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Feeding Formula Eliminates the Necessity of Bacterial Dysbiosis and Induces Inflammation and Injury in the Paneth Cell Disruption Murine NEC Model in an Osmolality-Dependent Manner. Nutrients 2020 Mar 26;12(4)



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Pubmed Central ID




Scopus ID

2-s2.0-85082571970   1 Citation


Necrotizing enterocolitis (NEC) remains a significant cause of morbidity and mortality in preterm infants. Formula feeding is a risk factor for NEC and osmolality, which is increased by the fortification that is required for adequate growth of the infant, has been suggested as a potential cause. Our laboratory has shown that Paneth cell disruption followed by induction of dysbiosis can induce NEC-like pathology in the absence of feeds. We hypothesized adding formula feeds to the model would exacerbate intestinal injury and inflammation in an osmolality-dependent manner. NEC-like injury was induced in 14-16 day-old C57Bl/6J mice by Paneth cell disruption with dithizone or diphtheria toxin, followed by feeding rodent milk substitute with varying osmolality (250-1491 mOsm/kg H2O). Animal weight, serum cytokines and osmolality, small intestinal injury, and cecal microbial composition were quantified. Paneth cell-disrupted mice fed formula had significant NEC scores compared to controls and no longer required induction of bacterial dysbiosis. Significant increases in serum inflammatory markers, small intestinal damage, and overall mortality were osmolality-dependent and not related to microbial changes. Overall, formula feeding in combination with Paneth cell disruption induced NEC-like injury in an osmolality-dependent manner, emphasizing the importance of vigilance in designing preterm infant feeds.

Author List

Lueschow SR, Kern SL, Gong H, Grobe JL, Segar JL, Carlson SJ, McElroy SJ


Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals, Newborn
Disease Models, Animal
Enterocolitis, Necrotizing
Gastrointestinal Microbiome
Infant Formula
Infant, Newborn
Infant, Newborn, Diseases
Intestine, Small
Mice, Inbred C57BL
Osmolar Concentration
Paneth Cells
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0