A distinct metabolomic pattern revealed intestinal microenvironment factor-mediated food allergy in a BALB/c mouse model

Intestinal immune homeostasis plays a critical role in the pathogenesis of food allergy. However, the association between intestinal microenvironment factors and food allergy severity is not well studied. In this study, we established a gluten allergy (GA) BALB/c mouse model and revealed the intestinal luminal factor-mediated alterations in phenotypes and endotypes of GA, combined with untargeted metabolomic profiling of the colonic contents. Our results showed that gluten sensitization induced severe allergic responses in BALB/c mice, characterized by exacerbated clinical allergic and diarrheal symptoms, increased histamine, elevated gluten-specific immunoglobulin (Ig)E and IgG2a levels, and increased mast cell degranulation. In response to GA, T-cell balance was disrupted, with aberrant production of interleukin (IL)-4, interferon (IFN)-γ, IL-10, and IL-2 in the spleen. GA led to a disrupted intestinal microenvironment homeostasis, including increased pH and water content, impaired intestinal antioxidant capacity and epithelial barrier function, decreased short-chain fatty acid production, and microbial dysbiosis, which was strongly correlated with GA severity. By metabolomic profiling, we found 29 differential expressed metabolites (DEMs) associated with GA, with 9 down-regulated and 20 up-regulated. A total of 11 out of all DEMs were classified into dipeptides, and 10 of them were up-regulated in the GA mice. Pathway enrichment analysis showed that most of the DEMs were enriched into the bile secretion metabolic route.