Pellizzon, M. | Search bioRxiv

bioRxiv2025

Wheat fiber-induced peripheral regulatory T-cells suppress development of colitis

Reduced dietary fiber intake is associated with, and may have contributed to, the post-mid-20th century increase in immune-mediated chronic inflammatory diseases, including inflammatory bowel disease. Reduced fiber intake has resulted, in part, from highly refined foods. For example, modern methods of producing bread removes much of the fiber naturally present in wheat kernels. Accordingly, we hypothesized that wheat fiber might protect against chronic inflammatory diseases. We tested this notion in a murine T-cell transfer colitis model. Rag1-/- mice were fed open-source low-fiber diets enriched, or not with wheat fiber (WF) and then administered CD45Rbhi T-cells. WF conferred robust protection in this colitis model as assessed by an array of clinical, histopathologic, morphologic, and immune-related parameters. WFs protection against colitis associated with a microbiota-dependent increase in Foxp3+ T-cell (Tregs), which could be recapitulated in vitro. WF did not induce Tregs in CNS1-/- mice nor did WF protect against T cell transfer colitis driven by transplant of colitogenic T-cells from CNS1-/- mice. Thus, enriching diet with WF has potential to promote microbiota-dependent peripheral Treg development and, consequently, protect against chronic inflammatory diseases.

immunology↗

bioRxiv2024

Purified diets containing high levels of soluble fiber and grain-based diets promote similar gastrointestinal morphometry yet distinct microbial communities

Grain-based diets (GBDs) are widely used in rodent studies but their utility is limited due to batch-to-batch variability resulting from inconsistent ingredients. Purified diets (PDs) are composed of only known and refined ingredients and offer a solution to the constraints of GBDs. However, unlike GBDs, PDs commonly used as control diets typically contain little to no soluble fiber. We therefore sought to identify a combination of fibers in PDs that best recapitulates the gastrointestinal morphometry and intestinal microbial composition of mice fed GBDs. Adult male mice (n=30) were randomly assigned to one of six diets--two GBDs and four PDs with varying insoluble and soluble fiber composition--for 28 days. 16S rRNA gene sequencing was used to compare microbial profiles across different gastrointestinal (GI) niches and diets. Gut microbiotas and cecal weights were distinct between mice fed the two GBDs, indicating that GBDs are unreliable controls in diet-based studies. Unexpectedly, intestinal microbial richness decreased as the amount of soluble fiber in the PDs increased and the addition of multiple soluble fibers did not rescue this effect. Mice fed PDs with high soluble fiber content ([≥] 75% of dietary fiber was soluble fiber) best recapitulated GI morphometry of mice fed GBDs, but intestinal microbial communities were distinct between PD- and GBD-fed mice. Although supplementing PDs with soluble fiber improved GI morphometry, further research to determine the optimal mixture of soluble and insoluble fibers is required to more closely mirror the intestinal microbial diversity observed in mice fed GBDs. ImportanceDietary fibers are essential for maintaining gut health. Insoluble fibers aid in fecal bulking and water retention while soluble fiber is a fermentative substrate for intestinal microbial communities. GBDs are commonly used in preclinical research but the variability in ingredients across batches impedes reproducibility. PDs, which are composed of highly refined ingredients, pose a potential solution but the most widely used low-fat control PDs contain no soluble fiber. This study intended to identify a PD with a combination of fibers that promotes murine gut health and microbial diversity. A PD with optimal fiber composition would aid in the standardization and reproducibility of studies investigating intestinal physiology and the gut microbiota.

microbiology↗