kvj Kocatepe Veterinary Journal 2147-6853 Afyon Kocatepe University Bütirik Asit: Yapısı, Özellikleri ve Sağlık Üzerine Etkileri Butyric Acid: Structure, Properties and Effects on Health Çağlar Abdullah Tomar Oktay Ekiz Teslime 03 01 2017 10 3 213 225 03 23 2017 08 30 2017 Copyright © 2008, Kocatepe Veterinary Journal 2008 Kocatepe Veterinary Journal

Kısa zincirli yağ asitleri; bağırsak lümeninde, sindirilmemiş diyet karbonhidratları gibi çeşitli maddelerin bakteriyel fermantasyonuyla üretilen organik asitlerdir. Fermente edilebilir karbonhidrattan kolonik kısa zincirli yağ asitleri oluşumu, kolonik epitelyumun morfolojik ve işlevsel bütünlüğünün korunması gibi birçok fonksiyon için önemlidir. Üretilen bu kısa zincirli yağ asitlerinden birisi de, bütirik asittir. Bütirik asit (bütirat) sütte doğal olarak bulunan bir maddedir. Gıda maddeleri ve içecek endüstrisinde uygulamaları çok iyi bilinen bütirik asitin birçok kullanım alanı bulunmaktadır. Çeşitli üretim yöntemleri ile elde edilen bütirik asit, doğrudan ve dolaylı olarak farklı fizyolojik etkilere sahiptir. Diğer kısa zincirli yağ asitleri ile karşılaştırıldığında, biyolojik fonksiyonları arasında ayrı bir yere sahip olan bütirik asit, epitel hücreleri için enerji kaynağıdır. Bu madde, kolonik sağlığı etkileyen çok çeşitli hücresel işlevleri de etkilemektedir. Bütirat, kolonik savunma bariyerinin çeşitli bileşenlerini takviye ederek ve oksidatif stresi azaltarak inflamasyon ve karsinogenez inhibisyonu gibi çeşitli kolonik mukozal fonksiyonlar üzerinde güçlü etkiler gösterir. Ayrıca bu madde, yetersiz bütirik asit metabolizması sonucunda insanlarda gelişen ülseratif kolitin ve sindirim sisteminde görülen Crohn hastalığına sahip kişilerin tedavisinde de kullanılmaktadır. Bu derlemenin amacı, bütirik asitin önemi ve insan sağlığı üzerinde sahip olduğu çeşitli fonksiyonları hakkında genel bir bakış sağlamaktır.

Short chain fatty acids are organic acids produced in the intestinal lumen by bacterial fermentation of various substances such as undigested diet carbohydrates. Colonic short chain fatty acids formation from fermentable carbonhydrate is important for many functions, such as preserving the morphological and functional integrity of the colonic epithelium. One of these short chain fatty acids produced is butyric acid. Butyric acid (butyrate) is a naturally-found substance in milk. There are many applications of butyric acid, which are well known in foodstuffs and beverage industry. Butyric acid obtained by various production methods has different direct and indirect physiological effects. When compared to other short chain fatty acids, butyric acid, which has a distinctive biological function, is a source of energy for epithelial cells. This substance affects a wide range of cellular functions that affect colonic health. Butyrate has strong effects on various colonic mucosal functions such as inflammation and inhibition of carcinogenesis by supplementing various components of the colonic defense barrier and reducing oxidative stress. It is also used in the treatment of people with Crohn's disease in the digestive tract and ulcerative colitis that develop in humans as a result of inadequate butyric acid metabolism. The purpose of this review is to provide an overview of the importance of butyric acid and the various functions that butyric acid has on human health.

 Butyric acid Butyrate Short-chain fatty acids Colon Health Bütirik asit Bütirat Kısa zincirli yağ asitleri Kolon Sağlık Abrahamse SL, Pool-Zobel BL, Rechkemmer G. Potential of short chain fatty acids to modulate the induction of DNA damage and changes in the intracellular calcium concentration by oxidative stress in isolated rat distal colon cells. Carcinogenesis. 1999;20:629–34. Alam S, Stevens D, Bajpai R. Production of butyric acid by batch fermentation of cheese whey with Clostridium beijerinckii. Journal of Industrial Microbiology & Biotechnology. 1988; 2(6):359-364. Anonim2015a.http://nutriad.com/2015/01/butyrate-feeding-the-gut-and-beyond-for-animal-health-2/; Erişim tarihi: 01.03.2017. Anonim2015b.http://sanitasaglik.com/articles/24_09_2012_10_36_22.pdf Erişim tarihi: 01.03.2017. Anonim2015c.http://www.drahmetdobrucali.com/hastaliklar/inflamatuvar-barsak-hastaliklari/; Erişim tarihi: 01.03.2017. Anonim2015d.http://www.turkiyeklinikleri.com/article/en-irritabl-bagirsak-sendromu-62364.html; Erişim tarihi: 01.03.2017. Arends MJ. Pathways of colorectal carcinogenesis. Appl Immunohistochem Mol Morphol. 2013;21:97–102. Armstrong DW, Yamazaki H. Natural flavours production: a biotechnological approach. Trends in Biotechnology. 1986;4:264-268. Augeron C, Laboisse CL. Emergence of permanently differentiated cell clones in a human colonic cancer cell line in culture after treatment with sodium butyrate. Cancer Res. 1984;44:3961. Aukema HM, Davidson LA, Pence BC, Jiang Y.-H, Lupton JR, Chapkin RS. Butyrate alters activity of specific CAMP-receptor proteins in a transgenic mouse colonic cell line. J. Nutr. 1997;127:18. Basson R, Berman J, Burnett A, Derogatis L, Ferguson D, Fourcroy J et al. Report of the international consensus development conference on female sexual dysfunction: definitions and classifi cations. J Urol.2000;163(3):888–893. Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev. 1990;70:567-90. Berry RD, Paraskeva C. Expression of carcinoembryonic antigen by adenomaand carcinoma-derived epithelial cell lines: possible marker of tumour progression and modulation of expression by sodium butyrate. Carcinogenesis. 1988;9:447. Bilgin M, Kırbaşlar Ş, Özcan Ö, Dramur U. Bütirik asidin ekstraksiyonunda çözücü seçimi, ukmk11, 2014. Bornet FR, Brouns F, Tashiro Y, Duvillier V. Nutritional aspects of shortchain fructooligosaccharides: natural occurrence, chemistry, physiology and health implications. Dig Liver Dis. 2002;34(2):111–120. Brouns F, Kettlitz B, Arrigoni, E. Resistant starch and “the butyrate revolution”. Trends in Food Science & Technology.2002;13(8):251-261. Butzner JD, Parmar R, Bell CJ, Dalal V. Butyrate enema therapy stimulating mucosal repair in experimental colitis in rat. Gut.1996;38:568–573. Butzner JD, Parmar R, Bell CJ, Dalal V. Butyrate enema therapy stimulates mucosal repair in experimental colitis in the rat. Gut. 1996;38:568–73. Calabresse C, Venturini L, Ronco G, Villa P, Chomienne C, Belpomme D. Butyric acid and its monosaccharide ester induce apoptosis in the HL-60 cell line. Biochemical and biophysical research communications. 1993;195(1):31-38. Canani RB, Costanzo D, Leone L, Bedogni G, Brambilla P, Cianfarani S, Nobili V, Pietrobelli A, Agostoni C. Epigenetic mechanisms elicited by nutrition in early life. Nutr Res Rev. 2011; 24(2):198–205. Chapman MA, Grahn MF, Boyle MA, Hutton M, Rogers J, Williams NS. Butyrate oxidation is impaired in the colonic mucosa of sufferers of quiescent ulcerative colitis.Gut.1994;35:73. Christl SU, Eisner HD, Dusel G, Kasper H, Scheppach W. Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa. Digestive diseases and sciences. 1996;41(12):2477-2481. Clausen MR, Tvede M, Mortensen PB. Short-chain fatty acids in pouch contents from patients with and without pouchitis after ileal pouch-anal anastomosis. Gastroenterology. 1992; 103(4):1144-1153. Crabbendam PM, Neijssel OM, Tempest DW. Metabolic and energetic aspects of the growth of Clostridium butyricum on glucose in chemostat culture. Arch. Microbiol. 1985;142(4): 375–382. Cummings JH, Antoine JM, Azpiroz F, Bourdet-Sicard R, Brandtzaeg P, Calder PC, Gibson GR, Guarner F, Isolauri E, Pannemans D, Shortt C, Tuijtelaars S, Watzl B. PASSCLAIM--Gut health and immunity. Eur J Nutr. 2004;43(2):ii118-ii73. D’Argenio G, Ciacci C, Sorrentini I, Iovino P, Gatto A, Cosenza V, Mazzacca G. Serum transglutaminase in inflammatory bowel diseases, J. Clin. Gastroenterol.1990;12:400. D’Argenio G, Cosenza V, Sorrentini I, De Ritis F, Delle Cave M, Della Valle N, Lombardi G, Mazzacca G. Sodium butyrate, 5-ASA and intravenous factor XIII therapies in experimental colitis in the rat, Proc. Falk. Symp. (Strasbourg). 1993;73. D’Argenio G, Cosenza V, Sorrentini I, De Ritis F, Gatto A, Delle Cave M et al. Butyrate, mesalamine, and factor XIII in experimental colitis in the rat: effects on transglutaminase activity. Gastoenterology. 1994;106:399–404. D'Argenio G, Mazzone, G, Caporaso N. Butyrate in the treatment of experimental models of colitis. Digestive and Liver Disease Supplements.2007;1(1),13-17. Della Ragione F, Criniti V, Della Pietra V, Borriello A, Oliva A, Indaco S et al. Genes modulated by histone acetylation as new effectors of butyrate activity. FEBS Lett. 2001;499:199–204. Di Sabatino A, Cazzola P, Ciccocioppo R, Morera R, Biancheri P, Rovedatti L, Cantoro L, Vanoli A, Tinozzi FP, Tinozzi S, Corazza, G. R. Efficacy of butyrate in the treatment of mild to moderate Crohn's disease. Digestive and Liver Disease Supplements. 2007;1(1):31-35. Druaux D, Mangeot G, Endrizzi A, Belin JM. Bacterial bioconversion of primary aliphatic and aromatic alcohols into acids: effects of molecular structure and physico-chemical conditions. J Chem Technol Biotechnol. 1997;68:214–218. Duncan M, Davison JS, Sharkey KA. Endocannabinoids and their receptors in the enteric nervous system. Aliment Pharmacol Ther. 2005; 22(8):667–683. Dziedzak JD. Biotechnology and flavor development: an industrial research perspective. Food Technol.1986;40:108–20. Fayolle F, Marchal R, Ballerini D. Effect of controlled substrate feeding on butyric acid production by Clostridium tyrobutyricum. J. Ind. Microbiol. 1990;6:179–183. Gasbarroni A, Lauritano EC. Foreword. Digestive and Liver Disease Supplements. 2007;1(1):1. Gaudier E, Jarry A, Blottière HM Aubert JP, Laboisse C, Cherbut C et al. Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am J Physiol Gastrointest Liver Physiol. 2004;287:G1168–74. German JB, Dillard CJ. Fractionated milk fat: composition, structure, and functional properties. Food Technol. 1998;52:33. Gill CI, Rowland IR. Diet and cancer: assessing the risk. Br J Nutr. 2002;88(1):73–87. Hague A, Elder DJ, Hicks DJ, Paraskeva C. Apoptosis in colorectal tumour cells: induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate. Int J Cancer. 1995;60:400–406. Hamer HM, Jonkers DM, Bast A, Vanhoutvin SA, Fischer MA, Kodde A, Troost FJ, Venema K, Brummer RJM. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans. Clinical Nutrition.2009;28(1):88-93. Hamer HM. Short chain fatty acids and colonic health. Thesis, Universiteit Maastricht, Holland, 2009. Hamer HM. Short chain fatty acids and colonic health.Thesis, Universiteit Maastricht, Holland, 2009. Huang YL, Wu Z, Zhang L, Cheung CM, Yang ST. Production of carboxylic acids from hydrolyzed corn meal by immobilized cell fermentation in a fibrous-bed bioreactor. Bioresource technology. 2002;82(1): 51-59. Jacobs LR. Relationship between dietary fiber and cancer: metabolic, physiologic, and cellular mechanisms. Experimental Biology and Medicine. 1986; 183(3): 299-310. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA: a cancer journal for clinicians.2010;60(5):277–300. Jensen RG, Kroger M. The importance of milk and milk products in the diet. Handbook of dairy foods and nutrition. 2000;1-64. Jensen RG, Lammi-Keefe CJ. Current status of research on the composition of bovine and human milk lipids, in Lipids in Infant Nutrition, Huang, Y.S., and Sinclair, A.J., Eds; AOCS Press, Champaign, IL, 168-191, 1998. Jensen RG. Handbook of Milk Composition, Academic Press, New York, 1995. Jiang L, Wang J, Liang S, Wang X, Cen P, Xu Z. Butyric acid fermentation in a fibrous bed bioreactor with immobilized Clostridium tyrobutyricum from cane molasses. Bioresource Technology. 2009;100(13): 3403-3409. Katan MB, Zock PL, Mensink RP. Dietary oils, serum lipoproteins, and coronary heart disease. Am. J. Clin. Nutr. 1995;61(l):1368. Krauss RM, Deckelbaum RJ, Ernst N, Fisher E, Howard BV, Knopp RH, Kotchen T, et. al. Dietary guidelines for healthy Americans: a statement for health professionals by the Nutrition Committee. American Heart Association. 1996; Circulation, 94: 1795-1800. Kumar CM, Rachappaji KS, Nandini CD, Sambaiah K, Salimath PV. Modulatory effect of butyric acid—a product of dietary fiber fermentation in experimentally induced diabetic rats. The Journal of nutritional biochemistry. 2002;13(9):522-527. Lefranc L, Cie E. A process for the manufacture of butyric acid and other fatty acids with recovery of the gases of fermentation. Br. Pat. 1923;186:572. Lehninger AL, Nelson DL, Cox, MM. Principles of Biochemistry, Ed;Worth, New York.1993. Levitt MD. Malabsorption of starch: a normal phenomena. Gastroenterology. 1983; 85:769–770. Liu X, Zhu Y, Yang ST. Butyric acid and hydrogen production by Clostridium tyrobutyricum ATCC 25755 and mutants. Enzyme and Microbial Technology. 2006; 38(3): 521-528. Liu XG, Yang ST. Butyric acid and hydrogen production by Clostridium tyrobutyricum ATCC 25755 and mutants. Enzyme Microb. Technol. 2006;38:521–528. Liu XG, Zhu Y, Yang ST. Kinetics of butyric acid fermentation of glucose and xylose by Clostridium tyrobutyricum wild type and mutant. Process Biochem. 2006;41:801–808. Luhrs H, Gerke T, Muller JC Melcher R, Schauber J, Boxberge F et al. Butyrate inhibits NF-kB activation in lamina propria macrophages in patients with ulcerative colitis. Scand J Gastroenterol. 2002;37:458–66. Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proc Nutr Soc. 2003;62:67–72. McIntosh GH, Leu RK, Royle PJ, Young GP. A comparative study of the influence of differing barley brans on DMH‐induced intestinal tumours in male Sprague‐Dawley rats. Journal of gastroenterology and hepatology.1996;11(2): 113-119. McIntyre A, Gibson PR, Young GP. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993;34(3):386-391. Michel-Savin D, Marchal R, Vandecasteele JP. Control of the selectivity of butyric acid production and improvement of fermentation performance with Clostridium tyrobutyricum. Appl. Microbiol. Biotechnol. 1990; 32:387–392. Mortensen PB, Clausen MR. short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol.1996;216:132–48. Novogrodsky A, Dvir A, Ravid A, Shkolnik T, Stenzel KH, Rubin AL, Zaizov R. Effect of polar organic compounds on leukemic cells. Butyrate-induced partial remission of acute myelogenous leukemia in a child.Cancer.1983;51:9. Ohta T, Furukawa N, Yonemori F, Wakitani K. JTT-608 controls blood glucose by enhancement of glucose-stimulated insulin secretion in normal and diabetes mellitus rats. European journal of pharmacology.1999;367(1):91-99. Oktay E. İnflamatuar barsak hastalıkları: etyopatogenez, semptomatoloji, tanı ve komplikasyonlar. Gastrointestinal Sistem Hastalıkları. İÜ Cerrahpaşa Tıp Fakültesi Sürekli Tıp Eğitimi Sempozyum Dizisi. 2001: 199-206. Oltmer S, Engelhardt WV. Absorption of shortchain fatty acids from the in-situ-perfused caecum and colon of the guinea pig. Scand J Gastroenterol. 1994;29(11):1009–1016. Parodi PW. Cows’ milk fat components as potential anticarcinogenic agents. J. Nutr. 1997;127:1055. Perrin P, Cassagnau E, Burg C, Patry Y, Vavasseur F, Harb J. et al. An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis. Gastroenterology. 1994;107:1697–1708. Playne MJ. Propionic and butyric acids, In: Comprehensive Biotechnology, Ed; Moo-Young, Pergamon Press, Oxford, UK, 1985; pp 731–759. Playne MJ. Propionic and butyric acids. In: Comprehensive Biotechnology, Ed; Moo-Young M, Oxford, Pergamon Press, vol. 3, 198; 731–59. Pouillart PR. Role of butyric acid and its derivatives in the treatment of colorectal cancer and hemoglobinopathies. Life sciences. 1998; 63(20): 1739-1760. Pryde EM. Carboxylic acids (economic aspects), In: Encyclopedia of Chemical Technology. Ch 41, John Wiley and Sons, New York, 1978; pp 853–859. Raman M, Ambalam P, Doble M. Probiotics and Bioactive Carbohydrates in Colon Cancer Management. Springer, 2016. Rechkemmer G, Ronnau K, Engelhardt WV. Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut. Comp Biochem Physiol A Comp Physiol. 1988; 90(4):563–568. Rezaie A, Parker RD, Abdollahi M. Oxidative stress and pathogenesis of inflammatory bowel disease: an epiphenomenon or the cause? Dig Dis Sci.2007;52:2015–21. Riggs MG, Whittaker RG, Neumann JR, Ingram VM. n-Butyrate causes histone modification in HeLa and friend erythroleukaemia cells. Nature.1977; 268:462–463. Roberfroid, MB. Inulin-Type Fructans: Functional Food Ingredients, CRC Press, 2005. Roediger WE. Role of anaerobic bacteria in the metabolic welfare of the colonic mucose in man. Gut. 1980;21:793–798. Roediger WE. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980;21:793–798. Roediger WE. The starved colon--diminished mucosal nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33:858-862. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982;83:424-429. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982;83:424–429. Roediger WE.Colon and Nutrition, Ed; H. Kasper and H. Goebell , Lancaster Press, Falk Symposium, 1981;32 1l-25. Roediger WEW. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet.1980;2:712. Rombeau J, Kripke SA, Settle RG. Short-chain fatty acids: production, absorption, metabolism, and intestinal effects, In: Dietary Fiber: Basic and Clinical Aspects, Ed; David Kritchevsky, Plenum Press, New York, 1986; pp. 317–339. Rosignoli P, Fabiani R, De Bartolomeo A, Spinozzi F, Agea E, Pelli MA, Morozzi G. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells. Carcinogenesis.2001;22:1675–80. Scarpellini E, Lauritano EC, Lupascu A, Petruzzellis C, Novi ML, Roccarina D, Gabrielli M, Serricchio M, Gasbarrini G, Gasbarrini, A. Efficacy of butyrate in the treatment of diarrhoea-predominant irritable bowel syndrome. Digestive and Liver Disease Supplements.2007;1(1):19-22. Scheppach W, Bartram HP, Richter F. Role of short-chain fatty acids in the prevention of colorectal cancer. Eur J Cancer. 1995; 31A:1077–1080. Scheppach W, Christl SU, Bartram HP, Richter F, Kasper H. Effect of short chain fatty acids on the inflamed colonic mucosa. Scand J Gastroenterol.1997;32:53–57. Scheppach W, Fabian C, Ahrens F, Spengler M, Kasper H. Effect of starch malbsorption on colonic function and metabolism in humans. Gastroenterology. 1988;95:1549–1555. Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, Richter F, Dusel G, Kasper H. The effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology .1992;103(1):51–56. Segain JP, Raingeard D, Bourreille A Leray V, Gervois N, Rosales C et al. Butyrate inhibits inflammatory responses through NF-kB inhibition: implications for Crohn’s disease. Gut. 2000;47: 397–403. Segain JP, Raingeard de la Blétière D, Bourreille A, Leray V, Gervois N, Rosales C, Ferrier L, Bonnet C, Blottière HM, Galmiche JP. Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. Gut. 2000;47:397-403. Sharpei FHJ. Microbial flavours and fragrances, In: Comprehensive Biotechnology, Ed; HW Blanch, S Drew and DIC Wang. Pergamon Press, Oxford, UK, 1985; pp. 965-979. Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M.Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol.2005;11:403–6. Smith CJ, Bryant MP. Introduction to metabolic activities of intestinal bacteria. Am J Clin Nutr. 1979;32:149–57. Smith JG, German JB. Molecular and genetic effects of dietary derived butyric acid.Food Technol.1995;49:87. Smith JG, Yokoyama WH, German JB. Butyric acid from the diet: actions at the level of gene expression. Critical Reviews in Food Science.1998; 38(4): 259-297. Sneath PHA. Bergey’s Manual of Systematic Bacteriology 2. Baltimore: Waverly Press, 1986;1141–200. Soergel KH. Colonic fermentation: metabolic and clinical implications. The clinical investigator. 1994;72(10):742-748. Spina L, Cavallaro F, Fardowza NI, Lagoussis P, Bona D, Ciscato C, Rigante A, Vecchi M. Butyric acid: pharmacological aspects and routes of administration. Digestive and Liver Disease Supplements. 2007;1(1): 7-11. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:1031–1064. Topping DL, Clifton PM. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev. 2001;81:1031–1064. Treem WR, Ahsan N, Kastoff G, Hyams JS. Fecal Short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr.1996;23:280–6. Van Andel JG, Zouttberg GR, Crabbendam PM, Breure AM. Glucose fermentation by Clostridium butyricum grown under a self generated gas atmosphere in chemostat culture. Appl. Microbiol. Biotechnol. 1985; 23:21–26. Van den Heuvel JC, Verschuren PG, Beeftink HH, de Beer D. Determination of the critical concentration of inhibitory products in a repeated fed-batch culture. Biotechnology techniques. 1992;6(1):33-38. van Nuenen MHC, Meyer D, Venema K. The effect of various inulins and clostridium dificile on the metabolic activity of the human colonic microbiota in vitro. Microbial Ecology in Health and Disease. 2003;15:137-44. Vandák D, Telgarsky´ M, Šturdík E. Influence of growth factor supplements on butyric acid production from sucrose by Clostridium butyricum. Folia Microbiol. 1995;40:669–672. Vandák D, Zigová J, Šturdík E, Schlosser Š. Evaluation of solvent and pH for extractive fermentation of butyric acid. Process Biochemistry. 1997; 32(3): 245-251. Velazquez OC, Lederer HM, Rombeau JL. Butyrate and the colonocyte. Production, absorption, metabolism, and therapeutic implications. Adv Exp Med Biol.1997;427:123–34. Vernia P, Cittadini M, Caprilli R, Torsoli A. Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate, Digest. Dis. Sci. 1995;40:305. Vernia P. Butyrate in the treatment of ulcerative colitis. Digestive and Liver Disease Supplements. 2007;1(1):27-30. Wachtershauser A, Stein J. Rationale for the luminal provision of butyrate in intestinal diseases. Eur J Nutr. 2000;39:164–71. Watzl B, Girrbach S, Roller M. Inulin, oligofructose and immunomodulation. Br J Nutr. 2005;93(1):49-55. Watzl B, Girrbach S, Roller M. Inulin, oligofructose and immunomodulation. Br J Nutr. 2005;93(1):49-55. Widmer J, Fassihi KS, Schlichter SC, Wheeler KS, Crute BE, Nicole KING, Nutile-Mcmenemy N, Noll WW, Daniel S, HA J, Kim KH, Witters LA. Identification of a second human acetyl-CoA carboxylase gene. Biochemical Journal.1996. 316(3); 915-922. Willims EA, Coxhead JM, Mathers JC. Anti-cancer effects of butyrate: use of micro-array technology to investigate mechanisms. Proc Nutr Soc. 2003;62:107–15. Wollowski I, Rechkemmer G, Pool-Zobel BL. Protective role of probiotics and prebiotics in colon cancer. Am J Clin Nutr. 2001;73:S451–5. Wong JM, De Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. Journal of clinical gastroenterology. 2006; 40(3): 235-243. Wong JM, De Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. Journal of clinical gastroenterology. 2006; 40(3):235-243. Wu Z, Yang ST. Extractive fermentation for butyric acid production from glucose by Clostridium tyrobutyricum. Biotechnol. Bioeng. 2003;82:93–102. Zhu Y, Wu Z, Yang ST. Butyric acid production from acid hydrolysate of corn fiber by Clostridium tyrobutyricum in a fibrous bed bioreactor. Process Biochem. 2002;38:657–666. Zigova J, Šturdik E. Advances in biotechnological production of butyric acid. Journal of industrial microbiology & biotechnology. 2000;24(3):153-160. Zoran DL, Barhoumi R, Burghardt RC, Chapkin RS, Lupton JR.Diet and carcinogen alter luminal butyrate concentration and intracellular pH in isolated rat colonocytes. Nutri Cancer. 1997;27(3):222–230.