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

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.