The effects of next generation probiotics on metabolic dysfunction-associated steatotic liver disease: a parallel, double-blind, randomized, placebo-controlled trial

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with dysbiosis of the gut microbiota. We evaluated the effect of next generation probiotics (Lactobacillus delbrueckii subsp. Lactis [LL001], L. helveticus [LH001], and Pediococcus pentosaceus KID7 [PPKID7]) on liver function parameters and stool microbiome in patients with MASLD. Methods: We conducted a double-blind parallel trial of 110 patients diagnosed with MASLD. Participants were randomly assigned to four groups given three probiotics (3 capsules [9 × 109 CFU]/day, n = 85) or placebo (n = 25) alongside sylimarin for 8 weeks. Clinical characteristics, serum samples, and stool samples for 16 S rRNA gene sequencing were collected at the start and end point of the study. The primary endpoint was improvement in liver function. Results: In the probiotic group, LL001 treatment improved alanine transaminase (87.3 ± 8.2 to 71.1 ± 6.0 U/L, P = 0.01) and aspartate transaminase levels (64.9 ± 4.9 to 50.0 ± 3.5 U/L, P < 0.01), LH001 group showed body weight reduction (78.4 ± 3.0 to 77.2 ± 2.8 kg, P = 0.01), and PPKID7 reduced cholesterol levels (186.1 ± 7.0 to 178.0 ± 7.9 mmol/L, P = 0.03). Probiotics treatment decreased the abundance of Proteobacteria and increased the abundance of Ruminococcaceae and Lachnospiraceae in the LL001 group. In the pre- and post-comparison of probiotic treatment at the level of the top 20 genera, a tendency was observed to decrease the genera Haemohlius and Ruminococcus_g2 while increasing the genus Bifidobacterium. Conclusion: Eight weeks of probiotics supplementation was associated with changes in the stool microbiome and improvements in the blood biochemical parameters of MASLD. Registration number of clinical trial: NCT04555434.