Tryptophan metabolites derived from Lactiplantibacillus plantarum Y42 regulate the AhR/Nrf2/NF-κB axis to ameliorate colitis in mice

Y42 (Y42) in metabolizing Trp to alleviate colitis in mice. The results showed that compared to Trp alone or Y42 alone, the combined intervention of Trp and Y42 significantly improved the Disease Activity Index (DAI), colon length, organ index, intestinal permeability and intestinal barrier function in pseudo-germ-free mice with colitis. Furthermore, the combined intervention of Y42 and Trp significantly increased the levels of tryptophan metabolites, including indole-3-lactic acid (ILA), indole-3-carboxaldehyde (IAld), 3-indole-propionic acid (IPA) and indole-3-acetic acid (IAA) in the serum, and activated the AhR and Nrf2 signaling pathways in the colon while inhibiting the NF-κB signaling pathway of the mice. Meanwhile, the expression of AhR in the colon was significantly positively correlated with the levels of ILA, IAld, IPA, and IAA in the serum, the expression of tight junction proteins in the colon, and the expression of Nrf2 in the colon. It was also significantly negatively correlated with the expression of NF-κB and IκB-α in the colon. Therefore, in mice, Y42 may activate the AhR signaling pathway by metabolizing Trp to produce ILA, IPA, IAA, and IAld, thereby activating the Nrf2 signaling pathway and inhibiting the NF-κB signaling pathway, ultimately alleviating colonic inflammation and barrier function damage. These results indicate that Y42 can be combined with Trp or food materials rich in Trp as synbiotics for colitis treatment.