Protective Effects of a Novel Probiotic Bifidobacterium pseudolongum on the Intestinal Barrier of Colitis Mice via Modulating the Pparγ/STAT3 Pathway and Intestinal Microbiota

新型益生菌伪长双歧杆菌通过调节Pparγ/STAT3通路和肠道菌群对结肠炎小鼠肠道屏障的保护作用

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作者:Weiling Guo, Bingyong Mao, Shumao Cui, Xin Tang, Qiuxiang Zhang, Jianxin Zhao, Hao Zhang

Abstract

Colitis has become a major health concern worldwide. The objective of the present study was to determine the probiotic influence of different strains of B. pseudolongum (Bp7 and Bp8) on alleviating colitis and to explore its possible potential mechanisms. Our results displayed that Bp7 and Bp8 intervention effectively reduced dextran sodium sulfate (DSS)-caused body weight loss and the release of several pro-inflammatory factors (interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α)) and increased the activities of antioxidant enzymes (T-AOC, SOD, and GSH) and the concentrations of tight junction proteins (occludin, claudin-1, and ZO-1). Moreover, Bp7 and Bp8 intervention drastically down-regulated the expression of colonic MyD88, NF-κB, iNOS and COX2 and drastically elevated the expression of colonic STAT3, Nrf2, and PPARγ. Gas chromatography-mass spectrometry results revealed that the cecal levels of isobutyric, butyric, and isovaleric acids were drastically increased in colitis mice intervened with Bp7 and Bp8. Moreover, 16S rRNA sequencing revealed that Bp7 and Bp8 intervention modulated the intestinal microbiota structure, particularly by enhancing the proportion of Eubacterium coprostanoligenes group, Marvinbryantia, Enterorhabdus, Faecalibaculum, Coriobacteriaceae UCG 002, Alistipes, and Bifidobacterium, which are relevant to the levels of cecal isobutyric acid, butyric acid, isovaleric acid, and inflammatory cytokines. Collectively, these findings suggest that Bp7 and Bp8 intervention alleviates the intestinal barrier function, possibly by blocking the secretion of proinflammatory cytokines, maintaining the intestinal physical barrier integrity, activating the PPARγ/STAT3 pathway, and modulating intestinal microbiota composition. Our study also suggested that B. pseudolongum is a promising probiotic for colitis treatment.

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