Fungal dysbiosis facilitates inflammatory bowel disease by enhancing CD4+ T cell glutaminolysis

Minhao Yu; Hui Ding; Shuai Gong; Yang Luo; Haiping Lin; Yifei Mu; Hao Li; Xiaobo Li; Ming Zhong

doi:10.3389/fcimb.2023.1140757

Fungal dysbiosis facilitates inflammatory bowel disease by enhancing CD4+ T cell glutaminolysis

Front Cell Infect Microbiol. 2023 Apr 14:13:1140757. doi: 10.3389/fcimb.2023.1140757. eCollection 2023.

Authors

Minhao Yu¹, Hui Ding^{2

3}, Shuai Gong^{2

3}, Yang Luo¹, Haiping Lin¹, Yifei Mu¹, Hao Li¹, Xiaobo Li^{2

3}, Ming Zhong¹

Affiliations

¹ Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Shanghai Institute of Digestive Disease, National Health Commission (NHC) Key Laboratory of Digestive Diseases, Shanghai, China.

Abstract

The fungal microbiota is an important component of the complex multikingdom microbial community colonizing the mammalian gastrointestinal tract and has an important role in immune regulation. However, how fungi regulate inflammatory bowel disease (IBD) is poorly understood. This study found that intestinal fungi regulate immune responses in IBD. Antibiotic-mediated depletion of fungi facilitated the development of IBD. Fungi greatly enhanced oxidative phosphorylation (OXPHOS) by enhancing glutaminolysis. Mechanistically, we found that fungi could activate the dectin-1-Syk- NF-κB signaling pathway to promote the expression of key enzymes and transporters involved in glutaminolysis. In summary, our findings reveal that fungal interactions in the human gut could be a promising therapeutic target for IBD.

Keywords: CD4 T cell +; IBD - inflammatory bowel disease; fungi - fungi interactions; glutaminolysis; oxidative phosphorylation (OXPHOS).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes
Dysbiosis* / microbiology
Fungi
Gastrointestinal Microbiome*
Humans
Inflammatory Bowel Diseases* / microbiology
Mammals

Grants and funding

This work was supported by the National Natural Science Foundation of China (81873555) and Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University (YG2021QN29).