome: a comprehensive evaluation of the review literature. Nutr. Rev. 78, 798–812 (2020).
Ruiz-Ojeda, F. J., Plaza-Díaz, J., Sáez-Lara, M. J. & Gil, A. Effects of sweeteners on the gut microbiota: a review of experimental studies and clinical trials. Adv. Nutr. 10, S31–S48 (2019).
González, T. D. J. B., Zuidema, T., Bor, G., Smidt, H. & van Passel, M. W. Study of the aminoglycoside subsistence phenotype of bacteria residing in the gut of humans and zoo animals. Front. Microbiol. 6, 1550 (2016).
Xin, Z. et al. Isolation, identification and characterization of human intestinal bacteria with the ability to utilize chloramphenicol as the sole source of carbon and energy. FEMS Microbiol. Ecol. 82, 703–712 (2012).
Taguer, M. & Maurice, C. The complex interplay of diet, xenobiotics, and microbial metabolism in the gut: Implications for clinical outcomes. Clin. Pharmacology Therapeutics 99, 588–599 (2016).
Pryor, R. et al. Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy. Cell 178, 1299–1312.e29 (2019).
Anwar, S. et al. Trigonelline inhibits intestinal microbial metabolism of choline and its associated cardiovascular risk. J. Pharm. Biomed. Anal. 159, 100–112 (2018).
Mirzaei, M. K. & Maurice, C. F. Ménage à trois in the human gut: interactions between host, bacteria and phages. Nat. Rev. Microbiol. 15, 397–408 (2017).
Sutcliffe, S. G., Shamash, M., Hynes, A. P. & Maurice, C. F. Common oral medications lead to prophage induction in bacterial isolates from the human gut. Viruses 13, 455 (2021). Screen of five drugs against eight gut bacterial strains showing that medications can cause prophage induction.
Viennois, E. et al. Dietary emulsifiers directly impact adherent-invasive E. coli gene expression to drive chronic intestinal inflammation. Cell Rep. 33, 108229 (2020).
Collins, J. et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature 553, 291–294 (2018).
Shil, A. & Chichger, H. Artificial sweeteners negatively regulate pathogenic characteristics of two model gut bacteria, E. coli and E. faecalis. Int. J. Mol. Sci. 22, 5228 (2021).
Chhabra, R. S. Intestinal absorption and metabolism of xenobiotics. Env. Health Perspect. 33, 61–69 (1979).
Scott, T. A. et al. Host-microbe co-metabolism dictates cancer drug efficacy in C. elegans. Cell 169, 442–456.e418 (2017).
García-González, A. P. et al. Bacterial metabolism affects the C. elegans response to cancer chemotherapeutics. Cell 169, 431–441.e8 (2017).
Md Masud Parvez, A. B. et al. Quantitative investigation of irinotecan metabolism, transport, and gut microbiome activation. Drug Metab. Dispos. 49, 683–693 (2021).
Geller, L. T. et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357, 1156–1160 (2017).
Artacho, A. et al. The pretreatment gut microbiome is associated with lack of response to methotrexate in new-onset rheumatoid arthritis. Arthritis Rheumatol. 73, 931–942 (2021).
Gratz, S. W. et al. Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro. Mol. Nutr. Food Res. https://doi.org/10.1002/mnfr.201600680 (2017).
Daud, N. et al. Prevalent human gut bacteria hydrolyse and metabolise important food-derived mycotoxins and masked mycotoxins. Toxins 12, 654 (2020).
He, Z. et al. Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23. Cell Metab. 33, 1358–1371.e55 (2021). Demonstration of the contribution of microbial metabolism of widely used food colorants to a common gastrointestinal disease.
Shimada, T. & Fujii-Kuriyama, Y. Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1. Cancer Sci. 95, 1–6 (2004).
Van de Wiele, T. et al. Human colon microbiota transform polycyclic aromatic hydrocarbons to estrogenic metabolites. Environ. Health Perspect. 113, 6–10 (2005).
Goodson, W. H. et al. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women. Carcinogenesis 32, 1724–1733 (2011).
Sauer, S. J. et al. Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor-negative inflammatory breast cancer cells. Carcinogenesis 38, 252–260 (2017).
Brochado, A. R. et al. Species-specific activity of antibacterial drug combinations. Nature 559, 259–263 (2018).
Maier, L. et al. Unravelling the collateral damage of antibiotics on gut bacteria. Nature 599, 120–124 (2021).
Farha, M. A. & Brown, E. D. Chemical probes of escherichia coli uncovered through chemical-chemical interaction profiling with compounds of known biological activity. Chem. Biol. 17, 852–862 (2010).
Erickson, T. B. et al. “Waste not, want not” — leveraging sewer systems and wastewater-based epidemiology for drug use trends and pharmaceutical monitoring. J. Med. Toxicol. 17, 397–410 (2021).
Zeng, X. et al. MASI: microbiota–active substance interactions database. Nucleic Acids Res. 49, D776–D782 (2021).
Aziz, R. K., Saad, R. & Rizkallah, M. R. PharmacoMicrobiomics or how bugs modulate drugs: an educational initiative to explore the effects of human microbiome on drugs. BMC Bioinformatics 12, A10 (2011).
Lynch, S. V., Ng, S. C., Shanahan, F. & Tilg, H. Translating the gut microbiome: ready for the clinic? Nat. Rev. Gastroenterol. Hepatol. 16, 656–661 (2019).
Taroncher-Oldenburg, G. et al. Translating microbiome futures. Nat. Biotechnol. 36, 1037–1042 (2018).
Liu, X. et al. Magnetic living hydrogels for intestinal localization, retention, and diagnosis. Adv. Funct. Mater. 31, 2010918 (2021).
Mark Mimee, P. N. et al. An ingestible bacterial-electronic system to monitor gastrointestinal health. Science 360, 915–918 (2018).
A.E.L. is supported by the Health Protection Research Unit in Chemical and Radiation Threats and Hazards, funded by the National Institute for Health Research (NIHR). K.R.P. and A.E.L. acknowledge funding by UK Medical Research Council (project no. MC_UU_00025/11). M.Z.-K. is supported by the postdoctoral fellowship from the AXA Research Fund. U. Hofer is acknowledged for helpful comments on the manuscript.
K.R.P. and M. Z.-K. are inventors in patent applications related to the findings and concepts discussed in this review (K.R.P.: US patent application numbers 16966307 and 16966322; M. Z.-K.: US patent application number 17257394). A.E.L. declares no competing interests.
Peer review information
Nature Reviews Microbiology thanks Filipe Cabreiro, Benoit Chassaing and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The human gut microbiota can be considered as an organ or supra-organ as it is essential for a wide range of functions, from digestion to immune modulation, and is thus fundamental to the host physiology.
- Precision medicine
A medicinal approach whereby molecular data is used to make an optimal choice regarding therapeutic intervention in an individualized or in a stratified manner.
Compounds foreign to the human body, including drugs, pollutants, toxins, and food additives and contaminants. It has been suggested that, throughout a lifetime, an individual is exposed to around 10,000 to 100,000 different xenobiotics at varying concentrations.
- Second liver
The gut microbiota is often also referred to as second liver, as it is involved in metabolic processes and can contribute to biotransformation of xenobiotics.
- Alpha diversity
The diversity of microbial species/strains within an individual microbiota or within an individual sample.
- Glucose tolerance
The ability of our bodies to deal with a glucose load to keep our blood glucose levels stable.
Essential components of food used for the growth and/or maintenance of the constituents of the body; the main macronutrients are proteins, carbohydrates and lipids.
Chemical elements essential for healthy growth and development, albeit required only in trace amounts, such as vitamins or minerals.
An imbalance in the composition of the gut microbial strains contributing to a disease state or undesirable symptoms.
- Food contact material
Materials that are intended to be in contact with food such as packaging and cooking utensils.
A set of small molecules, or metabolites, that are present extracellularly.
Phages (or bacteriophages) are viruses that can infect bacteria. Most phages in the gut replicate through incorporation of the phage genome into the bacterial genome, leading to the formation of latent prophages. Stress, such as DNA-damage or xenobiotic exposure, can induce prophages into the virulent stage, leading to viral replication and cell lysis.
About this article
Cite this article
Lindell, A.E., Zimmermann-Kogadeeva, M. & Patil, K.R. Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota. Nat Rev Microbiol 20, 431–443 (2022). https://doi.org/10.1038/s41579-022-00681-5
Frontiers of Environmental Science & Engineering (2022)