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

Abstract

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.