Intestinal microbes that survive chemo can rid the gut of excess chemo drugs and produce a vitamin that helps to stem nausea.
Chemotherapy doesn't just kill cancer cells. It also affects the microbes in the digestive tract.
Researchers at UC San Francisco have discovered that some gut bacteria can reduce the side effects of these potent treatments, and that one family of cancer drugs may actually boost these protective bacteria.
The phenomenon could help physicians to predict the severity of a patient's side effects and points the way to supplements that could help those whose guts aren't sufficiently protecting them.
"These studies emphasize the important relationship between the gut microbiome and drug toxicity," said Peter Turnbaugh , PhD, a professor of microbiology and immunology at UCSF. "A more detailed understanding of this relationship could provide new strategies to optimize the treatment of cancer and other diseases."
Clearing drugs from the body
Turnbaugh's team found that colorectal cancer patients taking a class of chemotherapy drugs known as fluoropyrimidines had much less diverse microbiomes in their digestive systems. But the surviving bacteria did something amazing.
"They were able to gobble up the chemotherapy and chemically transform it into a harmless byproduct," said Kai Trepka , a student in the Medical Scientist Training Program at UCSF who co-authored the study along Wesley Kidder , MD, MPH, an associate professor of medicine who specializes in gastrointestinal cancer. It published April 16 in Science Translational Medicine .
The team also saw that measuring the abundance of helpful bacteria could predict whether a patient would develop the kind of severe side effects, like nausea or vomiting, that make it hard for people to complete their treatment.
When the researchers gave these drug-processing microbes to mice experiencing severe chemotherapy side effects, their symptoms greatly improved, suggesting that humans may be able to use the bacteria as probiotics.
Clues to influencing the microbiome
A second study, published May 20 in the journal mBio , revealed the microbiome can also protect patients from the painful numbness or tingling sensation that is another common side effect of chemotherapy, by producing vitamin K2.
When the researchers looked at the microbiomes of 56 colon cancer patients, they saw again that the fluoropyrimidine drugs had killed off some of the organisms and bolstered the populations of others.
Among those that thrived during chemotherapy was a nonpathogenic strain of E. coli that produced vitamin K2. The researchers gave K2 to mice who'd been treated with fluoropyrimidine drugs, and their side effects resolved.
Patients who reported fewer side effects also had more K2 in their microbiomes.
"For a long time, the microbiome has seemed like a black box," Kidder said. "We're now starting to be able to shine little flashlights and find clues to how we can influence it for the better — in this case, better outcomes for cancer patients."
Authors: Additional authors on the Science Translational Medicine study: Than Kyaw, Taylor Halsey, Christine Olson, Edwin Ortega, Cecilia Noecker, Vaibhav Upadhyay, Dalila Stanfield, Paige Steiding, Benjamin Guthrie, Peter Spanogiannopoulos, Darren Dumlao, Jessie Turnbaugh, Matthew Stachler, Erin Van Blarigan, Alan Venook and Chloe Atreya, of UCSF.
Additional authors on the mBio study include: Benjamin Guthrie, Christine Olson, Chen Zhang, Edwin Ortega, Lorenzo Ramirez and Chloe Atreya from UCSF, Lars Hillege, Xueyan Fu, Romy Aarnoutse, Judith de Vos-Geelen , Liselot Valkenburg-van Iersel, Irene van Hellemond, Arnold Baars, Johanna Vestjens, John Penders, Marjolein Smidt and Janine Ziemons of Maastricht University, The Netherlands, and Adam Deutschbauer of Lawrence Berkeley National Laboratory.
Funding: The studies were supported by the National Institutes of Health (grants R01CA255116, R01DK114034, and R01HL122593, F30CA257378, R01HL122593, R01CA255116 and R01DK114034), the USDA (grant 58-8050-3-003) and the Parkinson's Disease Foundation (grant PF-PRF-932695).
About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health , which serves as UCSF's primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu , or see our Fact Sheet .
