Microbiome Role in Cancer, IBD, Obesity, and Infections
This is a companion to the story, Recruiting Microbes to Fight Autoimmune Diseases
Researchers in Mayo Clinic's Center for Individualized Medicine Microbiome Program are studying not only how the body's microbes affect health, but also how to manipulate the microbiome to treat diseases ranging from rheumatoid arthritis to several kinds of cancer.
"The vision of the program is to bring the cutting-edge science in the microbiome to help translate it to diagnostics and therapeutics for patients," says Purna Kashyap, M.B.B.S., who together with Nicholas Chia, Ph.D., are the Bernard and Edith Waterman co-directors of the Mayo Clinic Center for Individualized Medicine Microbiome Program.
Mayo's studies on the microbe Prevotella histicola and autoimmune disease (see companion article) is part of the program's portfolio, but researchers are examining the microbiome's influence on other diseases, as well.
Clostridium difficile infection
Infection by the bacteria C. diff often occurs in hospitals after antibiotic treatment wipes out the patient's gut microbiome. In turn, the microbiome is overwhelmed by the fast-reproducing C. diff bacteria. Routine treatment with more antibiotics often leads to recurring and potentially dangerous infections.
Recently, doctors at Mayo and elsewhere have succeeded in stopping C. diff infections by transplanting stool from a healthy patient into the patient's gut — the "kitchen sink approach," in Dr. Kashyap's words. Mayo researchers are now conducting clinical trials with more standardized doses of bacteria-containing pills. "We're getting closer to what we would consider treatment," says Dr. Kashyap.
Mayo's research has identified characteristics of the microbiome that predispose a patient to C. diff infections and what accounts for those characteristics. "We are trying to work on both ends of the spectrum, which is to prevent C. diff infection and to treat C. diff infection," Dr. Kashyap says. "Both approaches are ways of tackling the disease."
Inflammatory bowel disease
Mayo Clinic researchers are testing fecal transplants for treatment of inflammatory bowel disease, an autoimmune disorder in which the immune system attacks the lining of the intestinal tract. Because the body's microbiome interacts with the immune system, researchers suspect that restoring diversity and normalcy to the microbiome will relieve inflammation of the intestinal lining.
"The idea is if the gut microbiome is driving the disease, maybe if we have a reset or do a complete changeover, we may be able to either treat the disease or interrupt the cycle where it's perpetuating the disease," says Dr. Kashyap.
Researchers are investigating whether there are ways to change the microbiome directly to help patients lose weight.
The microbiome appears to influence obesity in several ways. First, the microbes digest food the body alone cannot, scavenging additional calories. But also, "there appears to be microbial control of appetite and satiety, which means microbes can affect the neural-hormonal signaling which controls our appetite," says Dr. Kashyap. Furthermore, microbe byproducts, such as short-chain fatty acids and bile acids, play a role in human metabolism, contributing not only to obesity, but also adult-onset diabetes and coronary artery disease.
Mayo researchers are investigating the relationship between the body's native microbes and various cancers.
For example, Dr. Chia's research has shown that various polyps that form in the intestine — often a precursor to colorectal cancer — harbor different bacterial communities, "suggesting there might be different paths to cancer, all of which start from the microbiome," says Dr. Kashyap.
Researchers also have been examining distinctive characteristics of bacteria in the lining of the uterus that appear to be associated with endometrial cancer and may cause or drive the progression of the disease.
"If we know that there are certain microbial signatures that are enriched in endometrial cancer, then we could use a noninvasive test now to screen for endometrial cancer. There's a big need because it's hard to screen for early-stage cancer. And, two, if these same bacteria are in fact causing the cancer, then they also become a target for treatment," says Dr. Kashyap.
"The main message that we want to send out is that the microbiome program at Mayo is one of the places where there is innovation specifically to help transform patient care," says Dr. Kashyap. "Our goal is to make this a translational program where we can do something meaningful for the patient."
– Greg Breining, January 2019
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