Periodontitis exacerbates metabolic dysfunction-associated steatotic liver disease via the gut microbiota-derived tryptophan metabolism-AHR axis in obesity

作者：Rixin Chen, Jun Qian, Qunyi Wang, Yue Li, Zhonghan Xu, Miaomiao Zhang, Min Wang, Hua Nie, Wenrong Yang, Xin Tong, Fuhua Yan · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.106037 · 被引用次数：16 · 研究领域：Oral microbiology and periodontitis research、Gut microbiota and health、Liver Disease Diagnosis and Treatment

Background Periodontitis is linked to metabolic dysfunction-associated steatotic liver disease (MASLD); however, the underlying mechanisms remain unclear. Methods Periodontitis was investigated in male mice with high-fat diet (HFD)-induced MASLD. Gut microbiome and metabolomic profiling were conducted using16S rRNA gene sequencing, along with both untargeted and targeted metabolomic profiling via liquid chromatography–tandem mass spectrometry. Intestinal barrier integrity was evaluated by histopathological analysis. Faecal microbiota transplantation was conducted and the vital role of the aryl hydrocarbon receptor (AHR) was confirmed using Ahr gene knockout ( Ahr −/− ) mice. The protective roles of tryptophan derivative indole-3-propionic acid (IPA) and the tryptophan-metabolising probiotic Limosilactobacillus reuteri were assessed following their administration via oral gavage. The impact of endotoxin-mediated hyperinflammation on hepatic mitochondrial dynamics was examined in vitro . Findings Periodontitis promoted MASLD, gut microbiota dysbiosis, and tryptophan metabolism depletion, leading to intestinal barrier dysfunction, systemic inflammation, and endotoxin overexpression in HFD-fed mice. Periodontitis-accelerated MASLD was attenuated in HFD-fed Ahr −/− mice. In an AHR-dependent manner, IPA or L. reuteri alleviated the detrimental effects of periodontitis on MASLD progression, intestinal barrier impairment, systemic inflammation, and endotoxin translocation to the live...