Researchers uncover new way gut bacteria disrupt drug effectiveness
A milestone study published in the journal Nature is reporting how gut bacteria can accumulate quantities of therapeutic drugs and potentially reduce their effectiveness. The research builds on growing insights into the ways our microbiome can either reduce or enhance the activity of certain medicines.
We know the bacteria living inside our gut can play a role in the efficacy of therapeutic drugs. Researchers last year, for example, found a metabolite produced by certain bacteria can block the effects of a common drug used to treat diabetes.
Other studies have discovered compelling interactions between the microbiome and cancer treatments, with some types of bacteria increasing the toxicity of chemotherapy while others can enhance the beneficial effects.
This new research, a collaborative effort from scientists at the European Molecular Biology Laboratory and the University of Cambridge, set out to specifically investigate a number of drug/bacteria combinations. The study focused on 15 commonly used oral drugs and their interactions with 25 common strains of gut bacteria.
Kiran Patil, co-lead on the study, says the findings were unexpected. Most of the detected drug/bacteria interactions were due to the drugs accumulating within the bacteria, and this was surprising as bioaccumulation was not previously considered to be a significant factor in gut bacteria influencing therapeutic drug action.
“It was surprising that the majority of the new interactions we saw between bacteria and drugs were the drugs accumulating in the bacteria,” says Patil. “Until now, biotransformation was thought to be the main way that bacteria affect the availability of drugs to the body.”
Overall, the study reports 70 specific interactions between drugs and bacteria, 29 of which were new. And strikingly, 17 of those 29 newly reported interactions were due to drugs accumulating within bacteria. Drugs such as rosiglitazone (for diabetes), montelukast (for asthma), and roflumilast (for chronic obstructive pulmonary disease), were all found to accumulate within certain species of bacteria.
To understand in detail the molecular basis of bioaccumulation the researchers closely investigated a widely used antidepressant called duloxetine. Not only was this drug found to accumulate within certain species of bacteria, it also changed the metabolites secreted by those bacteria. This disruption subsequently altered the composition of several bacterial populations.
Finally, using a worm model, the researchers found bioaccumulating bacteria could absorb enough specific drug molecules to alter a drug’s therapeutic actions. The behavioral effects of duloxetine in nematode worms were different when the worms harbored gut bacteria known to accumulate the drug compared to worms without those bacterial species.
It’s still very early days for this kind of research, and while we are learning more about how gut bacteria interacts with therapeutic drugs, the complexity of these interactions makes broad clinical translations incredibly challenging. Patil says the unique composition of every individual’s microbiome is likely to mean these bacteria/drug interactions will vary from person to person.
“The next steps for us will be to take forward this basic molecular research and investigate how an individual’s gut bacteria tie with the differing individual responses to drugs such as antidepressants – differences in whether you respond, the drug dose needed, and side effects like weight gain,” says Patil. “If we can characterize how people respond depending on the composition of their microbiome, then drug treatments could be individualized.”
The new study was published in the journal Nature.
Source: University of Cambridge