Multi-kingdom gut microbiota analyses define bacterial-fungal interplay and microbial markers of pan-cancer immunotherapy across cohorts

Xiaowen Huang¹, Muni Hu¹, Tiantian Sun¹, Jiantao Li², Yilu Zhou¹, Yuqing Yan¹, Baoqin Xuan¹, Jilin Wang¹, Hua Xiong¹, Linhua Ji³, Xiaoqiang Zhu¹, Tianying Tong¹, Lijun Ning¹, Yanru Ma¹, Ying Zhao¹, Jinmei Ding¹, Zhigang Guo⁴, Youwei Zhang⁵, Jing-Yuan Fang¹, Jie Hong⁶, Haoyan Chen⁷

Affiliations

¹ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
² Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
⁴ Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
⁵ Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou, China.
⁶ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Electronic address: jiehong97@sjtu.edu.cn.
⁷ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Electronic address: haoyanchen@sjtu.edu.cn.

PMID: 37944495
DOI: 10.1016/j.chom.2023.10.005

Free article

Multi-kingdom gut microbiota analyses define bacterial-fungal interplay and microbial markers of pan-cancer immunotherapy across cohorts

Xiaowen Huang et al. Cell Host Microbe. 2023.

Free article

. 2023 Nov 8;31(11):1930-1943.e4.

doi: 10.1016/j.chom.2023.10.005.

Authors

Affiliations

¹ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China.
² Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
⁴ Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
⁵ Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou, China.
⁶ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Electronic address: jiehong97@sjtu.edu.cn.
⁷ State Key Laboratory of Systems Medicine for Cancer, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, Shanghai, China. Electronic address: haoyanchen@sjtu.edu.cn.

PMID: 37944495
DOI: 10.1016/j.chom.2023.10.005

Abstract

The effect of gut bacteria on the response to immune checkpoint inhibitors (ICIs) has been studied, but the relationship between fungi and ICI responses is not fully understood. Herein, 862 fecal metagenomes from 9 different cohorts were integrated for the identification of differentially abundant fungi and subsequent construction of random forest (RF) models to predict ICI responses. Fungal markers demonstrate excellent performance, with an average area under the curve (AUC) of 0.87. Their performance improves even further, reaching an average AUC of 0.89 when combined with bacterial markers. Higher enrichment of exhausted T cells is detected in responders, as predicted by fungal markers. Multi-kingdom network and functional analysis reveal that the fungus Schizosaccharomyces octosporus may ferment starch into short-chain fatty acids in responders. This study provides a fungal profile of the ICI response and the identification of multi-kingdom microbial markers with good performance that may improve the overall applicability of ICI therapy.

Keywords: bacteria; fungi; immunotherapy; metagenome; multi-kingdom; pan-cancer.

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Declaration of interests The authors declare no competing interests.

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Multi-kingdom gut microbiota analyses define bacterial-fungal interplay and microbial markers of pan-cancer immunotherapy across cohorts

Affiliations

Multi-kingdom gut microbiota analyses define bacterial-fungal interplay and microbial markers of pan-cancer immunotherapy across cohorts

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Medical