普拉梭菌活性产物-微生物抗炎分子通过调控细胞紧密连接蛋白表达修复糖尿病小鼠肠道屏障

Translated title of the contribution: Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression

Jihao Xu, Rongrong Liang, Wang Zhang, Kuangyi Tian, Jieyao Li, Xianming Chen, Tao Yu, Qikui Chen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: Impaired intestinal barrier structure and function have been validated as an important pathogenic process in type 2 diabetes mellitus (T2DM). Gut dysbiosis is thought to be the critical factor in diabetic intestinal pathogenesis. As the most abundant commensal bacteria, Faecalibacterium prausnitzii (F. prausnitzii) play important roles in gut homeostasis. The microbial anti-inflammatory molecule (MAM), an F. prausnitzii metabolite, has anti-inflammatory potential in inflammatory bowel disease (IBD). Thus, we aimed to explore the function and mechanism of MAM on the diabetic intestinal epithelium. Methods: 16S high-throughput sequencing was used to analyze the gut microbiota of db/db mice (T2DM mouse model). We transfected a FLAG-tagged MAM plasmid into human colonic cells to explore the protein-protein interactions and observe cell monolayer permeability. For in vivo experiments, db/db mice were supplemented with recombinant His-tagged MAM protein from E. coli BL21 (DE3). Results: The abundance of F. prausnitzii was downregulated in the gut microbiota of db/db mice. Immunoprecipitation (IP) and mass spectroscopy (MS) analyses revealed that MAM potentially interacts with proteins in the tight junction pathway, including zona occludens 1 (ZO-1). FLAG-tagged MAM plasmid transfection stabilized the cell permeability and increased ZO-1 expression in NCM460, Caco2, and HT-29 cells. The db/db mice supplemented with recombinant His-tagged MAM protein showed restored intestinal barrier function and elevated ZO-1 expression. Conclusions: Our study shows that MAM from F. prausnitzii can restore the intestinal barrier structure and function in DM conditions via the regulation of the tight junction pathway and ZO-1 expression.

Translated title of the contributionFaecalibacterium prausnitzii-derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression
Original languageChinese
Pages (from-to)224-236
Number of pages13
JournalJournal of Diabetes
Volume12
Issue number3
DOIs
StatePublished - Mar 1 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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