Study on Dianthus superbus L. against Acute Liver Injury via the Gut–Liver Axis — Regulation of Gut Microbiota and Tryptophan Metabolism to Activate AhR Signaling

Abstract Background Dianthus superbus L. (DS) treats liver diseases, but its ALI mechanism via gut microbiota/metabolites is unclear. Purpose Investigate DS effects on CCl₄-induced ALI and mechanisms. Methods DS components (HPLC-MS/MS) were identified. ALI rats received DS. Liver/colon injury, fibrosis (biochemistry, histology, IHC, IF, WB for α-SMA, Collagen I, Occludin, ZO-1), serum metabolomics, fecal 16S rRNA, and tryptophan-targeted metabolomics were assessed. Antibiotics and FMT from DS-treated donors explored microbiota roles. Results 37 components, including Kaempferol and Aurantiamide, were identified. DS attenuated ALI, reducing hepatic α-SMA/Collagen I while increasing AhR/Cyp1a1, and upregulating colonic Occludin/ZO-1. FMT replicated DS benefits. Untargeted metabolomics linked effects to Linoleic/Tryptophan metabolism. 16S rRNA showed increased beneficial microbiota (HT002, Lactobacillus, Romboutsia); FMT confirmed Lactobacillus enrichment. DS normalized tryptophan metabolites (4-Hydroxybenzoic acid, L-Kynurenine, Indole-3-carboxaldehyde). Conclusion DS ameliorates ALI gut-microbiota-dependently by modulating tryptophan metabolism, enhancing intestinal barrier function, activating AHR signaling, and suppressing fibrosis biomarkers, indicating its potential as a microbiota modulator for ALI. Importance Acute liver injury is a serious health threat with limited treatment options. This study explores how a traditional medicinal herb, Dianthus superbus L. (DS), protects the liver through an unexpected route: the gut. We discovered that DS works by rebalancing the community of gut bacteria, which in turn improves the intestinal barrier and fine-tunes the body’s tryptophan metabolism. This cascade of effects ultimately activates a key cellular pathway (AhR) that reduces liver inflammation and fibrosis. Our findings not only clarify how this traditional remedy works but also highlight the critical role of the gut-liver axis, positioning DS as a promising, microbiota-targeting therapeutic candidate for preventing and treating liver disease.