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.
Liu et al. (Wed,) studied this question.