Chemotherapy drugs induce different gut microbiota disorder pattern and NODs/RIP2/NF-kB signaling pathway activation that lead to different degrees of intestinal injury

The chemotherapy-induced intestinal injury limit drugs clinical use. Intestinal injury involves multiple signaling pathways and the disruption of microbiota. Our results suggest that the degree of intestinal injury caused by different drugs of the first-line colorectal chemotherapy regimen is related to the change pattern of microbiota. We found L-OHP caused the most severe change of gut microbiota, and showed considerable overlap of the microbiota changes pattern with 5-FU and CPT-11, which may provide a new basis for further elucidating the mechanism and clinical treatment of intestinal injury caused by chemotherapy.

化疗诱导的肠损伤制约了相关化疗药物的临床应用。肠损伤涉及多条信号通路的异常以及微生物群稳态的失衡。本研究结果表明，结直肠癌一线化疗方案中不同药物所致的肠损伤程度，与肠道微生物群的变化模式存在显著关联。我们发现，奥沙利铂（L-OHP）引发的肠道菌群变化最为剧烈，且其菌群变化模式与氟尿嘧啶（5-FU）、伊立替康（CPT-11）存在较高的重叠性；该发现可为进一步阐明化疗诱导肠损伤的分子机制与临床治疗方案提供全新的理论基础。