Cross, T.-W. L. | Search bioRxiv

bioRxiv2026

Impaired Fermentation in the Absence of Gut Microbiota Promotes Inulin-Induced Intestinal Inflammation

Background and aims: Inflammatory bowel diseases (IBD) are characterized by altered gut microbiota composition and impaired dietary fiber fermentation, which can complicate symptom management. Although inulin is a well-established prebiotic fiber, it can exacerbate gut inflammation under certain conditions. We hypothesized that impaired microbial fermentation leaves intact inulin in the gut to activate epithelial immune receptors and promote inflammation, whereas effective fermentation reduces this pro-inflammatory signaling. Methods: We used germ-free (GF) and conventional (CONV) interleukin-10 knockout (Il10-/-) and wild-type (WT) C57BL/6J mice to assess the role of microbial fermentation and host genetic susceptibility in IBD. GF Il10-/- mice were colonized with fecal microbiota from ulcerative colitis (UC) patients or healthy individuals with fiber intolerance (FI). Mice were fed inulin or structurally distinct, physicochemically matched fiber analogs. Colonic inflammatory and barrier-related gene expression and protein levels were assessed by qPCR and ELISA. Results: In GF Il10-/- mice, inulin, but not cellulose, induced weight loss, diarrhea, and rectal prolapse. Increased colonic toll-like receptor expression (TLR2, TLR4) as well as elevated serum amyloid A (SAA) and lipocalin-2 levels indicated immune activation by unfermented inulin in GF mice. Colonization with dysbiotic microbiota attenuated these effects. {beta}-fructan fibers including fructooligosaccharides and chicory-derived inulin elicited marked inflammatory responses, whereas agave-derived inulin did not, highlighting the influence of fiber composition in inflammation associated with IBD. Conclusions: Effective microbial fermentation is essential for host tolerance to fermentable fibers. These findings underscore the need of personalized nutrition when recommending fiber supplementation in immune-compromised individuals or those with gut dysbiosis.

immunology↗

bioRxiv2024

A gnotobiotic mouse model with divergent equol-producing phenotype: potential for determining microbial-driven health impacts of soy isoflavone daidzein

The implications of soy consumption on human health have been a subject of debate, largely due to the mixed evidence regarding its benefits and potential risks. The variability in responses to soy has been partly attributed to differences in the metabolism of soy isoflavones, compounds with structural similarities to estrogen. Approximately one-third of humans possess gut bacteria capable of converting soy isoflavone daidzein into equol, a metabolite produced exclusively by gut microbiota with significant estrogenic potency. In contrast, lab-raised rodents are efficient equol producers, except for those raised germ-free. This discrepancy raises concerns about the applicability of traditional rodent models to humans. Herein, we designed a gnotobiotic mouse model to differentiate between equol producers and non-producers by introducing synthetic bacterial communities with and without the capacity into female and male germ-free mice. These gnotobiotic mice display equol-producing phenotypes consistent with the capacity of the gut microbiota received. Our findings confirm the models efficacy in mimicking human equol production capacity, offering a promising tool for future studies to explore the relationship between endogenous equol production and health outcomes like cardiometabolic and fertility. This approach aims to refine dietary guidelines by considering individual microbiome differences.

microbiology↗