THE INTERACTIONS OF DIET AND COLONIC MICROFLORA IN REGULATING COLONICMUCOSAL GROWTH

The colonic mucosa can adapt its growth to alterations in diet. Metabo lites from colonic microflora are frequently implicated as the primary factor in mediating the colonic mucosal response to diet; however, th ere is also evidence indicating that diet may have a direct effect in mediating this response. The aim of this study was to determine the ro le of diet, microflora, and microflora metabolites in altering the gro wth of the colonic mucosa. Two 28-day feeding studies were conducted u sing Sprague-Dawley rats. The first study compared the growth of the c olonic mucosa in germ-free and conventional rats fed 6 different diets . The second study compared the growth of the colonic mucosa to the co ncentration of bacterial-derived short-chain fatty acids (SCFAs), bile acids, and ammonia. The diets that were fed consisted of (1) AIN-76a diet without dietary fiber; (2) standard AIN-76a diet, which contained 5% cellulose; (3) AIN-76a diet with 5% guar gum; (4) a ''Western'' hu man diet with 20% fat and 10% cellulose; (5) AIN-76a diet formulated t o mimic Diet 4 in fat content but with 2.5% cellulose; and (6) Purina Rodent Chow. Quantitative volumetric and stereologic analysis was used to assess changes in total colonic mucosal volume as a measure of muc osal growth. In germ-free rats, Diets 2-4 and 6 induced a significant increase (18-38%) in mucosal volume compared to Diet 1. In conventiona l animals, only Diets 4 and 6 induced a significant increase (up to 63 %) in mucosal volume compared to Diet 1. Relative to the germ-free ani mals, only conventional animals on Diets 4 and 6 had an increase in mu cosal volume. The increases in mucosal volume in Diets 4 and 6 were no t consistently associated with increased SCFAs, ammonia, or bile acids . There was a wide range in the colonic concentrations of SCFAs (2-fol d), ammonia (6-fold), and bile acids (10-fold). The presence of coloni c microflora in and of itself does not lead to enhanced colonic mucosa l growth. Rather, there are unique interactions between specific types of diet and microflora that lead to a growth-promoting effect. This e ffect could not be explained by alterations in the concentration of SC FAs, ammonia, or bile acids in colonic contents.