The intestinal microbiome encodes vast metabolic potential, and multidisciplinary approaches are enabling a mechanistic understanding of how bacterial enzymes impact the metabolism of diverse pharmaceutical compounds, including chemotherapeutics. Microbiota alter the activity of many drugs and chemotherapeutics via direct and indirect mechanisms; some of these alterations result in changes to the drug’s bioactivity and bioavailability, causing toxic gastrointestinal side effects. Gastrointestinal toxicity is one of the leading complications of systemic chemotherapy, with symptoms including nausea, vomiting, diarrhea, and constipation. Patients undergo dose reductions or drug holidays to manage these adverse events, which can significantly harm prognosis, and can result in mortality. Selective and precise targeting of the gut microbiota may alleviate these toxicities. Understanding the composition and function of the microbiota may serve as a biomarker for prognosis, and predict treatment efficacy and potential adverse effects, thereby facilitating personalized medicine strategies for cancer patients.
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We sincerely apologize to colleagues whose work we could not include due to space constraints. SME is supported by funds from National Science Foundation GRFP (DGS-1650116). APB is supported by Pilot and Feasibility funds from P30 DK034987. The authors acknowledge Drs. Seth Crockett and Matthew Redinbo for critical reading of this manuscript.
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Ervin, S.M., Ramanan, S.V. & Bhatt, A.P. Relationship Between the Gut Microbiome and Systemic Chemotherapy. Dig Dis Sci 65, 874–884 (2020). https://doi.org/10.1007/s10620-020-06119-3
- Gastrointestinal toxicity