Lacticaseibacillus rhamnosus CCFM1060 Modulates gut microbiota and intestinal barrier Function: Alcoholic liver disease Mitigation through Nrf2/HO-1 and NF-κB Pathways

Long-term and/or excessive ethanol intake can lead to alcoholic liver disease (ALD). Gut dysbiosis contributes to a critical role in the pathogenesis of ALD. Here, we explored the impact of viable and dead Lacticaseibacillus rhamnosus CCFM1060 on the gut microbiota of alcohol-treated mice. The findings indicated that CCFM1060 V and D (viable and dead) administration improved the gut microbiota composition. Specifically, CCFM1060 D restored the abundance of butyric acid-producing bacteria, Alistipes, Lachnospiraceae, and Ruminococcaceae in ethanol-induced mice; CCFM1060 V improved the abundance of g_Dubsiela, g_Bifdobacterium, g_Ruminococcaceae_UCG_014_2, the SCFA-producing bacteria which were decreased in alcoholic hepatitis. Furthermore, the interventions improved the microstructure of the ileum, including the villi and crypts. They reinforced the intestinal barrier by increasing the RNA and protein expression of claudin-1, occludin, and ZO-1 in the colon. Also, they have been shown to enhance the liver’s antioxidant function by suppressing the synthesis of MDA and boosting the concentrations of GSH and SOD through the Nrf2/HO-1 pathway. In addition, interventions can suppress mice’s levels of TNF-α and IL-6, IL-1β in serum, presumably via the TRL4/MyD88/NF-κB pathway. Together, these results suggest that CCFM1060 can modulate the gut microbiota structure, reinforce the intestinal barrier, improve intestinal homeostasis, enhance liver antioxidant capacity, and mitigate inflammation response, eventually protecting the liver from ethanol-induced injury.