The gut microbiotas with metabolites regulate the protective role of miR-30a-5p in myocardial infarction

Abstract

This study demonstrates that the loss of miR-30a-5p worsened myocardial infarction-induced heart failure and impaired intestinal permeability by downregulating Claudin-1, Occludin, and ZO-1. Transplantation of fecal microbiota from miR-30a-5p-knockout mice aggravated MI damage in wild-type mice. The 16S rDNA sequencing of the gut microbiota showed that KO downregulated Lactobacillus and probiotics treatment (mostly Lactobacillus) rescued the KO-aggravated MI damage. Metabolomics of intestinal contents, along with further studies, suggested that ABCC1 is the critical pathway for miR‐30a‐5p‐modulated MI. • MiR-30a-5p loss worsened myocardial infarction-induced heart failure and harmed intestinal permeability. • Transplantation of fecal microbe from miR-30a-5p-knockout mice aggravated MI damage in wild-type mice. • Probiotics treatment (mostly Lactobacillus ) rescued the KO-aggravated MI damage MI. • ABCCI is the critical pathway for miR-30a-5p-modulated MI. Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI. This study aims to elucidate the connections between miR-30a-5p, MI, gut microbiota, and gut microbial metabolite-related pathways, to explore potential strategy for preventing and treating MI. We evaluated the effects of knocking out (KO) or overexpressing (OE) miR-30a-5p on MI by assessing cardiac structure and function, myocardial enzyme levels, and apoptosis. Then, we applied 16S rDNA sequencing and metabolomics to explore how intestinal microecology and its microorganisms affect miR-30a-5p-regulated MI. The results showed that KO exacerbated MI, whereas OE improved MI damage, compared to the wild-type (WT) mice. KO exacerbated intestinal barrier structure deterioration and further downregulated the expression of Cloudin-1, Occludin, and ZO-1 in MI mice. 16S rDNA sequencing-analyzed gut microbiome of KO and WT mice found that KO mainly reduced g_ Lactobacillus . Transplanting fecal microorganisms from KO mice aggravated MI damage in WT mice. However, administering probiotics (mainly containing Lactobacillus) helped neutralize these damages. Intriguingly, fecal microbiota transplantation from OE mice reduced MI damage. Analysis of intestinal microbial metabolites in KO and WT mice found that KO may mainly affect ABC transporters. ABCC1 was identified as the target of KO-aggravated MI. Furthermore, fecal transplantation microorganisms of MI patients aggravated MI injury in mice and miR-30a-5p and ABCC1 were involved in the process. Our findings demonstrate that miR-30a-5p regulates MI by affecting intestinal microbiota homeostasis and targeting ABCC1. This highlights the critical importance of maintaining a healthy gut microbiota homeostasis in MI management.

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