{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T20:53:51Z","timestamp":1788209631160,"version":"build-2803163510"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5T32HL007734"],"award-info":[{"award-number":["5T32HL007734"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["2T32DK007754-22"],"award-info":[{"award-number":["2T32DK007754-22"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Formula feeding is associated with necrotizing enterocolitis (NEC), a life-threatening gastrointestinal illness affecting premature infants. The presence of undigested fat in enteral formula may mediate NEC severity. The immobilized lipase cartridge (ILC) is an FDA-cleared digestive device that hydrolyzes triglyceride fat in formula into readily absorbable free fatty acids and monoglycerides. We hypothesized that use of a new ILC prototype designed to support increased feeding frequency in infants will reduce NEC mortality and disease severity in a murine model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NEC was induced in C57BL\/6J mice from post-natal day 4\u20136 via oral gavage of lipopolysaccharide-containing formula 4x\/day and hypoxia (5% O\n                      <jats:sub>2<\/jats:sub>\n                      ) exposure 2x\/day. Littermates were randomized to one of five groups: dam-fed (normal controls), ILC-digested formula, placebo-processed formula, NEC\u2009+\u2009ILC-digested formula, NEC+placebo-processed formula. Weights and mortality were measured daily. Mice were euthanized on P7 for assessment of NEC severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Normal controls had better survival rates than formula-fed and NEC mice. The NEC\u2009+\u2009ILC group exhibited lower clinical and histologic severity scores compared to the NEC+placebo group on masked evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The administration of formula pre-digested by the ILC improved clinical sickness, gut appearance, and histologic severity of NEC compared to placebo. These findings support further investigation of the ILC as a non-invasive, preventive therapy for NEC in humans.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0348200","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:43:23Z","timestamp":1777571003000},"page":"e0348200","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["A digestive cartridge reduces intestinal injury in a murine model of necrotizing enterocolitis"],"prefix":"10.1371","volume":"21","author":[{"given":"Sarah Z.","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djanira","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savas T.","family":"Tsikis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas I.","family":"Hirsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikayla","family":"Quigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4578-7017","authenticated-orcid":true,"given":"Valeria","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Fligor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carter R.","family":"Petty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Loring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Davia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhye","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-2926","authenticated-orcid":true,"given":"Mark","family":"Puder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"issue":"3","key":"pone.0348200.ref001","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000489677","article-title":"Risk Factors for Necrotizing Enterocolitis: A Prospective Multicenter Case-Control Study","volume":"114","author":"DJC Berkhout","year":"2018","journal-title":"Neonatology"},{"key":"pone.0348200.ref002","doi-asserted-by":"crossref","first-page":"864397","DOI":"10.3389\/fped.2022.864397","article-title":"Infection Prevention and Management in Pediatric Short Bowel Syndrome","volume":"10","author":"L Merras-Salmio","year":"2022","journal-title":"Front Pediatr"},{"key":"pone.0348200.ref003","doi-asserted-by":"crossref","first-page":"1079894","DOI":"10.3389\/fped.2022.1079894","article-title":"Risk factors for necrotizing enterocolitis in neonates: A meta-analysis","volume":"10","author":"Y Su","year":"2023","journal-title":"Front Pediatr"},{"issue":"5","key":"pone.0348200.ref004","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.3390\/nu12051322","article-title":"The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis","volume":"12","author":"E Altobelli","year":"2020","journal-title":"Nutrients"},{"issue":"2","key":"pone.0348200.ref005","article-title":"Barriers to breastfeeding: supporting initiation and continuation of breastfeeding: ACOG committee opinion, number 821","volume":"137","year":"2021","journal-title":"Obstet Gynecol"},{"issue":"3","key":"pone.0348200.ref006","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2015-3123","article-title":"Impact of Donor Milk Availability on Breast Milk Use and Necrotizing Enterocolitis Rates","volume":"137","author":"A Kantorowska","year":"2016","journal-title":"Pediatrics"},{"issue":"33","key":"pone.0348200.ref007","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.15585\/mmwr.mm7133a1","article-title":"Donor human milk use in advanced neonatal care units - United States, 2020","volume":"71","author":"EO Boundy","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"5","key":"pone.0348200.ref008","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3390\/nu8050279","article-title":"Review of Infant Feeding: Key Features of Breast Milk and Infant Formula","volume":"8","author":"CR Martin","year":"2016","journal-title":"Nutrients"},{"issue":"3","key":"pone.0348200.ref009","first-page":"838","article-title":"Fat digestion in the newborn. 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