Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors - Original Research

Sep 24, 2026

Upload by Ivy

Immune checkpoint inhibitors improve survival in gastrointestinal cancer but trigger immune-related adverse events (irAEs). This prospective study analyzes whether gut microbiome features relate to irAEs in 95 patients with advanced or unresectable gastrointestinal cancers. Baseline fecal metagenome sequencing identifies differences in bacterial composition and metabolic pathways. Enriched taxa, urea-cycle related metabolism, and distinct organ or endocrine toxicity patterns associate with irAEs, providing a foundation for future mechanistic work and prediction.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Background and clinical need for predicting irAEs

Methods

Prospective cohort and metagenome sequencing approach

Results

Taxa and metabolic pathways linked to irAEs

Links across cancer types and organ/endocrine toxicities

TYPE Original Research PUBLISHED 03 March 2023 DOI 10.3389/fcimb.2023.1099063 OPEN ACCESS EDITED BY Yolanda Lo´ pez-Vidal, Faculty of Medicine, National Autonomous University of Mexico, Mexico REVIEWED BY Tatiana V. Karpinets, University of Texas MD Anderson Cancer Center, United States Jessica Galloway-Pena, Texas A&M University, United States Satoshi Shiba, National Cancer Center Research Institute, Japan *CORRESPONDENCE Lin Shen [linshenpku@163.com](linshenpku@163.com)[ ](linshenpku@163.com)Zhi Peng [zhipeng@bjmu.edu.cn](zhipeng@bjmu.edu.cn) †These authors have contributed equally to this work and share ﬁrst authorship SPECIALTY SECTION This article was submitted to Intestinal Microbiome, a section of the journal Frontiers in Cellular and Infection Microbiology RECEIVED 16 November 2022 ACCEPTED 13 February 2023 PUBLISHED 03 March 2023 CITATION Zhang Y, Cheng S, Zou H, Han Z, Xie T, Zhang B, Dai D, Yin X, Liang Y, Kou Y, Tan Y, Shen L and Peng Z (2023) Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors. Front. Cell. Infect. Microbiol. 13:1099063 . doi: 10.3389/fcimb.2023.1099063 COPYRIGHT © 2023 Zhang, Cheng, Zou, Han, Xie, Zhang, Dai, Yin, Liang, Kou, Tan, Shen and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors Yifan Zhang 1†, Siyuan Cheng 1,2†, Hua Zou 3, Zihan Han 1,4, Tong Xie 1, Bohan Zhang 1, Die Dai 3, Xiaochen Yin 3, Yong Liang 3, Yan Kou 3, Yan Tan 3, Lin Shen 1* and Zhi Peng 1* 1 Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China, 2 Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, China, 3Xbiome, Shenzhen, China, 4 Department of Colorectal Surgery, China-Japan Friendship Hospital, Beijing, China Introduction: The 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. Methods: In 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. Results: In 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. KEYWORDS immune-related adverse event, gut microbiome,

FAQs

What is the purpose of this study?

To determine whether gut microbiome characteristics are associated with immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors.

How were the gut microbiome data collected and analyzed?

Baseline fecal samples were analyzed using metagenome sequencing to compare bacterial composition and metabolic pathways.

Which microbiome findings were associated with irAEs?

Certain bacterial species were enriched in patients without severe irAEs, while urea-cycle related metabolic pathways were associated with irAEs.

Do irAEs differ across cancer types and organs?

Yes. The study reports that irAEs in different cancer types and toxicity in specific organs and the endocrine system correlate with different gut microbiota profiles.

Sep 24, 2026

Upload by Ivy