Bacterial Enzymes in the Oral and Gut Microbiome Inactivate Common Diabetes Drug Like Acarbose, Study Says

Groundbreaking new research by a team of researchers from Princeton University shows how common diabetes drugs like acarbose can be inactivated by various bacterial enzymes produced in the human oral and gut microbiome. Researchers speculated that the process explains why the medication isn't effective in some diabetic patients compared to others.

One of the most compelling areas in the rapidly emerging study field of the gut microbiome is looking at how gut bacteria affect different medications activities. Some of the early discoveries show how the microbiome can either boost cancer treatments efficacy or amplify the toxicity of chemotherapy.

Recent studies at the European Molecular Biology Laboratory and the University of Cambridge broadly attempted to begin a large task of characterizing general drug and bacteria interactions. The first report found many interactions between 15 oral drugs and 25 common gut bacteria.

Antidiabetic Drug Resistance in Human Gut Microbiome

(Photo : Nataliya Vaitkevich from Pexels)

The recent research published in the journal Nature, titled "The human microbiome encodes resistance to the antidiabetic drug acarbose" focused on a specific task of documenting across the molecular and mechanistic levels of how human bacteria inside influences the activity of a single drug, a common diabetes drug known as Acarbose.

Acarbose, according to MedlinePlus, is a significantly effective diabetes drug that inhibits enzymes needed to deconstruct carbohydrates. Originally, it was discovered to be secreted by bacteria thriving in soil. The bacteria uses molecules to stifle the growth of other bacteria. Additionally, it relies on other enzymes known as acarbose kinase to inactivate it so that the bacteria's own growth isn't hindered.

Researchers wondered if other types of bacteria can also secrete similar enzymes that inactivate acarbose and whether there are mechanisms that occur in bacteria thriving inside the human body to the same effect. The first step was to analyze DNA sequences from human microbiome bacteria and identify genes that have the potential of making enzymes similar to acarbose kinase, reports NewAtlas.

After honing in on several probable influential genes, the team focused on the most common gene. After engineering a species of oral bacteria with the identified gene, researchers discovered that it produced resistance to acarbose in the form of an enzyme similar to acarbose kinase.

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Complex Relationships of Bacteria in the Microbiome

The new family of microbiome proteins discovered is dubbed "Maks" for microbiome-derived-acarbose-kinases. Once identified, maks were detected by researchers in a wide variety of human oral and gut bacteria. However, despite the groundbreaking discovery, the findings only raise more questions for scientists to answer.

Mohamed Donia, a researcher working on the study, says that it didn't make sense to the team as to why a bacteria thriving inside the human body of healthy humans would develop specific resistance mechanisms to acarbose, given that a vast majority of individuals have never been exposed to the drug.

Further investigation by the team showed how there are, in fact, bacterial species inside the human microbiome that produced acarbose. Hence, the current hypothesis is that maks arose in the human microbiome bacteria to outcompete other bacteria that make molecules similar to acarbose.