<i>Bacteroides intestinalis</i> -Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging because of insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal <i>Bacteroides intestinalis</i> (<i>B</i>. <i>intestinalis</i>) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between <i>B</i>. <i>intestinalis</i> and its substrate, insoluble wheat arabinoxylan abundant in dietary fiber (inWAX), enhances the production of anti-diabetic and anti-steatotic bile acid species, anti-inflammatory and antioxidant phenolic compounds, and a spectrum of neuroactive compounds. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen implicating pathways governing circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high-fat diet-induced obesity, where <i>B</i>. <i>intestinalis</i> and inWAX improve glucose tolerance. Our findings uncover a mechanistic framework linking <i>B</i>. <i>intestinalis</i>-mediated fiber fermentation to gut-metabolism-immune crosstalk and establish a rational foundation for precision synbiotic design.