DEAR MAYO CLINIC: I’ve had recurring instances of C. diff. that normally is treated with antibiotics. I have read about fecal transplant as a potential treatment. How does this work?

ANSWER: Clostridium difficile, also known as Clostridioides difficile and often called C. diff., is a bacterium that causes gastrointestinal symptoms ranging from diarrhea to life-threatening inflammation of the colon. In many cases, antibiotics are an effective treatment. If the infection recurs after two or three rounds of antibiotics, a fecal transplant may be an appropriate alternative.

C. diff. bacteria are found throughout the environment — in soil; air; water; human and animal feces; and food products, such as processed meats. C. diff. is now the most common infection affecting hospital patients. The most common risk factors for C. diff. are taking antibiotics, being older than 65, and being in a hospital or other health care facility.

Taking antibiotics can lead to C. diff. infection by disrupting the healthy balance of bacteria that’s normally present in your intestines. The intestines contain about 1,000–2,000 different kinds of bacteria. Many of them help protect your body from infection. When you take antibiotics to treat an infection, such as for a sinus, urinary tract or kidney infection, those drugs destroy many of the helpful bacteria in the gut along with the bacteria causing the infection. Without enough healthy bacteria to keep it in check, C. diff. quickly can grow out of control.

While antibiotics can contribute to C. diff. infection, some antibiotics, such as vancomycin or fidaxomicin, also can effectively eliminate C. diff. infection. In about 75% to 80% of people who get C. diff., one round of antibiotics is enough to get rid of the infection and prevent it from recurring.

For the other 20% to 25%, a recurrence happens because the antibiotics again take out too much of the good bacteria with the C. diff. Once C. diff. infection recurs, the chances of it returning again after a second round of antibiotics is 40%. After three or more occurrences, the risk of another infection rises to 60%.

One way to break the cycle of recurrent infections is to restore the natural balance of healthy bacteria in the intestines. This can be done through a process known as fecal microbiota transplantation. The procedure — considered investigational at this time — restores healthy intestinal bacteria by placing another person’s processed stool into the colon of a person affected by recurrent C. diff. infections.

Potential donors need to go through a strict screening process that involves an extensive list of medical history questions before they can be approved as donors. They also need to undergo comprehensive testing for infections in the blood and stool.

Once a donor is approved, his or her stool is collected, mixed with saline water and filtered. Then the stool mixture is transferred into the patient’s colon, most commonly via a colonoscope — a thin, flexible tube with a small camera at the tip.

The procedure is considered to be generally safe. The Food and Drug Administration, however, recently released a report about two patients who underwent fecal transplantation and contracted drug-resistant infections. It’s unclear if these cases were related to fecal transplants for C. diff. or if the fecal transplants were done for another condition. More needs to be learned about those incidents, but they speak to the importance of carefully and methodically screening donors.

Clinical trials to study fecal transplants are underway at medical centers across the country, including Mayo Clinic. So far, research has shown that this procedure can reduce the risk of contracting another C. diff. infection in people who have had three or more of the infections. In this patient population, the risk has been reduced from 60% down to less than 15%. With these findings in mind, this treatment appears to show significant promise in providing a more effective treatment option for recurrent C. diff. infections. — Dr. Sahil Khanna, Gastroenterology, Mayo Clinic, Rochester, Minnesota

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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.

Obesity

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.

Cancer

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

The post Microbiome Role in Cancer, IBD, Obesity, and Infections appeared first on Mayo Clinic News Network.

Listen: Mayo Clinic Radio 11/26/16

On this special Thanksgiving edition of Mayo Clinic Radio, you’ll hear from three patients who have reason to give thanks. First, we revisit an unusual transplant story. Gastroenterologist Dr. Sahil Khanna and patient Stephanie Bennett explain how fecal transplant was used to treat her Clostridium difficile infection. Also on the program, licensed acupuncturist Sara Bublitz and her patient, Heather Spaniol, share how alternative therapies, including cupping, helped manage the pain after a battle with flesh-eating bacteria. And, hear a repeat of the story of Jimmy Dunbar, a transplant patient waiting for a heart transplant.

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Here's the Mayo Clinic Radio podcast.

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Listen to the program on Saturday, Nov. 26, at 9:05 a.m. CST, and follow #MayoClinicRadio.

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Access archived shows.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

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Listen to the program on Saturday, Nov. 26, at 9:05 a.m. CST.

Miss the show?  Here's the Mayo Clinic Radio podcast.

Follow #MayoClinicRadio, and tweet your questions.

Mayo Clinic Radio is on iHeartRadio.

Mayo Clinic Radio produces a weekly one-hour radio program highlighting health and medical information from Mayo Clinic.

Access archived shows.

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Here's the Mayo Clinic Radio podcast.

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Clostridium difficile

, also called C. difficile, is a bacterium that can cause symptoms ranging from diarrhea, abdominal cramping and fever to life-threatening inflammation of the colon. Some patients with C. difficile do not benefit from standard therapy and the condition frequently comes back.

Now researchers in the Mayo Clinic Center for Individualized Medicine have new hope for selecting the right treatments for patients to stop the infection and alleviate painful symptoms sooner. They have discovered changes in the gut microbiome, the community of bacteria in the digestive tract, that predict how a patient with C. difficile will respond to treatment.

Purna Kashyap, M.B.B.S., of the Department of Gastroenterology and Hepatology, and associate director of the Center for Individualized Medicine Microbiome Program, and colleagues conducted a study of patients with C. difficile, finding gut microbiome signatures that predict treatment response and recurrence. This is important because those patients who will not benefit from the standard antibiotic therapy or have a high likelihood of recurrence can be given alternative therapies sooner. The study of “Gut Microbiome Predictors of Treatment Response and Recurrence in Primary Clostridium Difficile Infection” is published in the Aug. 2 edition of Alimentary Pharmacology and Therapeutics.

“In this study, we identified microbiome markers at the time of initial diagnosis that can predict response to therapy in patients with C. difficile infection. This would allow early identification of patients who are less likely to respond to conventional treatment and candidates for alternate therapy such as fecal microbiota transplant,” says Dr. Kashyap.

The study included 88 patients who had experienced their first episode of C. difficile infection. Researchers collected and analyzed pre-treatment stool samples using DNA-sequencing for the gene encoding 16S rRNA, to identify changes in the gut microbiome. Investigators then correlated these bacterial changes to how well patients responded to treatment, enabling them to identify predictors of treatment response and recurrence.

“This study highlights the utility of next generation microbiome-based precision medicine tools for personalized treatment approaches. Our findings provide an example of how microbiome-based diagnostics can improve patient care by selecting the right treatment for patients,” says Dr. Kashyap.

Each year in the United States, more than half a million people get sick with C. difficile. In the past, C. difficile occurred most frequently in patients taking antibiotics or those over age 65 in a hospital or long term care facility. However, the number of younger, healthy adults with C. difficile is increasing and in recent years, C. difficile infections have become more frequent, severe and difficult to treat.

According to Dr. Kashyap, the next phase of research will focus on validating the findings and developing laboratory tests to identify microbiome predictors.

Additional authors on the research team include Sahil Khanna, M.B.B.S., Robin Patel, M.D., Darrell Pardi, M.D., and Bradley Schmidt, all of Mayo Clinic; Emmanuel Montassier, M.D., Ph.D.,  Université de Nantes, France; and Dan Knights, Ph.D., University of Minnesota.

The study was supported by the Mayo Clinic Center for Individualized Medicine, and grants from the Minnesota Partnership for Biotechnology and Genomics, and National Institutes of Health.

Join us to learn more about the microbiome and other aspects of precision medicine

Learn more about ongoing research efforts in the Center for Individualized Medicine’s Microbiome Program, including current research projects and stories about how this research has helped patients.

Hear experts discuss the latest research in precision medicine, including exploration of the microbiome, and how individualized medicine can improve treatments for many conditions, such as heart disease, cancer, rheumatoid arthritis, Alzheimer's disease and autism.

Attend Individualizing Medicine 2016: Advancing Care Through Genomics. The Mayo Clinic Center for Individualized Medicine, is hosting the fifth annual genomics conference, October 5–6, in Rochester, Minn.

• For a complete schedule and list of speakers, visit the conference website.
• You may also learn more about the conference on the video blog series, “Story by Story.”
• Follow the latest news related to the conference on the Center for Individualized Medicine blog, Facebook, LinkedIn or Twitterat @MayoClinicCIM and use the hashtag #CIMCon16.

The Mayo Clinic Center for Individualized Medicine is hosting the conference with support from the Satter Foundation.

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