抗代謝薬の腸内細菌叢および代謝産物相互作用の探索による治療の最適化
Jingyang Chen1,2, Yanan Wang1,2, Lei Xu1,2
1Department of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Abstract:
Antimetabolite drugs are cornerstones in treating various cancers and autoimmune diseases; however, their clinical utility is often hampered by systemic toxicity caused by drug-induced gut microbiota dysbiosis. Predicting patient responses remains a significant challenge. Several studies have highlighted the influence of gut microbiota on antimetabolite treatment outcomes, revealing complex bidirectional interactions between the drugs and microbial communities. This review synthesizes the effects of common antimetabolites (including 5-fluorouracil, methotrexate, gemcitabine, capecitabine, 6-mercaptopurine, and thioguanine) on gut microbial communities and outlines a framework (pharmacokinetics, endogenous metabolite production, immune modulation, and apoptotic pathway modulation) for assessing chemotherapy-microbiota interactions. Additionally, potential microbial biomarkers for predicting treatment responses and strategies for manipulating the gut microbiota to enhance therapeutic efficacy are discussed. Therefore, advances in methodologies such as metagenomics and real-time microbial monitoring will be essential for unraveling these interactions and promoting the precise application of antimetabolite drugs.
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