Probiotics and Postbiotics Produced by <i>Lacticaseibacillus rhamnosus</i> 1.0320 Isolated from Traditional Fermented Dairy Products Alleviate DSS-Induced Colitis by Modulating the Gut Microbiota and Intestinal Metabolism

Postbiotics are emerging as promising alternatives to probiotics. However, the mechanisms underlying their regulation of the gut microbiota-metabolite axis, signaling pathways, and multiomics interactions, as well as the key bioactive components responsible for their efficacy variations, remain poorly characterized. This study investigated the protective effects of <i>Lactobacillus rhamnosus</i> 1.0320 (probiotic, 1.0320) and heat-killed <i>Lactobacillus rhamnosus 1.0320</i> (postbiotic, HK 1.0320) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Results demonstrated that HK1.0320 significantly alleviated UC symptoms, mitigated colonic damage, restored the intestinal barrier, attenuated oxidative stress, regulated MPO activity, suppressed TLR4/MAPK/NF-κB pathway key proteins (TLR4, MyD88, JNK, p38, and p65), decreased pro-inflammatory cytokine secretion, modulated gut microbiota, and enhanced SCFA production. Untargeted metabolomics revealed that HK1.0320 is rich in bioactive components such as carboxylic acids and alleviates UC through its own or intestinal metabolic modification. This study clarifies the postbiotic colitis-relief mechanism and highlights their potential in functional foods or precision nutrition.