Table_6_Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors.xlsx

IntroductionThe wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.
MethodsIn this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.
ResultsIn summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.

引言：免疫检查点抑制剂（immune checkpoint inhibitors）的广泛应用显著提升了癌症患者的生存预期。免疫治疗在为患者带来临床获益的同时，也会引发一系列免疫相关不良事件（immune-related adverse events，irAEs）。越来越多的研究证据表明，肠道菌群对免疫治疗应答以及irAEs的发生发展至关重要。
研究方法：本前瞻性研究共纳入95例接受免疫治疗的晚期/不可切除胃肠道癌症患者，针对肠道菌群与irAEs的关联开展了全面分析。采用宏基因组测序（metagenome sequencing）技术，对受试者的基线粪便样本进行细菌组成与代谢通路差异分析。
研究结果：本研究明确了胃癌、食管癌及结肠癌患者中与irAEs发生相关的细菌物种与代谢通路。在未发生严重irAEs的患者体内，瘤胃球菌（Ruminococcus callidus）与解木聚糖拟杆菌（Bacteroides xylanisolvens）呈富集状态。多条参与尿素循环的微生物代谢通路（包括瓜氨酸与精氨酸生物合成）与irAEs存在关联。此外我们还发现，不同癌症类型的irAEs、特定器官及内分泌系统毒性，分别对应不同的肠道菌群特征。本研究结果为后续的机制探索提供了重要依据。