Intestinal Flora and Myocarditis: Potential Mechanisms and Therapeutic Strategies Affecting Disease Progression and...

Myocarditis is a clinically challenging form of inflammatory heart disease with heterogeneous etiologies, limited diagnostic tools, no targeted therapies, and a substantial risk of progression to heart failure or sudden cardiac death, particularly in young adults. Emerging evidence has increasingly associated myocarditis with gut microbiota dysbiosis. This review explores the gut-myocarditis axis, highlighting key mechanisms and therapeutic strategies. Significant alterations in gut microbial composition are observed in myocarditis patients and animal models. Gut microbiota influences disease development through multiple pathways: compromised intestinal barrier integrity leading to bacterial translocation and systemic inflammation via MAMP/PRR signaling (e.g., TLRs, NLRs); production of metabolites-including pro-inflammatory trimethylamine N-oxide (TMAO), anti-inflammatory short-chain fatty acids (SCFAs), and immunomodulatory bile acids-that regulate host inflammatory responses, immune cell differentiation, oxidative stress, and fibrotic remodeling; and molecular mimicry, where microbial peptides (e.g., from Bacteroides thetaiotaomicron) trigger cross-reactive autoimmune responses against cardiac proteins. Regarding therapeutic strategies, this review discusses fecal microbiota transplantation (FMT), probiotics, prebiotics, dietary modulation, and emerging approaches including engineered bacteria and oral nanomedicines. Although these strategies hold promise, their efficacy and safety remain to be validated in large-scale clinical trials, and further investigation is warranted.