Improved understanding of exposome-drug interactions could help prescribe effective drug doses

According to scientific estimations, humans are exposed to at least 10,000 to 100,000 environmental and exogenous compounds in an individual lifetime, which is mainly absorbed through our diet.

"Our body can effectively detoxify most of these substances, but various molecules, as well as co-exposures, can impact drug efficacy," says Benedikt Warth, deputy head of the Department of Food Chemistry and Toxicology at the Faculty of Chemistry and coordinator of the newly founded national exposome research infrastructure, EIRENE Austria.

Fragmented knowledge

Think of the well-known instruction not to drink alcohol in combination with antibiotics or pain relievers. "Ethanol is a well-studied toxin that can alter the effect of the active agent," says Warth.

Bisphenol A (BPA) is another popular environmental toxin that practically everybody has accumulated in his or her body, although mostly in very low concentrations not considered to be critical for human health. BPA, a crucial component in plastics production, has shown to interact with various anti-cancer therapeutics, which can result in drug resistance and reduced effectiveness.

Genistein, a phytoestrogen derived from soybeans and a prominent active agent in hormone drugs for menopausal symptoms, can also affect various drugs, in particular hormone-relevant chemotherapeutics against breast cancer, the researchers explain in their article. These interactions can have negative as well as positive effects.

Among the tens of thousands to hundreds of thousands of molecules that humans are exposed to, countless could interact with therapeutics, especially under certain conditions or in critical phases of life such as pregnancy or adolescence."

Manuel Pristner, PhD Student, University of Vienna

Exposome & health effects

"Today's high-resolution mass spectrometry enables us to measure a very large number of molecules in parallel. This way, we can systematically investigate the network of relationships between the so-called exposome, i.e. all measurable exposures, and certain active agents," says Warth. Furthermore, improved bio-informatic algorithms enable the researchers to analyze the generated big data sets.

To date, researchers have been specifically looking for the effect of a certain molecule on a specific receptor. "With the new technologies at hand, we can expand the approach and not only use a fishing rod, but a fishing net to implement a comprehensive screening strategy, which might lead to discoveries that we would not have been able to make based on rational hypothesis," say the chemists.

Personalized medicine

There are different reasons why certain active agents work well in one person and less or not at all in another, depending on an individual genome, the presence of certain receptors, the activity of enzymes, or simply chemical reactivity.

effective n avoiding side effects.

Individualized medication for a patient through a standardized pre-screening of his or her exposome "are still future dreams," according to Warth, "but the systematic approach could be ground-breaking and also benefit the early stages of drug development."