• MILESTONES

The microbiota influences metabolism of host-directed drugs

Credit: G. Marshall / Springer Nature Limited

Peppercorn and Goldman demonstrated that the anti-inflammatory drug, salicylazosulfapyridine, could be degraded in conventional rats and when cultured with human gut bacteria, but not in germ-free rats, indicating a role for the gut microbiota in drug transformations. An increasing number of studies have confirmed the role of the microbiota, not limited to the gut, in drug metabolism and highlighted the implications for drug inactivation, efficacy and toxicity.

Further reading

Clayton, T. A. et al. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc. Natl Acad. Sci. USA 106, 14728–14733 (2009).

Lindenbaum, J., Rund, D. G., Butler, V. P. J., Tse-Eng, D. & Saha, J. R. Inactivation of digoxin by the gut flora: reversal by antibiotic therapy. N. Eng. J. Med. 305, 789–794 (2010).

Wallace, B. D. et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330, 831–835 (2010).

Haiser, H. J. et al. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science 341, 295–298 (2013).

Liang, X. et al. Bidirectional interactions between indomethacin and the murine intestinal microbiota. eLife 4, e08973 (2015).

Klatt, N. R. et al. Vaginal bacteria modify HIV tenofovir microbicide efficacy in African women. Science 356, 938–945 (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).

Spanogiannopoulos, P., Bess, E. N., Carmody, R. N. & Turnbaugh, P. J. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat. Rev. Microbiol. 14, 273–287 (2016).

Koppel, N., Maini Rekdal, V. & Balskus, E. P. Chemical transformation of xenobiotics by the human gut microbiota. Science 356, eaag2770 (2017).

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