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)
Date
04/01/2020Pubmed ID
32224880Pubmed Central ID
PMC7230818DOI
10.3390/nu12040900Scopus ID
2-s2.0-85082571970 1 CitationAbstract
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 SJAuthors
Justin L. Grobe PhD Associate Professor in the Physiology department at Medical College of WisconsinJeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Disease Models, Animal
Dysbiosis
Enterocolitis, Necrotizing
Gastrointestinal Microbiome
Humans
Infant Formula
Infant, Newborn
Infant, Newborn, Diseases
Inflammation
Intestine, Small
Mice
Mice, Inbred C57BL
Osmolar Concentration
Paneth Cells
