Barnesiella intestinihominis improves gut microbiota disruption and intestinal barrier integrity in mice with impaired glucose regulation
Xiaojia Liu, Ling Wang, Huang Bing, Yi Jiao, Yaqun Guan, Rebiya Nuli
Abstract
Introduction Impaired glucose regulation (IGR) is a prediabetic state closely associated with gut microbiota dysbiosis. Our previous metagenomic analysis identified a significant deficiency of Barnesiella intestinihominis ( B. intestinihominis ) in IGR patients ( p < 0.01). The present study was therefore designed to investigate the therapeutic potential of B. intestinihominis supplementation in a high-fat diet (HFD)-induced IGR mouse model and to explore its potential mechanisms of action. Methods A mouse model of IGR was established by HFD. The treatment group received a daily supplementation of live B. intestinihominis (1×10 8 CFU) for 5 weeks. Gut microbiota composition was analyzed. Colonic expression levels of tight junction proteins (ZO-1 and occludin) and cytokines (IL-10, TNF-α, IL-6) were measured. In vitro experiments using Caco-2 human intestinal epithelial cells were conducted to assess the direct effects of B. intestinihominis . B. intestinihominis fermentation broth, heat-inactivated bacterial solution, and bacterial solution were co-cultured with Caco-2 cells. Cell viability was assessed using the CCK-8 assay, and the expression levels of tight junction proteins were evaluated. Trans-epithelial electrical resistance (TEER) and alkaline phosphatase activity were also assessed in the Caco-2 model. Results Daily supplementation with B.intestinihominis significantly attenuated HFD-induced hyperglycemia in mice. It also modulated the gut microbiota, evidenced by an increased abundance of beneficial Ligilactobacillus and a reduction in pathogenic Lachnoclostridium . Furthermore, B. intestinihominis administration upregulated the expression of colonic tight junction proteins (ZO-1 and occludin) and the anti-inflammatory cytokine IL-10, while simultaneously inhibiting the pro-inflammatory mediators TNF-α and IL-6. In vitro , the fermentation broth of B.intestinihominis (10%) increased Caco-2 cell viability, and heat-inactivated bacteria (1×10 7 CFU) enhanced ZO-1 expression. However, neither treatment significantly affected trans-epithelial electrical resistance (TEER) nor alkaline phosphatase activity in Caco-2 cells. Discussion These findings suggest that intestinal probiotics B. intestinihominis may ameliorate IGR by modulating the gut microbiota, enhancing intestinal barrier integrity, and attenuating inflammation, thus supporting their potential as a therapeutic intervention for metabolic disorders.