The Combination of Indole‐3‐Carbinol and Tryptophan Provides Additive Benefits in Enhancing Innate Immunity Against Salmonella Colitis in Mice

Salmonella spp. remains a significant global public health concern, capable of causing a spectrum of diseases. The aryl hydrocarbon receptor (AhR) is known to confer protective effects in Salmonella ‐induced colitis. Although indole‐3‐carbinol (I3C) and tryptophan (Trp) are known dietary sources of AhR ligands, their combined effects on Salmonella pathogenesis have yet to be fully characterized. We employed a well‐established Salmonella colitis model using 6–8‐week‐old female C57BL/6 mice to evaluate the combined effects of I3C and Trp. Mice were pretreated with oral gavage of I3C (100 mg/kg/day), Trp (100 mg/kg/day), or both for seven consecutive days before infection. The I3C + Trp combination significantly alleviated clinical signs of colitis, reduced cecal mRNA expression of proinflammatory cytokines (IL‐1β, IL‐6, CXCL2, IL‐17α), and increased expression of immune‐modulating genes (IL‐22, CRAMP, ATG16L1) compared to individual treatments. Immunohistochemical staining revealed decreased zonulin and claudin‐2, and increased occludin, AhR, and vitamin D receptor expression in the cecal mucosa. The combination of I3C and Trp exerts additive protective effects against Salmonella ‐induced colitis by modulating host immune responses and enhancing epithelial barrier integrity. These results suggest dietary AhR ligands may serve as a promising complementary approach for the prevention and management of invasive salmonellosis.