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Metabolic engineering of commensal bacteria for gut butyrate delivery and dissection of host-microbe interaction

Metab Eng . . 2023-09; 
Xu Gong , Hongwei Geng , Yun Yang , Shuyi Zhang , Zilong He , Yubo Fan , Fengyi Yin , Zhifa Zhang , Guo-Qiang Chen
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Gene Synthesis Heterologous genes were codonoptimized and synthesized under the control of Pfnrs promoter in pYYD (Yang et al., 2015) plasmids by GenScript (Nanjing, China), including phaA from Cupriavidusnecator (Uniprot Entry P14611), thil from C. acetobutylicum (Uniprot Entry Q7DFN1), thl from C. tyrobutyricum (Uniprot Entry E3VJQ0), hbd-crt from Clostridium acetobutylicum (Uniprot Entry P52041, P52046), hbd-crt from Clostridium tyrobutyricum (Uniprot Entry W6N632, W6NI97), phaB from Chromatiurn vinosum (Liebergesell and Steinbüchel, 1992), phaB from Halomonas bluephagenesis (Ling et al., 2018), phaJ from Aeromonas caviae (Uniprot Entry O32472), ter from Treponema denticola (Uniprot Entry Q73Q47), ptb-buk from Bacillus subtilis (Uniprot Entry P54530, P54532), ptb from C. acetobutylicum (Uniprot Entry P58255), buk1 from C. acetobutylicum (Uniprot Entry Q45829) and buk2 from C. acetobutylicum (Uniprot Entry Q97II1). Get A Quote

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 intestin... More

Keywords

Butyrate; Colitis; Engineered bacteria; In situ delivery; Pyroptosis.