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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Elsevier
2025-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725003602 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Muni Hu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-aa85d1e785b943888a24bd3d94e15c29 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-aa85d1e785b943888a24bd3d94e15c292025-08-20T02:12:19ZengElsevierCell Reports2211-12472025-05-0144511558910.1016/j.celrep.2025.115589Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotypeMuni Hu0Xiaoqiang Zhu1Xiaowen Huang2Li Hua3Xiaolin Lin4Hangyu Zhang5Ye Hu6Tianying Tong7Lingxi Li8Baoqin Xuan9Ying Zhao10Yilu Zhou11Jinmei Ding12Yanru Ma13Yi Jiang14Lijun Ning15Yue Zhang16Zhenyu Wang17Jing-Yuan Fang18Youwei Zhang19Xiuying Xiao20Jie Hong21Huimin Chen22Jiantao Li23Haoyan Chen24State Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, China; Baoshan Branch, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200444, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDepartment of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaDepartment of Gastroenterology, Shanghai Jiaotong University School of Medicine Xinhua Hospital, Shanghai, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaDepartment of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou 221009, ChinaSchool of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, ChinaState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, China; Corresponding authorShanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Corresponding authorState Key Laboratory of Systems Medicine for Cancer, NHC Key Laboratory of Digestive Diseases, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai Cancer Institute, Shanghai 200001, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725003602CP: Microbiology |
| spellingShingle | 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 Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype Cell Reports CP: Microbiology |
| title | Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype |
| title_full | Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype |
| title_fullStr | Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype |
| title_full_unstemmed | Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype |
| title_short | Optimizing anti-PD-1/PD-L1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome-based enterotype |
| title_sort | optimizing anti pd 1 pd l1 therapy efficacy and fecal microbiota transplantation donor selection through gut mycobiome based enterotype |
| topic | CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725003602 |
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