Genomic and phenotypic study reveals the probiotic L. paracasei BGI-N2 alleviates constipation via serotonin modulation

The global prevalence of constipation has been increasing in recent years, posing an urgent need for safer and more effective therapeutic strategies. Given the favorable safety profile and beneficial modulatory effects on gut health, probiotic supplements have emerged as a promising therapeutic avenue for managing constipation. This study explored the probiotic properties of Lacticaseibacillus paracasei BGI-N2 (BGI-N2) by integrating complete genomic and phenotypic analysis. Results indicated that the high-precision complete genome of BGI-N2 comprised 3,102,337 bp with a 46.4% GC content and 2,937 coding sequences, including multiple genes related to carbon source fermentation, gastrointestinal tolerance, and antioxidant activities. In vitro assays demonstrated that BGI-N2 had robust tolerance to extreme gastrointestinal conditions and significant inhibition against common enteropathogens. Notably, supplementation with BGI-N2 effectively enhanced intestinal motility in aluminum sulfate-induced constipated zebrafish and accelerated gastrointestinal transit. Specifically, BGI-N2 increased motilin and serotonin expression while reducing nitric oxide levels; upregulated kitla, kitlb, and kitb to promote interstitial cells of Cajal development; and increased local serotonin accumulation through coordinated upregulation of biosynthetic genes (tph1a, tph1b, tph2) and downregulation of the serotonin transporter gene (sert) in zebrafish. Collectively, this study provided comprehensive genomic resources for BGI-N2 while establishing a theoretical foundation for its efficacy in alleviating constipation in zebrafish.