Tryptophan‐Derived Microbial Metabolite Indole‐3‐Acetic Acid Ameliorates Periodontitis Through AhR / CYP1A1 ‐Mediated Macrophage Polarisation

ABSTRACT Aim To investigate the association between tryptophan‐derived microbial metabolites and periodontitis, and to assess whether the differential tryptophan metabolite indole‐3‐acetic acid (IAA) could ameliorate periodontitis and elucidate its potential mechanism. Materials and Methods The association between tryptophan‐derived metabolites and periodontitis was evaluated using targeted metabolomics analysis, 16S rRNA gene amplicon sequencing and correlation analysis. The impact of the differential metabolite IAA on periodontitis was assessed with micro‐computed tomography (micro‐CT), histological staining and real‐time quantitative polymerase chain reaction (RT‐qPCR). The effects of IAA on macrophages under an inflammatory microenvironment, along with its potential mechanism, were explored using RT‐qPCR, enzyme‐linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot. Results IAA, a differential tryptophan metabolite, was identified in the saliva of patients with periodontitis and periodontally healthy individuals. Local application of IAA in experimental mice with periodontitis alleviated the immune‐inflammatory response and reduced periodontal tissue destruction. Mechanistically, IAA induced M2 macrophage polarisation by activating the AhR/CYP1A1 axis, thereby contributing to the amelioration of periodontal destruction. Conclusions These findings highlight the potential role of the microbial metabolite IAA in the development and treatment of periodontitis, offering a new perspective for intervention strategies based on microbial metabolites for periodontitis.