Multi-omics reveals the attenuation of metabolic cardiomyopathy in mice by alkaloids in extracts from Clausena lansium (Lour.) via the transition of gastrointestinal microbiota to an alternative homeostasis

[Display omitted] •Alkaloids in WE contribute to protective effects against HFD-induced cardiomyopathy.•Interaction between GI microbiota and WE induces the generation of compounds with health beneficial effects.•Instead of the restoration of state before treating, a novel GI microbiota homeostasis is achieved after WE administration. Wampee has various biological functions, and the current study assesses its protective effects against metabolic cardiomyopathy (CMP) by focusing on gastrointestinal microbiota. The composition of wampee extract (WE) was determined, and mice were subjected to CMP model induction before handled with WE. WE improved heart function, reduced intestine permeability, and suppressed inflammation, and the function was attributed to alkaloids including girinimbine and stachydrine. The CMP model and WE had little influence on the alpha diversity, while CMP model changed the beta-diversity of mice microbiota. Duncaniella, Ruminococcus, Aspergillus, and Penicillium were positively correlated with the progression of metabolic CMP, while Muribaculum, Paramuribaculum, and Prevotella were negatively correlated, the abundance of which were restored by WE. The changes in microbes increased function enrichment in pathways related to immune responses and produced cardio-protective metabolites such as norleucine. WE induced a new homeostasis in the GI microbiota of CMP mice, thereby attenuating metabolic CMP.