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In this study, the contribution and mechanisms of microbiota\u2013aspirin interactions in intestinal injury are investigated. In a mouse model, aspirin\u2010induced enteropathy is found to be more severe in microbiota\u2010replete than in microbiota\u2010depleted mice, implicating a detrimental role of gut microbiota. Co\u2010cultivation 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,\n                    <jats:italic>Lysinibacillus sphaericus<\/jats:italic>\n                    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\n                    <jats:italic>L. sphaericus<\/jats:italic>\n                    and EstB as central drivers of aspirin enterotoxicity, highlight the functional importance of gut microbiota in drug metabolism, and suggest microbiota\u2010 and metabolite\u2010guided precision prevention strategies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517747","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T01:49:07Z","timestamp":1765590547000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut Bacterium\n                    <i>Lysinibacillus Sphaericus<\/i>\n                    Exacerbates Aspirin\u2010induced Intestinal Injury by Production of Carboxylesterase EstB"],"prefix":"10.1002","volume":"13","author":[{"given":"Zeyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Division of Gastrointestinal Surgery Center the First 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