A Heat-Inactivated Two-Strain Lacticaseibacillus paracasei Fermented Milk as a Postbiotic for Functional Constipation: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND/

OBJECTIVES

Functional constipation (FC) commonly affects middle-aged and older adults, but current pharmacological treatments have limitations. Postbiotics may offer safety advantages, but clinical evidence is limited. This randomized controlled trial evaluated the efficacy and safety of a heat-inactivated two-strain Lacticaseibacillus paracasei fermented milk in adults with FC.

METHODS

One hundred adults aged 45-75 years with Rome IV-defined FC received the fermented milk or placebo for 4 weeks. The primary outcome was the change in weekly spontaneous bowel movement (SBM) frequency from baseline to week 4. Secondary outcomes included complete spontaneous bowel movement (CSBM) frequency, whole-gut transit time (WGTT), constipation symptom scores, quality of life, serum biomarkers, and adverse events. Primary analysis was per-protocol (n = 96); intention-to-treat analysis was applied to primary and key secondary outcomes.

RESULTS

Dropout was 4% (n = 4, 2 per group), and adherence was >80% in both groups. The intervention showed no significant benefit over placebo for the primary outcome or for most secondary clinical outcomes. Although both groups improved within-group, no significant between-group differences were observed at week 4 for changes in SBM (MD = -0.14, 95% CI: -0.85, 0.57; p = 0.683), CSBM (MD = 0.27, 95% CI: -0.61, 1.15; p = 0.543), or WGTT (MD = -1.55 h, 95% CI: -7.65, 4.55; p = 0.614). Symptom and quality-of-life scores also did not differ between groups. Exploratory biomarker analyses showed significantly greater increases in serum VIP and ACh in the intervention group (VIP: MD = 105.23 ng/L, p < 0.001; ACh: MD = 42.95 ng/L, p = 0.035). No adverse events were reported.

CONCLUSIONS

Four weeks of this postbiotic was safe but did not significantly improve bowel function or symptoms in the overall FC population. The increases in serum VIP and ACh suggest engagement of neurotransmitter-related pathways; however, these exploratory findings do not imply causation or clinical efficacy and warrant confirmation in longer-duration trials (Clinical Trial Registry: ChiCTR2500111771).