ASU researchers discover new digestive process for medication
Art by Jason Drees/ASU
“Detoxification” is a word most of us have heard, usually in the context of shakes or supplements. But what does it actually mean? In our bodies, it is the natural, or medicinally assisted, removal of toxic substances through the kidneys, liver and lungs.
One part of this detoxification process is sulfonation, a step the body uses to make certain molecules safer and easier to remove.
A new study from researchers at Arizona State University suggests those “detoxifying” microbes in our body’s digestive system may be helping tag — or mark and identify — and clear potentially harmful chemicals from the body, something scientists once thought only human cells could do.
The discovery could help explain why people sometimes respond differently to the same medication, even when they take identical doses.
“If gut microbes can carry out these reactions, they could potentially change how long a drug remains active, how quickly it is cleared or how strong its effects and side effects are,” said Dhara Shah, the study’s lead author and assistant professor with the Biodesign Institute's Center for Fundamental and Applied Microbiomics.
In sulfonation, cells attach a tiny cluster of atoms, known as a sulfo group, to substances like medications, food byproducts and other natural chemicals made by the body.
The sulfo group can turn oily, hard-to-remove compounds into forms that dissolve more easily in water. This allows the kidneys and digestive systems to carry them out of the body.
ASU researchers found that a common gut bacterium, Phocaeicola vulgatus, carries an enzyme capable of performing sulfonation. The new findings raise the possibility that gut bacteria may play a more active role in removing toxins than previously recognized.
The bacterial enzyme identified in the ASU study, known as BvASST, can transfer sulfo groups among a range of naturally occurring compounds found in the gut.
Acetaminophen offers a clear example. In the liver, human enzymes normally convert part of the drug into a sulfonated form that can be safely excreted. The ASU team found that the bacterial enzyme could interact with both the active drug and its tagged version in the lab. That means, in theory, gut microbes might help speed up drug clearance, or, in some cases, reverse it.
The implications may extend beyond medications. Some sulfonated compounds, known as phenolic sulfates, tend to build up in certain health conditions, including chronic kidney disease and autism spectrum disorder. These molecules are often byproducts of both human and microbial metabolism, and their levels can reflect how well the body is processing and clearing chemical waste.
“This bacterial enzyme might help detoxify certain compounds but might be less efficient when other similar molecules are present at the same time,” said Rosa Krajmalnik-Brown, co-author of the study and director of the Biodesign Center for Health Through Microbiomes. “For example, p-cresol is one such phenolic compound elevated in autism that potentially competes with other molecules for sulfation, thus potentially interfering with their clearance from the body.”
That competition could matter for molecules that affect brain signaling, such as dopamine, which was tested in the study.
“Microbial sulfonation could affect how long they persist in the body and how they impact physiology,” Shah said.
The researchers are careful to emphasize what they don’t yet know. It remains unclear how active this bacterial enzyme is inside a real human gut, where conditions are far more complex than in a controlled laboratory setting.
“The main unknown is whether BvASST is active and influential in living systems,” Shah said.
To establish this, researchers will need to demonstrate these reactions in microbial cultures, followed by animal models and eventually in humans.
If future studies confirm that gut microbes routinely help process drugs and toxins, the work could one day influence how physicians approach dosing, side effects and personalized medicine.
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