A multi-strain probiotic formulation alleviates chronic constipation in middle-aged and older adults: A randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Chronic constipation is prevalent among middle-aged and older adults, with current interventions often limited by modest efficacy and adverse effects. Probiotics have emerged as a safe, promising modality; we aimed to evaluate a 28-day multi-strain probiotic in this population using clinical and mechanistic endpoints.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial in adults with chronic constipation: 132 were randomized (probiotics n = 66; placebo n = 66), and 100 completed per protocol (50/50).The primary endpoint was weekly complete spontaneous bowel movements (CSBMs) at day 28; secondary endpoints included Bristol Stool Form Scale (BSFS), Patient Assessment of Constipation Symptoms (PAC-SYM), bloating scores, and multi-omics profiling (gut microbiota and fecal metabolites at days 0/14/28), with targeted fecal short-chain fatty acids (SCFAs). A pre-specified responder was defined as week-4 CSBMs ≥3 and increases ≥1 from baseline.

RESULTS

At day 28, probiotics yielded higher CSBMs than placebo (4.53 ± 1.17 vs 2.40 ± 1.01, P < 0.0001), improved stool form (higher BSFS), reduced PAC-SYM, and markedly alleviated bloating (0.70 ± 0.46 vs 2.60 ± 0.93, P < 0.0001). Microbiologically, α-diversity increased and β-diversity separated between groups at days 14 and 28 (PERMANOVA P = 0.003 and 0.001); Faecalibacterium, Lactobacillus, and Bifidobacterium increased, whereas Enterobacter, Collinsella, and Oscillibacter declined. Untargeted metabolomics indicated enrichment of SCFA biosynthetic pathways (butanoate/propanoate), and targeted assays confirmed higher fecal acetate and butyrate at day 28 (P < 0.01 and P < 0.05), with no significant change in propionate or valerate (both P > 0.05). Responder rates were 88 % (44/50) with probiotics versus 26 % (13/50) with placebo; within the probiotic arm, ΔFaecalibacterium and Δbutyrate correlated positively with ΔCSBM, while ΔEnterobacter correlated negatively.

CONCLUSIONS

In middle-aged and older adults with chronic constipation, a 28-day multi-strain probiotic significantly increases bowel movement frequency, improves symptoms-especially bloating-and favorably remodels gut microbiota and SCFA-related pathways, supporting its use as a nutritional intervention.

TRIAL REGISTRATION: ChiCTR2200065905.