Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype
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<sup>+</sup> 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<sup>+</sup> 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.
Authors
- Jing‐Yuan Fang (ORCID: https://orcid.org/0000-0003-2282-0248)
- Yilu Zhou (ORCID: https://orcid.org/0000-0002-4090-099X)
- Baoqin Xuan
- Jie Hong (ORCID: https://orcid.org/0000-0001-9579-0794)
- Jinmei Ding
- Xiaoqiang Zhu (ORCID: https://orcid.org/0000-0001-7486-0853)
- Lingxi Li (ORCID: https://orcid.org/0000-0002-9471-9774)
- Xiuying Xiao (ORCID: https://orcid.org/0000-0002-9873-0380)
- Haoyan Chen (ORCID: https://orcid.org/0000-0001-6722-8534)
- Yanru Ma
- Lijun Ning (ORCID: https://orcid.org/0000-0001-7646-1784)
- Xiaowen Huang (ORCID: https://orcid.org/0000-0001-6323-7070)
- Huimin Chen (ORCID: https://orcid.org/0009-0005-8628-2946)
- Hao‐Li Zhang (ORCID: https://orcid.org/0000-0002-6322-5202)
- Hua Li (ORCID: https://orcid.org/0000-0003-4205-7518)
- Zhenyu Wang (ORCID: https://orcid.org/0000-0002-7884-732X)
- Ying Zhao (ORCID: https://orcid.org/0000-0002-7927-4906)
- Xiao Lin (ORCID: https://orcid.org/0000-0002-8805-7129)
- Jiantao Li (ORCID: https://orcid.org/0000-0003-0596-8902)
- Youwei Zhang (ORCID: https://orcid.org/0000-0001-9374-329X)
- Yi Jiang (ORCID: https://orcid.org/0000-0003-0825-6409)
- Ye Hu (ORCID: https://orcid.org/0000-0001-7255-5409)
- Tianying Tong
- Muni Hu
- Yue Zhang (ORCID: https://orcid.org/0000-0002-7786-0231)
Institutions
- Xuzhou Medical College (CN)
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- XinHua Hospital (CN)
- Shanghai Chest Hospital (CN)
- Shanghai Cancer Institute (CN)
- Xuzhou Central Hospital (CN)
- Shanghai Institute of Hematology (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-20
- DOI
- https://doi.org/10.1016/j.celrep.2025.115589
- Citations
- 9
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 7.25