Recent research consensus has highlighted the role of
intestinal
luminal factors in the association between intestinal microenvironment
homeostasis and food allergy. However, the association between intestinal
immune homeostasis and food allergy-related proteomic features remains
elusive. In this study, we aimed to investigate the changes in gluten
allergy (GA)-defined phenotypes and endotypes and intestinal microenvironment
factors in BALB/c mice and linked GA to colonic proteomic signatures.
Combined with increased allergy and diarrhea scores, intense antibody
responses and abnormalities in T-cell cytokine production were induced
in mice. GA-associated disruption of intestinal microenvironment homeostasis
was underlined by the increased colonic pH, decreased intestinal antioxidant
capacity, impaired intestinal barrier function, and decreased production
and imbalanced proportions of short-chain fatty acids. 16S rRNA amplicon
sequencing showed that the gut microbiota dysbiosis in mice was characterized
by significant enrichment of six bacterial taxonomic units, including
Prevotellaceae, Escherichia Shigella, Alloprevotella, Escherichia coli, Bacteroides vulgatus, and Lachnospiraceae
bacterium DW59, which was correlated with immune end points. Using
a label-free proteomics quantitative approach, 24 differentially expressed
proteins linking GA-induced gut dysbiosis were identified, with four
of them enriched in the serine endopeptidase inhibitor activity pathway.
The development of GA in mice was associated with changes in specific
intestinal luminal factors and may be mediated by serine protease
activity-associated metabolic routes.