The Gut Microbiome’s Impact on Drug Efficacy

image representing the gut surrounded by gut microbiota

In groundbreaking research published in Nature Metabolism, Tian et al. explore how the gut microbiome can diminish the effectiveness of acarbose, a medication prescribed for diabetes mellitus patients.

Acarbose functions by reducing glucose absorption in the gut, primarily through inhibiting enzymes like α-glucosidase and amylase. α-Glucosidase, located on the epithelial cells of the gut, breaks down complex carbohydrates into smaller glucose molecules for absorption. Similarly, amylase, produced by the pancreas and salivary glands, processes complex carbohydrates into absorbable glucose molecules.

The study reveals that Klebsiella grimontii, a facultative anaerobic bacterial species within the gut microbiome, compromises acarbose’s efficacy. This bacterium produces an enzyme known as acarbose-preferred glucosidase (Apg), which neutralizes acarbose by converting it into acarviosine and acarviosine-glucose. These by-products cannot inhibit α-glucosidase and amylase, allowing them to continue breaking down carbohydrates into glucose, which is then absorbed by the gut.

The presence of Klebsiella grimontii varies among individuals, explaining why acarbose’s effectiveness differs from person to person.

This discovery underscores the necessity for personalized medicine approaches, considering the unique gut microbiome composition of each patient.

Resources:

https://www.nature.com/articles/s42255-023-00796-w


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