Short-Chain Fatty Acids in the Human Colon: Relation to Gastrointestinal Health and Disease

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Abstract
Fermentation, the process whereby anaerobic bacteria break down carbohydrates to short-chain (C2-C6) fatty acids (SCFAs), is an important function of the large bowel. SCFAs constitute approximately two-thirds of the colonic anion concentration (70–130 mmol/1), mainly as acetate, propionate, and butyrate. Gastroenterologists have, in spite of these facts, addressed this scientific field surprisingly late, in contrast to veterinarians, for whom the fermentative production of SCFAs has been acknowledged as a principal mechanism of intestinal digestion in plant-eating animals for decades. Interest in the effects of SCFA production on the human organism has been growing rapidly in the last 10 years, because gastrointestinal functions and beneficial effects are associated with these acids. SCFAs are of major importance in the understanding of the physiological function of dietary fibre and their possible role for colonic neoplasia. SCFA production and absorption are closely related to the nourishment of the colonic mucosa and sodium and water absorption, and mechanisms of diarrhoea. Patients with severe malabsorption compensate by the fermentation of otherwise osmotic active saccharides to SCFAs, which are readily absorbed and used as energy fuels in the organism. SCFA production from dietary carbohydrates is a mechanism whereby considerable amounts of calories can be salvaged in short-bowel patients with remaining colonic function if dietary treatment is adjusted. SCFA enemas are a new and promising treatment modality for patients with ulcerative colitis. The effect has been attributed to the oxidation of SCFAs in the colonocytes. An impressive number of papers have described the effects of butyrate on various cell functions, the significance of which is still unknown. Up until now, attention has been related especially to cancer prophylaxis and treatment. Diminished production of SCFAs appears to be involved in antibiotic-associated diarrhoea, diversion colitis, and possibly in pouchitis. The interaction between bacterial fermentation, ammonia metabolism, and bacterial growth and protein synthesis appears to be the main mechanism of action of lactulose treatment in hepatic coma. Pathological and extremely high rates of saccharide fermentation explain the severe deterioration in patients with D-lactate acidosis. Hence, this scientific field has come late to clinical working gastroenterologists, but as work is progressing the production of SCFAs in the large bowel becomes involved in several well-known intestinal disorders.