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Allergy has become a public health problem worldwide, but effective diagnostic and therapeutic approaches are limited currently. Amino acids are essential macronutrients that potentially participated in the allergy process. This work aimed to investigate whether amino acids can be applied as a mediator for allergy diagnosis and therapy. Two cohort studies were performed to investigate the correlation between fecal amino acids and allergy responses, and a spleen cell model was used to validate the role of amino acids in regulating allergy. In a cohort study with 193 volunteers, fecal proline was found to be negatively correlated with serum IgE, and detailed data analysis revealed that people with high-IgE-mediated allergy had decreased odds of high intestinal proline. In another cohort study with distinct allergic and non-allergic individuals, proline concentration was significantly lower in the allergic group. Daily diet and metagenomics analysis showed that the proline intake and microbiota amino acid metabolism were not significantly different, implying that the body’s proline metabolism might be different between allergic and non-allergic individuals. Furthermore, the spleen cell model demonstrated that proline specifically targeted Th2 and Treg activity. Overall, this work revealed a tight correlation between gut proline and serum IgE, indicating proline as a promising biomarker and a potential therapeutic method for allergic diseases.

Celiac disease (CD) is a prevalent disorder with autoimmune features. Dietary exposure of wheat gluten (including gliadins and glutenins) to the small intestine activates the gluten-reactive CD4+ T cells and controls the disease development. While the human leukocyte antigen (HLA) is the single most important genetic factor of this polygenic disorder, HLA-DQ2 recognition of gluten is the major biological step among patients with CD. Gluten epitopes are often rich in Pro and share similar primary sequences. Here, we simulated the solution structures changes of a variety of gluten epitopes under different pH and temperatures, to mimic the fermentation and baking/cooking processes. Based on the crystal structure of HLA-DQ2, binding of differently processed gluten epitopes to DQ2 was studied in silico. This study revealed that heating and pH change during the fermentation process impact the solution structure of gluten epitope. However, binding of differently treated gluten epitope peptide (GEP) to HLA-DQ2 mainly depended on its primary amino acid sequence, especially acidic amino acid residues that play a pivotal role in their recognition by HLA-DQ2.