High-fat diet-induced gut microbiota functional reprogramming is associated with metabolic inflammation and cardiac remodeling through the gut-heart axis in mice.

BACKGROUND: Gut microbiota alterations have been implicated in the progression of metabolic syndrome (MetS), which increases the risk of cardiovascular disease (CVD) and is influenced by lifestyle factors. However, the specific gut microbiota changes and their functional roles in MetS remain incompletely understood. AIMS: We aimed to identify key gut microbial taxa associated with MetS and to explore their potential functional implications. METHODS: Six-week-old male C57BL/6J mice were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks. Body weight and adiposity, metabolic parameters (fasting blood glucose, oral glucose tolerance test, and serum insulin), systemic inflammatory markers (IL-6, TNF-α, CRP, and high-sensitivity CRP), and cardiovascular phenotypes (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) were assessed. Cardiac remodeling was evaluated by heart weight-to-body weight ratio and myocardial histopathology using hematoxylin and eosin (H&E) and Masson's trichrome staining. Cecal contents were collected for 16S rRNA gene sequencing. RESULTS: HFD feeding induced a MetS-like phenotype characterized by obesity, insulin resistance, dyslipidemia, systemic inflammation, and early cardiac remodeling in mice. 16S rRNA sequencing revealed significant alterations in gut microbial composition, including enrichment of inflammation-associated taxa such as Escherichia-Shigella, Parasutterella, Faecalibaculum, and the Clostridium innocuum group, together with depletion of potentially beneficial bacteria including Roseburia, Alistipes, Parabacteroides, Prevotellaceae_UCG-001, and Rikenellaceae_RC9_gut_group. Functional prediction analyses indicated alterations in microbial pathways related to phosphotransferase systems, xenobiotic degradation, infectious disease signaling, DNA repair, transcriptional regulation, replication, recombination, and mobile genetic elements. BugBase phenotype analysis further demonstrated increased facultatively anaerobic, stress-tolerant, biofilm-forming, and potentially pathogenic microbial phenotypes following HFD exposure. CONCLUSION: Our findings suggest that HFD-induced Mets is associated with gut microbiota dysbiosis and functional remodeling, suggesting a potential involvement of microbiota-mediated metabolic pathways and host-microbiota interactions in cardiometabolic abnormalities.