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Alginate oligosaccharide (AOS), a marine-derived bioactive polysaccharide, exhibits prebiotic, anti-inflammatory and antioxidant properties that are effective against various inflammatory diseases. In this study, a mouse model of SAP was established by intraperitoneal injection of cerulein (100 \u03bcg\/kg) and lipopolysaccharide (5 mg\/kg), and the mice were pretreated with AOS (200 mg\/kg) by gavage for 4 consecutive weeks to explore the potential protective efficacy and underlying mechanisms. The results shown that AOS attenuated the severity of SAP, as evidenced by reduced serum amylase and lipase levels, as well as alleviated histopathological injury in both pancreatic and ileal tissues. AOS suppressed the overproduction of pro-inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\u03b1) in serum, pancreas, and ileum at protein or mRNA levels. Moreover, AOS effectively diminished pancreatic and ileal inflammatory infiltration and oxidative stress in SAP mice, accompanied by inhibited the TLR4\/MyD88\/NF-\u03baB pathway and activated the Nrf2\/HO-1 antioxidant axis. Furthermore, AOS restored intestinal barrier integrity, as manifested by upregulated expression of tight junction proteins (claudin-1, occludin, ZO-1), reduced serum diamine oxidase, and decreased bacterial translocation from the gut to the pancreas. It was revealed by 16S rRNA sequencing that AOS ameliorated SAP-induced gut dysbiosis by restoring microbial diversity, normalizing the Firmicutes\/Bacteroidetes ratio, enriching beneficial genera (Lactobacillus, Blautia), and enhancing cecal short-chain fatty acid (acetic, propionic, butyric acid) production. Collectively, our findings demonstrate that AOS exerts comprehensive protective effects against SAP through suppression of inflammatory signaling and oxidative stress, as well as restoring gut homeostasis. These results suggest that AOS may serve as a promising prebiotic-based nutritional strategy for the management of SAP.<\/jats:p>","DOI":"10.3390\/biom16060917","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:01:17Z","timestamp":1782813677000},"page":"917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alginate Oligosaccharide Alleviates Severe Acute Pancreatitis in Mice via Suppression of Oxidative Stress, Inflammation and Modulation of Intestinal Epithelial Barrier Integrity"],"prefix":"10.3390","volume":"16","author":[{"given":"Xianglong","family":"Ou","sequence":"first","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Basic Medicine and Forensic Sciences, North Sichuan Medical College, Nanchong 637100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyue","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibin","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1310-5309","authenticated-orcid":false,"given":"Bangyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), China West Normal University, Nanchong 637002, China"},{"name":"Nanchong Key Laboratory of Wildlife Nutrition Ecology and Disease Control, China West Normal University, Nanchong 637002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1053\/j.gastro.2018.12.041","article-title":"Organ failure due to systemic injury in acute pancreatitis","volume":"156","author":"Garg","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1016\/j.ajpath.2017.08.017","article-title":"Human pancreatic acinar cells: Proteomic characterization, physiologic responses, and organellar disorders in ex Vivo pancreatitis","volume":"187","author":"Lugea","year":"2017","journal-title":"Am. 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