The Glucoamylase Inhibitor Acarbose Has a Diet-Dependent and Reversible Effect on the Murine Gut Microbiome.
Baxter NT, Lesniak NA, Sinani H, Schloss PD, Koropatkin NM
mSphere. 02 2019
COMMENT: A safe and effective treatment for type 2 diabetes and prediabetes is the oral administration of acarbose, an inhibitor of the host (gluco)amylases of the small intestine. This inhibition prevent starch digestion in the small intestine, decreasing the postprandial blood glucose levels. As a consequence, a higher level of dietary starch reaches the distal intestine to be used as a fermentation substrate for the colonic bacterial community. Starch fermentation may be beneficial to host because it favors the production of short-chain fatty acids (SCFA). In this work, the authors investigate the effect in the murine gut community of two doses of acarbose in two distict diet backgrounds.
Here, we examined the effect of acarbose therapy on the gut community structure in mice fed either a high-starch (HS) or high-fiber diet rich in plant polysaccharides (PP).
The low dose of acarbose, tested only in the HS background, did not result in a significant change in the community structure from that of the control diet lacking acarbose. However, the high-acarbose diet changed the community in the HS diet background with a massive increase in the Bacteroidaceae and the Bifidobacteriaceae, which in both cases, was largely attributed to increases in single OTUs. There was a nearly concomitant decrease in the abundances of both the Verrucomicrobiaceae, mainly, A. muciniphila, and the Bacteroidales S24-7 with the high acarbose in the HS background. Acarbose elicited different changes when administered in a PP diet, most notably, a jump in the Lachnospiraceae from 10% to 30% of the community with acarbose, and a striking decrease in Bacteroidales S24-7. For both diets with acarbose, the abundances of Bifidobacteriaceae and Bacteroidales S24-7 were quite similar. Acarbose administration enhanced Bifidobacteriaceae representation in both cases, whereas it decreased S24-7 in both diets.
(...) the intestinal communities of mice in the high acarbose or low-high group that went from the high dose to the control diet quickly shifted to cluster with those of the control group, suggesting that acarbose treatment did not irreversibly change the gut community.
In the PP diet background, high acarbose had statistically significant effects on both acetate (P 0.0057) and butyrate (P 0.033) levels by increasing the detectable amounts of these molecules.
(...) acarbose feeding changes the gut community structure in a reversible and diet-dependent manner, which may have implications for how these medications are ideally administered in humans for enhanced therapeutic potential.