Interactions between <i>Parabacteroides goldsteinii</i> CCUG 48944 and diet ameliorate colitis in mice via regulating gut bile acid metabolism

Inflammatory bowel disease (IBD) is a chronic disorder linked to an increased risk of colorectal cancer (CRC) and is characterized by significant dysbiosis in the gut microbiota. The commensal bacterium <i>Parabacteroides goldsteinii</i> (<i>P. goldsteinii</i>) has shown potential in modulating host metabolism and inflammatory responses. In this study, we investigated the probiotic properties of <i>P. goldsteinii</i> and its mechanism of action in IBD models, with a particular focus on bile acid metabolism and diet-microbiota interactions. Fecal samples from patients with ulcerative colitis (<i>n</i> = 14), Crohn's disease (<i>n</i> = 22), and healthy controls (<i>n</i> = 13) were analyzed to assess <i>P. goldsteinii</i> relative abundance. In dextran sulfate sodium (DSS)-induced colitis and azoxymethane (AOM)/DSS-induced CRC mouse models, administration of <i>P. goldsteinii</i> significantly attenuated inflammation and tumorigenesis, particularly under fiber-free diet conditions. Metabolomic profiling revealed an enrichment of secondary bile acids in <i>P. goldsteinii</i>-treated mice, suggesting a link between bile acid metabolism and its anti-inflammatory effects. Further mechanistic studies using bile salt hydrolase inhibitors and <i>Tgr5</i> knockout mice confirmed the role of bile acid regulation in mediating the therapeutic benefits of <i>P. goldsteinii</i>. Additionally, we found that dietary factors significantly influenced the colonization and metabolic activity of <i>P. goldsteinii</i>, thereby modulating its probiotic efficacy. This highlights the potential for microbiome-based therapies tailored to specific dietary contexts in the treatment of IBD. Our findings demonstrate that <i>P. goldsteinii</i> can modulate gut bile acid metabolism to alleviate colitis, making it a promising candidate for probiotic applications in IBD management, with dietary modulation enhancing its therapeutic potential.