Butyrate Ameliorates ISO-Induced Cardiac and Intestinal Injury in Rats via Modulation of Bitter Taste Receptors (Tas2rs) and GPR41/43 to Inhibit NLRP3 Activation.

Background

The gut microbiota and its metabolite short-chain fatty acids (SCFAs) regulate host physiology, but whether butyrate, a key SCFA, protects against myocardial injury via the gut-heart axis remains unclear.

Objectives

This study aimed to investigate the cardioprotective effect of butyrate in a rat model of isoproterenol (ISO)-induced myocardial injury and to explore its underlying gut-heart mechanism.

Methods

In this experimental study, male Sprague-Dawley rats received intragastric butyrate pre-treatment followed by ISO injection to induce myocardial injury. Cardiac function, myocardial remodeling, gut-heart homeostasis, intestinal barrier integrity, and the expression of Tas2r, GPR41/43, and NLRP3 pyroptosis pathway components were assessed.

Results

Butyrate pre-treatment significantly restored cardiac function (LVEF increased by 19.67 units; 95% CI, 11.17-28.16; p < 0.001) and ameliorated electrophysiological abnormalities (QTc shortened by 63.21 ms; 95% CI, 45.45-80.97; p < 0.0001). Mechanistically, butyrate suppressed aberrant myocardial Tas2r signaling (Tas2r137 reduced by 1.06 units; 95% CI, 0.37-1.74; p < 0.01), upregulated GPR41/43, inhibited NLRP3 inflammasome activation (NLRP3 reduced by 1.23 units; 95% CI, 0.13-2.33; p < 0.05), and repaired intestinal barrier integrity, thereby reducing bacterial translocation and secondary injury.

Conclusions

Butyrate ameliorates ISO-induced myocardial injury through a simultaneous gut-heart mechanism, acting on both the cardiac Tas2r137/GPR41/43-NLRP3 pathway and intestinal barrier protection. These findings identify butyrate as a key functional molecule in gut-heart crosstalk and suggest its potential as a therapeutic agent for myocardial injury.