Efficacy of Bifidobacterium animalis subsp. lactate BL-99 in relieving functional constipation: a randomized placebo-controlled clinical trial.

Abstract

Current therapies for functional constipation (FC) often exhibit limited long-term efficacy. Probiotics, particularly Bifidobacterium animalis subsp. lactis BL-99 (BL-99), may offer a novel approach to alleviate FC symptoms. This randomized, double-blind, placebo-controlled trial (No. WXSY-YXLL-AF/SC-11/01.0) enrolled 41 FC patients who completed the full 6-week study. Participants were randomly assigned to receive either BL-99 (1 × 10¹¹ colony-forming units per day) or placebo for 4 weeks in this population trial. After completing the 4-week intervention period, administration was discontinued and participants entered a 2-week observation following-up period for continued monitoring. Primary endpoint data collected after trial completion were the changes in the Patient Assessment of Constipation Symptoms (PAC-SYM, 12-item scale) score, evaluated on the first day (0 day), the 28th day (week 4), and the 42th day (week 6). Secondary outcomes included fecal metagenomic profiling to evaluate gut microbiota alterations. After 4 weeks of intervention, the BL-99 group demonstrated significant reductions in PAC-SYM scores compared to the placebo, particularly in domains of "abdominal discomfort" (Δ = 1.8 vs. 0.9, p = 0.007) and "pain during defecation" (Δ = 2.1 vs. 1.0, p = 0.003). These improvements persisted at the 2-week post-treatment follow-up (p < 0.05). Metagenomic analysis revealed that BL-99 enriched Bifidobacterium and Faecalibacterium while suppressing Clostridium species, shifting gut microbiota composition closer to that of the healthy controls. Functional annotation highlighted significant downregulation of infection-related pathways (e.g., bacterial invasion and LPS biosynthesis) and metabolic disease-associated pathways (e.g., insulin resistance) in the BL-99 group (q < 0.05). This trial suggests that 4-week BL-99 supplementation effectively alleviates FC symptoms, partially through microbiota modulation and metabolic pathway regulation. The sustained post-treatment effects warrant further investigation into its long-term benefits.