Caulerpa lentillifera (CL), also called sea grape, is a type of edible green alga which was reported to have antioxidative and immunomodulatory potential. This study aimed to investigate the hepatoprotective effects of CL in a rat model of chronic ethanol exposure. Wistar rats were assigned to four groups and supplied with an isocaloric control liquid diet (group C), an ethanol liquid diet (group E), a control liquid diet supplemented with 5% CL (group CC), or an ethanol liquid diet supplemented with 5% CL (group EC) for a 12-week experimental period. Ethanol feeding induced steatosis, inflammation, and changes in the gut microbiota by the end of the study, whereas CL supplementation significantly improved liver injuries and decreased circulatory endotoxin levels. Moreover, we also found that CL reversed ethanol-induced elevation of hepatic toll-like receptor 4 (TLR4), MyD88 protein expression, the phosphorylated-nuclear factor (NF)-κB-to–NF–κB ratio, and proinflammatory cytokine concentrations. Additionally, CL also increased the abundance of Akkermansia and tight junction proteins and diminished the Firmicutes-to-Bacteroidetes ratio. Dietary CL inhibited the progression of alcoholic liver disease, and some of the possible mechanisms may be strengthening the intestinal barrier function, alleviating dysbiosis, and modulating the TLR4 pathway.
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