Faecalibacterium prausnitzii‐derived microbial anti‐inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression

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.

Dysbiosis of Gut Microbiota and Short-Chain Fatty Acids in Encephalitis: A Chinese Pilot Study

“…We observed enrichment of disease-promoting pathogens, such as the family Enterobacteriaceae ( 30 ), in encephalitis patients. Conversely, some taxa that were depleted in the patient group, such as the genus Faecalibacterium , were previously believed to confer antiinflammatory benefits ( 31 ). These findings likely reflect numerous variables, including derangements in host physiology, multiple treatment exposures, and the presence of nosocomial pathogens.…”

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

“…Interestingly, the reversal of hyperglycemia, conditional deletion of GLUT2 from the IECs and inhibition of glucose metabolism will fix the barrier dysfunction and prevent the spread of bacteria (76). Xu et al have shown that Faecalibacterium prausnitzii, one of the most frequent commensal bacteria in normal individuals with essential roles in gut homeostasis, generates anti-inflammatory molecules that enhance the expression of tight junctions and improve intestinal integrity during diabetes (77). However, in some cases, gut microbiota dysbiosis or altered microbial composition of the intestines could induce T2DM and lead to its progression (78).…”

Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity

“…Multiple lines of investigation have suggested that epithelial barrier dysfunction may result from the loss of beneficial species due to intestinal dysbiosis. In db/db mice that spontaneously develop type 2 diabetes, epithelial dysfunction is accompanied by underrepresentation of the major butyrate producer, Faecalibacterium prausnitzii (76). F. prausnitzii is also nearly absent from Crohn's disease-associated gut microbiota (63,77).…”