Microbiome is once again leading scientists toward a new understanding of how human gut bacteria can impact the efficacy and side-effects of certain cancer therapies
Anatomic pathology researchers already know that a person’s genetics can affect the results of cancer treatments. Now it is becoming clear that a patient’s microbiome—which includes gut bacteria—may also impact the efficacy of particular cancer treatments. A recent study showed that gut bacteria can be used to determine whether a cancer drug will work for a certain individual and also if the patient might suffer side effects from certain cancer treatments.
Working with this knowledge, diagnostic test companies may possibly develop new clinical laboratory tests designed to help physicians better diagnose and treat cancer patients. This, in turn, advances personalized medicine and treatments for chronic diseases tailored to patients’ specific physiologies and conditions. This is a healthcare trend where medical laboratories can expect to play a critical role.
Gut Bacteria as Important as Genetics in Cancer Treatments
A recent article published in the journal Nature: npj Biofilms and Microbiomes, outlined a correlation between gut bacteria and side effects of irinotecan (sold as Camptosar), a drug used to treat metastatic colorectal cancer.
Libusha Kelly, PhD, Assistant Professor in the Departments of Systems and Computational Biology, and Microbiology and Immunology, led researchers from the Albert Einstein College of Medicine located in Bronx, N.Y., in conducting the study.
“We’ve known for some time that people’s genetic makeup can affect how they respond to a medication,” noted Kelly in an Einstein news release. “Now, it’s becoming clear that variations in one’s gut microbiome—the population of bacteria and other microbes that live in the digestive tract—can also influence the effects of treatment.”
Irinotecan is administered intravenously to colorectal cancer patients in an inactive form and is metabolized to an active form by liver enzymes. The drug is later converted back to an inactive form by other liver enzymes and the addition of a Glucuronidase chemical group. The irinotecan then enters the intestine for expulsion by the body.
Taken from the Einstein College of Medicine published study, the graph above illustrates “Two distinct metabolizer phenotypes or ‘metabotypes’ based on % SN-38 formation during a time course incubation of SN-38G with fecal samples from 20 individuals quantified by LC-MS/MS. Participants were sub-grouped into low (n = 16) and high (n = 4) metabolizer phenotypes. All samples were run in triplicate and values are the mean ± sem.” (Graphic copyright: Nature/Albert Einstein College of Medicine.)
However, bacteria residing in the digestive tract of some individuals prevent the medication from metabolizing properly and reactivates the medication, which transforms the irinotecan into a toxic substance that can cause side effects.
To perform the research, Kelly and her team collected fecal samples from 20 healthy individuals and treated those samples with inactive irinotecan. The samples were then examined and categorized by whether or not they were able to metabolize or reactivate the drug.
Identifying Potential for Side Effects in Patients a Powerful Tool for Medical Laboratories
Irinotecan can cause severe diarrhea and dehydration in up to 40% of patients who take the medication. By focusing on the presence of beta-glucuronidase (enzymes that are used to catalyze the breakdown of complex carbohydrates) the researchers found that gut bacteria can also be used to distinguish which patients will encounter side effects from the drug.
“As you can imagine, such patients are already quite ill, so giving them a treatment that causes intestinal problems can be very dangerous,” said Kelly in the news release. “At the same time, irinotecan is an important weapon against this type of cancer.”
Four of the 20 subjects in the study were determined to be high metabolizers. Due to differences in the composition of their microbiomes, the team concluded that the high metabolizers were more likely to experience side effects from irinotecan.
The research also demonstrated that beta-glucuronidase enzymes in the gut may adversely interact with some commonplace drugs, such as ibuprofen and other nonsteroidal anti-inflammatory medications (NSAIDs), morphine, and Tamoxifen, a drug that is prescribed mainly to breast cancer patients.
“In these cases, the issue for patients may not be diarrhea,” states Kelly in the news release. “Instead, if gut bacteria reactivate those drugs, then patients might be exposed to higher-than-intended doses. Our study provides a broad framework for understanding such drug-microbiome interactions.”
Microbiome Takes Center Stage in Pathology Research
As Dark Daily previously reported, from extending life to developing more powerful treatments for chronic diseases, the human microbiome is quickly becoming an important subject of research studies. The findings from such studies will trigger advances in precision medicine. And, the clinical laboratory assays developed from this research will give physicians the knowledge needed to select the most appropriate drug therapies and treatments for individual patients.
—JP Schlingman
Related Information:
Gut Bacteria Can Stop Cancer Drugs from Working
Gut Microbiome May Make Chemo Drug Toxic to Patients
Human Microbiome Signatures of Differential Colorectal Cancer Drug Metabolism
