Acarbose Enhances Human Colonic Butyrate Production

Abstract

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.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study

“…The dose-response effect of acarbose on the risk of colorectal cancer we observed concords with a previous clinical biomarker study demonstrating that each dose (50-200 mg) of acarbose enhances colonic butyrate production, which has colonic differentiating and nutritional effects (28). In the current study, the associations persisted after adjustment for the confounding factors.…”

The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein

“…These concentrations of BT chosen are well within the physiological range of concentrations of this compound in the human colon, since the concentration of short-chain fatty acids in the human colon may reach 70 -130 mM after digestion of dietary fiber, with 20 -30% of these corresponding to BT (9,47), and BT concentrations in human feces were found to range from 11 to 25 mM (30,66).…”

“…The Caco-2 cell line was obtained from the Deutsche Sammlung von Mikroorganismen and Zellkulturen (Braunschweig, Germany) and was used between passage numbers [53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71]. The cells were maintained in a humidified atmosphere of 5% CO 2-95% air and were grown in Minimum Essential Medium (Sigma, St. Louis, MO) containing 5.55 mM glucose and supplemented with 15% fetal calf serum, 25 mM HEPES, 100 U/ml penicillin, 100 g/ml streptomycin, and 0.25 g/ml amphotericin B (all from Sigma).…”

Comparisons of Effects on Intestinal Short-Chain Fatty Acid Concentration after Exposure of Two Glycosidase Inhibitors in Mice

“…24) Acarbose treatment in rats contributes to a higher level of SCFA in the colon, 4) and Weaver et al have also showed increased colonic butyrate production in human studies of acarbose supplementation. 25) SCFAs are an indispensable waste product to the microbial community, 26) meanwhile for colonic epithelium and immune modulation SCFAs especially butyrate are thought to be beneficial. 27,28) The short-chain fatty acid receptors Free Fatty Acid Receptor 2 (FFA2 or GPR43) and Free Fatty Acid Receptor 3 (FFA3 or GPR41) are activated by acetate, propionate and butyrate 29) but the metabolic function of them remains controversial.…”