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

真菌失调通过增强 CD4+ T 细胞谷氨酰胺分解促进炎症性肠病

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

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.

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