Ozone rectal insufflation inhibits the development of atherosclerosis in ApoE-/-mice, which is mediated by the regulation of gut microbiota and metabolites.

INTRODUCTION

Atherosclerotic cardiovascular disease is the world's leading cause of death. Researches have proven that ozone therapy can effectively inhibit the development of atherosclerosis; however, the underlying mechanisms remain unclear. This study aims to explore how ozone rectal insufflation (O3-RI) prevents atherosclerosis.

METHODS

O3-RI therapy involves administering medical ozone via rectal injection to prevent multiple diseases. ApoE-/- mice were fed a high-fat diet (HFD) to induce atherosclerosis. Gut microbiota was identified by 16S rRNA sequencing. Microbial metabolites were determined by liquid chromatography-mass spectrometry(LC-MS).

RESULTS

O3-RI reduced serum LDL-C levels by approximately 29.6% and decreased both atherosclerotic lipid areas and plaque area in ApoE-/- mice. Additionally, O3-RI improved gut microbiota imbalance caused by a high-fat diet in these mice. Notably, O3-RI increased beneficial microorganisms like and , which help reduce atherosclerosis. Additionally, O3-RI also increased the levels of short-chain fatty acids, such as propionic acid and butyric acid, At the same time, it decreased harmful microbial metabolites, like TMA and TMAO in fecal samples.

DISCUSSION

This research indicates that O3-RI effectively inhibits atherosclerosis and reduces serum LDL-C levels. These effects are likely linked to ozone's optimization of gut microbiota and regulation of microbial metabolites in ApoE-/- mice. The non-invasive O3-RI may play a crucial role in managing and treating atherosclerosis. The non-invasive O3-RI may play a crucial role in the managing and treating of atherosclerosis.