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Common bacteria found in the human gut could be inactivating a class of drugs used in the treatment of many common conditions such as migraines, depression, type 2 diabetes, prostate cancers, warned a new study published in the Nature Chemistry.
The class of drugs involve more than 400 medications approved by the US Food and Drug Administration. These medicines target 'G protein-coupled receptors' (GPCR), a family of proteins that sit embedded on cell membranes, a thin layer that forms the outer boundary of a living cell.
They act as an “inbox for messages” and constitute the largest family of proteins targeted by approved drugs. “Understanding how GPCR-targeted drugs interact with human gut microbiota is critical for advancing personalised medicine initiatives,” Qihao Wu, assistant professor in the Pitt School of Pharmacy at the University of Pittsburgh and the first author of the paper, said in a statement. Personalised medicine is an emerging practice that uses an individual’s genetic profile to guide decisions to prevent, diagnose and treat diseases.
This research, the expert added, could help open up new avenues for drug design and therapeutic optimisation to ensure that treatments work better and safer for every individual. Factors such as age, genetic makeup and diet also influence the effectiveness of drugs.
Previous studies have reported that gut microbes can breakdown orally administered drugs into different chemical structures. Their accumulation could reduce the availability of the drug to the body and potentially reduce their efficacy.
The human gut is home to hundreds of different species of bacteria, which are important in health and diseases. One study revealed that more than 3,000 species reside in the human gut. The composition of bacterial species varies significantly between people.
The gut microbes are linked to a wide range of conditions including obesity, immune response and mental health, studies have shown.
In this study, researchers wanted to gain more insights into how microbes breakdown common medications. They built a synthetic microbial community composed of 30 common bacterial strains found in the human gut. They then added each of 127 GPCR-targeting drugs individually and checked if the drugs were chemically transformed to different substances.
Their results showed that gut microbes broke down 30 of the 127 tested drugs. Of them, effects were more pronounced, meaning that original concentrations were heavily depleted, after being transformed into different compounds.
Next, the team specifically focused on Iloperidone, which is often used to treat schizophrenia and bipolar I disorder. One bacterial strain in particular, Morganella morganii, a bacteria commonly found in the environment and in the intestinal tracts of humans, inactivated iloperidone by transforming it to a range of different compounds, both in the lab and in mice.
The researchers flagged that more research is needed to have concrete answers on how the gut microbes influence medications.
The pipeline created in this study can help researchers investigate interactions between gut bacteria and compounds found in food, Wu added. “For example, we identified a couple of phytochemicals in corn that may affect gut barrier function. Notably, we observed that the gut microbiome could potentially protect us from these phytochemicals by detoxifying them.”
Next, the team said, they wish to work out the mechanisms through which microbes break down and transform medications. This could potentially identify strategies for improving therapeutic efficacy and enhancing food and drug safety, they added.
