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Distinct Gut Microbiome and Metabolome Profiles Associate with Differential Responses to Immunotherapy in Colorectal Cancer.

Created on 06 Aug 2026

Authors

Fang Liang, Jing Li, Yingkun Yue, Jiaxin Pan, Chenyu Liu, Duo Cheng, Nan Zhang, Kunkun Li, Feifei Chu, Huili Wu

Published in

Polish journal of microbiology. Volume 75. Issue 2. Pages 168-194. Jun 01, 2026. Epub Jun 30, 2026.

Abstract

The composition of the intestinal microbiome has been identified as a key factor influencing the efficacy of immune checkpoint inhibitors. This study aimed to systematically evaluate the potential associations among gut microbiota, metabolic profiles, and clinical outcomes in patients with MSI-H advanced colorectal cancer (CRC) treated with immunotherapy. Twenty advanced CRC patients receiving immunotherapy were enrolled and categorized into clinical benefit response (CBR) and non-benefit (NCB) groups based on treatment efficacy. Fecal samples were analyzed using metagenomic sequencing and untargeted metabolomics. The results revealed significant enrichments of s_Clostridium unclassified and metabolites such as guanosine, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, and quercetin 3-(6"-malonyl-glucoside) in the CBR group, suggesting their potential positive predictive value for immunotherapy response. Conversely, the NCB group showed significant enrichments of s_Roseburia hominis, s_Marseilla massiliensis, and metabolites including pyrophosphate, riboflavin, and PC(22:5(4Z,7Z,10Z,13Z,16Z)/14:0), indicating a possible association with treatment resistance. By integrating fecal metagenomics and metabolomics, this study reveals distinctive "flora-metabolite" interactions linked to therapeutic response in advanced CRC patients undergoing immunotherapy. Specific microbial and metabolic profiles were positively or negatively correlated with immunotherapy outcomes, highlighting their potential not only as predictive biomarkers but also as a theoretical foundation for developing individualized immunotherapy strategies based on microecological modulation.

PMID:
42560299
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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