Food allergens are the key triggers of allergic diarrhea, causing damage to the immune-rich ileum. This weakens the mucosal barrier and tight junctions, increases intestinal permeability, and exacerbates allergen exposure, thereby worsening the condition. Sesamin, a natural lignan isolated from sesame seed, has shown potential in regulating immune responses, but its effects on intestinal health remain unclear. In this study, we constructed an ovalbumin (OVA)-induced allergic diarrhea mouse model, which demonstrated increased mast cell degranulation, reduced tight junction integrity, and impaired intestinal barrier function. Pro-inflammatory cytokines were significantly increased in the ileum, along with unbalanced cluster of differentiation 4 (CD4) T-cell immunity, altered gut microbiota composition, and disrupted bacterial metabolism. Sesamin treatment significantly alleviated intestinal damage by modulating gut microbiota abundance, enhancing short-chain fatty acid (SCFA) production, and increasing SCFA receptor expression. This study suggests that sesamin may be a promising therapeutic candidate for allergic diarrhea and intestinal injury.
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