文章标题：Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype
作者列表：Muni Hu, Xiaoqiang Zhu, Xiaowen Huang, Li Hua, Xiaolin Lin, Hangyu Zhang, Ye Hu, Tianying Tong, Lingxi Li, Baoqin Xuan, Ying Zhao, Yilu Zhou, Jinmei Ding, Yanru Ma, Yi Jiang, Lijun Ning, Yue Zhang, Zhenyu Wang, Jing-Yuan Fang, Youwei Zhang, Xiuying Xiao, Jie Hong, Huimin Chen, Jiantao Li, Haoyan Chen
发表时间：2025-4-20
期刊：Cell Reports
影响因子：6.9
DOI:10.1016/j.celrep.2025.115589
Abstract
Introduction
Immunotherapy has demonstrated significant success in treating various hematological and metastatic solid malignancies.1,2,3,4 The impact of the gut microbiome on therapeutic responses has been validated through numerous clinical and preclinical trials.5 Ongoing investigations in gut microbiome profiling have opened avenues for its potential as a therapeutic tool or target. The term “gut microbiome” refers to the complex and diverse community of microorganisms, including bacteria, fungi, viruses, and other microbes, that inhabit the gastrointestinal tract of humans. Given the predominant presence of intestinal bacteria, comprising over 99% of the total gut microbiome,6 it has been a subject of profound interest. Research focusing on intestinal bacteria and immunotherapy has expanded, fueled by preclinical experiments affirming the impact of intestinal bacteria and their metabolites on tumor immunity.7,8 Nevertheless, with increasing research, the role of the gut mycobiome in the occurrence, progression, and treatment of diseases is becoming increasingly apparent.9,10,11,12,13 A recent study14 revealed that the gut mycobiome, outperforming its bacterial counterpart, exhibits superior precision in predicting the efficacy of immunotherapy.
Serving as a valuable framework for the exploration of the gut microbiome and its relation to human diseases, enterotypes are defined as distinct clusters or groups of microbial communities present in the human gut microbiome. Introduced initially in 2011, this classification, based on the genus-level analysis of human intestinal bacteria, identified three primary types: Bacteroides, Prevotella, and Ruminococcus.15 Enterotypes are generally considered stable and closely tied to the host’s lifestyle or physiological state.16,17 The majority of research on enterotypes has centered on gut bacteria, but there has also been exploration of fungal and viral communities to enable the categorization of individuals based on specific host phenotypes. In recent times, researchers have classified the human gut mycobiome at the genus level using fecal internal transcribed spacer sequencing data. They identified distinct enterotypes based on the gut mycobiome, revealing correlations with specific diseases and age.18 Additionally, another study indicated that classification of the human gut virome is linked to the therapeutic success of patients with inflammatory bowel disease.19 Hence, the utilization of enterotypes has been instrumental in investigating potential connections between microbial patterns and diverse health conditions.
Here, we utilized a metagenomic analysis pipeline to profile fungus abundance in patients undergoing anti-PD1/PD-L1 immunotherapy following previous studies.20,21 Our initial analysis revealed the presence of two distinct gut mycobiome-based enterotypes (favorable type and unfavorable type) that correlated with the efficacy of immunotherapy. Favorable-type patients harbored higher cytotoxic CD8+ T cell proportions in the TME, as determined by multi-omics data analysis. Noteworthy is the finding that individuals undergoing fecal microbiota transplantation (FMT) from favorable-type donors exhibited an elevated response rate to anti-PD-1/PD-L1 therapy. Our study provides novel insights into the gut mycobiome-based enterotype, presenting possibilities for improving the efficacy of anti-PD-1/PD-L1 immunotherapy and aiding in the identification of optimal FMT donors.
