文献类型：期刊文献

英文题名：Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses

作者：Zhu, Xiaoqiang[1,2];Hu, Muni[1];Huang, Xiaowen[1];Li, Lingxi[1];Lin, Xiaolin[3];Shao, Xiaoyan[4];Li, Jiantao[5];Du, Xiaoyue[6];Zhang, Xinjia[7];Sun, Rongrong[4];Tong, Tianying[1];Ma, Yanru[1];Ning, Lijun[1];Jiang, Yi[1];Zhang, Yue[1];Shao, Yuqi[1];Wang, Zhenyu[1];Zhou, Yilu[1];Ding, Jinmei[1];Zhao, Ying[1];Xuan, Baoqin[1];Zhang, Hongyang[7];Zhang, Youwei[4];Hong, Jie[1];Fang, Jing-Yuan[1];Xiao, Xiuying[3];Shen, Bo[6];He, Songbing[8];Chen, Haoyan[1]

机构：[1]Shanghai Jiao Tong Univ, Renji Hosp, Shanghai Inst Digest Dis, Shanghai Canc Inst,State Key Lab Syst Med Canc,Div, Shanghai, Peoples R China;[2]Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Sch Med, Dept Gastroenterol, Chengdu, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Oncol, Shanghai, Peoples R China;[4]Xuzhou Med Univ, Xuzhou Cent Hosp, Dept Med Oncol, Clin Sch, Xuzhou, Peoples R China;[5]Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai Lung Canc Ctr, Sch Med, Shanghai, Peoples R China;[6]Nanjing Med Univ, Jiangsu Canc Hosp, Jiangsu Inst Canc Res, Dept Oncol,Affiliated Canc Hosp, Nanjing, Peoples R China;[7]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai, Peoples R China;[8]Soochow Univ, Dept Gen Surg, Affiliated Hosp 1, Suzhou, Jiangsu, Peoples R China

年份：2025

卷号：37

期号：4

起止页码：806

外文期刊名：CELL METABOLISM

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001464082100001)】；

基金：The authors are grateful for all the subjects who participated in the study. This work was supported by grants from The National Key Research and Development Plan of the Ministry of Science and Technology (2022YFE0125300) , The National Natural Science Foundation of China (82472886, 82073115, 82230016, 82272979, 82302890, 823B2077, 82272863, 81973346, and 82172892) , The Shanghai Sailing Program (no. 23YF1431400) , Key Medical Disciplines of Jiangsu Province's 14th Five-Year Plan (ZDXK202237) , The Gusu Medical Key Talent Project of Suzhou City of China (GSWS2020005) , The New Pharmaceutics and Medical Apparatuses Project of Suzhou City of China (SLJ2021007) , the Provincial-level Talent Program for National Center of Technology Innovation for Biopharmaceuticals (NCTIB2024JS0101) , and the Sichuan Science and Technology Program (25NSFSC2036) .

语种：英文

摘要：Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.