(P20-025-23) Protection Against Acute Colitis in Human Microbiota Associated Mice Consuming Whole Grain Sorghum Flour Is Not Directly Attributable to Dietary Resistant Starch

Objectives: Preclinical studies suggest that consuming whole grain foods rich in resistant starch (RS), such as sorghum flour, promotes a gut microbial community that may protect against intestinal inflammation. However, these studies have not considered the baseline variation in the human gut microbiome that influences the efficacy of clinical RS interventions. Here, we evaluated protection against colitis in different lines of human microbiota associated (HMA) mice consuming sorghum flour and assessed whether RS from sorghum specifically influenced colitis outcomes in HMA mice.

Methods: Germ-free C57BL/6 mice were colonized with one of three human fecal microbiotas via oral gavage. To assess the effects of whole grain sorghum, mice were fed either a fiber-free diet or a diet containing 30% commercial sorghum flour (w/w). To test the effects of sorghum RS, mice were fed either a fiber-free diet or one of four diets containing 30% flour from either a wild-type sorghum line (Wheatland or Tx430) or a near-isogenic, low RS, waxy mutant. Two weeks later, mice were provided either dextran sulfate sodium (DSS; 1.25% w/v) or water for seven days.

Results: HMA mice consuming a 30% sorghum flour diet experienced less body weight loss and colon shortening, had lower microscopic disease scores, and produced fewer pro-inflammatory cytokines and chemokines (IL-1β, TNF-α, IL-6, KC, and MCP-1) and lipocalin-2 in the intestinal mucosa compared to mice consuming a fiber-free diet. No significant differences in protection from colitis were observed between mice consuming wild-type versus waxy sorghum. Notably, diet-dependent effects on colitis severity (weight loss, colon shortening and lipocalin-2) were observed among the five dietary treatments that were not directly attributable to RS content. Microbiome-dependent effects on colitis severity were also observed among the three human fecal microbiotas.

Conclusions: Collectively, our results indicate that human gut microbiota variation and sorghum flour composition, but not dietary RS content, influence the severity of a DSS colitis injury. However, diet-dependent differences in colitis severity suggest that subtle differences in whole grain sorghum flour composition may be important determinants of gut health.

Funding Sources: USDA-NIFA and NU Collaboration Initiative