The role of mast cells (MCs) in ulcerative colitis (UC) is controversial. This study investigated the relationship between FcεRI, a high-affinity IgE receptor on MCs, gut microbiota, and DSS-induced colitis in mice. Anti-FcεRI showed high diagnostic value for UC. FcεRla knockout ameliorated DSS-induced colitis, correlated with increased *Lactobacillus* abundance and NLRP6 inflammasome pathway activation. *Lactobacillus plantarum* supplementation also protected against colitis, an effect lost in a lactic acid-deficient variant. FcεRla deficiency mitigated colitis, potentially due to increased *Lactobacillus*. This highlights the link between allergic reactions, microbiota, and colitis.
