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

Author
item PUIMAN, PATRYCJA - Sophia Children'S Hospital
item STOLL, BARBARA - Children'S Nutrition Research Center (CNRC)
item MOLBAK, LARS - Technical University Of Denmark
item DE BRUIJN, ADRIANUS - Sophia Children'S Hospital
item SCHIERBEEK, HENK - Sophia Children'S Hospital
item BOYE, METTE - Technical University Of Denmark
item BOEHM, GUNTHER - Sophia Children'S Hospital
item RENES, INGRID - Sophia Children'S Hospital
item VAN GOUDOEVER, JOHANNES - Sophia Children'S Hospital
item Burrin, Douglas - Doug

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2012
Publication Date: 2/1/2013
Citation: Puiman, P., Stoll, B., Molbak, L., De Bruijn, A., Schierbeek, H., Boye, M., Boehm, G., Renes, I., Van Goudoever, J., Burrin, D.G. 2013. Modulation of the gut microbiota with antibiotic treatment suppresses whole body urea production in neonatal pigs. American Journal of Physiology - Gastrointestinal and Liver Physiology. 304(3):G300-G310.

Interpretive Summary: There is increasing evidence that the microbes present in the gut can have important metabolic and functional effects on the developing infant and adults. Most premature infants also are treated with antibiotics in the early days after birth to prevent infection from harmful bacteria. Probiotic or live bacteria have been fed to infants and shown to stabilize the gut microbe population and benefit their health. The intestinal absorption and metabolism of dietary amino acids is a vital gut function that supports normal growth and development of premature infants. Thus, the aim of the study was to test how antibiotics and probiotics affect amino acid metabolism using neonatal piglets as a model of the human infant. We found that neither antibiotics nor probiotics altered the metabolism and balance of threonine, a key amino acid in the gut growth and function. However, antibiotics and probiotics reduced the production of urea by the liver and synthesis of protein by the intestine. Our results suggest that antibiotics and probiotic may reduce bacteria numbers and thus the synthesis of ammonia in the gut, but this does not translate into improved protein balance and growth in the developing neonate.

Technical Abstract: 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 microbiota by antibiotics and probiotics reduced hepatic ureagenesis 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 microbiota are localized to the gut and liver and have limited impact on whole body growth and anabolism in neonatal piglets.