Abstract
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)-y,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.
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