Regulation of autoimmune myocarditis by host responses to the microbiome

Abstract

The extensive, diverse communities that constitute the microbiome are increasingly appreciated as important regulators of human health and disease through inflammatory, immune, and metabolic pathways. We sought to elucidate pathways by which microbiota contribute to inflammatory, autoimmune cardiac disease. We employed an animal model of experimental autoimmune myocarditis (EAM), which results in inflammatory and auto-immune pathophysiology and subsequent maladaptive cardiac remodeling and heart failure. Antibiotic dysbiosis protected mice from EAM and fibrotic cardiac dysfunction. Additionally, mice derived from different sources with different microbiome colonization profiles demonstrated variable susceptibility to disease. Unexpectedly, it did not track with segmented filamentous bacteria (SFB)-driven Th17 programming of CD4+ T cells in the steady-state gut. Instead, we found disease susceptibility to track with presence of type 3 innate lymphoid cells (ILC3s). Ablating ILCs by antibody depletion or genetic tools in adoptive transfer variants of the EAM model demonstrated that ILCs and microbiome profiles contributed to the induction of CCL20/CCR6-mediated inflammatory chemotaxis to the diseased heart. From these data, we conclude that sensing of the microbiome by ILCs is an important checkpoint in the development of inflammatory cardiac disease processes through their ability to elicit cardiotropic chemotaxis.

Microorganisms and cardiovascular diseases: importance of gut bacteria

“…The gut microbiota is a complex ecosystem of symbiotic bacteria. It contributes to the mammalian host physiology and metabolism by (i) aiding the processing of the apparently indigestible nutrients, (ii) supplying the necessary metabolites, and (iii) activating the host's protective immune system to some extent [19,20]. Macrophages, neutrophils, monocytes, innate lymphoid cells, and bacterial metabolism products like short-chain fatty acids (SCFAs) are known to inhibit the growth of pathogens by producing primary and secondary bile acids, and butyrate [21].…”

“…Alteration/changes within the gut microflora may pose significant impact on the regulation of host biochemical and metabolic design. The knowledge on (i) gut microflora, (ii) associations between the microbiome and the inflammasome, (iii) the innate immune system, (iv) role of bile acids, (v) the gut permeability may aid potential preventive strategy against CVD and coupling microorganisms to the pathogenesis of the autoimmune disease [19,[35][36][37][38][39]. Indeed, the gut microorganisms are one of the important main factors influencing systemic immune responses and metabolic dysfunctions among the individuals with obesity.…”

“…The lipopolysaccharide (LPS) from P. gingivalis was suggested to be responsible for the inflammation-induced CVD through the elevated oxidative stress (increased ROS) and mitochondrial dysfunction [42]. Another interesting study using mouse model showed the mechanisms by which the microorganisms may control the pathogenic inflammation in the heart and the novel innate immune responses [19]. A generalized model of heart diseases induced by the gut bacteria has been clarified in Fig.…”

The Role of Microbiologic Agents in the Progression of the Atherosclerosis: A comprehensive review

“…Barin JG showed that gut microbial dysbiosis may trigger autoimmune myocarditis and it may lead to subsequent maladaptive cardiac remodeling and heart failure. So, we can conclude that gut microbiota have a significant impact on the cardiac function by the distant immugenic effects [ 47 ].…”

Microbiota and Myopericarditis: The New Frontier in the Car-Diological Field to Prevent or Treat Inflammatory Cardiomyo-Pathies in COVID-19 Outbreak

“…Similarly, in animal models of experimental autoimmune myocarditis, an increase in microbial diversity and richness has been observed [ 9 ]. Interestingly, it was also observed that in different mice with different gut microbiota colonization profiles, susceptibility to autoimmune myocarditis varied immensely [ 10 ].…”