Lactobacillus plantarum modulates intestinal homeostasis through tryptophan metabolism-AhR signaling axis

• L. plantarum D266 from fermented foods ameliorates IBD by inhibiting ໿intestinal inflammation and gut ໿barrier damage. • L. plantarum D266 regulates tryptophan metabolism and produces ILA, ໿thereby activating the AhR signaling. • Tryptophan diet mediates the beneficial effects of L. plantarum D266 and AhR activation. • AhR deletion abrogates L. plantarum D266-mediated protective effects. Inflammatory bowel disease (IBD) is a prevalent condition characterized by dysregulation of the intestinal immune response and impaired barrier function, with probiotics emerging as a promising ໿microbial-based solution. Although ໿previous studies have reported that Lactobacillus plantarum D266 ( L. plantarum D266), isolated from traditional Chinese fermented foods, ameliorates ໿irritable bowel syndrome (IBS), its underlying role and precise mechanism in IBD remain elusive. Here, L. plantarum D266 administration contributed to IBD-alleviating symptoms by inhibiting ໿intestinal inflammation and gut ໿barrier damage. Further investigation revealed that ໿supplementation with L. plantarum D266 ໿altered aberrant composition of gut microbiota, enhanced tryptophan metabolism and metabolized tryptophan into ໿indole-3-lactate (ILA), ໿thereby activating the aryl hydrocarbon receptor (AhR) signaling and ໿increasing IL-22 production to ໿regulate intestinal homeostasis. Moreover, a tryptophan-enriched diet potentiated L. plantarum D266-mediated beneficial effects. However, dietary tryptophan restriction or ໿AhR deletion abrogated the protective effects of L. plantarum D266 against IBD progression. Our findings demonstrated that L. plantarum D266 with ILA-producing capacity was mediated by AhR signaling to໿ regulate IBD-associated dysbiosis of intestinal homeostasis, offering insights for potential nutritional intervention ໿for promoting gut health.