# Gut Bacterium Lysinibacillus Sphaericus Exacerbates Aspirin‐induced Intestinal Injury by Production of Carboxylesterase EstB

## TL;DR

A gut bacterium, Lysinibacillus sphaericus, worsens aspirin-induced intestinal damage by converting aspirin into a more harmful compound, salicylic acid.

## Contribution

Identifies Lysinibacillus sphaericus and its enzyme EstB as key drivers of aspirin-induced intestinal injury.

## Key findings

- Gut microbiota exacerbate aspirin-induced intestinal injury in mice.
- Lysinibacillus sphaericus produces EstB, which converts aspirin to salicylic acid, increasing toxicity.
- Inhibiting EstB with flavanomarein prevents aspirin biotransformation and intestinal damage.

## Abstract

Aspirin provides long‐term health benefits but can cause gastrointestinal toxicity, and the role of gut microbiota in aspirin metabolism and enterotoxicity remains unclear. In this study, the contribution and mechanisms of microbiota–aspirin interactions in intestinal injury are investigated. In a mouse model, aspirin‐induced enteropathy is found to be more severe in microbiota‐replete than in microbiota‐depleted mice, implicating a detrimental role of gut microbiota. Co‐cultivation experiments revealed that gut microbes facilitated the biotransformation of aspirin into salicylic acid, a metabolite more harmful than aspirin itself in disrupting epithelial cell integrity and renewal, both in vitro and in vivo. Through metagenomic screening, selective bacterial interrogation, and functional validation, Lysinibacillus sphaericus is identified as the culprit bacterium, and its secreted carboxylesterase EstB as the key enzyme catalyzing aspirin hydrolysis to salicylic acid. Importantly, inhibition of microbial EstB with the dietary compound flavanomarein abrogated aspirin biotransformation and prevented intestinal injury. Together, these findings reveal L. sphaericus and EstB as central drivers of aspirin enterotoxicity, highlight the functional importance of gut microbiota in drug metabolism, and suggest microbiota‐ and metabolite‐guided precision prevention strategies.

Schematic overview illustrating the detrimental role of gut microbiota in aspirin‐induced intestinal injury. L. sphaericus and its secreted carboxylesterase EstB are identified as key drivers that catalyze aspirin hydrolysis into salicylic acid, thereby exacerbating intestinal injury. Inhibition of EstB by the dietary compound flavanomarein effectively blocked aspirin biotransformation and alleviated intestinal toxicity, highlighting a potential microbiota‐targeted strategy for prevention.