Title: Short-Chain Fatty Acids Acids And Therapeutic Potential

Key words: colonic bacteria, acetic acid, propionic acid, isobutyric acid, colorectal cancer, intracolonic infusion

Date: May 1999

Category: 8. The Gut

Type: Article

Author: Dr van Rhijn

 

Short-Chain Fatty Acids Acids And Therapeutic Potential

Introduction

There is a growing interest in short chain fatty acids (SCFA) and their potential therapeutic1 effect in humans. This paper assesses whether there is any basis for their biological effects.

What are SCFA ?

Colonic bacteria produce approximately 300 - 400 mmol SCFA per day as the principal end products from the metabolism (fermentation) of undigested complex carbohydrates, proteins2, and non-starch polysaccharides with the primary function of salvaging energy. The main SCFA include acetate, butyrate, propionate and to a lesser degree intermediates such as ethanol, lactate and succinate3. They are further oxidised by cross-feeding species in the colon4 and rapidly absorbed5 into the bloodstream. The concentration in the faeces is usually inversely related to the transit time. SCFA (acetic, proprionate and isobutyric acid) were all significantly reduced by a reduction of transit time6. The host may then salvage energy7 (7 - 8 % daily energy) and thus regulate metabolism from SCFA absorption.

Biological effects of SCFA

SCFA stimulate water & electrolyte absorption (Na+ ) in the colon, improve the integrity of colonic endothelium by affecting epithelial cell transport and colonocyte metabolism (specific metabolic ‘fuel’ for the colonocyte)8. They acidify gut contents and also affect colonic blood flow and motility9. Butyrate has effects in the modulation of nucleic acid metabolism, gene expression and cell growth. Intracolonic SCFA infusion led to an increase in RNA, DNA and protein content of colonic mucosa10 and intravenous infusion led to marked hypertrophy of the jejenum without an effect on the colon11. They reversibly alter in vitro properties of human colorectal cancer cell lines by prolonging doubling time and slowing down growth rates12 on colonic epithelial cell proliferation, thus the maintenance of mucosal integrity and growth. They may influence hepatic control of lipid and carbohydrates and provide energy to muscle, kidney heart and brain. They also induce gamma-globulins.

Therapeutic Potential

Following this discussion, clinical uses suggested for SCFA are in the management of inflammatory bowel disorders13 (Crohn's disease and ulcerative colitis14, 15, 16), and an important protection against diarrhoea. Propionate is cleared by the liver and may act as a gluconeogenic precursor17 and is involved in the reduction of plasma lipids. Butyrate is an essential fuel for the colonic epithelium. It may also play a role in preventing colon cancer through its ability to inhibit DNA synthesis and stimulation of apoptosis. Other clinical implications are in enteral feeds during bowel rest, and in anastomotic scar healing following surgery by improving nonspecific immune responses18 and in beta chain hemoglobinopathies19.

Conclusion

Measurements of SCFA productions rates in the colon has proved to be exceptionally difficult and a specific therapeutic role remains to be defined. Much more research is required, but preliminary evidence suggests promising therapeutic potential.

 

References

  1. Cook, S.I. & Sellin, J.H. Review article: short chain fatty acids in health and disease. Ailment. Pharmacol. Ther. 1998; 12:6, 499 - 507.
  2. Cummings, J.H. & Macfarlane, G.T. A Review: the control and consequences of bacterial fermentation in the human colon. J. Appl. Bacteriol. 1991; 70: 443 – 459.
  3. Gibson, G. R. Dietary modulation of the human gut microflora using prebiotics. Brit. J. Nutr. 1998; 80 (Suppl.) 2, S209 - S212.
  4. Cummings, J.H. & Macfarlane, G.T. Role of intestinal bacteria in nutrient metabolism. Clin. Nutr. 1997; 16: 3 - 11.
  5. Rupin, H. et al. Absorption of short chain fatty acids by the colon. Gastroenterology. 1980; 78, 1500 - 1507.
  6. Kelly, S.M. et al. A 3-month, double-blind, controlled trial of feeding with sucrose polyester in human volunteers. B. J. Nutr. 1998; 80: 41 – 49.
  7. Gibson, G.R. & Roberfroid, M.B. Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics. J. Nutr. 1995: 125: 1401 – 1412.
  8. Cummings, J.H. et al. Physiological and Clinical Aspects of Short Chain Fatty Acid Metabolism. Cambridge: Cambridge University Press. 1995
  9. Wilson, A.J. & Gibson, P.R. Short-chain fatty acids promote the migration of colonic epithelial cells in vitro. Gastroenterology. 1997; 113:2, 478 - 496.
  10. Kripke, S.A. et al. Stimulation of intestinal mucosal growth with intracolonic infusion of short-chain fatty acids. JPEN. J. Parent. Ent. Nutr. 1989; 13: 109 – 116.
  11. Koruda, M.J. et al. Effect of parental nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection. Gastroenterology. 1988: 95: 715 – 720.
  12. Sakata, T. Stimulatory effects of short chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors. Br. J. Nutr. 1987; 58: 95 - 103.
  13. Leleiko, N.S. & Walsh, M.J. The role of glutamine, short-chain fatty acids and nucleotides in intestinal adaptation to gastrointestinal disease. Pediatr. Clin. North America. 1996; 43 (2):451 - 470.
  14. Roediger, W.E.W. & Nance, S. Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br. J. of Experim. Path. 1986; 67, 773 - 782.
  15. Scheppach, W. Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA Studt Group. Dig. Dis. Sci. 1996; 41:11, 2254 - 2259.
  16. Breuer, R.I. et al. Short-chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial. Gut. 1997; 40:4, 485 - 491.
  17. Mineo, H. et al. Chemical specificity of short-chain fatty acids in stimulating insulin and glucagon secretion in sheep. Am. J. Physiol. 1994; 267:2, Pt1, E234 - E241.
  18. Pratt, V.C. et al. Short-chain fatty acid-supplementated total parental nutrition improves nonspecific immunity after intestinal resection in rats. JPEN J. Parenter Enteral Nutr. 1996; 20:4, 264 - 271.
  19. Liakopoulous, E. et al. Stimulation of fetal hemoglobin production by short chain fatty acids. Bolld. 1995; 86:8, 3227 - 3235.