Drugs’ hidden side effects

gut microbiome stomach intestines bacteria

One in four drugs with human targets has been found to inhibit the growth of bacteria in the gut, causing antibiotic-like side effects

A research team from the European Molecular Biology Laboratory (EMBL) has screened more than 1,000 marketed drugs against 40 representative bacteria from the human gut, and found that more than a quarter (27%) of non-antibiotic drugs affect growth of at least one bacterial species in the gut microbiome.

These non-antibiotic drugs included including antidiabetics, non-steroidal anti-inflammatories, and antipsychotics.

It has become increasingly clear from numerous studies that antibiotics have a large impact on gut bacteria (collectively referred to as the gut microbiome), causing gastrointestinal side effects.

However, it has now been shown that commonly used non-antibiotic drugs can also cause changes in the gut microbiome composition.

Fourteen of the human-targeted drugs in the study, published in Nature, had not been previously reported to have direct antibacterial activity.

Bacterial species with higher abundance across healthy individuals were found to be significantly more susceptible to human-targeted drugs, suggesting that these types of drugs have an even larger impact on the gut microbiome than other types.

Many of the in vitro microbiome shifts also translated in vivo, as the researchers’ observations were found to agree with the few clinical microbiome studies for which medication was recorded.

However as the authors screened only a representative subset of species, and individual microbiomes actually harbour hundreds of species, they warn the data is likely to underreport the true extent of how human-targeted drugs impact on gut bacteria.

This impact could also be potentially linked to antibiotic resistance.

“The number of unrelated drugs that hit gut microbes as collateral damage was surprising,” says corresponding author Peer Bork, Strategic Head of Bioinformatics at EMBL Heidelberg, Germany.

“Especially since we show that the actual number is likely to be even higher.

“This shift in the composition of our gut bacteria contribute to drug side effects, but might also be part of the drugs’ beneficial action.”

Fellow author Athanasios Typas said the results were “scary”, especially considering the amount of non-antibiotic drugs people take, often for long periods of time.

“Still, not all drugs will impact gut bacteria and not all resistance will be common,” said Dr Typas.

“In some cases, resistance to specific non-antibiotics will trigger sensitivity to specific antibiotics, opening paths for designing optimal drug combinations.”

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