NF-kB Regulation and the Chaperone System Mediate Restorative Effects of the Probiotic Lactobacillus fermentum LF31 in the Small Intestine and Cerebellum of Mice with Ethanol-Induced Damage

SIMPLE SUMMARY: Probiotics are live microorganisms that offer health benefits, primarily by improving the gut microbiota. A study involving mice explored the impact of Lactobacillus fermentum LF31 (L. fermentum), a probiotic, when combined with ethanol consumption over 12 weeks. The research found that L. fermentum influenced the NF-κB signaling pathway in the small intestine, inducing the expression of Hsp60, Hsp90, and IkB-α. It also suppressed the expression of pro-inflammatory molecules like IL-6 and TNF-α. These effects coincided with the restoration of the intestinal barrier damaged by ethanol, including the production of tight junction proteins, reducing the ethanol-induced intestinal permeability. Notably, the benefits of L. fermentum extended to the cerebellum, where it downregulated markers associated with glial inflammation. This indicates that the probiotic has anti-inflammatory and cytoprotective properties, not only in the gut but also in the brain, mitigating ethanol-induced gut permeability and neuroinflammation. Overall, this study suggests that L. fermentum may be a valuable tool in treating intestinal diseases caused by factors such as inflammation and dysbiosis and could be considered for therapeutic use in combination with other therapies for such conditions. ABSTRACT: Probiotics are live microorganisms that yield health benefits when consumed, generally by improving or restoring the intestinal flora (microbiota) as part of the muco-microbiotic layer of the bowel. In this work, mice were fed with ethanol alone or in combination with the probiotic Lactobacillus fermentum (L. fermentum) for 12 weeks. The modulation of the NF-κB signaling pathway with the induction of Hsp60, Hsp90, and IkB-α by the probiotic occurred in the jejunum. L. fermentum inhibited IL-6 expression and downregulated TNF-α transcription. NF-κB inactivation concurred with the restoration of the intestinal barrier, which had been damaged by ethanol, via the production of tight junction proteins, ameliorating the ethanol-induced intestinal permeability. The beneficial effect of the probiotic on the intestine was repeated for the cerebellum, in which downregulation of glial inflammation-related markers was observed in the probiotic-fed mice. The data show that L. fermentum exerted anti-inflammatory and cytoprotective effects in both the small intestine and the cerebellum, by suppressing ethanol-induced increased intestinal permeability and curbing neuroinflammation. The results also suggest that L. fermentum could be advantageous, along with the other available means, for treating intestinal diseases caused by stressors associated with inflammation and dysbiosis.