New insights into how commonly used drugs affect the gut microbiota

The impact of medications on the gut microbiota is greater than previously thought. A new research published in Nature claims.

What is already known on this topic
The prevalence of cardiometabolic disorders such as type 2 diabetes and obesity continue to rise, and people often have to take several medications for months or even years. This can lead to alterations in the gut microbiota and in the collection of metabolites found in the blood, which complicates the discovery of disease biomarkers.

What this research adds
Researchers investigated the effects of 28 different drugs and several drug combinations and found that many commonly used drugs, including antibiotics and medications used to treat cardiometabolic disorders, have powerful effects on gut microbes. Although many drugs negatively impact the composition of the gut microbiota, others, including aspirin, can have a positive influence on gut bacteria and their hosts. For example, cholesterol-lowering drugs combined with aspirin can reduce the blood levels of harmful fats associated with cardiovascular disease, and diuretics combined with blood pressure medications can increase the levels of intestinal Roseburia, a beneficial bacterium that is known to lower inflammation levels.

Conclusions
The findings may help to identify new uses for approved drugs and develop personalized strategies for preventing or treating specific disorders.

The community of microbes living in our gut may be altered not only by disease, but also by the drugs that we use to treat disease. New research now shows that the impact of medications on the gut microbiota is greater than previously thought.

The findings, published in Nature, may help to identify new uses for approved drugs and develop personalized strategies for preventing or treating specific disorders.

“We know that the microbiome can reflect the status of a patient’s health and provide a range of biomarkers to assess the severity of diseases,” says study co-first author Rima Chakaroun at the University of Leipzig Medical Center. “What is often overlooked, however, is that the medication used to treat a disease also affects the state of the microbiome.”

Chakaroun and her colleagues note that the prevalence of cardiometabolic disorders such as type 2 diabetes and obesity continue to rise, and people often have to take several medications for months or even years. This can lead to alterations in the gut microbiota and in the collection of metabolites found in the blood, which complicates the discovery of disease biomarkers.

To disentangle the effect that diseases have on host microbiotas from the effect of medications, the team investigated the effects of 28 different drugs and several drug combinations using a statistical approach that accounts for the effects of multiple confounding factors. 

Drugs impacts

The researchers analyzed data from MetaCardis, a research project investigating the role of gut microbes in cardiometabolic disease. The data include clinical and microbiota information from 2,173 people, some of whom have diseases such as type 2 diabetes and obesity.

In particular, the team investigated the effects of eight types of commonly used medications, including antibiotics, antidiabetics, and drugs used to treat high blood pressure and heart rhythm disorders. Many of these drugs have powerful effects on gut microbes, the researchers found. 

While the negative impact of antibiotics on gut bacteria is well-known, the findings suggest that such effects accumulate over time. Repeated antibiotic treatments over the course of five to 10 years were associated with a less diverse gut microbiota and signs of antimicrobial resistance, the researchers found.

The team also discovered that a class of medications that reduce the production of stomach acid are linked to negative changes in the gut microbiota.

Beneficial effects

Although many drugs negatively impact the composition of the gut microbiota, others such as aspirin can have a positive influence on gut bacteria and their hosts, the team found. 

For example, cholesterol-lowering drugs combined with aspirin can reduce the blood levels of harmful fats associated with cardiovascular disease, and diuretics combined with blood pressure medications can increase the levels of intestinal Roseburia. This bacterium is known to convert dietary fiber into butyric acid, a molecule that lowers inflammation levels in people.

“We found that drugs can have a more pronounced effect on the host microbiome than disease, diet, and smoking combined,” says study co-senior author Peer Bork at the European Molecular Biology Laboratory. The results also suggest that understanding how drugs affect people and their microbiotas can help discover biomarkers of diseases, the authors say.