Mechanism of high-fat diet exacerbating α-lactalbumin-induced allergic responses: Microbiome and metabolomic insights.

High-fat diet (HFD) is a key contributor in exacerbating food allergy, but there is little in-depth research on the mechanisms by which HFD affects allergic responses induced by α-lactalbumin (ALA). The mechanism of HFD exacerbating ALA-induced allergic responses (H-ALA) was studied via microbiome and metabolomics. HFD induced alterations in body weight and temperature in ALA-sensitized mice, while exacerbating allergic responses by increasing ALA-specific IgG/IgE levels and disrupting Th1/Th2 cytokine balance. In H-ALA, 16S rRNA gene sequencing revealed that Staphylococcus and Bilophila were the dominant genera, and untargeted metabolomics demonstrated an upregulation of histidine accompanied by reduced indole-3-acetic acid. Correlation analysis and subsequent mechanistic validation suggested that HFD might exacerbate ALA-induced allergic responses through promoting the expansion of Staphylococcus and elevating histidine levels. These findings will provide a theoretical foundation for the prevention and intervention of HFD-exacerbated food allergy.