Liubov Sichel

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.

Background. 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, trans-aminase activity, and anthropometric parameters in patients with MASLD. Methods. In a randomized, double-blind, placebo-controlled trial (NCT06352697), 52 patients 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 primary endpoints were FLI, HSI, and TyG. Additionally, lipid profile, ALT, AST and GGT activities, inflammatory markers and body composition indices were assessed. Results. In the ITT analysis, FLI decreased significantly more in the postbiotic group compared to placebo (p=0.049). HSI decreased in both groups without a significant difference between them (p=0.737), and a downward trend was observed for TyG. In the PP analysis (n=24 in each group), postbiotics were associated with a significant de-crease in waist circumference (p=0.003) and a trend towards a decrease in visceral fat (p=0.079). ALT activity decreased by 17.5% (p=0.011), AST by 10.4% (p=0.007), but gradually returned to baseline values after treatment discontinuation. Lipid profile and inflammation indices did not change significantly. All adverse events were mild and self-limiting. Conclusions. Three months of postbiotic L. rhamnosus lysate DV-NRRL B-68023 ad-ministration was well tolerated and improved noninvasive measures of steatosis and abdominal obesity in patients with MASLD. The effect on transaminases was transient. Postbiotics may be considered as an additional noninvasive approach to the treatment of MASLD in combination with lifestyle changes.

Microbiome-targeted interventions have shown promise for metabolic health, yet clinical evidence remains inconsistent, particularly across stages of metabolic disease. This study evaluated the metabolic effects, safety, and tolerability of EDC-HHA01, a microbiome-informed, non-pharmacologic intervention, in adults with prediabetes (PD) or Type 2 Diabetes (T2DM). In a randomized, double-blind, placebo-controlled clinical trial, participants received EDC-HHA01 or placebo for six months. The study was adequately powered (≥80%) for the primary endpoint. Outcomes included changes in glycated hemoglobin (HbA1c), indices of insulin resistance, markers of metabolic endotoxemia, safety-related laboratory parameters, and exploratory patient-reported measures. Analyses were stratified by metabolic status and background metformin use. In participants with PD, EDC-HHA01 supplementation was associated with a statistically and clinically meaningful reduction in HbA1c compared with placebo, supported by concordant improvements in fasting insulin, insulin resistance indices, and reductions in endotoxemia markers. In participants with T2DM, changes were directionally similar but attenuated and did not reach statistical significance. The intervention was well tolerated, with no serious adverse events, high adherence, and no clinically relevant adverse changes in renal or lipid parameters. Exploratory patient-reported outcomes indicated favorable acceptability but were not interpreted as efficacy endpoints. EDC-HHA01 was associated with biologically coherent, stage-dependent metabolic effects, most evident in PD. These findings support further investigation of microbiome-informed strategies as metabolic support in early-stage dysregulation.

Background: Microbiome-targeted interventions have shown promise for metabolic health, yet clinical evidence remains inconsistent, particularly across stages of metabolic disease. This study evaluated the metabolic effects, safety, and tolerability of EDC-HHA01, a microbiome-informed, non-pharmacologic intervention, in adults with prediabetes (PD) or Type 2 Diabetes (T2DM). Methods: In a randomized, double-blind, placebo-controlled clinical trial, participants received EDC-HHA01 or placebo for six months. The study was adequately powered (≥80%) for the primary endpoint. Outcomes included changes in glycated hemoglobin (HbA1c), indices of insulin resistance, markers of metabolic endotoxemia, safety-related laboratory parameters, and exploratory patient-reported measures. Analyses were stratified by metabolic status and background metformin use. Results: In participants with PD, EDC-HHA01 supplementation was associated with a statistically and clinically meaningful reduction in HbA1c compared with placebo, supported by concordant improvements in fasting insulin, insulin resistance indices, and reductions in endotoxemia markers. In participants with T2DM, changes were directionally similar but attenuated and did not reach statistical significance. The intervention was well tolerated, with no serious adverse events, high adherence, and no clinically relevant adverse changes in renal or lipid parameters. Exploratory patient-reported outcomes indicated favorable acceptability but were not interpreted as efficacy endpoints. Conclusions: EDC-HHA01 was associated with biologically coherent, stage-dependent metabolic effects, most evident in PD. These findings support further investigation of microbiome-informed strategies as metabolic support in early-stage dysregulation.