The Tianma Anshen Dingxuan Formula Regulates Gut Microbiota and Metabolites in a Rat Model of Vertigo With Liver Yang Hyperactivity.

Abstract

INTRODUCTION: Vertigo is a prevalent clinical disorder that significantly compromises the quality of life of a patient. Among the syndrome patterns recognized in traditional Chinese medicine (TCM), vertigo due to liver-yang hyperactivity (LYH) is the most common subtype. This study explored the underlying therapeutic mechanisms of Tianma Anshen Dingxuan formula (TADF) on vertigo induced by LYH through the analysis of gut microbiota and their metabolites. METHODS: A total of 30 Sprague-Dawley rats were assigned to control, LYH vertigo model, and TADF groups. The LYH vertigo model was established through intragastric administration of aconite decoction combined with unilateral labyrinthectomy. Behavioral changes and colonic histopathology were conducted. The concentrations of 5-hydroxytryptamine (5-HT), dopamine (DA), and norepinephrine (NE) in the rat hypothalamus were quantified using the enzyme-linked immunosorbent assay (ELISA). The gut microbiota and metabolites were analyzed using 16S rRNA gene sequencing and ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). Spearman correlation analysis was performed to explore the relationships among the microbiota, metabolites, and behavioral indices. RESULTS: Treatment with TADF significantly improved behavioral indices (such as reduced head tilt, normalized reflexes) and colonic inflammation (lower histopathological scores, p&#x2009;<&#x2009;0.01), whereas it significantly reduced the concentrations of 5-HT, DA, and NE in the rat hypothalamus (p&#x2009;<&#x2009;0.05). Additionally, TADF modulated gut microbiota by upregulating both p_Patescibacteria and o_Oscillospirales while downregulating g_Bifidobacterium. Metabolomics identified 16 biomarkers (for instance, N-acetylneuraminate) enriched in pathways like tryptophan metabolism. Spearman analysis revealed correlations between microbiota (g_Ruminococcus), metabolites (chlorphenoxamine), and behavioral scores. CONCLUSION: Collectively, this study is the first to demonstrate the therapeutic effect of TADF on vertigo-afflicted rats. TADF significantly improved the levels of microbiota-mediated metabolites by restoring the impaired gut microbiota.