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Is Bacteria in the Gut Compromising the Efficacy and Safety of the Drugs We Take?

Posted on July 2nd, 2019 by in Pharma R&D

Even the most reliable drugs don’t work exactly the same for everyone who takes them. The reason for this is an ongoing mystery, but a new study just published in Nature suggests that it may have a lot to do with the microbiome.

The microbiome refers to the communities of microorganisms living in our bodies, and scientists in this burgeoning field are uncovering the relationship between the microbiome and our overall health. “Spurred by advances in sequencing technology, along with disciplines like epigenomics and metabolomics, we know more than we ever have done about the 100 trillion or so bacteria in the gut,” notes Pharmaceutical Technology.

Biotechs like Vedanta Biosciences and PanTheryx are among the promising companies working to make medicines based on what they are learning about the microbiome, and there is even a growing list of conferences and forums that specialize in the topic. Every day, researchers are unlocking new secrets in the microbiome that could lead to the development of novel treatments.

New study shows how microbes modify drugs

Recently a research team, led by Andrew Goodman of Yale University School of Medicine, sought to better understand the impact that the microbiome has on orally administered drugs. For the study, which was performed principally through lab cultures but also included some follow-up tests in mice, the team measured the ability of 76 human gut bacteria to metabolize 271 orally administered drugs, ranging from the cancer drug Gleevec to the popular antidepressant Prozac. What they found is that many drugs are chemically modified by the microorganisms.

“The results showed that the bacteria metabolized two-thirds of the drugs. Small groups of bacteria targeted some of the drugs, while bacterial armies devoured others,” reports David DiSalvo of Forbes. “One of the features of this study involved using a technology called mass spectrometry to identify and classify the metabolites that remained after bacteria consumed the drugs. The researchers then matched the metabolites to particular bacteria to better understand what parts of the drugs they targeted, and the enzymes they used to break down their lunch.”

Previous studies

The notion that the microbiome might compromise a drug’s effectiveness is not a brand new one, and there has been some previous research investigating this connection. For example, researchers at Wake Forest School of Medicine reviewed over 100 published studies in humans and rodents, gaining some insight into how gut bacteria might be inhibiting (or enhancing) the efficacy of anti-diabetic drugs.

“Certain drugs work fine when given intravenously and go directly to the circulation, but when they are taken orally and pass through the gut, they don’t work,” explained Hariom Yadav, Ph.D. of Wake Forest Baptist Medical Center. “Conversely, metformin, a commonly used anti-diabetes drug, works best when given orally but does not work when given through an IV.”

Insights from the Yale University study

This latest study was far larger in scope than earlier studies and reviews, and went much further by testing such a large number of drugs (read more details on the study here). What are some key takeaways from the study?

1. An explanation of why people react to the same drug in different ways. We now have better evidence that the uniqueness of each person’s microbiome could have a very consequential impact on how they metabolize a drug.

2. Better understanding of potential for side effects. DiSalvo points out that the study’s findings “enlighten potentially dangerous long-term side effects of bacteria breaking down drugs and leaving toxic pieces behind,” which he says should be an important consideration for drug manufacturers.

3. Considering the microbiome when recommending medications. Analyzing a patient’s microbiome could become a precursor to prescribing certain medications, as understanding the individual’s gut bacteria could help a physician determine what will be most effective.

As Andreu Prados of Gut Microbiota for Health concludes, “These findings are a step forward in understanding which drugs should be given to a patient in order to minimize their toxic side effects and also opens up the option of manipulating the gut microbiome to achieve an enhanced therapeutic response.”

Researchers specializing in the microbiome still have much more to learn and share, but it is certain that drug makers need to be well aware of the impact that gut bacteria is having on drugs and what it can mean for those taking them.

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