A digestive cartridge reduces intestinal injury in a murine model of necrotizing enterocolitis
BACKGROUND: 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. METHODS: NEC was induced in C57BL/6J mice from post-natal day 4-6 via oral gavage of lipopolysaccharide-containing formula 4x/day and hypoxia (5% O2) exposure 2x/day. Littermates were randomized to one of five groups: dam-fed (normal controls), ILC-digested formula, placebo-processed formula, NEC + ILC-digested formula, NEC+placebo-processed formula. Weights and mortality were measured daily. Mice were euthanized on P7 for assessment of NEC severity. RESULTS: Normal controls had better survival rates than formula-fed and NEC mice. The NEC + ILC group exhibited lower clinical and histologic severity scores compared to the NEC+placebo group on masked evaluation. CONCLUSION: 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.
Authors
- Scott C. Fligor (ORCID: https://orcid.org/0000-0003-4591-9371)
- Thomas I. Hirsch (ORCID: https://orcid.org/0000-0002-1373-2388)
- Savas T. Tsikis (ORCID: https://orcid.org/0000-0001-7588-8372)
- Sarah Wang (ORCID: https://orcid.org/0000-0003-3080-6665)
- Greta Loring (ORCID: https://orcid.org/0000-0002-8800-4393)
- Juhye Kang (ORCID: https://orcid.org/0000-0002-7153-6430)
- Mark Puder (ORCID: https://orcid.org/0000-0002-7941-2926)
- Mikayla Quigley (ORCID: https://orcid.org/0000-0002-5143-9879)
- Carter R. Petty
- Amy Pan
- Djanira Fernandes (ORCID: https://orcid.org/0000-0001-7216-5136)
- Stephen Davia
- Valeria Ruiz
Institutions
- Boston Children's Hospital (US)
- Harvard University (US)
- NKT Therapeutics (United States) (US)
- Boston Children's Museum (US)
Publication Details
- Journal
- PLoS ONE
- Published
- 2026-04-30
- DOI
- https://doi.org/10.1371/journal.pone.0348200
- Primary Topic
- Infant Nutrition and Health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Heart, Lung, and Blood Institute