Investigating gut microbiome link to chemotherapy-induced nausea

By Susan Murphy

Komal Singh, Ph.D., a nurse-scientist in Mayo Clinic's Department of Nursing, is a recipient of the 2022 Gerstner Family Career Development Awards. The competitive awards are presented annually by Mayo Clinic Center for Individualized Medicine to researchers who are conducting innovative investigations to predict, prevent, treat and cure diseases using individualized medicine approaches. 

Dr. Singh is investigating individualized strategies to help mitigate symptoms of chemotherapy-induced nausea in patients receiving chemotherapy for breast cancer. Her research focuses on the complex link between nausea-related symptoms and the gut microbiome — a population of bacteria, viruses, and fungi that inhabit the gastrointestinal tract. 

Chemotherapy, which is made of powerful chemicals to kill fast-growing cancer cells in the body, is known to change the species diversity and composition of the gut microbiome. 

Symptoms that can co-occur with chemotherapy-induced nausea include vomiting, dry mouth, diarrhea, lack of appetite, mouth sores, weight loss, and a change in the way food tastes. Despite advances in anti-nausea treatments, up to 60% of oncology patients experience symptoms. 

"The uncomfortable and sometimes debilitating symptoms can lead to compromised nutritional status, decrements in quality of life, and even a discontinuation of cancer treatment," says Dr. Singh, who began her career as a nurse and went on to acquire her Ph.D. in symptom science. She wanted to better understand why her patients with the same diagnosis would experience vastly different symptoms and treatment outcomes. She says her inspiration to help patients comes from her mom, who was a doctor, her aunt, who was a nurse, and her grandmother, a midwife.

"By identifying changes in gut microbiome diversity and composition, this study could potentially guide new therapeutic approaches and lead to improved patient outcomes," Dr. Singh says.

Dr. Singh will also investigate the bidirectional communication between the gut microbiome and the brain, called the "microbiome-gut-brain axis," which is known to be associated with other symptoms, such as depression, fatigue, sleep disturbance, and neuropathy.

Unraveling the gut microbiome

For the study, Dr. Singh is using multi-omics technologies — specifically, metabolomics and metagenomics — to analyze stool samples from patients undergoing chemotherapy for breast cancer. She'll compare samples of patients with and without symptoms of chemotherapy-induced nausea. 

Metabolomics is the study of metabolites, which are substances created when the body breaks down food, chemicals, or its own tissue. Dr. Singh says gut microbiome metabolites regulate inflammation and immune function. Metagenomics is the study of genetic material in microbes. Altogether, multi-omics is a combination of two or more "omics" approaches. Additional multi-omics examples include genomics, mapping genomes; proteomics, the study of proteins; epigenomics, the study of epigenetic changes on DNA; and transcriptomics, the study of RNA molecules.  

"By studying metabolomics and metagenomics, we hope to better understand the correlation between metabolites and the microbiome and the perturbed metabolic pathways associated with microbiome diversity," Dr. Singh explains. "If we can tailor interventions to keep the microbiome as diverse and as abundant as it was before chemotherapy, patients might not experience as many adverse side effects from chemotherapy."

Cultivating a healthy microbiome

Dr. Singh says there are several potential individualized approaches for restoring microbiome health in oncology patients. For example, Dr. Singh explains that chemotherapy is associated with a reduction in the abundance of probiotic species, or "good" bacteria, such as lactobacilli and enterococci. 

"Preclinical studies have shown that supplementing lactobacilli and enterococci can improve the efficacy of some chemotherapy regimens," Singh says.

She says other interventions could include individualized fecal material transplants to adjust metabolites and microbiome composition profiles.

"Or it could be as simple as offering patients probiotics before, during, and/or after treatments," she says. "Or prescribing a combination of diet and exercise regimen to improve levels of metabolites." Overall, Dr. Singh hopes her studies will show that having a healthy and balanced microbiome is key to healing.

The Gerstner Family Career Development Awards are benefactor-sponsored initiatives that promote a specialized workforce for individualized medicine discovery, translation and application. Made possible by a grant from the Louis V. Gerstner, Jr. Fund at Vanguard Charitable, the awards provide important seed money for early-stage investigators interested in launching a career in individualized medicine.

Learn more

Learn more about chemotherapy.

Also read these articles:

• "Get ready for possible side effects of chemotherapy."
• "Chemotherapy nausea and vomiting: Prevention is best defense."

A version of this article was originally published on the Mayo Clinic Center for Individualized Medicine blog.