Gut Permeability in Very Low Birth Weight Infants

Detailed Summary

Necrotizing enterocolitis (NEC) is a life-threatening, gastrointestinal emergency characterized by increased intestinal permeability, affects approximately 7 to 10% of infants \<1500 g birthweight, and typically occurs within 7 to 14 days of birth. Mortality is as high as 30-50%. Prematurity is the greatest risk factor for the development of NEC due to the physiological immaturity of the gastrointestinal tract and altered or abnormal gut microbiota. Several studies have demonstrated that the initiation of an intense systemic and local inflammatory cascade leads to intestinal necrosis. The human intestine is lined by a single layer of cells exquisitely responsive to multiple stimuli and is populated by a complex climax community of microbial partners. Under normal circumstances, these intestinal cells form a tight but selective barrier to "friends and foes": microbes and most environmental substances are held at bay, but nutrients are absorbed efficiently. Epithelial barrier integrity is itself dynamic and matures over time starting soon after birth, though the mechanisms regulating dynamic permeability are poorly understood. Low birth weight, prematurity, and early postnatal age are associated with a leaky gut. Although intestinal permeability is higher at birth in preterm than term infants, there is usually rapid maturation of the intestinal barrier over the first few days of life in both populations. The investigators hypothesize that increased levels of measures of intestinal permeability (urine lactulose/rhamnose (LA/Rh), and fecal alpha1- antitrypsin will identify infants at high risk for NEC and that intestinal probiotic strains will be associated with intestinal barrier maturation. The purpose of the study is to determine whether clinical factors in combination with non-invasive stool test such as antitrypsin (A1AT) and microbiota composition profile are associated with intestinal permeability determined by excretion of non-metabolized sugar probes in urine (LA/Rh ratio). These studies may lead to a non-invasive screening test to identify preterm infants at risk for NEC.

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