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Bacteroides intestinalis–Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

ABSTRACT: 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 by insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis (B. intestinalis) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B. intestinalis and its preferred substrate, insoluble wheat arabinoxylan abundant in dietary fiber, enhances the production of anti-inflammatory, antioxidant, and anti-diabetic phenolic compounds and bile acid species. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen that improve 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 BI and inWAX improves glucose tolerance along with an increased production of neuroactive compounds. Our findings uncover a mechanistic framework linking B. intestinalis-mediated fiber fermentation to gut–liver–brain crosstalk and establish a rational foundation for precision synbiotic design.

ORGANISM(S): Mus musculus

PROVIDER: GSE318341 | GEO | 2026/03/12

REPOSITORIES: GEO

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Project description:Analysis of non-differentiated Caco-2 intestinal epithelial cell line treated with polydextrose fermentation metabolites fermented for 48 hours in 4-stage in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse and distal colon in sequence , as well as with medium, 100 mM NaCl and 5 mM butyrate. Polydextrose, a soluble fiber fermented in colon, was fermented with the in vitro colon simulator in three amounts of 0%, 1% and 2%. Results provide insight into the mechanisms underlying colon cancer cells and a comparison of a complex fiber metabolome to 5 mM butyrate and 100 mM NaCl. Furthermore, the results give insight of dosage effect of increasing the concentration of fiber. High level of dietary fiber has been epidemiologically linked to protection against the risk for developing colon cancer. The mechanisms of this protection are not clear. Fermentation of dietary fiber in the colon results in production of for example butyrate that has drawn attention as a chemopreventive agent. Polydextrose, a soluble fiber that is only partially fermented in colon, was fermented in an in vitro colon simulator, in which the conditions mimic the human proximal, ascending, transverse and distal colon in sequence. The subsequent fermentation metabolome were applied on colon cancer cells, and the gene expression changes studied. Polydextrose fermentation down-regulated classes linked with cell cycle, and affected number of metabolically active cells. Further, up-regulated effects on classes linked with apoptosis implicate that polydextrose fermentation plays a role in induction of apoptosis in colon cancer cells. The up-regulated genes involved also key regulators of lipid metabolism, such as PPARg and PGC-1α. These results offer hypotheses for the mechanisms of two health benefits linked with consumption of dietary fiber, reducing risk of development of colon cancer, and dyslipidemia. Non-differentiated Caco-2 cells were treated with polydextrose fermentation metabolites from the vessels representing different parts of the colon, or with 100 mM NaCl or with 5 mM butyrate for 24 hours. For polydextrose fermentation three concentrations of polydextrose were used: 0%, 1% and 2% for a simulation that lasted for 48 hours. Polydextrose fermentation samples from total of 12 vessels, as well as from medium sample, 5 mM butyrate and 100 mM NaCl were analysed as single replica.

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Bacteroides intestinalis–Driven Arabinoxylan Fermentation Mitigates Inflammatory and Metabolic Dysfunction

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