Pharmacomicrobiomics – The role of the gut microbiome in the response to drugs

In the past 30 days, nearly half of all US children and adults will have taken a prescription drug. In fact, prescription drug use is increasing in many countries. Although microbiome research has uncovered exciting ways that your gut microbes respond to diet, less is known about their interaction with these drugs that we consume at an ever increasing rate.

This complex field of study has an appropriately complex name – ‘Pharmacomicrobiomics’. This article will explore what we know about the influence of prescription drugs on the gut microbiome, the influence of the gut microbiome on drug efficacy and the potential of pharmacomicrobiomics to develop personalized medicine in the future.

Many drugs have low efficacy – does the gut microbiome play a role?

Surprisingly, many of the most common drugs on the market have very low efficacy rates, meaning they only work in some people. A review of 17 of the most commonly consumed prescription drugs found that only 11 of them showed ‘minimal clinically important differences’ compared to a placebo. Proton pump inhibitors (PPIs) for reduction of gastric acid were the most effective drugs, whilst aspirin for preventing heart disease and statins for lowering cholesterol were the least effective. In fact, statins only seem to work in around half of those who take them. So what does this have to do with your gut microbiome?

Many factors may contribute to the efficacy of prescription drugs including your age, your genes or existing diseases. However, only recently evidence has begun to show that the composition of your gut microbiome may determine the efficacy of certain drugs. This is because certain gut microbes interact with and metabolize certain drugs, which can have downstream effects on drug effectiveness. As human gut microbiomes are highly individualised, this means that the composition of your gut microbiome may determine why a particular prescription drug works for your neighbour, but not for you.

Drugs affect your gut microbes

Antibiotics have a major impact on the gut microbiome, however large studies, examining thousands of people have recently identified that non-antibiotic prescription drugs also have a major impact on gut microbiome composition. A study of nearly 4000 people worldwide found that medication usage had the biggest effect on the gut microbiome composition out of all the other factors that were studied, including weight, diet and bowel habits. Similar results were found in a separate study of >2700 people which showed that PPIs had the biggest effect on the gut microbiome, similar in effect to antibiotics. PPIs are commonly prescribed to treat heartburn or gastric ulcers and are often prescribed for long-term use. However, this may impair the acidic barrier between the upper and lower gastrointestinal tract, leading to long-term gut microbiome alterations, particularly increases in Streptococcaceae. In fact, other results show that roughly one quarter of non-antibiotic drugs have an inhibitory effect on the growth of the most common gut bacterial strains. This study, which examined >1000 common drugs, found that all classes of drugs showed some sort of antibacterial effect on human gut microbes, with anti-neoplastic drugs, hormones and compounds that target the nervous system having the most widespread effects.

Although many medications appear to have large impacts on the gut microbiome, these may not always be bad changes. In certain circumstances, the beneficial effects of particular drugs are due in part to the changes they cause to the gut microbiome. The effects of Metformin, a drug prescribed to treat and prevent Type 2 diabetes, may be due the its effects on the gut microbiome, by increasing the abundance of Akkermansia muciniphila, a bacterial species associated with metabolic health. Statins, which are commonly prescribed to lower blood cholesterol, may also have beneficial effects on the gut microbiome, whereby those who take statins are less likely to have an obesity-associated gut microbiome.

But your gut microbes also affect your drugs

The gut microbiome contains at least 100 times more genes than the human genome, which means that the gut microbiome has much greater capability to metabolise different nutrients and drugs than the human body. This means that the gut microbiome may enhance or reduce the effectiveness of particular drugs. Digoxin is a drug used to treat heart problems such as arrhythmias, however it can be inactivated by a gut bacterium called Eggerthella lenta, which lowers the effectiveness of the drug. Certain bacterial enzymes can even have toxic effects, for example by reactivating cancer drugs thereby causing severe diarrhea. However, this can be prevented by inhibiting the bacterial enzyme. On the other hand, sulfasalazine, a drug prescribed to treat rheumatoid arthritis, only becomes active after it is metabolised by the gut microbiome. There may be many more drug-microbe interactions that are yet uncovered. A large study that examined the ability of 76 common gut bacteria to metabolize 271 oral drugs found that two thirds of the drugs were metabolized by at least one bacterial strain and each strain metabolized 11-95 drugs. Resources such as the Microbe-Drug Association Database have begun to systematically log all known interactions between human gut microbes and common drugs, which may help to identify new beneficial or harmful drug-microbe interactions in the future.

The future of pharmacomicrobiomics

It’s clear that many drugs have both good and bad effects on the gut microbiome, whilst the gut microbiome also has an effect on drugs and their effectiveness. This emerging research suggests that the gut microbiome could be used in a number of ways to improve medicine:

  1. Improve effectiveness of drugs: Recent evidence has shown that giving a fecal transplant, which causes major changes to the gut microbiome, may improve patients’ responses to cancer therapy. Fecal transplants, probiotics and prebiotics may therefore have potential as adjunctive treatments for a wide range of medical therapies in the future.

  2. Design personalised medical treatments: Testing the composition of the gut microbiome, amongst other biological factors, has been used to create personalised diets to improve blood sugar. These advances in personalised nutrition may pave the way for personalised medicine, where each patient’s individual gut microbiome, amongst other factors, may determine their own personalised medical treatment.

  3. Predict who will respond to treatment: Gut microbiome profiles can be used to predict who will successfully respond to medical treatments for diabetes, inflammatory bowel disease and Clostridium difficile infection. The growing use of gut microbiome analysis in medicine means that it could be used as a valuable prognostic tool to predict success of medical treatments in the future.

Still need more advice?

Microbiome Insights is a leading provider of end-to-end microbiome sequencing and bioinformatic analyses. We have decades of experience working with leading researchers in industry and academia, providing the expertise to address all aspects of complex studies. If you have questions about your microbiome study, the Microbiome Insights team will be happy to help.

 

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Microbiome Insights, Inc. is a global leader providing end-to-end microbiome sequencing and comprehensive bioinformatic analysis. The company is headquartered in Vancouver, Canada where samples from around the world are processed in its College of American Pathologist (CAP) accredited laboratory. Working with clients from pharma, biotech, nutrition, cosmetic and agriculture companies as well as with world leading academic and government research institutions, MBI has supported over 630 microbiome studies from basic research to commercial R&D and clinical trials. The company's team of expert bioinformaticians and data scientists deliver industry leading insights including biomarker discovery, machine-learning based modelling and customized bioinformatics analysis.