Digested Early Preterm Human Milk Suppresses Tumor Necrosis Factor-induced Inflammation and Cytotoxicity in Intestinal Epithelial Cells

Objectives: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract. Methods: Fully differentiated Caco-2 cells were exposed to digested HM (n = 10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F-2-isoprostane, and cytotoxicity by released lactate dehydrogenase. Results: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses. Conclusions: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis.