Restoration of ethanol-induced Bifidobacterium pseudocatenulatum depletion ameliorates alcohol-associated liver disease.

Bifidobacterium genus was significantly depleted in ALD patients compared to healthy controls, as demonstrated in a cohort of 127 subjects.

• The cohort consisted of 127 subjects total.
• Functional screening of Bifidobacterium species identified B. pseudocatenulatum as a protective strain.
• Depletion of Bifidobacterium was characterized as a feature of gut microbial dysbiosis in ALD patients.
• This finding motivated the investigation of B. pseudocatenulatum as a probiotic candidate.

Oral administration of B. pseudocatenulatum ameliorated hepatomegaly, steatosis, and serum transaminase levels in a murine ALD model.

• The murine ALD model was established using a Lieber-DeCarli ethanol diet.
• B. pseudocatenulatum was administered orally for 8 weeks.
• Outcomes measured included hepatomegaly, hepatic steatosis, and serum transaminase levels.
• These improvements indicate reduced liver injury and fat accumulation following probiotic intervention.

B. pseudocatenulatum intervention restored intestinal barrier function in ethanol-fed mice.

• Restoration of barrier function was indicated by reduced lipopolysaccharide-binding proteins.
• Tight junction protein expression was upregulated following probiotic treatment.
• Gut barrier disruption is a key pathological feature of ALD.
• These findings suggest the probiotic mitigated intestinal permeability associated with ethanol exposure.

B. pseudocatenulatum treatment mitigated gut microbial dysbiosis, reducing pathogenic taxa and enriching beneficial bacteria.

• Pathogenic Escherichia-Shigella and Parabacteroides were reduced following probiotic intervention.
• Beneficial bacteria Bifidobacterium and Blautia were enriched after treatment.
• Microbiome shifts were accompanied by changes in lipid metabolism.
• Microbiome analysis was performed as part of the murine ALD model study.

B. pseudocatenulatum-derived short-chain fatty acids downregulated hepatic lipogenic genes and pro-inflammatory cytokines.

• Hepatic lipogenic genes downregulated included Cd36, Fasn, and Accα.
• Pro-inflammatory cytokines downregulated included Il-1β, Ccl2, and Tnf-α.
• The mechanistic pathway involved short-chain fatty acids produced by B. pseudocatenulatum.
• These mechanistic findings provide a molecular basis for the observed hepatoprotective effects.