Personalised medicine, or pharmacogenomics, means targeting drugs and treatments based on a person’s genetics. This approach has significantly improved outcomes for cancer patients in recent years. Now research is showing that a person’s gut microbiome (the bacteria and other microbes found in a person’s digestive tract) could play a similarly important role in predicting the effectiveness of a treatment for an individual.
Published in the journal Nature npj Biofilms and Microbiomes, a recent study has demonstrated that gut bacteria can be used to determine if a cancer drug will work for a particular person and also if they are likely to experience side effects. The study was based on previous evidence showing people metabolise drugs in different ways depending on their microbiome.
It is still early days but this research may in future provide a basis for new pathology tests which would help clinicians to better manage cancer treatments and even treatments for other diseases, too.
To test the theory that a person’s microbiome could affect how they metabolise cancer drugs, researchers at the Albert Einstein College of Medicine in New York collected faecal samples from 20 healthy individuals and treated the samples with irinotecan – a chemotherapy drug used to treat colorectal cancer.
When the researchers analysed the treated samples they found those containing a large amount of an enzyme produced by gut bacteria called beta-glucuronidase, were less able to metabolise the drug. For patients being treated with irinotecan, this inability to metabolise the drug means they absorb the toxic substance rather than excrete it as waste, leading to side effects which can include diarrhoea and dehydration.
Commenting on the study, lead researcher A/Professor Libusha Kelly explained the impact of side effects on patients: “Patients with colorectal cancer are already quite ill, so giving them a treatment that causes intestinal problems can be very dangerous. At the same time, irinotecan is an important weapon against this type of cancer.”
The research also demonstrated that beta-glucuronidase enzymes in the gut can interact with other medicines, including common drugs such as ibuprofen and morphine. This interaction can “reactivate” the drugs in the liver, causing patients to absorb higher than intended doses.
Emily Balskus is a biochemist at Harvard University, she says that in the future pathology testing could be used to screen people’s microbiomes and determine if a drug will work for them. If someone’s microbiome looks like it might affect drug processing, doctors could prescribe an enzyme inhibitor or put the patient on a diet that provides the bacteria with an alternate food source, which could stop beta-glucuronidase enzymes from interfering with the metabolism of the drug.
Pathology Awareness Australia ambassador Dr Nick Musgrave is an Anatomical Pathologist with a special interest in gastrointestinal conditions. He is looking forward to finding out where research of this kind will lead;
“Year by year we’re learning more about the impact of the microbiome on our health. The news that it impacts the metabolism of certain chemotherapeutic agents is further proof of this. It will be interesting to see if the microbiome also has an impact on other treatments. Of course these are very early days in our understanding of the effects of an individual’s microbiome and how to manage these effects.”
Pathology Awareness Australia Limited (PAA) is a not-for-profit group formed in 2013 to raise awareness of the value of pathology in healthcare. Recognising that pathology is a vital and highly skilled medical profession, that goes on largely unseen in laboratories across the country, PAA created the Know Pathology Know Healthcare campaign. Although 100% of cancers are diagnosed by pathology and around 70% of medical decisions use pathology results, it is mostly invisible to the public. The Know Pathology Know Healthcare initiative raises awareness of pathology and improves health literacy by providing news, access to information about tests and events that educate the public and parliamentarians.