Abstract
Catabolism of amino acids (AA) by intestinal bacteria greatly affects their bioavailability in the systemic circulation and the health of animals and humans. This study tests the novel hypothesis that l-glutamine regulates AA utilization by luminal bacteria of the small intestine. Pure bacterial strains (Streptococcus sp., Escherichia coli and Klebsiella sp.) and mixed bacterial cultures derived from the jejunum or ileum of pigs were cultured in the presence of 0–5 mM l-glutamine under anaerobic conditions. After 3 h of incubation, samples were taken for the determination of AA utilization. Results showed concentration-dependent increases in the utilization of glutamine in parallel with the increased conversion of glutamine into glutamate in all the bacteria. Complete utilization of asparagine, aspartate and serine was observed in pure bacterial strains after the 3-h incubation. The addition of glutamine reduced the net utilization of asparagine by both jejunal and ileal mixed bacteria. Net utilization of lysine, leucine, valine, ornithine and serine by jejunal or ileal mixed bacteria decreased with the addition of glutamine in a concentration-dependent manner. Collectively, glutamine dynamically modulates the bacterial metabolism of the arginine family of AA as well as the serine and aspartate families of AA and reduced the catabolism of most AA (including nutritionally essential and nonessential AA) in jejunal or ileal mixed bacteria. The beneficial effects of glutamine on gut nutrition and health may involve initiation of the signaling pathways related to AA metabolism in the luminal bacteria of the small intestine.
Similar content being viewed by others
Abbreviations
- AA:
-
Amino acids
- CFU:
-
Colony forming unit
- EAA:
-
Nutritionally essential amino acid
References
Almaas E (2007) Optimal flux patterns in cellular metabolic networks. Chaos 17:026107
Almaas E, Kovács B, Vicsek T et al (2004) Global organization of metabolic fluxes in the bacterium Escherichia coli. Nature 427:839–843
Bergen WG, Wu G (2009) Intestinal nitrogen recycling and utilization in health and disease. J Nutr 139:821–825
Brosnan JT, Brosnan ME (2012) Glutamate: a truly functional amino acid. Amino Acids (in press)
Burnside K, Lembo A, de los Reyes M et al (2010) Regulation of hemolysin expression and virulence of Staphylococcus aureus by a serine/threonine kinase and phosphatase. PLoS ONE 5:e11071
Burrin DG, Davis TA (2004) Proteins and amino acids in enteral nutrition. Curr Opin Clin Nutr Metab Care 7:79–87
Chaussee MS, Somerville GA, Reitzer L et al (2003) Rgg coordinates virulence factor synthesis and metabolism in Streptococcus pyogenes. J Bacteriol 185:6016–6024
Chen GJ, Russell JB (1989) Transport of glutamine by Streptococcus bovis and conversion of glutamine to pyroglutamic acid and ammonia. J Bacteriol 171:2981–2985
Chen LX, Yin YL, Jobgen WS et al (2007) In vitro oxidation of essential amino acids by jejunal mucosal cells of growing pigs. Livest Sci 109:19–23
Chen LX, Li P, Wang JJ et al (2009) Catabolism of nutritionally essential amino acids in developing porcine enterocytes. Amino Acids 37:143–152
Claus SP, Tsang TM, Wang Y et al (2008) Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol Syst Biol 4:219
Dai ZL, Zhang J, Wu G et al (2010) Utilization of amino acids by bacteria from the pig small intestine. Amino Acids 39:1201–1215
Dai ZL, Li XL, Xi PB et al (2011a) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids. doi:10.1007/s00726-011-0846-x
Dai ZL, Li XL, Xi PB et al (2011b) Regulatory role for l-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids. doi:10.1007/s00726-011-1067-z
Dai ZL, G Wu, Zhu WY (2011c) Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci 16:1768–1786
Dhavala P, Krasotkina J, Dubreuil C et al (2008) Expression, purification and crystallization of Helicobacter pylori l-asparaginase. Acta Crystallogr, Sect F: Struct Biol Cryst Commun 64:740–742
Eller C, Crabill MR, Bryant MP (1971) Anaerobic roll tube media for nonselective enumeration and isolation of bacteria. Appl Microbiol 22:522–529
Fernández M, Zúñiga M (2006) Amino acid catabolic pathways of lactic acid bacteria. Crit Rev Microbiol 32:155–183
Flynn NE, Patryak M, Seely J et al (2010) Glycine oxidation and conversion into amino acids in Saccharomyces cerevisiae and Candida albicans. Amino Acids 39:605–608
Forchhammer K (2007) Glutamine signalling in bacteria. Front Biosci 12:358–370
Fuller MF, Reeds PJ (1998) Nitrogen cycling in the gut. Annu Rev Nutr 18:385–411
Haynes TE, Li P, Li XL et al (2009) l-Glutamine or l-alanyl-l-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Amino Acids 37:131–142
Hou YQ, Wang L, Zhang W et al (2011) Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids. doi:10.1007/s00726-011-1191-9
Kalhan SC, Bier DM (2008) Protein and amino acid metabolism in the human newborn. Annu Rev Nutr 28:389–410
Kudsk KA (2006) Immunonutrition in surgery and critical care. Annu Rev Nutr 26:463–479
Lara AR, Taymaz-Nikerel H, Mashego MR et al (2009) Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses. Biotechnol Bioeng 104:1153–1161
Li XL, Rezaei R, Li P et al (2011) Composition of amino acids in feed ingredients for animal diets. Amino Acids 40:1159–1168
Metges CC, Petzke KJ (2005) Utilization of essential amino acids synthesized in the intestinal microbiota of monogastric mammals. Br J Nutr 94:621–622
Montagne L, Piel C, Lallès JP (2004) Effect of diet on mucin kinetics and composition: nutrition and health implications. Nutr Rev 62:105–114
Ollenschläger G, Roth E, Linkesch W et al (1988) Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects. Eur J Clin Invest 18:512–516
Prüß BM, Nelms JM, Park C et al (1994) Mutations in NADH: ubiquinone oxidoreductase of Escherichia coli affect growth on mixed amino acids. J Bacteriol 176:2143–2150
Reeds PJ, Burrin DG (2001) Glutamine and the bowel. J Nutr 131(9 Suppl):2505S–2508S
Ren WK, Luo W, Wu MM et al (2011) Dietary l-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus. Amino Acids. doi:10.1007/s00726-011-1134-5
Rhoads MJ, Wu G (2009) Glutamine, arginine, and leucine signaling in the intestine. Amino Acids 37:111–122
Samal A (2008) Conservation of high-flux backbone in alternate optimal and near-optimal flux distributions of metabolic networks. Syst Synth Biol 2:83–93
Satterfield MC, Dunlap KA, Keisler DH et al (2011) Arginine nutrition and fetal brown adipose tissue development in nutrient-restricted sheep. Amino Acids. doi:10.1007/s00726-011-1168-8
Satterfield MC, Dunlap KA, Keisler DH et al (2012) Arginine nutrition and fetal brown adipose tissue development in diet-induced obese sheep. Amino Acids. doi:10.1007/s00726-012-1235-9
Sawers G (1998) The anaerobic degradation of l-serine and l-threonine in enterobacteria: networks of pathways and regulatory signals. Arch Microbiol 171:1–5
Shiloach J, Reshamwala S, Noronha SB et al (2010) Analyzing metabolic variations in different bacterial strains, historical perspectives and current trends—example E. coli. Curr Opin Biotechnol 21:21–26
Stoll B, Henry J, Reeds PJ et al (1998) Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. J Nutr 128:606–614
Van Acker BAC, Hulsewe KWE, Wagenmarkers AJM et al (1998) Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate. Clin Sci 95:339–346
Vining LC, Magasanik B (1981) Serine utilization by Klebsiella aerogenes. J Bacteriol 146:647–655
Wallace RJ (1996) Ruminal microbial metabolism of peptides and amino acids. J Nutr 126:1326S–1334S
Wang X, Qiao S, Yin Y et al (2007) A deficiency or excess of dietary threonine reduces protein synthesis in jejunum and skeletal muscle of young pigs. J Nutr 137:1442–1446
Wang JJ, Chen LX, Li P et al (2008) Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J Nutr 138:1025–1032
Watford M (1999) Is there a requirement for glutamine catabolism in the small intestine. Br J Nutr 81:261–262
Williams BA, Bosch MW, Boer H et al (2005) An in vitro batch culture method to assess potential fermentability of feed ingredients for monogastric diets. Anim Feed Sci Technol 123–124:445–462
Wu G (1997) Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol Gastrointest Liver Physiol 272:G1382–G1390
Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128:1249–1252
Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17
Wu G (2010) Functional amino acids in growth, reproduction, and health. Adv Nutr 1:31–37
Wu G, Borbolla AG, Knabe DA (1994) The uptake of glutamine and release of arginine, citrulline and proline by the small intestine of developing pigs. J Nutr 124:2437–2444
Wu G, Meier SA, Knabe DA (1996) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584
Wu G, Davis PK, Flynn NE et al (1997) Endogenous synthesis of arginine plays an important role in maintaining arginine homeostasis in postweaning growing pigs. J Nutr 127:2342–2349
Wu G, Collins JK, Perkins-Veazie P et al (2007a) Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J Nutr 137:2680–2685
Wu G, Bazer FW, Davis TA et al (2007b) Important roles for the arginine family of amino acids in swine nutrition and production. Livest Sci 112:8–22
Wu G, Bazer FW, Davis TA et al (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37:153–168
Wu G, Bazer FW, Johnson GA et al (2011a) Important roles for l-glutamine in swine nutrition and production. J Anim Sci 89:2017–2030
Wu G, Bazer FW, Burghardt RC et al (2011b) Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40:1053–1063
Xi PB, Jiang ZY, Zheng CT et al (2011a) Regulation of protein metabolism by glutamine: implications for nutrition and health. Front Biosci 16:578–597
Xi PB, Jiang ZY, Dai ZL et al (2011b) Regulation of protein turnover by l-glutamine in porcine intestinal epithelial cells. J Nutr Biochem. doi:10.1016/j.jnutbio.2011.05.009
Yao K, Yin YL, Li XL et al (2011) Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids. doi:10.1007/s00726-011-1060-6
Yin YL, Huang RL, Li TJ et al (2010) Amino acid metabolism in the portal-drained viscera of young pigs: effects of dietary supplementation with chitosan and pea hull. Amino Acids 39:1581–1587
Acknowledgments
This work was supported by the Natural Science Foundation of China (30810103909), the National Basic Research Program of China (2004CB117500-4), and Texas AgriLife Research Hatch Project (H-8200). We are grateful to Dr. J. Fleming, Dr. H. J. Gao, and Dr. J. J. Wang for technical assistance and helpful discussion. Z.-L. Dai thanks the China Scholarship Council for support of his study at Texas A&M University between 17 February 2009 and 28 February 2010.
Conflict of interest
The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Dai, ZL., Li, XL., Xi, PB. et al. l-Glutamine regulates amino acid utilization by intestinal bacteria. Amino Acids 45, 501–512 (2013). https://doi.org/10.1007/s00726-012-1264-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-012-1264-4