Gut check on cancer
What does a healthy microbiome have to do with cancer and recovery after treatment?
Cracking the mysteries of the human microbiome—those teeming communities of bacteria, fungi, and viruses that live on and within each of us—remains one of medicine’s most exciting frontiers. At the Masonic Cancer Center, University of Minnesota, a new series of studies funded by philanthropy delves deeper into the mystery, looking at the connection between the gut microbiome and cancer.
Each person’s gut microbiome is an entirely unique environment influenced by genetics, diet, and life experiences. It’s even considered its own organ.
Scientists now know that a healthy microbiome can help promote digestion, ward off potentially harmful organisms that enter the body, and boost overall health. But how the microbiome influences cancer development and treatment is still unknown.
“It’s intuitive that microbes in the gut might have something to do with colon cancer, and that’s one area we’re studying more deeply,” says Alexander Khoruts, M.D., a professor in the Medical School’s Division of Gastroenterology, Hepatology, and Nutrition and a University of Minnesota Health gastroenterologist. “Patients receiving chemotherapy for leukemia are always also treated with potent antibiotics, and their microbiomes are literally decimated, causing severe, life-threatening complications. What if we could repair the microbiome?”
To intervene, scientists first have to understand more about the trillions of microorganisms that make up the microbiome. As recently as 2008, scientists believed the human microbiome was fixed at birth, unchangeable—which they now know is not the case. Since then, researchers, including Khoruts, have generated a wealth of knowledge about the microbiome, which has been called the second genome.
And just as scientists mapped the human genome, they’ve been working on mapping the microbiome through the National Institutes of Health’s Human Microbiome Project.
Looking for answers
At the Masonic Cancer Center, Khoruts coleads a team with Timothy Starr, Ph.D., an assistant professor in the Medical School’s Department of Obstetrics, Gynecology, and Women’s Health, that’s hoping to answer several questions about the microbiome’s relationship with cancer.
Their research recently got a $1.2 million lift from the inaugural Chainbreaker ride, a grassroots bike tour in Minnesota that raised money to support Masonic Cancer Center research. Every rider-raised dollar went to the cause.
Today the Chainbreaker Breakthrough Cancer Research Grant is funding seven studies that fall into two main areas: the role of the microbiome in people who undergo intensive chemotherapy or blood or marrow transplant, and the relationship between the microbiome and colon cancer.
“What exactly goes wrong in the microbiome that might cause colon cancer?” Starr asks. “Unfortunately, we can’t yet isolate the differences between someone who has colon cancer and someone who’s healthy. But we are homing in on those differences.”
In one Chainbreaker-funded study, Starr’s team will collect samples from human microbiomes—collections of gut microbes derived from stool samples—from both healthy people and people who have colorectal cancer.
They’ll place those microbiomes into mice, then test to discover whether the human microbiomes affect the growth of mouse cancer. If they find that the healthy microbiome is protective against cancer, they will then give the mice a form of restorative microbiome therapy.
How exactly does one go about restoring the microbiome?
Today it’s been made easier, thanks to the Masonic Cancer Center team’s secret weapon: the Molecular and Cellular Therapeutics Facility on the University’s St. Paul campus, which manufactures drug and tissue products in accordance with the pharmaceutical industry standard.
That’s no small resource; only a handful of institutions engaged in research have such a facility.
One treatment that already has a successful track record is what Starr calls “Alex Khoruts’ healthy microbiome pills.” The innocuous-looking dark pink capsules, which are manufactured at the Molecular and Cellular Therapeutics Facility, have helped hundreds of patients recover from the crippling gut infection Clostridium difficile, or C. diff.
Infected patients undergo what’s called a fecal microbiota transplant (FMT), which is the transfer of stool from a healthy donor into the gastrointestinal tract of the patient. The donor stool, rich with healthy microbial communities, replenishes the patient’s damaged gut microbiome.
While FMTs are commonly done via colonoscopy, Khoruts has made the procedure much easier for University of Minnesota Health patients: today, they simply swallow the capsules he has developed, which are derived from healthy human microbiota.
Finding long-term health
In a Chainbreaker-funded clinical trial, Khoruts’ team will try to normalize patients’ microbiomes as quickly as possible after blood or marrow transplant by giving them capsules similar to those developed to treat C. diff.; another group of patients will receive placebo pills for comparison.
“I anticipate we can make a substantive impact on improving outcomes for leukemia patients,” Khoruts says, “but we need to be cautious about overhyping this. Not only is the microbiome a new research frontier, it’s a very complex frontier.”
In a related study, Lucie Turcotte, M.D., a pediatric hematologist-oncologist at University of Minnesota Masonic Children’s Hospital and an assistant professor in the Medical School’s Department of Pediatrics, will look into whether microbiome changes are a long-term side effect of cancer treatment.
“During bone marrow transplantation, patients receive immunosuppressive drugs, antibiotics, and chemotherapies that change the way the bowel functions,” she explains. “Sometimes they also rely on intravenous nutrition, which literally starves the intestinal microbes and alters the microbiome composition. But how long do those changes persist? Five to 10 years later, will these patients still have changes to their microbiomes?”
Because the U already has a strong long-term follow-up program in place for survivors of childhood cancers, Turcotte has access to a large pool of former patients. She hopes to recruit 80 individuals within the next year, asking each to complete a brief survey and send in stool samples that can be compared with samples from the general population.
She’ll also be comparing samples from transplant survivors with those from family members who live in the same home.
“If we can identify differences in the patients’ gut microbiomes,” Turcotte says, “then we can look at how to restore their microbiomes to help promote long-term health and potentially avoid problems [associated with cancer treatment] like increased frailty and accelerated aging.”
More knowledge, more support
While the Chainbreaker-funded work at the U is just beginning, Khoruts is 15 years into his microbiome research. His team is grateful to the Minnesota Colorectal Cancer Research Foundation, Mezin-Koats Colon Cancer Research Fund, and Achieving Cures Together, all of which have also supported the U’s Microbiota Therapeutics Program.
Excited and optimistic about the research, Khoruts hopes more people will rally around these studies.
“We all need to understand that, like any other organ, the microbiome can become dysfunctional,” Khoruts says. “Our ultimate goal is to be able to diagnose that dysfunction and then offer a treatment. And with our comprehensive resources here at the U, we’re in a good position to move forward with that work.”