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. 1985 May;75(5):1448–1454. doi: 10.1172/JCI111847

Carbohydrate fermentation in the human colon and its relation to acetate concentrations in venous blood.

E W Pomare, W J Branch, J H Cummings
PMCID: PMC425482  PMID: 3998144

Abstract

There is now substantial evidence that some dietary polysaccharides, notably dietary fiber, escape absorption in the small bowel and are then broken down in the large intestine of man. The main end products of this colonic digestive process, which is anerobic, are short chain fatty acids (SCFA), and acetic, propionic, and butyric acids. Although these acids are known to be absorbed from the colon, their subsequent fate and significance is unknown. We have measured venous blood SCFA levels in healthy subjects after a 16-h fast, and then following oral doses of either 50 mmol SCFA, 5, 10, or 20 g doses of the fermentable carbohydrate lactulose, or 20 g of pectin. Fasting venous blood acetate was 53.8 +/- 4.4 mumol/liter (SEM) (n = 14). Fasting arterial blood acetate, taken simultaneously with venous blood in six subjects, was higher; 125.6 +/- 13.5 mumol/liter (arterial) vs. 61.1 +/- 6.9 mumol/liter (venous). Significant levels of propionate or butyrate were not detected in any blood samples. Following an oral dose of 50 mmol mixed SCFA, venous blood acetate reached a peak of 194.1 +/- 57.9 mumol/liter at 45 min and returned to fasting levels at 2 h. Blood acetate also rose in response to lactulose, peak levels occurring 2-4 h after the dose: 5 g, 98.6 +/- 23.1 mumol/liter; 10 g, 127.3 +/- 18.2 mumol/liter; and 20 g, 181.3 +/- 23.9 mumol/liter. Pectin fermentation was much slower, with blood acetate levels starting to rise after 6 h and remaining elevated at about twice fasting levels for the subsequent 18 h. However, areas under the blood acetate curves were closely related (r = 0.97; n = 5), whatever the source of acetate. These studies show that the large intestine makes an important contribution to blood acetate levels in man and that fermentation may influence metabolic processes well beyond the wall of this organ.

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Selected References

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  1. ANNISON E. F., WHITE R. R. Further studies on the entry rates of acetate and glucose in sheep, with special reference to endogenous production of acetate. Biochem J. 1962 Sep;84:546–552. doi: 10.1042/bj0840546. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson I. H., Levine A. S., Levitt M. D. Incomplete absorption of the carbohydrate in all-purpose wheat flour. N Engl J Med. 1981 Apr 9;304(15):891–892. doi: 10.1056/NEJM198104093041507. [DOI] [PubMed] [Google Scholar]
  3. Argenzio R. A., Southworth M. Sites of organic acid production and absorption in gastrointestinal tract of the pig. Am J Physiol. 1975 Feb;228(2):454–460. doi: 10.1152/ajplegacy.1975.228.2.454. [DOI] [PubMed] [Google Scholar]
  4. Argenzio R. A., Southworth M., Stevens C. E. Sites of organic acid production and absorption in the equine gastrointestinal tract. Am J Physiol. 1974 May;226(5):1043–1050. doi: 10.1152/ajplegacy.1974.226.5.1043. [DOI] [PubMed] [Google Scholar]
  5. Argenzio R. A., Whipp S. C. Inter-relationship of sodium, chloride, bicarbonate and acetate transport by the colon of the pig. J Physiol. 1979 Oct;295:365–381. doi: 10.1113/jphysiol.1979.sp012974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ballard F. J. Supply and utilization of acetate in mammals. Am J Clin Nutr. 1972 Aug;25(8):773–779. doi: 10.1093/ajcn/25.8.773. [DOI] [PubMed] [Google Scholar]
  7. Bergman E. N., Wolff J. E. Metabolism of volatile fatty acids by liver and portal-drained viscera in sheep. Am J Physiol. 1971 Aug;221(2):586–592. doi: 10.1152/ajplegacy.1971.221.2.586. [DOI] [PubMed] [Google Scholar]
  8. Bond J. H., Jr, Engel R. R., Levitt M. D. Factors influencing pulmonary methane excretion in man. An indirect method of studying the in situ metabolism of the methane-producing colonic bacteria. J Exp Med. 1971 Mar 1;133(3):572–588. doi: 10.1084/jem.133.3.572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bond J. H., Jr, Levitt M. D. Fate of soluble carbohydrate in the colon of rats and man. J Clin Invest. 1976 May;57(5):1158–1164. doi: 10.1172/JCI108383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bond J. H., Jr, Levitt M. D., Prentiss R. Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements. J Lab Clin Med. 1975 Apr;85(4):546–555. [PubMed] [Google Scholar]
  11. Buckley B. M., Williamson D. H. Origins of blood acetate in the rat. Biochem J. 1977 Sep 15;166(3):539–545. doi: 10.1042/bj1660539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cochran G. C. A review of the analysis of free fatty acids [C2-C6]. J Chromatogr Sci. 1975 Sep;13(9):440–447. doi: 10.1093/chromsci/13.9.440. [DOI] [PubMed] [Google Scholar]
  13. Cummings J. H. Fermentation in the human large intestine: evidence and implications for health. Lancet. 1983 May 28;1(8335):1206–1209. doi: 10.1016/s0140-6736(83)92478-9. [DOI] [PubMed] [Google Scholar]
  14. Cummings J. H. Short chain fatty acids in the human colon. Gut. 1981 Sep;22(9):763–779. doi: 10.1136/gut.22.9.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cummings J. H., Southgate D. A., Branch W. J., Wiggins H. S., Houston H., Jenkins D. J., Jivraj T., Hill M. J. The digestion of pectin in the human gut and its effect on calcium absorption and large bowel function. Br J Nutr. 1979 May;41(3):477–485. doi: 10.1079/bjn19790062. [DOI] [PubMed] [Google Scholar]
  16. Dankert J., Zijlstra J. B., Wolthers B. G. Volatile fatty acids in human peripheral and portal blood: quantitative determination vacuum distillation and gas chromatography. Clin Chim Acta. 1981 Mar 5;110(2-3):301–307. doi: 10.1016/0009-8981(81)90359-4. [DOI] [PubMed] [Google Scholar]
  17. Hennings S. J., Hird F. J. Concentrations and metabolism of volatile fatty acids in the fermentative organs of two species of kangaroo and the guinea-pig. Br J Nutr. 1970 Mar;24(1):145–155. doi: 10.1079/bjn19700017. [DOI] [PubMed] [Google Scholar]
  18. Hoover W. H., Heitmann R. N. Effects of dietary fiber levels on weight gain, cecal volume and volatile fatty acid production in rabbits. J Nutr. 1972 Mar;102(3):375–379. doi: 10.1093/jn/102.3.375. [DOI] [PubMed] [Google Scholar]
  19. Imoto S., Namioka S. Nutritive value of acetate in growing pigs. J Anim Sci. 1983 Apr;56(4):858–866. doi: 10.2527/jas1983.564858x. [DOI] [PubMed] [Google Scholar]
  20. Jenkins D. J., Thorne M. J., Camelon K., Jenkins A., Rao A. V., Taylor R. H., Thompson L. U., Kalmusky J., Reichert R., Francis T. Effect of processing on digestibility and the blood glucose response: a study of lentils. Am J Clin Nutr. 1982 Dec;36(6):1093–1101. doi: 10.1093/ajcn/36.6.1093. [DOI] [PubMed] [Google Scholar]
  21. Knowles S. E., Jarrett I. G., Filsell O. H., Ballard F. J. Production and utilization of acetate in mammals. Biochem J. 1974 Aug;142(2):401–411. doi: 10.1042/bj1420401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kurtz D. J., Levy H. L., Plotkin W., Kishimoto Y. A rapid method for the quantitative analysis of short-chain fatty acids in serum or plasma. Clin Chim Acta. 1971 Oct;34(3):463–466. doi: 10.1016/0009-8981(71)90102-1. [DOI] [PubMed] [Google Scholar]
  23. LINDENEG O., MELLEMGAARD K., FABRICIUS J., LUNDQUIST F. MYOCARDIAL UTILIZATION OF ACETATE, LACTATE AND FREE FATTY ACIDS AFTER INGESTION OF ETHANOL. Clin Sci. 1964 Dec;27:427–435. [PubMed] [Google Scholar]
  24. La Brooy S. J., Male P. J., Beavis A. K., Misiewicz J. J. Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time. Gut. 1983 Oct;24(10):893–896. doi: 10.1136/gut.24.10.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lai J. C., Silk D. B., Williams R. Plasma short-chain fatty acids in fulminant hepatic failure. Clin Chim Acta. 1977 Jul 15;78(2):305–310. doi: 10.1016/0009-8981(77)90320-5. [DOI] [PubMed] [Google Scholar]
  26. Levitt M. D. Production and excretion of hydrogen gas in man. N Engl J Med. 1969 Jul 17;281(3):122–127. doi: 10.1056/NEJM196907172810303. [DOI] [PubMed] [Google Scholar]
  27. Lundquist F., Sestoft L., Damgaard S. E., Clausen J. P., Trap-Jensen J. Utilization of acetate in the human forearm during exercise after ethanol ingestion. J Clin Invest. 1973 Dec;52(12):3231–3235. doi: 10.1172/JCI107523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McArthur B., Sarnaik A. P. Quantification of short-chain fatty acids in plasma. Clin Chem. 1982 Sep;28(9):1983–1984. [PubMed] [Google Scholar]
  29. McNeil N. I., Cummings J. H., James W. P. Short chain fatty acid absorption by the human large intestine. Gut. 1978 Sep;19(9):819–822. doi: 10.1136/gut.19.9.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Owens F. N., Isaacson H. R. Ruminal microbial yields: factors influencing synthesis and bypass. Fed Proc. 1977 Feb;36(2):198–202. [PubMed] [Google Scholar]
  31. Pethick D. W., Lindsay D. B., Barker P. J., Northrop A. J. Acetate supply and utilization by the tissues of sheep in vivo. Br J Nutr. 1981 Jul;46(1):97–110. doi: 10.1079/bjn19810013. [DOI] [PubMed] [Google Scholar]
  32. Remesy C., Demigne C. Determination of volatile fatty acids in plasma after ethanolic extraction. Biochem J. 1974 Jul;141(1):85–91. doi: 10.1042/bj1410085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Remesy C., Demigne C. Partition and absorption of valatile fatty acids in the alimentary canal of the rat. Ann Rech Vet. 1976;7(1):39–55. [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Roediger W. E. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982 Aug;83(2):424–429. [PubMed] [Google Scholar]
  37. Ruppin H., Bar-Meir S., Soergel K. H., Wood C. M., Schmitt M. G., Jr Absorption of short-chain fatty acids by the colon. Gastroenterology. 1980 Jun;78(6):1500–1507. [PubMed] [Google Scholar]
  38. Rémésy C., Demigné C., Chartier F. Origin and utilization of volatile fatty acids in the rat. Reprod Nutr Dev. 1980;20(4B):1339–1349. doi: 10.1051/rnd:19800725. [DOI] [PubMed] [Google Scholar]
  39. Sallee V. L., Dietschy J. M. Determinants of intestinal mucosal uptake of short- and medium-chain fatty acids and alcohols. J Lipid Res. 1973 Jul;14(4):475–484. [PubMed] [Google Scholar]
  40. Sandberg A. S., Ahderinne R., Andersson H., Hallgren B., Hultén L. The effect of citrus pectin on the absorption of nutrients in the small intestine. Hum Nutr Clin Nutr. 1983 May;37(3):171–183. [PubMed] [Google Scholar]
  41. Saunders D. R., Wiggins H. S. Conservation of mannitol, lactulose, and raffinose by the human colon. Am J Physiol. 1981 Nov;241(5):G397–G402. doi: 10.1152/ajpgi.1981.241.5.G397. [DOI] [PubMed] [Google Scholar]
  42. Seufert C. D., Mewes W., Soeling H. D. Effect of long-term starvation on acetate and ketone body metabolism in obese patients. Eur J Clin Invest. 1984 Apr;14(2):163–170. doi: 10.1111/j.1365-2362.1984.tb02107.x. [DOI] [PubMed] [Google Scholar]
  43. Skutches C. L., Holroyde C. P., Myers R. N., Paul P., Reichard G. A. Plasma acetate turnover and oxidation. J Clin Invest. 1979 Sep;64(3):708–713. doi: 10.1172/JCI109513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Stevens C. E., Stettler B. K. Transport of fatty acid mixtures across rumen epithelium. Am J Physiol. 1966 Jul;211(1):264–271. doi: 10.1152/ajplegacy.1966.211.1.264. [DOI] [PubMed] [Google Scholar]
  45. Tangerman A., van Schaik A., Meuwese-Arends M. T., van Tongeren J. H. Quantitative determination of C2-C8 volatile fatty acids in human serum by vacuum distillation and gas chromatography. Clin Chim Acta. 1983 Oct 14;133(3):341–348. doi: 10.1016/0009-8981(83)90281-4. [DOI] [PubMed] [Google Scholar]
  46. Tollinger C. D., Vreman H. J., Weiner M. W. Measurement of acetate in human blood by gas chromatography: effects of sample preparation, feeding, and various diseases. Clin Chem. 1979 Oct;25(10):1787–1790. [PubMed] [Google Scholar]
  47. Tyler J. E., Dibdin G. H. Gas chromatography of volatile fatty acids. Method involving separation from biological material by vacuum distillation. J Chromatogr. 1975 Feb 19;105(1):71–77. doi: 10.1016/s0021-9673(01)81089-x. [DOI] [PubMed] [Google Scholar]
  48. Vreman H. J., Dowling J. A., Raubach R. A., Weiner M. W. Determination of acetate in biological material by vacuum microdistillation and gas chromatography. Anal Chem. 1978 Jul;50(8):1138–1141. doi: 10.1021/ac50030a033. [DOI] [PubMed] [Google Scholar]
  49. WRONG O., METCALFE-GIBSON A., MORRISON R. B., NG S. T., HOWARD A. V. IN VIVO DIALYSIS OF FAECES AS A METHOD OF STOOL ANALYSIS. I. TECHNIQUE AND RESULTS IN NORMAL SUBJECTS. Clin Sci. 1965 Apr;28:357–375. [PubMed] [Google Scholar]
  50. Whitehead J. S., Kim Y. S., Prizont R. A simple quantitative method to determine short chain fatty acid levels in biological fluids. Clin Chim Acta. 1976 Nov 1;72(3):315–318. doi: 10.1016/0009-8981(76)90193-5. [DOI] [PubMed] [Google Scholar]

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