Lacticaseibacillus paracasei subsp. paracasei K56 alleviates stress-exacerbated colitis by modulating gut microbiota and immune homeostasis

Environmental stressors and probiotics modulate gut microbiota, regulating intestinal barrier function and immune homeostasis. As a potential functional food ingredient, probiotics exhibit various health-promoting properties, including the alleviation of gastrointestinal disorders. This study investigated the exacerbating effects of chronic unpredictable mild stress (CUMS) on dextran sulfate sodium (DSS)-induced colitis and the protective efficacy of Lacticaseibacillus paracasei subsp. paracasei K56 (K56) against this stress-aggravated inflammation. CUMS exposure activated the hypothalamic–pituitary–adrenal (HPA) axis and increased corticosterone levels. Compared with the DSS group, the CUMS + DSS group exhibited higher levels of disease activity index (DAI), histopathological damage, CSF1 expression, and pro-inflammatory cytokines. In mice with CUMS-exacerbated colitis, K56 pretreatment (10 9  CFU/d for 5 weeks) significantly attenuated body weight loss, colon shortening, and DAI. K56 concurrently restored Claudin-1 and Mucin-2 (MUC2) expression, elevated goblet cell counts, and reinforced intestinal barrier integrity. Additionally, K56 reduced pathogenic bacteria and enriched short-chain fatty acid (SCFA)-producing taxa, which increased fecal propionate and butyrate production. K56 also balanced T helper 17 (Th17) and regulatory T (Treg) cells in the colonic lamina propria. Our results indicate that K56 alleviates stress-exacerbated colitis through the microbiota/SCFA/immune axis, supporting its potential as a functional probiotic intervention for managing stress-aggravated intestinal inflammation.