Document Detail


Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis.
MedLine Citation:
PMID:  23007028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Premature infants fed formula are more likely to develop necrotizing enterocolitis (NEC) than those who are breastfed, but the mechanisms of intestinal necrosis in NEC and protection by breast milk are unknown. We hypothesized that after lipase digestion, formula, but not fresh breast milk, contains levels of unbound free fatty acids (FFAs) that are cytotoxic to intestinal cells.
METHODS: We digested multiple term and preterm infant formulas or human milk with pancreatic lipase, proteases (trypsin and chymotrypsin), lipase + proteases, or luminal fluid from a rat small intestine and tested FFA levels and cytotoxicity in vitro on intestinal epithelial cells, endothelial cells, and neutrophils.
RESULTS: Lipase digestion of formula, but not milk, caused significant death of neutrophils (ranging from 47 to 99% with formulas vs. 6% with milk) with similar results in endothelial and epithelial cells. FFAs were significantly elevated in digested formula vs. milk and death from formula was significantly decreased with lipase inhibitor pretreatment, or treatments to bind FFAs. Protease digestion significantly increased FFA binding capacity of formula and milk but only enough to decrease cytotoxicity from milk.
CONCLUSION: FFA-induced cytotoxicity may contribute to the pathogenesis of NEC.
Authors:
Alexander H Penn; Angelina E Altshuler; James W Small; Sharon F Taylor; Karen R Dobkins; Geert W Schmid-Schönbein
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-24
Journal Detail:
Title:  Pediatric research     Volume:  72     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-19     Completed Date:  2013-06-05     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  560-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cattle
Cell Death*
Enterocolitis, Necrotizing / etiology*,  pathology
Humans
Infant Food*
Infant, Newborn
Infant, Premature
Milk, Human*
Grant Support
ID/Acronym/Agency:
GM85072/GM/NIGMS NIH HHS; NS071580/NS/NINDS NIH HHS; R01 GM085072/GM/NIGMS NIH HHS; R01 NS071580/NS/NINDS NIH HHS
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