Skip to main content
Gut logoLink to Gut
. 1995 Jan;36(1):93–99. doi: 10.1136/gut.36.1.93

Colonic mucin synthesis is increased by sodium butyrate.

I A Finnie 1, A D Dwarakanath 1, B A Taylor 1, J M Rhodes 1
PMCID: PMC1382360  PMID: 7890244

Abstract

The effects of sodium butyrate and sodium bromo-octanoate (an inhibitor of beta oxidation) on colonic mucus glycoprotein (mucin) synthesis have been assessed using tissue from colonic resection samples. Epithelial biopsy specimens were incubated for 16 hours in RPMI 1640 with glutamine, supplemented with 10% fetal calf serum and N-acetyl-[3H]-glucosamine ([3H]-Glc NAc), and differing concentrations of sodium butyrate. Incorporation of [3H] Glc NAc into mucin by normal epithelium at least 10 cm distant from colonic cancer was increased in the presence of sodium butyrate in a dose dependent manner, with maximum effect (476%) at a concentration of 0.1 mM (number of specimens = 24 from six patients, p < 0.001). The increase in response to butyrate was not seen when specimens were incubated in the presence of the beta oxidation inhibitor sodium bromo-octanoate 0.05 M. The striking increase in mucin synthesis that results when butyrate is added to standard nutrient medium suggests that this may be an important mechanism affecting the rate of mucin synthesis in vivo and may also explain the therapeutic effect of butyrate in colitis.

Full text

PDF
93

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan A., Bristol J. B., Williamson R. C. Crypt cell production rate in ulcerative proctocolitis: differential increments in remission and relapse. Gut. 1985 Oct;26(10):999–1003. doi: 10.1136/gut.26.10.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burton A. F., Anderson F. H. Decreased incorporation of 14C-glucosamine relative to 3H-N-acetyl glucosamine in the intestinal mucosa of patients with inflammatory bowel disease. Am J Gastroenterol. 1983 Jan;78(1):19–22. [PubMed] [Google Scholar]
  3. Clamp J. R., Fraser G., Read A. E. Study of the carbohydrate content of mucus glycoproteins from normal and diseased colons. Clin Sci (Lond) 1981 Aug;61(2):229–234. doi: 10.1042/cs0610229. [DOI] [PubMed] [Google Scholar]
  4. Cope G. F., Heatley R. V., Kelleher J., Axon A. T. In vitro mucus glycoprotein production by colonic tissue from patients with ulcerative colitis. Gut. 1988 Feb;29(2):229–234. doi: 10.1136/gut.29.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cummings J. H., Pomare E. W., Branch W. J., Naylor C. P., Macfarlane G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987 Oct;28(10):1221–1227. doi: 10.1136/gut.28.10.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Finnie I. A., Taylor B. A., Rhodes J. M. Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism. Gut. 1993 Nov;34(11):1552–1558. doi: 10.1136/gut.34.11.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gold D. V., Shochat D., Miller F. Protease digestion of colonic mucin. Evidence for the existence of two immunochemically distinct mucins. J Biol Chem. 1981 Jun 25;256(12):6354–6358. [PubMed] [Google Scholar]
  8. Gum J. R., Kam W. K., Byrd J. C., Hicks J. W., Sleisenger M. H., Kim Y. S. Effects of sodium butyrate on human colonic adenocarcinoma cells. Induction of placental-like alkaline phosphatase. J Biol Chem. 1987 Jan 25;262(3):1092–1097. [PubMed] [Google Scholar]
  9. Harig J. M., Soergel K. H., Komorowski R. A., Wood C. M. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989 Jan 5;320(1):23–28. doi: 10.1056/NEJM198901053200105. [DOI] [PubMed] [Google Scholar]
  10. Illman R. J., Topping D. L., Trimble R. P. Effects of food restriction and starvation-refeeding on volatile fatty acid concentrations in the rat. J Nutr. 1986 Sep;116(9):1694–1700. doi: 10.1093/jn/116.9.1694. [DOI] [PubMed] [Google Scholar]
  11. Jass J. R. Diet, butyric acid and differentiation of gastrointestinal tract tumours. Med Hypotheses. 1985 Oct;18(2):113–118. doi: 10.1016/0306-9877(85)90043-x. [DOI] [PubMed] [Google Scholar]
  12. Jones D. A., Jackson M. J., Edwards R. H. Release of intracellular enzymes from an isolated mammalian skeletal muscle preparation. Clin Sci (Lond) 1983 Aug;65(2):193–201. doi: 10.1042/cs0650193. [DOI] [PubMed] [Google Scholar]
  13. Lukie B. E., Forstner G. G. Synthesis of intestinal glycoprotein. Incorporation of (I- 14 C) glucosamine in vitro. Biochim Biophys Acta. 1971 Feb 28;261(2):353–364. [PubMed] [Google Scholar]
  14. MacDermott R. P., Donaldson R. M., Jr, Trier J. S. Glycoprotein synthesis and secretion by mucosal biopsies of rabbit colon and human rectum. J Clin Invest. 1974 Sep;54(3):545–554. doi: 10.1172/JCI107791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McCormick D. A., Horton L. W., Mee A. S. Mucin depletion in inflammatory bowel disease. J Clin Pathol. 1990 Feb;43(2):143–146. doi: 10.1136/jcp.43.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McIntyre A., Young G. P., Taranto T., Gibson P. R., Ward P. B. Different fibers have different regional effects on luminal contents of rat colon. Gastroenterology. 1991 Nov;101(5):1274–1281. doi: 10.1016/0016-5085(91)90077-x. [DOI] [PubMed] [Google Scholar]
  17. Morita H., Kettlewell M. G., Jewell D. P., Kent P. W. Glycosylation and sulphation of colonic mucus glycoproteins in patients with ulcerative colitis and in healthy subjects. Gut. 1993 Jul;34(7):926–932. doi: 10.1136/gut.34.7.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Neutra M. R., Grand R. J., Trier J. S. Glycoprotein synthesis, transport, and secretion by epithelial cells of human rectal mucosa: normal and cystic fibrosis. Lab Invest. 1977 May;36(5):535–546. [PubMed] [Google Scholar]
  19. Parker N., Finnie I. A., Raouf A. H., Ryder S. D., Campbell B. J., Tsai H. H., Iddon D., Milton J. D., Rhodes J. M. High performance gel filtration using monodisperse highly cross-linked agarose as a one-step system for mucin purification. Biomed Chromatogr. 1993 Mar-Apr;7(2):68–74. doi: 10.1002/bmc.1130070204. [DOI] [PubMed] [Google Scholar]
  20. Raaka B. M., Lowenstein J. M. Inhibition of fatty acid oxidation by 2-bromooctanoate. Including effects of bromooctanoate on ketogenesis and gluconeogenesis. J Biol Chem. 1979 May 10;254(9):3303–3310. [PubMed] [Google Scholar]
  21. Raouf A. H., Tsai H. H., Parker N., Hoffman J., Walker R. J., Rhodes J. M. Sulphation of colonic and rectal mucin in inflammatory bowel disease: reduced sulphation of rectal mucus in ulcerative colitis. Clin Sci (Lond) 1992 Nov;83(5):623–626. doi: 10.1042/cs0830623. [DOI] [PubMed] [Google Scholar]
  22. Raouf A., Parker N., Iddon D., Ryder S., Langdon-Brown B., Milton J. D., Walker R., Rhodes J. M. Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect. Gut. 1991 Oct;32(10):1139–1145. doi: 10.1136/gut.32.10.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rhodes J. M. Colonic mucus and mucosal glycoproteins: the key to colitis and cancer? Gut. 1989 Dec;30(12):1660–1666. doi: 10.1136/gut.30.12.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roediger W. E., Nance S. Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br J Exp Pathol. 1986 Dec;67(6):773–782. [PMC free article] [PubMed] [Google Scholar]
  25. Roediger W. E. Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut. 1980 Sep;21(9):793–798. doi: 10.1136/gut.21.9.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roediger W. E. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980 Oct 4;2(8197):712–715. doi: 10.1016/s0140-6736(80)91934-0. [DOI] [PubMed] [Google Scholar]
  27. Ryder S. D., Parker N., Ecclestone D., Haqqani M. T., Rhodes J. M. Peanut lectin stimulates proliferation in colonic explants from patients with inflammatory bowel disease and colon polyps. Gastroenterology. 1994 Jan;106(1):117–124. doi: 10.1016/s0016-5085(94)94775-9. [DOI] [PubMed] [Google Scholar]
  28. Sakata T., Yajima T. Influence of short chain fatty acids on the epithelial cell division of digestive tract. Q J Exp Physiol. 1984 Jul;69(3):639–648. doi: 10.1113/expphysiol.1984.sp002850. [DOI] [PubMed] [Google Scholar]
  29. Scheppach W., Sommer H., Kirchner T., Paganelli G. M., Bartram P., Christl S., Richter F., Dusel G., Kasper H. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992 Jul;103(1):51–56. doi: 10.1016/0016-5085(92)91094-k. [DOI] [PubMed] [Google Scholar]
  30. Smith A. C., Podolsky D. K. Biosynthesis and secretion of human colonic mucin glycoproteins. J Clin Invest. 1987 Aug;80(2):300–307. doi: 10.1172/JCI113073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vernia P., Gnaedinger A., Hauck W., Breuer R. I. Organic anions and the diarrhea of inflammatory bowel disease. Dig Dis Sci. 1988 Nov;33(11):1353–1358. doi: 10.1007/BF01536987. [DOI] [PubMed] [Google Scholar]
  32. Wright N. A. Trefoil peptides and the gut. Gut. 1993 May;34(5):577–579. doi: 10.1136/gut.34.5.577. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES