Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype

Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype

Summary: Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome’s role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Cell Reports
Subjects:
CP: Microbiology
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725003602
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Summary:Summary: Immunotherapy has revolutionized cancer treatment, but response variability remains a challenge. The gut microbiome’s role in therapeutic efficacy is well established, but the impact of the gut mycobiome is less understood. Using unsupervised clustering, we identify two gut mycobiome-based enterotypes, favorable type and unfavorable type, characterized by distinct microbial compositions linked to immunotherapy outcomes. Favorable-type enterotypes exhibit higher fungal and bacterial alpha diversity, enriched butyrate-producing bacteria, and metabolic pathways related to butyric acid and sugar/starch metabolism. External validation confirms their predictive value in assessing immunotherapy efficacy. Multi-omics analysis reveals increased CD8+ T cell infiltration in the tumor microenvironment of favorable-type patients. Fecal microbiota transplantation (FMT) from favorable-type donors enhances anti-PD-1 sensitivity, promotes CD8+ T cell infiltration, and boosts butyrate production in vivo. These findings highlight the gut mycobiome’s role in immunotherapy response and support FMT from favorable-type donors as a potential strategy for improving treatment outcomes and patient stratification.
ISSN:2211-1247

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