1. Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction.
- Author
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Gong, Xu, Geng, Hongwei, Yang, Yun, Zhang, Shuyi, He, Zilong, Fan, Yubo, Yin, Fengyi, Zhang, Zhifa, and Chen, Guo-Qiang
- Subjects
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BUTYRATES , *ANAEROBIC bacteria , *BACTERIA , *PYROPTOSIS , *DISSECTION , *COLITIS , *GRAM-negative anaerobic bacteria , *BACTEROIDES fragilis - Abstract
An overwhelming number of studies have reported the correlation of decreased abundance of butyrate-producing commensals with a wide range of diseases. However, the molecular-level mechanisms whereby gut butyrate causally affects the host mucosal immunity and pathogenesis were poorly understood, hindered by the lack of efficient tools to control intestinal butyrate. Here we engineered a facultative anaerobic commensal bacterium to delivery butyrate at the intestinal mucosal surface, and implemented it to dissect the causal role of gut butyrate in regulating host intestinal homeostasis in a model of murine chronic colitis. Mechanistically, we show that gut butyrate protected against colitis and preserved intestinal mucosal homeostasis through its inhibiting effect on the key pyroptosis executioner gasdermin D (GSDMD) of colonic epithelium, via functioning as an HDAC3 inhibitor. Overall, our work presents a new avenue to build synthetic living delivery bacteria to decode causal molecules at the host-microbe interface with molecular-level insights. • Microbiota-derived metabolite butyrate has intimate correlation with diseases. • A probiotic was engineered to delivery butyrate at the intestinal mucosal surface. • Causal role of gut butyrate in regulating host intestinal homeostasis was dissected. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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