Lots of non-antibiotic drugs could contribute to antibiotic resistance and even alter our gut bacteria.
In a paper now published in the journal Nature, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, report that not only can many common non-antibiotic drugs alter gut bacteria, but they can also — like antibiotics — contribute to antibiotic resistance.
"This shift in the composition of our gut bacteria contributes to drug side effects," explains study author Peer Bork, who is a professor at EMBL and head of its Structural and Computational Biology Unit, "but might also be part of the drugs' beneficial action."
The human gut — also called the gastrointestinal tract — is home to huge colonies of bacteria and other microorganisms, collectively termed the gut microbiota.
This vast and varied microbial community has co-evolved with us over thousands of years to "form an intricate and mutually beneficial relationship."
Non-antibiotics disrupt balance in the gut
Studies of the complex relationship between the human body and its resident gut microbiota have revealed that disturbances in microbial composition can give rise to a huge number of diseases, ranging from persistent gut disorders to neurodevelopmental conditions.
These also show that antibiotic treatment can dramatically disrupt microbial balance — both in the short-term and the long-term — and reduce the diversity and richness of colonies.
In their study paper, Prof. Bork and his co-authors mention that recent research has revealed that a "few commonly used non-antibiotic drugs" have been associated with changes in gut microbe composition, and they note that the "extent of this phenomenon is unknown."
So, for their investigation, they compiled a panel of 40 species of gut bacteria that are typically found in the human gut and used it to screen more than 1,000 drugs currently on the market.
Of the 923 non-antibiotic drugs that were analyzed, the researchers discovered that 250 had disrupted the growth of at least one of the 40 species of gut bacteria in the panel.
They were surprised by the size of their result, especially as the drugs they tested included "members of all therapeutic classes."
Implications for antibiotic resistance
The researchers see the finding as just the start. There is still a lot of work to do to find out how the drugs interact with the gut microbes and how the interactions give rise to side effects in the body, as well as whether they are clinically relevant.
They think that a careful study of these interactions could be very useful for personalized medicine, given that each person's gut microbe composition is unique.
For instance, it might help us to understand why different people react differently to the same drug, even though it is intended to treat the same condition.
But one disturbing finding from the study is that it highlights a potential, previously unknown risk: that the use of non-antibiotic drugs may contribute to the growing problem of antibiotic resistance.
"Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species," explain the authors, "suggesting common resistance mechanisms, which we verified for some drugs." They call for additional research to investigate the problem further.
"This is scary," says co-author Dr. Athanasios Typas, who leads a group in the Genome Biology Unit at EMBL, "considering that we take many non-antibiotic drugs in our life, often for long periods."
On a more optimistic note, he does explain that "not all drugs will impact gut bacteria and not all resistance will be common," adding that there may also be cases in which "resistance to specific non-antibiotics will trigger sensitivity to specific antibiotics, opening paths for designing optimal drug combinations."
"The number of unrelated drugs that hit gut microbes as collateral damage was surprising. Especially since we show that the actual number is likely to be even higher."
Prof. Peer Bork