Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction.
Metab Eng
; 80: 94-106, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37717646
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.
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MEDLINE
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Colite
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Microbioma Gastrointestinal
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article