{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:09:46Z","timestamp":1780477786751,"version":"3.54.1"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wuxi City Double Hundred Top Talents","award":["BJ2023049"],"award-info":[{"award-number":["BJ2023049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hypertriglyceridemic acute pancreatitis (HTG-AP) progresses rapidly with poor prognosis. Intestinal barrier dysfunction and excessive oxidative stress contribute to its pathogenesis, but specific mediators linking gut injury, oxidative stress and pancreatic damage remain unclear. Here, we identify endogenous phenyllactic acid (PLA) as a critical metabolite regulating intestinal barrier integrity and oxidative homeostasis in HTG-AP. We noted serum PLA, a disease-associated metabolite whose reduction correlates with gut dysbiosis and pancreatic inflammation in HTG-AP. PLA supplementation in HTG-AP mice attenuated intestinal barrier dysfunction and mitigated intestinal oxidative stress, as evidenced by improved gut dysbiosis, reduced reactive oxygen species accumulation, restored superoxide dismutase activity, restored barrier integrity, reduced bacterial translocation to the pancreas, and decreased serum lipopolysaccharide levels, ultimately mitigating pancreatic injury. RNA sequencing of colonic tissue revealed peroxisome proliferator-activated receptor (PPAR) signaling as one of the most significantly altered pathways in HTG-AP. PPAR\u03b3 expression was markedly reduced in colonic epithelial cells and upregulated upon PLA treatment. Knockdown of colonic epithelial PPAR\u03b3 via adeno-associated virus abrogated the beneficial effects of PLA on intestinal barrier integrity, oxidative stress and pancreatic injury in HTG-AP mice. The protective effects of PLA were phenocopied by the PPAR\u03b3 agonist rosiglitazone. Collectively, these findings identified gut microbiota-derived PLA as an endogenously derived metabolite modulating intestinal oxidative stress and barrier function. Using male C57BL\/6J mice to establish an HTG-AP model, we further revealed that PLA exerts protective effects against HTG-AP by targeting colonic PPAR\u03b3 to modulate the gut\u2013pancreas axis, highlighting PLA as a promising candidate for targeted intervention in HTG-AP.<\/jats:p>","DOI":"10.3390\/antiox15060676","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:00:36Z","timestamp":1779955236000},"page":"676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenyllactic Acid Restores Intestinal Epithelial Barrier to Alleviate Hypertriglyceridemic Acute Pancreatitis via a PPAR\u03b3-Dependent Mechanism"],"prefix":"10.3390","volume":"15","author":[{"given":"Ze-Yun","family":"Cao","sequence":"first","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Zou","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Li","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Kong","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6575-7248","authenticated-orcid":false,"given":"Li-Long","family":"Pan","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Liang","family":"Dong","sequence":"additional","affiliation":[{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China"},{"name":"Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1001\/jamasurg.2023.8111","article-title":"Management of Gallstone Pancreatitis: A Review","volume":"159","author":"McDermott","year":"2024","journal-title":"JAMA Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1016\/j.cgh.2019.11.017","article-title":"Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis","volume":"18","author":"Matta","year":"2020","journal-title":"Clin. 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