Pediococcus acidilacticiPA53 Supplementation Improves Stool Form and Modulates Gut Microbiota and Inflammatory Responses in Adults With Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled Trial.

This study aimed to evaluate the efficacy and safety of Pediococcus acidilactici (P. acidilactici) PA53 in adults with functional constipation. In this randomized, double-blind, placebo-controlled trial, 87 adults with functional constipation were assigned to receive either P. acidilactici PA53 (3.0 × 1010 CFU/day) or a dextrin placebo in a 1:1 ratio for 8 weeks. The primary outcome was improvement in constipation symptoms, assessed by the Bristol Stool Form Scale (BSFS). Secondary outcomes included spontaneous bowel movements (SBMs), quality of life, serum biomarkers of intestinal function, inflammatory markers, and gut microbiota composition via 16S rRNA sequencing. At week 8, the PA53 group showed a significantly higher BSFS score than placebo (2.76 ± 0.93 vs. 2.03 ± 0.85, p = 0.004) and a significant within-group improvement from baseline (p = 0.001), indicating stool softening. The proportion of participants achieving 4-6 SBMs/week increased significantly in the PA53 group (from 16.7% to 38.1%, p = 0.028), but the between-group difference was not significant (p = 0.144). Within the PA53 group, motilin and interleukin-10 increased, while somatostatin and interleukin-6 decreased (all p < 0.05); however, no between-group differences were significant for any biomarker. Gut microbiota analysis revealed marked enrichment of Pediococcus and changes in microbial diversity in the PA53 group. PA53 was well tolerated with no adverse events. Overall, P. acidilactici PA53 safely improved stool form and was associated with beneficial changes in gut microbiota and inflammatory markers in adults with functional constipation. Effects on bowel movement frequency were not significant between groups and warrant further investigation. Clinical Trial Registration: NCT06761443 (ClinicalTrials.gov).