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

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

doi:10.33073/pjm-2026-016

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

Polish Journal of Microbiology

Volume 75 (2026): Issue 2 (June 2026)

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

Open Access

|Jun 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.

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Articles in this issue

DOI: https://doi.org/10.33073/pjm-2026-016 | Journal eISSN: 2544-4646 | Journal ISSN: 1733-1331

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Language: English

Page range: 168 - 194

Submitted on: Dec 25, 2025

Accepted on: Apr 22, 2026

Published on: Jun 30, 2026

Published by: Polish Society of Microbiologists

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

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Microbiology and virology

© 2026 Fang Liang, Jing Li, Yingkun Yue, Jiaxin Pan, Chenyu Liu, Duo Cheng, Nan Zhang, Kunkun Li, Feifei Chu, Huili Wu, published by Polish Society of Microbiologists
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Volume 75 (2026): Issue 2 (June 2026)