Lonicera trichosantha alleviates LPS-induced endometritis in mice by modulating the gut microbiota and host...

Endometritis is an inflammatory disorder of the endometrial lining. Conventional antibiotic therapy often fails to control the accompanying disruptive inflammation. The 95 % ethanol-eluted fraction of Lonicera trichosantha (95 %-LT), exhibits potent anti-inflammatory activity in vitro. Nevertheless, its efficacy in vivo and the mechanisms underlying its potential therapeutic effect on endometritis are largely unknown.

This study aimed to elucidate the protective effects of 95 %-LT against endometritis and to define its mechanism of action, specifically through the gut microbiota-metabolite axis.

The chemical profile of the 95 %-LT fraction was characterized using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic effects of 95 %-LT were systematically investigated using in vitro cellular inflammation models, a murine endometritis model, 16S ribosomal RNA (16S rRNA) gene sequencing, untargeted metabolomics, pseudo-germ-free (PGF) models, fecal microbiota transplantation (FMT), and in vivo supplementation with key bacterial strains and metabolites.

Three primary chemical constituents were identified in the 95 %-LT. Dose-dependent mitigation of endometrial pathological injury was achieved following intervention with 95 %-LT. Gut flora reconstruction induced by 95 %-LT was validated through 16S rRNA gene sequencing, among which the commensal beneficial bacterium Lactobacillus murinus exhibited the most remarkable enrichment. Concurrently, untargeted metabolomics showed that 95 %-LT enhanced the production of kynurenic acid (KYNA), a tryptophan-derived metabolite. FMT and PGF model experiments confirmed that the gut microbiota is indispensable for this therapeutic effect. Finally, in vivo supplementation verified that both L. murinus and KYNA function as key mediators underlying the efficacy of 95 %-LT.

Our results demonstrate that 95 %-LT alleviates endometritis by orchestrating a gut microbiota-dependent mechanism, specifically through the "L. murinus-KYNA axis". This study provides a mechanistic foundation for exploiting Tibetan medicine-derived compounds in endometritis therapy.