Gut inflammation favors adverse food reactions by disrupting the microbial metabolism of food triggers.

METHODS: We sensitized mice to different foods (dairy and gluten) after intestinal inflammation (chemically- and hapten-induced models), then mice were re-exposed to the sensitizing foods through diet enrichment. To study whether inflamed microbiota facilitates adverse food reactions, we employed gnotobiotic models and bacterial supplementation experiments. We assessed markers of intestinal inflammation and sensitization, clinical responses, RNA transcripts, and microbiota composition and function. In a translational approach, we recruited IBD patients in remission and healthy controls, recorded self-reported food intolerances and clinical responses to triggering foods, and collected feces for gut microbiota analyses.

RESULTS: Intestinal inflammation facilitates food sensitization by disrupting microbial antigen metabolism, recruiting mast cells to the colon, and favoring IgE production. In gnotobiotic models, inflammation-driven depletion of colonic bacteria involved in food digestion contributed to food sensitization. Upon re-exposure to triggering foods, sensitized mice experienced visceral pain and low-grade inflammation through mast-cell mediated mechanisms, which also worsened experimental colitis. Supplementation with depleted bacteria or treatment with mast cell stabilizers attenuated food-driven responses. In IBD patients, self-reported food intolerances were common and associated with microbial disruption and depletion of food-metabolizing bacteria.

CONCLUSION: Microbial metabolism of foods is disrupted after intestinal inflammation. This facilitates food sensitization, through colonic mast cell-mediated immune responses, which may explain the high number of adverse food reactions reported by IBD patients.