Reducing Endogenous Lactate Production Ameliorates Ovalbumin-Induced Food Allergy via Regulating Lactylation and Microbial Homeostasis in Mice

Our previous study found a significant elevation of lactate in ovalbumin (OVA)-allergic mice, while the specific functions of lactate in food allergy (FA) remain elusive. In this study, an inhibitor of lactate dehydrogenase was applied in the OVA-induced FA model to inhibit endogenous lactate generation. It was shown that reducing lactate levels mitigated allergic diarrhea (GSK group: 25% vs FA group: 100%), decreased the serum OVA-specific IgE, suppressed the Th2-type immune response, and restrained mast cell activation. Further analysis found that lactate reduction decreased the gene expression of lactate transporters (MCT1 and MCT4), inhibited jejunal protein lactylation, and improved the intestinal microbiota dysbiosis (such as upregulating the abundance of the <i>Clostridium</i> genus and <i>Limosilactobacillus_reuteri</i>), which might be the potential mechanism underlying its mitigation of food anaphylaxis. Collectively, this study unveiled the critical role of endogenous lactate in the development of FA, highlighting the potential of intervention strategies targeting lactate in FA alleviation.