Small Molecule Inhibition of the Polysaccharide Metabolism of Bacteroides fragilis

Several studies have indicated a link between the gut microbiota and autoimmune diseases. Especially of note is that an increase in the ratio of members of the Bacteroidetes phylum to the Firmicutes phylum has been associated with the development of Type 1 Diabetes (T1D). This anomaly has been shown in both murine models and human studies. These factors suggest that the ability to selectively inhibit the growth of Bacteroidetes members, while not disrupting the Firmicutes, could provide a potential therapy for those at high risk for developing the disease. We investigated a possible route of inhibition through the use of acarbose, a human α-amylase inhibitor, to disrupt the ability of Bacteroidetes to process complex carbohydrates. Using Bacteroides fragilis as a model Bacteroidetes organism, we have shown that acarbose inhibits the growth of B. fragilis in media containing the carbohydrates pullulan or potato starch. Conversely, Lactobacillus. reuteri, a model Firmicute, was unable to process these complex carbohydrates. The ability of both organisms to utilize simple sugars, such as maltose or glucose, was not significantly affected by acarbose. Specifically, acarbose failed to inhibit growth in the presence of glucose for either organism. These results suggest that acarbose can selectively inhibit the ability of members of the Bacteroidetes phylum to degrade and utilize complex carbohydrates, one of its primary nutrient sources, while not impacting Firmicute growth. Thus, we have uncovered a novel strategy involving small-molecule therapeutics to selectively target and potentially alter the composition of the gut microbiota.