Multi-Strain Probiotics Alleviate Alcoholic Liver Disease Via Microbiota-Metabolism Axis: A Randomized Controlled...

Alcoholic liver disease (ALD) remains a major global health burden, with over 283 million individuals affected by alcohol use disorder (AUD). Early-stage ALD is characterized by gut microbiota dysbiosis, intestinal barrier dysfunction, and endotoxemia. Traditional therapies focusing solely hepatoprotection or lipid reduction often show limited efficacy due to their inability to restore the gut-liver axis balance. This study aimed to evaluate the adjuvant efficacy of a multi-strain probiotic formulation (including Weizmannia coagulans BC99, Lacticaseibacillus rhamnosus LRa05, Bifidobacterium animalis subsp. lactis BLa80, and Weizmannia coagulans BC179) combined with polyene phosphatidylcholine (Essentale^®) in improving liver function and metabolic profiles in ALD patients.A randomized, single-blind, placebo-controlled clinical trial was conducted in 42 ALD patients. Participants received either Essentale^® plus probiotics or Essentale^® plus placebo for 30 days. Liver function tests, serum lipids, fecal microbiota (16 S rRNA sequencing), and fecal metabolites (GC-MS) were assessed at baseline, day 15, and day 30.Compared to placebo, the probiotic group showed significant reductions in ALT, AST, GGT, and TG, along with increased HDL-C levels. Probiotics promoted the enrichment of Bifidobacterium, Faecalibacterium, and Akkermansia, and improved microbial diversity. Metabolomic profiling revealed upregulation of anti-inflammatory and antioxidant metabolites (e.g., EGCG, S-methylglutathione) and downregulation of pro-inflammatory lipotoxic intermediates. Spearman analysis confirmed correlations between key bacterial genera and liver/metabolic biomarkers.Multi-strain probiotics effectively modulate the gut-liver axis by reshaping gut microbiota and metabolic networks, thereby enhancing the therapeutic efficacy of conventional hepatoprotective drugs in ALD. These findings support their clinical potential as a safe and complementary strategy for managing ALD.