Lumen illuminated : Intestinal defense mechanisms in the neonate

Preterm births constituted 7.6% of live births in 2007 in the Netherlands (http://www. perinatreg.nl). In the United States, premature infants comprised 12.8% of live births and the incidence of premature live births is rising because of the improved perinatal care. With the rising incidence of preterm births and the improving survival rates of (extremely) very low birth weight neonates, efforts to decrease morbidity concerning short and long term outcome remain a challenge in the neonatal intensive care unit (NICU). Necrotizing enterocolitis (NEC) is the most common surgical emergency involving the gastrointestinal tract of preterm neonates and affects 2-7% of all premature infants. Both the incidence of NEC and its fatality rate are inversely related to birth weight and gestational age. Treatment is still limited to immediate restriction of enteral feeds and broad-spectrum antibiotics. Although most cases of NEC are managed medically, an estimated 20-40% of infants undergo surgery. Mortality rates from NEC range from 15-30% but mortality rates for infants requiring surgery are as high as 50%, and are highest for the smallest, most immature infants. Survivors of NEC are at increased risk for complications such as short bowel syndrome and impaired neurodevelopment. Stoll and colleagues reported that between 18 and 22 months of corrected gestational age, infants who recovered from NEC in the postnatal period were at high risk for adverse outcomes, including poor growth, cerebral palsy, vision and hearing impairment, and decreased neuromotor development. Furthermore, infants who are surgically treated are more likely to have growth impairment and adverse neurodevelopmental outcomes than infants who were treated medically

Enteral arginine does not increase superior mesenteric arterial blood flow but induces mucosal growth in neonatal pigs1-3

Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemiareperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100-250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L.kg-1.h-1) pigs than in the TPN pigs (1.23 ± 0.17 L.kg-1.h-1), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent

Modulation of the gut microbiota with antibiotic treatment suppresses whole body urea production in neonatal pigs

We examined whether changes in the gut microbiota induced by clinically relevant interventions would impact the bioavailability of dietary amino acids in neonates. We tested the hypothesis that modulation of the gut microbiota in neonatal pigs receiving no treatment (control), intravenously administered antibiotics, or probiotics affects whole body nitrogen and amino acid turnover. We quantified whole body urea kinetics, threonine fluxes, and threonine disposal into protein, oxidation, and tissue protein synthesis with stable isotope techniques. Compared with controls, antibiotics reduced the number and diversity of bacterial species in the distal small intestine (SI) and colon. Antibiotics decreased plasma urea concentrations via decreased urea synthesis. Antibiotics elevated threonine plasma concentrations and turnover, as well as whole body protein synthesis and proteolysis. Antibiotics decreased protein synthesis rate in the proximal SI and liver but did not affect the distal SI, colon, or muscle. Probiotics induced a bifidogenic microbiota and decreased plasma urea concentrations but did not affect whole body threonine or protein metabolism. Probiotics decreased protein synthesis in the proximal SI but not in other tissues. In conclusion, modulation of the gut micro biota by antibiotics and probiotics reduced hepatic urea genesis and intestinal protein synthesis, but neither altered whole body net threonine balance. These findings suggest that changes in amino acid and nitrogen metabolism resulting from antibiotic- or probiotic-induced shifts in the micro biota are localized to the gut and liver and have limited impact on whole body growth and anabolism in neonatal piglets