{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:07:21Z","timestamp":1768554441611,"version":"3.49.0"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T00:00:00Z","timestamp":1650758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK125415"],"award-info":[{"award-number":["DK125415"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5P20GM134973"],"award-info":[{"award-number":["5P20GM134973"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM103447"],"award-info":[{"award-number":["P20GM103447"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Necrotizing enterocolitis (NEC), an inflammatory disease of the intestine, is a common gastrointestinal emergency among preterm infants. Intestinal barrier dysfunction, hyperactivation of the premature immune system, and dysbiosis are thought to play major roles in the disease. Human milk (HM) is protective, but the mechanisms underpinning formula feeding as a risk factor in the development of NEC are incompletely understood. Hyaluronic acid 35 kDa (HA35), a bioactive glycosaminoglycan of HM, accelerates intestinal development in murine pups during homeostasis. In addition, HA35 prevents inflammation-induced tissue damage in pups subjected to murine NEC, incorporating Paneth cell dysfunction and dysbiosis. We hypothesized HA35 treatment would reduce histological injury and mortality in a secondary mouse model of NEC incorporating formula feeding. NEC-like injury was induced in 14-day mice by dithizone-induced disruption of Paneth cells and oral gavage of rodent milk substitute. Mortality and histological injury, serum and tissue cytokine levels, stool bacterial sequencing, and bulk RNA-Seq comparisons were analyzed. HA35 significantly reduced the severity of illness in this model, with a trend toward reduced mortality, while RNA-Seq analysis demonstrated HA35 upregulated genes associated with goblet cell function and innate immunity. Activation of these critical protective and reparative mechanisms of the small intestine likely play a role in the reduced pathology and enhanced survival trends of HA-treated pups subjected to intestinal inflammation in this secondary model of NEC, providing potentially interesting translational targets for the human preterm disease.<\/jats:p>","DOI":"10.3390\/nu14091779","type":"journal-article","created":{"date-parts":[[2022,4,24]],"date-time":"2022-04-24T22:22:41Z","timestamp":1650838961000},"page":"1779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Hyaluronic Acid 35 kDa Protects against a Hyperosmotic, Formula Feeding Model of Necrotizing Enterocolitis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-5383","authenticated-orcid":false,"given":"Kathryn","family":"Burge","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-8198","authenticated-orcid":false,"given":"Jeffrey","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MaJoi","family":"Trammell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-7612","authenticated-orcid":false,"given":"Shiloh R.","family":"Lueschow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-723X","authenticated-orcid":false,"given":"Steven J.","family":"McElroy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis, Sacramento, CA 95817, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-564X","authenticated-orcid":false,"given":"Hala","family":"Chaaban","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1056\/NEJMra1005408","article-title":"Necrotizing enterocolitis","volume":"364","author":"Neu","year":"2011","journal-title":"N. 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