Multiomics Analyses Demonstrate the Attenuation of Metabolic Cardiac Disorders Associated With Type 2 Diabetes by Stachydrine in Relation With the Transition of Gastrointestinal Microbiota

Abstract

Stachydrine (STA) has therapeutic effects on heart disorders. The current study assessed its effects on Type 2 diabetes (T2D) induced cardiac disorders by focusing on the heart–gut axis. Mice were subjected to high-fat diet (HFD) and streptozocin (STZ) to induce cardiac disorders such as inflammation and structural deteriorations, which were handled with STA. Changes regarding the composition and metabolism of gastrointestinal (GI) microbiota were then determined using a multiomics strategy, including amplicon sequencing and metabolomics. The data showed that STA improved heart function, reduced intestinal permeability, and suppressed inflammation in mice in a dose-dependent manner. However, the compound had little influence on the overall alpha diversity of gut microbiota, while it did influence the beta diversity. The analyses based on the multiomics strategy demonstrated that certain GI microbial groups, including Paramuribaculum, Allobaculum, Bifidobacterium, and Adlercreutzia, responded to the STA administration, which contributed to the alternatives of metabolites in the gut. Correlation analyses showed that Duncaniella and Ruminococcus negatively impacted health, while Muribaculum, Paramuribaculum, and Prevotella positively influenced intestinal permeability and heart health. Collectively, STA attenuated T2D-induced cardiac disorders by improving heart structure and function and suppressing inflammation, during which the GI homeostasis of the T2D mice changed to an alternative state that was different from that of healthy mice.