# Invasion of gut-derived escherichia coli extracellular vesicles exacerbates myocardial ischemia/reperfusion injury

## TL;DR

Gut bacteria EVs worsen heart damage after blood flow returns, and a treatment may help.

## Contribution

First study to show gut-derived E. coli EVs exacerbate heart injury and suggest glucagon-like peptide-2 as a treatment.

## Key findings

- E. coli EVs invade heart tissue during ischemia-reperfusion injury in mice and humans.
- EVs carry LPS and worsen inflammation and heart damage.
- Glucagon-like peptide-2 reduces EV translocation and heart injury.

## Abstract

Recent studies have highlighted the close relationship between gut microbiota and the cardiovascular system; however, the precise mechanisms and modes of their interaction remain incompletely understood. Among the various factors involved, bacterial extracellular vesicles (EVs) are often overlooked, despite their potential roles in multiple pathological processes. To investigate the role of bacterial EVs in shaping the inflammatory microenvironment following myocardial ischemia-reperfusion injury, we colonized the intestines of Rosa26.tdTomato reporter mice with Escherichia coli (E. coli) expressing Cre recombinase. Using FACS-beads and immunofluorescence techniques, we found that myocardial ischemia-reperfusion injury in mice significantly enhanced the invasion of gut-derived bacterial EVs. Meanwhile, in patients with ST-segment elevation myocardial infarction, we also confirmed the invasion of bacterial EVs via the FACS-bead method, and there was a significant correlation between extracellular vesicles in peripheral blood and LPS, suggesting that these EVs can be key carriers for LPS translocation. In this pathological process, invading E. coli EVs exacerbate the mobilization and infiltration of systemic and local inflammatory cells, thereby aggravating myocardial damage and impairing cardiac function. Notably, glucagon-like peptide-2 can effectively alleviate inflammatory responses and myocardial injury by inhibiting the translocation of E. coli-derived EVs. In conclusion, our study is the first to confirm the impact of gut-derived EVs on myocardial ischemia-reperfusion injury, revealing that E. coli EVs can amplify inflammatory responses. These findings provide new insights into the gut-heart axis and offer a theoretical basis for the therapeutic potential of glucagon-like peptide-2 in cardiovascular diseases.