Gut microbiota alters cardiac metabolism and immune system composition in viral myocarditis mice

The effects of the gut microbiota on the regulation of host physiology have recently garnered considerable attention, particularly in metabolism and the immune system. However, the role of the gut microbiota in viral myocarditis (VMC) remains to be fully elucidated.

Balb/c mice were injected with CVB3 to induce VMC. VMC mice were treated with fecal microbiota transplantation (FMT) or antibiotics (ABX) to evaluate the therapeutic effects of these interventions. Echocardiography, HE, and Masson's staining of the heart were used to assess cardiac function and pathological changes. 16S rDNA sequencing was conducted to explore alterations in gut microbial composition. UPLC-MS/MS-based metabolomics was used to detect disturbances of cardiac metabolic profiles. Flow cytometry was applied to analyze the dynamics of immune cell subsets, including M1, M2, Th1, Th2, Th17, and Treg cells. RT-PCR was performed to quantify cytokine expression levels in the heart.

FMT reduced cardiac inflammation and fibrosis, enhanced heart function, remodeled the structure of gut microbiota in VMC, and increased bacterial diversity, with an enrichment of p-Proteobacteria, the reduction of g-Pseudomonas, g-Streptococcus, and g-Ralstonia. Meanwhile, FMT induced alterations in cardiac metabolites in VMC, with enrichment of the steroid hormone biosynthesis pathway. A significant negative correlation was found between desoxycortone, corticosterone, 21-deoxycortisol, and cortodoxone with p_Spirochaetota and p_Kapabacteria. Furthermore, FMT reduced the proportions of M1 macrophages, Th1, and Th17 cells, as well as the cytokines TNF-a, IL-6, and IL-1β, and increased M2 macrophages and Treg cells. Regarding the role of antibiotics in VMC, our findings indicated that antibiotics altered the gut microbiota, myocardial metabolism, and immune response. Compared with antibiotics, FMT exerted a better effect on the alleviation of cardiac inflammation and fibrosis.

In VMC mice, the gut microbiota, which mediates disturbances in cardiac metabolites and the host immune response, may contribute significantly to the development of cardiac inflammation and fibrosis. Furthermore, FMT may represent a promising therapeutic approach for VMC.