Preventive effects of Faecalibacterium prausnitzii on chronic alcoholic liver injury and associated alterations in gut microbiota and host phenotypes in mice.

Abstract

Background and objective: Alcoholic liver disease (ALD) is a complex disorder with limited effective interventions; gut dysbiosis plays a pivotal role in its pathogenesis. Faecalibacterium prausnitzii , a core commensal of the healthy human gut, exhibits potent anti-inflammatory properties and supports intestinal barrier integrity; however, its role in ALD remains unclear. This study aimed to investigate the preventive effects of Faecalibacterium prausnitzii against chronic alcoholic liver injury and to explore associated host and microbial alterations.

Methods: Chronic ALD was induced in C57BL/6 J mice using the Lieber-DeCarli ethanol liquid diet for 6 weeks, with daily oral gavage of Faecalibacterium prausnitzii (1 × 10⁹ CFU mL-1). Serum and hepatic biochemical parameters, inflammatory cytokines, and ethanol-metabolizing enzyme activities were assessed. Liver and colon histopathology were evaluated by H&E staining. Intestinal barrier integrity was examined by immunofluorescence staining of tight junction proteins (ZO-1 and occludin). Gut microbiota composition was characterized by 16S rRNA gene sequencing, and host-microbe interactions were explored through correlation network analysis.

Results: Faecalibacterium prausnitzii administration was associated with significantly reduced serum ALT, AST, and total bile acids, as well as hepatic ALT, TC, LDL, and AKP, and increased HDL. It was also associated with attenuated hepatic steatosis and colonic barrier damage, lowered serum LPS, and upregulated colonic ZO-1 and occludin expression. Furthermore, Faecalibacterium prausnitzii was associated with suppressed pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in both liver and serum, increased anti-inflammatory IL-10, elevated activity of alcohol dehydrogenase (ADH) and increased, though to a lesser extent, activity of aldehyde dehydrogenase (ALDH). 16S rRNA sequencing revealed that Faecalibacterium prausnitzii administration was associated with partial counteraction of ethanol-induced dysbiosis, characterized by reduced expansion of Verrucomicrobiota (notably Akkermansia) and Monoglobus, and enrichment of butyrate-producing genera such as Bifidobacterium, Faecalibaculum, and Lactobacillus. PICRUSt2 functional prediction suggested enrichment in carbohydrate and lipid metabolism pathways. Correlation network analysis suggested that Akkermansia and Monoglobus were positively associated with liver injury, inflammation, and barrier disruption, whereas Faecalibaculum showed strong positive correlations with ADH/ALDH activity, intestinal barrier integrity, and metabolic homeostasis.

Conclusion: Our findings suggest that Faecalibacterium prausnitzii administration is associated with improvements in liver injury, inflammatory status, intestinal barrier function, and gut microbial composition in a preventive ALD model. These observations support the potential of Faecalibacterium prausnitzii as a candidate probiotic for further investigation in alcohol-related liver disease.