Drug research has focussed on personalised treatment—after it became known that an individual’s genome influence the way she responds to a certain drug. That discovery was a lodestone. Ever since, frontiers in this area of research are being breached and reset. The latest research indicates that a person’s microbiome—the bacteria and other microflora that inhabit a person’s git—are central to drug action. Gut microbes consume all “nutrients”—whether it is from food or from the drugs a person has ingested. This becomes a problem when they metabolise the drug in useless or even harmful compounds. Scientists at the Albert Einstein College of Medicine (AECM) in New York recently presented their findings from a study on the interaction of chemotherapy drug irinotecan and gut bacteria.
Irinotecan causes severe diarrhoea in some patients. Mice studies had found that caterial enzymes called beta-glucurinodases modified the structure of irinotecan and other drugs. In normal course, the liver would have detoxified the drug by fixing it with a chemical group called glucurinodate. But the bacterial enzymes causes the group to break away, turning the drug toxic. After observing irinotecan metabolism by bacteria present in faecal samples of 20 healthy individuals, the AECM team discovered that the people whose faeces showed higher gut bacterial metabolism contained strains that made higher quantities of beta-glucurinodases and also increased levels of proteins that transport compounds into cells, indicating that they were more likely to absorb the toxic drug metabolite and develop gastrointestinal problems. Given how animal microbiome is very different from human microbiome, the recent findings should tell us how flawed animal testing can be for many drugs. Tailoring a therapy will likely make the therapy itself more complex than it is now—in irinotecan’s case, for instance, enzyme inhibitors need to be included in the therapy—but the increased drug efficiency could make it a fair trade-off.