Earlier studies suggest that butyrate has colonic differentiating and nutritional effects and that acarbose increases butyrate production. To determine the effects of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or placebo (cornstarch), three times per day, with meals in a double-blind crossover study. Fecal concentrations of starch and starch-fermenting bacteria were measured and fecal fermentation products determined after incubation of fecal suspensions with and without added substrate for 6 and 24 h. Substrate additions were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch consumption was similar during acarbose and placebo treatment periods, but fecal starch concentrations were found to be significantly greater with acarbose treatment. Ratios of starch-fermenting to total anaerobic bacteria were also significantly greater with acarbose treatment. Butyrate in feces, measured either as concentration or as percentage of total short-chain fatty acids, was significantly greater with acarbose treatment than with placebo treatment. Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable placebo periods. The propionate in fecal total short-chain fatty acids was significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly greater in fermentations in samples collected during acarbose treatment, whereas production of acetate and propionate was significantly less. Fermentation decreased when acarbose was added directly to cornstarch fermentations. Acarbose effectively augmented colonic butyrate production by several mechanisms; it reduced starch absorption, expanded concentrations of starch-fermenting and butyrate-producing bacteria and inhibited starch use by acetate- and propionate-producing bacteria.

The nutritional effects of butyrate on the colonic mucosa and studies of transformed cells suggest that butyrate has anti-colon cancer effects. If butyrate has antineoplastic effects, mucosal growth contrasts between normal subjects and those with a history of colonic neoplasia would parallel changes in growth characteristics caused by butyrate in a colon neoplasia population. To test this hypothesis, rectal biopsies from a survey of colonoscopy patients (n = 50) with and without a history of colonic neoplasia (controls) were compared. Similarly, rectal biopsies were compared from subjects (n = 44) with a colon neoplasia history in an acarbose-placebo crossover trial. Control subjects in the colonoscopy survey had higher bromodeoxyuridine (BrdU) uptake than subjects with a history of neoplasia (P = 0.05). The control subjects also had a higher correlation of BrdU and Ki-67 labeling (P = 0.003). Both findings were paralleled by acarbose use. Acarbose augmented BrdU uptake (P = 0.0001) and improved the correlation of BrdU and Ki-67 labeling (P = 0.013). Acarbose also augmented fecal butyrate (P = 0.0001), which was positively correlated with Ki-67 labeling (P = 0.003). p52 antigen had an earlier pattern of crypt distribution in subjects with a history of colon neoplasia but was not affected by acarbose use. Lewis-Y antigen was expressed earlier in the crypt with acarbose but had similar expression in the colonoscopy survey groups. The use of acarbose to enhance fecal butyrate concentration produced mucosal changes paralleling the findings in control subjects as opposed to those with neoplasia, supporting the concept of an antineoplastic role for butyrate.