Department of Chemistry, University of North Carolina at Chapel Hill, 250 Bell Tower Drive, Chapel Hill, NC, 27599, USA.
Kasturba Medical College, Tiger Circle Road, Madhav Nagar, Manipal, Karnataka, 576104, India.
Dig Dis Sci. 2020 Mar;65(3):874-884. doi: 10.1007/s10620-020-06119-3.
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.
肠道微生物组编码了巨大的代谢潜力,多学科的方法正在使我们能够从机制上理解细菌酶如何影响各种药物化合物(包括化疗药物)的代谢。微生物组通过直接和间接机制改变许多药物和化疗药物的活性;其中一些改变导致药物的生物活性和生物利用度发生变化,从而引起胃肠道毒性副作用。胃肠道毒性是全身化疗的主要并发症之一,其症状包括恶心、呕吐、腹泻和便秘。为了管理这些不良反应,患者需要减少剂量或暂停用药,这会严重影响预后,并可能导致死亡。选择性和精确靶向肠道微生物组可能会减轻这些毒性。了解微生物组的组成和功能可以作为预后的生物标志物,并预测治疗效果和潜在的不良反应,从而为癌症患者提供个性化的医学策略。