Fish Physiology and Biochemistry

, Volume 39, Issue 6, pp 1567–1580 | Cite as

Effect of partially protected butyrate used as feed additive on growth and intestinal metabolism in sea bream (Sparus aurata)

  • R. Robles
  • A. B. Lozano
  • A. Sevilla
  • L. Márquez
  • W. Nuez-Ortín
  • F. J. Moyano


Butyrate is a short-chain fatty acid extensively used in animal nutrition since it promotes increases in body weight and other multiple beneficial effects on the intestinal tract. Although such effects have been demonstrated in several species, very few studies have assessed them in fish. On the other hand, little is known about the metabolic processes underlying these effects. In the present work, growth parameters and changes in more than 80 intestinal metabolites (nucleotides, amino acids and derivatives, glycolytic intermediates, redox coenzymes and lipid metabolism coenzymes) have been quantified in juvenile sea bream fed a butyrate-supplemented diet. Results showed a significant increase in the weight of fish receiving butyrate, while metabolomics provided some clues on the suggested effects of this feed additive. It seems that butyrate increased the availability of several essential amino acids and nucleotide derivatives. Also, the energy provision for enteric cells might have been enhanced by a decrease in glucose and amino acid oxidation related to the use of butyrate as fuel. Additionally, butyrate might have increased transmethylation activity. This work represents an advance in the knowledge of the metabolic consequences of using butyrate as an additive in fish diets.


Butyrate Sea bream Metabolomics Amino acids Growth 



This work was partially supported by projects P09-AGR-5234 (Consejería de Innovación. Junta de Andalucía) and BIO2011-29233-C02-01, MCINN/FEDER-EU.


  1. Alpers DH (1972) Protein synthesis in intestinal mucosa: the effect of route of administration of precursor amino acids. J Clin Invest 51(1):167. doi: 10.1172/jci106788 PubMedCrossRefGoogle Scholar
  2. Ardawi MSM, Newsholme EA (1985) Fuel utilization in colonocytes of the rat. Biochem J 231(3):713–719PubMedGoogle Scholar
  3. Bergman EN (1990) Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev 70(2):567–590PubMedGoogle Scholar
  4. Bjerkeng B, Storebakken T, Wathne E (1999) Cholesterol and short-chain fatty acids in diets for Atlantic salmon (Salmo salar L.): effects on growth, organ indices, macronutrient digestibility, and fatty acid composition. Aquac Nutr 5(3):181–191CrossRefGoogle Scholar
  5. Bond JH, Levitt MD (1976) Fate of soluble carbohydrate in the colon of rats and man. J Clin Invest 57(5):1158–1164. doi: 10.1172/jci108383 PubMedCrossRefGoogle Scholar
  6. Canani RB, Di Costanzo M, Leone L, Pedata M, Meli R, Calignano A (2011) Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol 17(12):1519–1528. doi: 10.3748/wjg.v17.i12.1519 PubMedCrossRefGoogle Scholar
  7. Canani RB, Di Costanzo M, Leone L (2012) The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clin Epigenetics 4(1):4. doi: 10.1186/1868-7083-4-4 CrossRefGoogle Scholar
  8. Darcy-Vrillon B, Souffrant WB, Laplace JP, Rerat A, Corring T, Vaugelade P, Gebhardt G, Kohler R (1991) Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. II. Ileal and faecal digestibilities and absorption of amino acids. Reprod Nutr Dev 31(5):561–573. doi: 10.1051/rnd:19910509 PubMedCrossRefGoogle Scholar
  9. De Wet F, Viljoen S (2012) Evaluating calcium butyrate and nucleotides for use in diets of mozambique tilapia Oreochromis mossambicus. Aquaculture Europe 2012. Book of abstracts. PragueGoogle Scholar
  10. Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman SJ (2011) The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13(5):517–526. doi: 10.1016/j.cmet.2011.02.018 PubMedCrossRefGoogle Scholar
  11. Figueiredo-Silva AC, Corraze G, Kaushik S, Peleteiro JB, Valente LMP (2010) Modulation of blackspot seabream (Pagellus bogaraveo) intermediary metabolic pathways by dispensable amino acids. Amino Acids 39(5):1401–1416. doi: 10.1007/s00726-010-0599-y PubMedCrossRefGoogle Scholar
  12. Fructuoso S, Sevilla A, Bernal C, Lozano AB, Iborra JL, Canovas M (2012) EasyLCMS: an asynchronous web application for the automated quantification of LC-MS data. BMC Res Notes 5(1):428. doi: 10.1186/1756-0500-5-428 PubMedCrossRefGoogle Scholar
  13. Galfi P, Bokori J (1990) Feeding trial in pigs with a diet containing sodium n-butyrate. Acta Vet Hung 38(1–2):3–17PubMedGoogle Scholar
  14. Gao Y, Storebakken T, Shearer KD, Penn M, Overland M (2011) Supplementation of fishmeal and plant protein-based diets for rainbow trout with a mixture of sodium formate and butyrate. Aquaculture 311(1–4):233–240. doi: 10.1016/j.aquaculture.2010.11.048 CrossRefGoogle Scholar
  15. Guilloteau P, Martin L, Eeckhaut V, Ducatelle R, Zabielski R, Van Immerseel F (2010) From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr Res Rev 23(2):366–384. doi: 10.1017/s0954422410000247 PubMedCrossRefGoogle Scholar
  16. Hume ID, Karasov WH, Darken BW (1993) Acetate, butyrate and proline uptake in the caecum and colon of prairie voles (Microtus ochrogaster). J Exp Biol 176:285–297PubMedGoogle Scholar
  17. Jordan HN, Phillips RW (1978) Effects of fatty acids on isolated ovine pancreatic islets. Am J Physiol 234(2):E162–E167PubMedGoogle Scholar
  18. Kihara M, Sakata T (1997) Fermentation of dietary carbohydrates to short-chain fatty acids by gut microbes and its influence on intestinal morphology of a detritivorous teleost Tilapia (Oreochromis niloticus). Comp Biochem Physiol A-Mol Integr Physiol 118(4):1201–1207. doi: 10.1016/s0300-9629(97)00052-2 CrossRefGoogle Scholar
  19. Kihara M, Sakata T (2001) Influences of incubation temperature and various saccharides on the production of organic acids and gases by gut microbes of rainbow trout Oncorhynchus mykiss in a micro-scale batch culture. J Comp Physiol B-Biochem Syst Environ Physiol 171(6):441–447CrossRefGoogle Scholar
  20. Kotunia A, Wolinski J, Laubitz D, Jurkowska M, Rome V, Guilloteau P, Zabielski R (2004) Effect of sodium butyrate on the small intestine development in neonatal piglets fed correction of feed by artificial sow. J Physiol Pharmacol 55(Suppl 2):59–68PubMedGoogle Scholar
  21. Lash LH, Hagen TM, Jones DP (1986) Exogenous glutathione protects intestinal epithelial-cells from oxidative injury. Proc Natl Acad Sci USA 83(13):4641–4645. doi: 10.1073/pnas.83.13.4641 PubMedCrossRefGoogle Scholar
  22. Lazzarino G, Amorini AM, Fazzina G, Vagnozzi R, Signoretti S, Donzelli S, Di Stasio E, Giardina B, Tavazzi B (2003) Single-sample preparation for simultaneous cellular redox and energy state determination. Anal Biochem 322(1):51–59. doi: 10.1016/j.ab.2003.07.013 PubMedCrossRefGoogle Scholar
  23. Li P, Gatlin DM (2006) Nucleotide nutrition in fish: current knowledge and future applications. Aquaculture 251(2–4):141–152. doi: 10.1016/j.aquaculture.2005.01.009 CrossRefGoogle Scholar
  24. Li XL, Rezaei R, Li P, Wu GY (2011) Composition of amino acids in feed ingredients for animal diets. Amino Acids 40(4):1159–1168. doi: 10.1007/s00726-010-0740-y PubMedCrossRefGoogle Scholar
  25. Lückstädt C (2006) Use of organic acids as feed additives—sustainable aquaculture production the non-antibiotic way. Int Aquafeed 9(2):21–26Google Scholar
  26. Manzanilla EG, Nofrarias M, Anguita M, Castillo M, Perez JF, Martin-Orue SM, Kamel C, Gasa J (2006) Effects of butyrate, avilamycin, and a plant extract combination on the intestinal equilibrium of early-weaned pigs. J Anim Sci 84(10):2743–2751. doi: 10.2527/jas.2005-509 PubMedCrossRefGoogle Scholar
  27. Mentschel J, Claus R (2003) Increased butyrate formation in the pig colon by feeding raw potato starch leads to a reduction of colonocyte apoptosis and a shift to the stem cell compartment. Metab-Clin Exp 52(11):1400–1405. doi: 10.1016/s0026-0495(03)00318-4 PubMedCrossRefGoogle Scholar
  28. Metges CC (2000) Contribution of microbial amino acids to amino acid homeostasis of the host. J Nutr 130(7):1857S–1864SPubMedGoogle Scholar
  29. Newsome SD, Fogel ML, Kelly L, del Rio CM (2011) Contributions of direct incorporation from diet and microbial amino acids to protein synthesis in Nile tilapia. Funct Ecol 25(5):1051–1062. doi: 10.1111/j.1365-2435.2011.01866.x CrossRefGoogle Scholar
  30. Nordrum S, Krogdahl A, Rosjo C, Olli JJ, Holm H (2000) Effects of methionine, cysteine and medium chain triglycerides on nutrient digestibility, absorption of amino acids along the intestinal tract and nutrient retention in Atlantic salmon (Salmo salar L.) under pair-feeding regime. Aquaculture 186(3–4):341–360. doi: 10.1016/s0044-8486(99)00385-3 CrossRefGoogle Scholar
  31. Nuez-Ortin WG (2011) Antimicrobial properties of Gustor B92 against pathogenic bacteria of freshwater fish and marine shrimp. In: Conference proceedings world aquaculture society 2011, Natal, BrazilGoogle Scholar
  32. Nuez-Ortin WG (2012) Antimicrobial properties of butyric acid and other organic acids against pathogenic bacteria affecting the main aquatic species. In: Conference proceedings aqua conference 2012, Prague, Czech RepublicGoogle Scholar
  33. Owen MAG, Waines P, Bradley G, Davies S (2006) The effect of dietary supplementation of sodium butyrate on the growth and microflora of Clarias gariepinus (Burchell 1822). XII international symposium fish nutrition and feeding, May 28–June 1, Book of abstracts: 149Google Scholar
  34. Pan M, Souba WW, Lin CM, Meng QH, Wolfgang CL, Stevens BR (2002) Specific induction of amino acid alanine uptake in intestinal cells. Gastroenterology 123(1):19–20Google Scholar
  35. Preinerstorfer B, Schiesel S, Laemmerhofer ML, Lindner W (2010) Metabolic profiling of intracellular metabolites in fermentation broths from beta-lactam antibiotics production by liquid chromatography-tandem mass spectrometry methods. J Chromatogr A 1217(3):312–328. doi: 10.1016/j.chroma.2009.11.051 PubMedCrossRefGoogle Scholar
  36. Reeds PJ, Burrin DG, Stoll B, Jahoor F, Wykes L, Henry J, Frazer ME (1997) Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets. Am J Physiol-Endocrinol Metab 273(2):E408–E415Google Scholar
  37. Rodriguez-Serrano F, Marchal JA, Rios A, Martinez-Amat A, Boulaiz H, Prados J, Peran M, Caba O, Carrillo E, Hita F, Aranega A (2007) Exogenous nucleosides modulate proliferation of rat intestinal epithelial IEC-6 cells. J Nutr 137(4):879–884PubMedGoogle Scholar
  38. Roediger WEW (1982) The effect of bacterial metabolites on nutrition and function of the colonic mucosa. Symbiosis between man and bacteria. In: Kasper H, Goebel H (eds) Colon and nutrition. Plenum Press, Lancaster, pp 11–24Google Scholar
  39. Sakata T, Yajima T (1984) Influence of short chain fatty acids on the epithelial cell division of digestive tract. Q J Exp Physiol Cogn Med Sci 69(3):639–648Google Scholar
  40. Scheppach W (1994) Effects of short chain fatty acids on gut morphology and function. Gut 35(1):S35–S38. doi: 10.1136/gut.35.1_Suppl.S35 PubMedCrossRefGoogle Scholar
  41. Scollo G, Terova G, Rimoldi S, Bernardini G, Antonini M, Saroglia M (2012) Does butyrate have a role in the protection of fish intestine? Results from a preliminary study on European sea bass (D. labrax) Aquaculture Europe. Book of abstracts. PragueGoogle Scholar
  42. Stoll B, Burrin DG (2006) Measuring splanchnic amino acid metabolism in vivo using stable isotopic tracers. J Anim Sci 84(Suppl):E60–E72PubMedGoogle Scholar
  43. Van den Berg RA, Hoefsloot HCJ, Westerhuis JA, Smilde AK, van der Werf MJ (2006) Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics 7. doi: 10.1186/1471-2164-7-142
  44. Van der Schoor SRD, van Goudoever JB, Stoll B, Henry JF, Rosenberger JR, Burrin DG, Reeds PJ (2001) The pattern of intestinal substrate oxidation is altered by protein restriction in pigs. Gastroenterology 121(5):1167–1175. doi: 10.1053/gast.2001.29334 PubMedCrossRefGoogle Scholar
  45. Webb J (1990) Intestinal absorption of protein hydrolysis products: a review. J Anim Sci 68:3011–3022PubMedGoogle Scholar
  46. Xia J, Psychogios N, Young N, Wishart DS (2009) MetaboAnalyst: a web server for metabolomic data analysis and interpretation. Nucleic Acids Res 37:W652–W660. doi: 10.1093/nar/gkp356 PubMedCrossRefGoogle Scholar
  47. Zheng (2009) The effect of sodium butyrate on the growth performance and intestinal mucous structure of fresh water fish. PhD thesis

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • R. Robles
    • 1
  • A. B. Lozano
    • 2
  • A. Sevilla
    • 3
  • L. Márquez
    • 4
  • W. Nuez-Ortín
    • 5
  • F. J. Moyano
    • 4
  1. 1.Centro Tecnológico de la Acuicultura de AndalucíaPuerto Sta. María, CádizSpain
  2. 2.Inbionova Biotech S.L., Edif. CEEIMUniversity of MurciaMurciaSpain
  3. 3.Department of Biochemistry and Molecular Biology B and Immunology, Faculty of ChemistryUniversity of MurciaMurciaSpain
  4. 4.Department of Biology and Geology, Engineering SchoolUniversity of AlmeríaAlmeríaSpain
  5. 5.NOREL S.A. Jesús AprendizMadridSpain

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