Quantifying communication along the gut-heart access following myocardial infarction in menopausal female mice

Objective: Post-myocardial infarction (MI) complications, such as systemic inflammation and adverse cardiac remodeling, instigates gut barrier dysfunction, gut dysbiosis and gut microbial translocation. Menopause exacerbates MI pathophysiology and gut barrier function presumably increasing gut microbial translocation to the heart. This study investigates microbial translocation along the gut-cardiac axis post-MI and dynamic changes in gut microbial beta-glucuronidase (GUS) activity as a measure of gut dysbiosis across the menopausal transition. Therefore, we hypothesized that menopause exacerbates cardiac pathophysiology, gut barrier dysfunction, and gut microbial translocation to the heart post-MI. Methods and Results: Female mice C57BL/6J mice at 9 weeks of age were given daily intraperitoneal injections of 4-vinylcyclohexene diepoxide (VCD) at a dose of 160 mg/kg for 20 consecutive days to induce menopause by 19 weeks of age; sesame oil (SO)-treated female mice served as controls. The probiotic Bifidobacterium animalis subspecies lactis 420 (B420) was gavaged (109 CFU) 24 hours prior to and immediately before permanent ligation of the left anterior descending (LAD) artery to induce MI. Forty-eight hours post-MI, heart tissue was collected, and gut microbial translocation was quantified by B420 levels in the cardiac infarct area using B420-specific PCR primers. Gut barrier function was measured by plasma fluorescein isothiocyanate-dextran (FITC-dextran) levels following FITC-dextran gavage 2 hours prior to sacrifice. To measure gut dysbiosis, fecal samples were collected from premenopausal and menopausal females, rehydrated in assay buffer and processed via mechanical disruption and sonication. Microbial GUS activity was assessed from these fecal samples using a fluorometric assay where hydrolysis of 4-Methylumbelliferyl-β-D-glucuronide (4MUG) indicated GUS activity normalized to total protein content. In general, menopausal mice following MI showed significant increased microbial translocation and gut barrier dysfunction and decreased GUS activity compared to premenopausal controls. Summary and Conclusions: In this proof-of-concept study, we provide evidence of direct translocation of gut microbes to the infarct area post-MI that increases in menopause. We provide further evidence that menopause, known to increase cardiac damage post-MI, also exacerbates gut barrier dysfunction and gut dysbiosis. Here, we further quantify communication along the gut-heart access that is impacted by hormonal status. Departmental Funding This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.