The Role of the Colonic Flora in Maintaining a Healthy Large Bowel Mucosa

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The large bowel epithelium lives in a symbiotic relationship with millions of bacteria. These bacteria ferment dietary fibre to the short chain fatty acids, of which butyrate appears to be the most important. A technique was developed which allowed the rate of oxidation of fuel sources to be measured in colonic mucosal biopsies. This combined manometric methods with radiotracer technology. In normal colonic mucosal biopsies the rate of oxidation of butyrate was far greater than glutamine and in turn glucose. In patients with quiescent ulcerative colitis there was a significant defect in the mucosal ability to oxidize butyrate. Following on from this in vitro experiment, an in vivo experiment was performed, studying the rate of metabolism of a butyrate enema, in patients with quiescent colitis compared to controls. This showed no significant defect in whole body butyrate metabolism as measured by the production of ¹³CO₂ from ¹³Cbutyrate. Hydrogen sulphide, a bacterial metabolite, was found to inhibit butyrate metabolism in the colonic cell culture line HT 29. However, this inhibition was prevented by the presence of glucose. Immunological studies found that butyrate, in physiological concentrations, inhibited phytohaemaglutinin induced proliferation of peripheral lymphocytes. Butyrate also induced expression of CD69 but not CD25. These studies show that butyrate, as well as being a major fuel source for the colonic epithelium, has an immunosuppressant effect on lymphocytes. This may play a major part in maintaining the homeostasis between the colonic epithelium and the colonizing bacteria.