Introduction

Gut microbial homeostasis is closely associated with myocardial infarction (MI). However, little is known about how gut microbiota influences miRNAs-regulated MI.

Objectives

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.

Methods

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.

Results

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 lactobacilli) 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.

Conclusions

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.

中文翻译：

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肠道菌群与代谢物调节 miR-30a-5p 在心肌梗死中的保护作用

 介绍

肠道微生物稳态与心肌梗死 （MI） 密切相关。然而，关于肠道微生物群如何影响 miRNA 调节的 MI 知之甚少。

 目标

本研究旨在阐明 miR-30a-5p、MI、肠道菌群和肠道微生物代谢物相关途径之间的联系，以探索预防和治疗 MI 的潜在策略。

 方法

我们通过评估心脏结构和功能、心肌酶水平和细胞凋亡来评估敲除 （KO） 或过表达 （OE） miR-30a-5p 对 MI 的影响。然后，我们应用 16S rDNA 测序和代谢组学来探索肠道微生态及其微生物如何影响 miR-30a-5p 调节的 MI。

 结果

结果表明，与野生型 （WT） 小鼠相比，KO 加剧了 MI，而 OE 改善了 MI 损伤。KO 加剧了肠屏障结构恶化，并进一步下调了 MI 小鼠 Cloudin-1 、 Occludin 和 ZO-1 的表达。KO 和 WT 小鼠 16S rDNA 测序分析的肠道微生物组发现，KO 主要降低g_Lactobacillus。移植 KO 小鼠的粪便微生物加重了 WT 小鼠的 MI 损伤。然而，服用益生菌（主要含有乳酸杆菌）有助于中和这些损伤。有趣的是，来自 OE 小鼠的粪便微生物群移植减少了 MI 损伤。对 KO 和 WT 小鼠肠道微生物代谢物的分析发现，KO 可能主要影响 ABC 转运蛋白。ABCC1 被确定为 KO 加重 MI 的靶点。此外，MI 患者的粪便移植微生物加重了小鼠的 MI 损伤，并且 miR-30a-5p 和 ABCC1 参与了该过程。

 结论

我们的研究结果表明，miR-30a-5p 通过影响肠道菌群稳态和靶向 ABCC1 来调节 MI。这凸显了维持健康的肠道微生物群稳态在 MI 管理中的重要性。