Multistrain Probiotics Plus Vitamin D Improve Gut Barrier Function and Gut Microbiota Composition in Irritable Bowel Syndrome Without Constipation: Results from a Double-Blind, Randomized, Placebo-Controlled Trial.

BACKGROUND: The disruption of the intestinal barrier and the imbalance of the gut microbiota (GM) seem to play a major role in the complex pathogenesis of irritable bowel syndrome (IBS). Specific microbial strains could improve the gut microenvironment, promoting anti-inflammatory pathways; similarly, vitamin D supplementation could play a role in enhancing the barrier integrity and modulating the immune response in the gut. This study aims to evaluate the efficacy of a new multistrain probiotic, combined with vitamin D, in improving gut barrier function in IBS without constipation. METHODS: In this phase IIb double-blind randomized placebo-controlled, parallel-group, multicenter, clinical trial, 35 patients were treated for 12 weeks with OttaBac®, a high concentration multistrain probiotic plus cholecalciferol, or placebo and were followed up until week 16. Symptoms, quality of life, intestinal permeability, fecal biomarkers, and microbiota composition were evaluated at 0, 12, and 16 weeks. RESULTS: Mean zonulin values showed a significant progressive reduction in the active group (-10.2 ng/mL at week 12, p = 0.0375; -19.5 ng/mL at week 16, p = 0.0002), with a significant difference between groups at week 16 in the per-protocol population (-19.01, p = 0.0053). The active group showed a more stable trend toward improvement in stool frequency and consistency at both week 12 and 16, with a significant improvement compared to the baseline and to the placebo group (-23.2, p = 0.0265, and 5.57 vs. -23.2, p = 0.0492, respectively). No differences were found in regards to the lactulose/mannitol ratio, Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) and Short Form Health Survey (SF-36) total scores, plasmalemmal vesicle associated protein-1 (PV-1), and citrulline levels. In the active group, Bifidobacterium animalis subsp. lactis and Streptococcus thermophilus levels were increased (p < 0.05), while those for Lachnospira were decreased (p < 0.05), and significant changes in Actinobacteria and Proteobacteria were observed (p < 0.05). Lactate (p < 0.01) and acetate (p < 0.05) levels increased post-treatment. Correlation analysis pointed out a significant association between the microbial biomarkers and the symptoms (p < 0.05). CONCLUSIONS: Probiotic plus vitamin D could improve IBS-associated symptoms through gut microbiota modulation and gut barrier enhancement, with persistent benefits after treatment discontinuation.