Gut Permeability and Microbiome in Preterm Infants

NEC, a life-threatening, GI emergency characterized by increased IP, affects approximately 7 to 10% of preterm neonates, and typically occurs within 7 to 14 days of birth with mortality as high as 30-50%. NEC symptoms mainly involve GI dysfunction, such as abdominal distension and feeding intolerance, but the presentation can be non-specific with few warning signs. Current therapies may be invasive, including surgical interventions that are often ineffective due to the rapid progression of the disease. Prematurity is the greatest risk factor for development of NEC due to physiological immaturity of the GI tract and altered levels of the normal GI microbiota. Several studies suggest that the initiation of an intense systemic and local inflammatory cascade leads to intestinal necrosis . Antenatal exposure to infection/inflammation may predispose the developing intestinal mucosa to subsequent injury or dysregulated inflammatory responses. Previous studies have linked presence of amniotic fluid infection/elevated cytokines, cord blood cytokines, and umbilical cord inflammation with risk for NEC in preterm neonates. In a rat model of NEC, maternal prenatal exposure to microbial LPS led to increased frequency and severity of intestinal injury. Taken together, these observations suggest that intestinal injury may be initiated in utero and contributes to increased IP at birth in the preterm neonate. Many of the defense mechanisms present in the mature intestine, such as peristalsis and tight junctions between intestinal epithelial cells are decreased in an immature intestine, and thus bacteria normally confined to the intestinal lumen are able to reach systemic organs and tissues. Bacterial translocation triggers the activation of an exaggerated inflammatory response, which leads to further epithelial damage. Our analysis of the initial cohort of 43 preterm infants, and others' previous studies have shown that IP is high at birth in preterms (\<33wk gestation) with a rapid