The Influence of the Glucoamylase Inhibitor Acarbose on Bacteroidetes Starch Utilization and Fitness in the Human Gut

Seminar Details
Wednesday, May 20, 2020 - 9:00am to 10:00am


Haley Brown, Ph.D.
Postdoctoral Fellow - Koropatkin Lab
Department of Microbiology and Immunology
Michigan Medicine


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Nicole Koropatkin, Ph.D.

Acarbose, used to treat type 2 diabetes, increases short-chain fatty acid (SCFA) output in diet and microbiota dependent manners and restructures the gut community. Acarbose prevents postprandial blood glucose spikes by inhibiting glucoamylases used to digest starch, thereby shunting more polysaccharide to the large intestine. Acarbose is minimally absorbed by the host and likely reaches the colon where it may alter bacterial glucoamylase activity. Indeed, recent studies demonstrated that gut bacterial species harbor different resistances to acarbose inhibition when growing in starch. The Bacteroidetes, a prominent gut phylum, deploy a starch utilization system (Sus) to recognize, degrade, and import starch. Strikingly, growth of the model bacterium Bacteroides thetaiotaomicron (BT) in starch is inhibited by acarbose, but a related species, Bacteroides ovatus (BO), is resistant. X-ray structural data and genetic manipulation of the only surface amylase, SusG suggest that this protein may not be the only Sus feature mediating susceptibility differences. Growth experiments imply that acarbose may differentially impair maltooligosaccharide recognition and transport through outer membrane proteins SusC/D. While BT and BO are being investigated to determine the molecular underpinnings of acarbose sensitivity and resistance, growth data from other species suggest that most are sensitive. Though the Bacteroidetes are implicated in the etiology of many of diseases, acarbose administration in humans reduces the abundance of a number of species in this phylum. Therefore, biochemical insight into acarbose influence on Sus is necessary given that impaired growth in culture may translate to decreased fitness in the gut.