Abstract
INTRODUCTION: Bacteroides is a crucial mucosal symbiotic bacterium in mammals, with Bacteroides thetaiotaomicron (B. thetaiotaomicron) being particularly noteworthy as a glyco-specialist due to its significant nutritional impact. However, the potential effects of B. thetaiotaomicron on host health remain underexplored. OBJECTIVES: This study aimed to investigate the patterns of microbial community changes and the molecular mechanisms mediated by microbial metabolites in alleviating piglet diarrhea through B. thetaiotaomicron intervention. METHODS: Cold stress was induced in piglets to trigger stress-induced diarrhea. The control group and B group were administered a blank medium and 1 × 10(8) CFU of B. thetaiotaomicron, respectively, on days 1, 3, and 5. The diarrhea rate and growth performance of the piglets were recorded during the experimental period. Based on 16S rRNA gene amplicon sequencing, microbial ecological networks analysis, and metabolomics analysis, the composition and changes of the colonic microbiota and metabolites were analyzed. The antibacterial capacity and anti-inflammatory molecular mechanisms of B. thetaiotaomicron metabolites were analyzed through in vitro antibacterial assays and inflammatory cell models. RESULTS: B. thetaiotaomicron administration alleviated diarrhea and improved the growth performance of piglets. It modulated the composition and interactions of the intestinal microbiota, with microbial metabolites primarily enriched in the tryptophan metabolism pathway-especially indole and its derivatives, which were closely associated with host phenotypes. In vitro co-culture experiments showed that B. thetaiotaomicron metabolites inhibited the growth of pathogenic bacteria. Further experiments demonstrated that these metabolites, including indole, enhanced epithelial barrier function and attenuated TNF-α-induced inflammation and apoptosis in Caco-2 cells, highlighting the involvement of the AHR-Nrf2 signaling pathway in mediating these protective effects. CONCLUSION: In conclusion, this study offers a theoretical framework for understanding the role of the symbiotic bacterium B. thetaiotaomicron in the gut microbiota ecosystem during diarrhea and its interactions with the host's intestinal tract.