Human Milk Oligosaccharides in the Prevention of Necrotizing Enterocolitis: A Journey From in vitro and in vivo Models to Mother-Infant Cohort Studies

Preterm infants who receive human milk instead of formula are 6- to 10-times less likely to develop necrotizing enterocolitis (NEC), one of the most common and devastating intestinal disorders that affects 5–10% of all very-low-birth-weight infants. Combined data from in vitro tissue culture models, in vivo preclinical studies in animal models, as well human mother-infant cohort studies support the hypothesis that human milk oligosaccharides (HMOs), complex sugars that are highly abundant in human milk but not in infant formula, contribute to the beneficial effects of human milk feeding in reducing NEC. The almost 20-year long journey of testing this hypothesis took an interesting turn during HMO in vivo efficacy testing and structure elucidation, suggesting that the original hypothesis may indeed be correct and specific HMO reduce NEC risk, however, the underlying mechanisms are likely different than originally postulated.