, Volume 36, Issue 10, pp 1459-1468

Short-chain fatty acids induce reversible injury of porcine colon

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Carbohydrate malabsorption frequently results in an increased net production of organic acids by colonic microorganisms and an acidification of colonic contents. Colonic structure and function during and following mucosal exposure to acetate at various H ion concentrations was examined under bothin vovo andin vitro conditions. An acetic acid dose and time-dependent injury of the surface epithelium sequentially resulted in (1) degeneration and extrusion of enterocytes and increased ion permeability (pH 5.0); (2) formation of subepithelial blisters and increased mucosal permeability to mannitol (pH 4.0), and (3) sloughing of surface epithelium and the abolition of active NaCl absorption (pH 3.0). Both acetate and lactate at pH 4.0 produced significantly greater injury than similarly acidified NaCl. Crypt cell structure and Cl secretory function were preserved, however, and migration of viable cells from adjacent crypts rapidly covered the denuded surface within 30–60 min of recovery. Normal structure and function were nearly restored in 2 hr. These results suggest that colonic mucosal injury is possible under conditions that may be present during carbohydrate malabsorption syndromes. They also provide evidence that the process of surface reepithelialization may be of central importance in the defense and repair of the colonic mucosa during such acid-induced injury.

This work was supported by grant DK 40584-01 from the National Institutes of Health and by the State of North Carolina.