Targeting gut microbiotasu-derived butyrate for Ferroptosis inhibition in Sepsis-induced myocardial dysfunction

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology Pub Date : 2025-12-01 Epub Date: 2025-10-24 DOI:10.1016/j.yjmcc.2025.10.005

Jianfei Xiong , Guoxiang Liu , Tianyuan Jia , Qian Yang , Changqing Zhu , Shiwei Wang

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引用次数: 0

Abstract

Background

Sepsis-induced myocardial dysfunction (SIMD) is a critical complication of sepsis, and ferroptosis has been identified as a key contributor to its pathogenesis. Emerging evidence suggests that sepsis profoundly disrupts the gut microbiota composition, leading to dysbiosis. Butyrate, a short-chain fatty acid produced by gut microbiota, has been implicated in ferroptosis regulation; however, its role in SIMD remains controversial. This study aims to elucidate the protective effects of gut microbiota-derived butyrate against SIMD through ferroptosis modulation.

Methods

This study assessed cardiac function using echocardiography and quantified myocardial injury biomarkers via ELISA. Myocardial iron deposition was evaluated using Prussian blue staining. The gut microbiota composition was analyzed using 16S rRNA gene sequencing. Ferroptosis-related protein expression in SIMD heart tissues and H9C2 cardiomyocytes was examined via western blotting to determine the regulatory role of butyrate.

Results

Sepsis-induced gut microbiota dysbiosis was characterized by a significant reduction in butyrate-producing bacteria. Echocardiographic assessments (CO, EF), myocardial injury markers (BNP, cTnI), histopathological analysis (H&E staining), and cardiomyocyte ultrastructure (TEM) demonstrated that butyrate administration significantly alleviated myocardial injury in SIMD. Mechanistically, butyrate mitigated oxidative stress by increasing GSH levels and reducing MDA levels. Furthermore, butyrate treatment reversed the sepsis-induced downregulation of GPX4 and suppressed the upregulation of ACSL4 and PTGS2, thereby inhibiting ferroptosis.

Conclusion

These findings highlight the protective role of butyrate in SIMD, with ferroptosis inhibition serving as a key cardioprotective mechanism. Targeting gut microbiota-derived butyrate may represent a promising therapeutic strategy for sepsis-induced myocardial injury.

Abstract Image

查看原文本刊更多论文

靶向肠道微生物源丁酸抑制败血症诱导的心肌功能障碍。

背景：脓毒症引起的心肌功能障碍（SIMD）是脓毒症的重要并发症，而铁下垂已被确定为其发病机制的关键因素。新出现的证据表明，败血症严重破坏肠道菌群组成，导致生态失调。丁酸盐是一种由肠道菌群产生的短链脂肪酸，与铁下垂调节有关；然而，它在SIMD中的作用仍然存在争议。本研究旨在阐明肠道微生物来源的丁酸盐通过调节铁下垂对SIMD的保护作用。方法：本研究采用超声心动图评估心功能，并通过ELISA定量心肌损伤生物标志物。普鲁士蓝染色评价心肌铁沉积。采用16S rRNA基因测序分析肠道菌群组成。通过western blotting检测SIMD心脏组织和H9C2心肌细胞中凋亡相关蛋白的表达，以确定丁酸盐的调节作用。结果：脓毒症引起的肠道菌群失调的特征是丁酸盐产生菌的显著减少。超声心动图（CO， EF）、心肌损伤标志物（BNP, cTnI）、组织病理学分析（H&E染色）和心肌细胞超微结构（TEM）显示，丁酸盐给药显著减轻了SIMD的心肌损伤。从机制上讲，丁酸盐通过增加GSH水平和降低MDA水平来减轻氧化应激。此外，丁酸盐处理逆转败血症诱导的GPX4下调，抑制ACSL4和PTGS2上调，从而抑制铁下垂。结论：这些发现表明丁酸盐在SIMD中的保护作用，抑制铁下垂可能是关键的心脏保护机制。靶向肠道微生物来源的丁酸盐可能是一种很有前途的治疗败血症引起的心肌损伤的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of molecular and cellular cardiology 医学-细胞生物学

CiteScore

10.70

自引率

0.00%

发文量

171

审稿时长

42 days

期刊介绍： The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.