(P31-06-26) Blueberry Supplementation Modulates Gut Microbiota and Intestinal Immunometabolic Pathways in Healthy Young Mice

Objectives: Dietary blueberry supplementation influences gut microbiota and immune responses, yet how these processes interact in the intestine of healthy hosts remains unclear. This study examined whether blueberry supplementation alters gut microbial composition and intestinal immune and metabolic pathways in male and female mice, and whether these responses are tissue-specific or systemic.

Methods: Three-week-old male and female C57BL/6J mice were assigned to either control or blueberry groups and fed an AIN-93G diet with or without 10% (w/w) blueberry powder for five weeks. Body weight and food intake were recorded weekly. Liver and ileal lamina propria tissues were collected for RNA sequencing, cecal contents for 16S rRNA microbiome profiling, and serum for metabolic hormone analyses.

Results: Body weight and food intake did not differ between groups. Blueberry supplementation induced marked changes in the ileal transcriptome in both sexes. Immune-related pathways, including IFN-γ response, immune activation, and TGF-β signaling, were increased, whereas pathways associated with cell proliferation (E2F, MYC, and G2M targets) were reduced. Pathway analysis further suggested a shift in intestinal energy metabolism, with higher oxidative phosphorylation and lower glycolysis signatures. In contrast, diet-related transcriptomic changes in the liver were minimal, and liver gene expression patterns were largely associated with sex differences. Blueberry feeding also altered gut microbial composition, including increased abundance of genera such as Bifidobacterium and the [Eubacterium] coprostanoligenes group, and functional prediction suggested shifts in microbial tryptophan metabolism. Metabolic hormone analysis showed lower ghrelin and higher leptin levels in blueberry-fed mice.

Conclusions: Blueberry supplementation promotes tissue-specific intestinal immune activation and metabolic remodeling in healthy mice, accompanied by gut microbiota restructuring. These findings provide insight into how dietary blueberry shapes intestinal immune–metabolic homeostasis.

Funding Sources: NIH and USDA