Abstract / Summary
Background and Objectives: Modulation of the gut–liver axis with non-viable microbial components is a promising approach to correct metabolic disorders. The aim of the study was to evaluate the short-term efficacy and safety of the postbiotic lysate Lactobacillus rhamnosus DV-NRRL B-68023 on non-invasive measures of hepatic steatosis, transaminase activity, and anthropometric parameters in patients with MASLD. Materials and Methods: In a randomized, double-blind, placebo-controlled trial (NCT06352697), 52 adults were assigned 1:1 to receive the postbiotic Del-Immune V® Extra (100 mg twice daily; n = 26) or placebo (n = 26) for 3 months followed by a 3-month follow-up without treatment. The registered co-primary endpoints were FLI, HSI, and TyG. Additionally, transaminases, lipid parameters, hs-CRP, and body composition indices were assessed. Results: In the ITT analysis (n = 52), FLI showed a nominal time-by-treatment interaction (p = 0.049), with a between-group difference in change at month 3 of −7.20 points (95% CI: −12.95 to −1.46). HSI and TyG did not differ significantly between groups. In exploratory ITT analyses, waist circumference showed a significant time-by-treatment interaction (p = 0.003), whereas the interaction for visceral fat was not significant (p = 0.079). ALT and AST decreased significantly within the postbiotic group, but the corresponding time-by-treatment interactions were not significant (p = 0.340 and p = 0.111, respectively). Lipid parameters and hs-CRP did not differ significantly between groups. All adverse events were mild and self-limiting. Conclusions: Three months of Lactobacillus rhamnosus lysate DV-NRRL B-68023 was well tolerated. Among the three registered co-primary surrogate indices, only FLI showed a nominal between-group difference; HSI and TyG did not. An exploratory reduction in waist circumference was observed, whereas the ALT and AST changes were not significantly different from placebo. These findings warrant confirmation in larger studies using direct liver assessments and longer follow-up.