Lactiplantibacillus plantarum P9 for chronic diarrhea in young adults: a large double-blind, randomized, placebo-controlled trial

Current treatments for chronic diarrhea have limited efficacy and several side effects. Probiotics have the potential to alleviate diarrhea symptoms. This randomized, double-blind, placebo-controlled trial evaluated the effects of administering the probiotic Lactiplantibacillus plantarum P9 (P9) in young adults with chronic diarrhea (Clinical Trial Registration Number: ChiCTR2000038410). The intervention lasted 28 days and included a 14-day post-intervention period. Participants were randomized into the P9 (n=93) and placebo (n=96) groups, with 170 subjects completing the double-blind intervention phase (n=85 per group). The primary endpoint was the diarrhea symptom severity score. Fecal shotgun metagenomics and metabolomics analyses were performed to investigate potential probiotic mechanisms. Both intention-to-treat (n=189) and per-protocol (n=170) analyses found a modest but significant reduction in diarrhea severity compared to placebo (20.0%, P=0.050; 21.4%, P=0.048, respectively). The symptom reduction was accompanied by various changes in patients’ gut microbiota and metabolome: increases in short-chain fatty acid-producers, a bile acid-metabolizing species, fecal metabolites of amino acids, acetate, and butyrate, and cumulative gene abundances of 15 carbohydrate-active enzyme subfamilies; decreases in fecal deoxycholic acid concentrations. Overall, this study supports probiotic use in managing chronic diarrhea in young adults. Limitations include the lack of blood parameter assessment and the short intervention period.