Heat-inactivated Lacticaseibacillus paracasei fermented milk fails to improve functional constipation symptoms but boosts VIP and ACh
Background
Functional constipation (FC) commonly affects middle-aged and older adults, significantly impacting quality of life. Current pharmacological treatments often have limitations, including side effects or incomplete relief. Postbiotics, defined as non-viable microbial components or metabolites, offer potential safety and stability advantages over live probiotics, making them an attractive alternative. However, robust clinical evidence for their efficacy in FC remains limited, creating a gap this study aimed to address by evaluating a specific heat-inactivated Lacticaseibacillus paracasei formulation.
Study Design
This randomized, double-blind, placebo-controlled trial enrolled 100 adults (45-75 years) with Rome IV-defined FC. Participants received either heat-inactivated two-strain Lacticaseibacillus paracasei fermented milk or a placebo daily for 4 weeks. The primary outcome measured 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).
Results
The intervention group showed no significant benefit over placebo for the primary outcome or most secondary clinical outcomes. Both groups improved within-group, but 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. No adverse events were reported, indicating good tolerability.
Exploratory biomarker analyses, however, revealed significantly greater increases in serum Vasoactive Intestinal Peptide (VIP) (MD = 105.23 ng/L, p < 0.001) and Acetylcholine (ACh) (MD = 42.95 ng/L, p = 0.035) in the intervention group, suggesting engagement of neurotransmitter-related pathways.
Key Findings
- Heat-inactivated Lacticaseibacillus paracasei fermented milk did not significantly improve weekly SBM frequency (MD = -0.14, p = 0.683).
- No significant improvements were observed for CSBM frequency (MD = 0.27, p = 0.543) or whole-gut transit time (MD = -1.55 h, p = 0.614).
- Serum Vasoactive Intestinal Peptide (VIP) levels significantly increased by 105.23 ng/L in the intervention group (p < 0.001).
- Serum Acetylcholine (ACh) levels significantly increased by 42.95 ng/L in the intervention group (p = 0.035).
- The postbiotic was well-tolerated, with no adverse events reported.
Why It Matters
This specific heat-inactivated Lacticaseibacillus paracasei fermented milk did not demonstrate clinical efficacy for improving bowel function or symptoms in the overall functional constipation population. For individuals seeking relief from FC, this particular postbiotic formulation, at this dose and duration, may not be a viable option. However, the significant increases in serum VIP and ACh are intriguing. These neurotransmitters play crucial roles in gut motility and secretion, suggesting a biological effect on the gut-brain axis despite the lack of symptomatic improvement. This finding warrants further research into different postbiotic formulations, dosages, durations, or specific patient subgroups that might respond, potentially guiding future development of more targeted interventions for gut health.
functional-constipation
postbiotic
lacticaseibacillus-paracasei
gut-health
rct
gastrointestinal