Microbiome research top priority

In June 2012, the National Institutes of Health (NIH) published results of its Human Microbiome Project — a five-year analysis of the microbiomes of more than 200 healthy people. The project, which identified thousands of microorganismal genera in healthy adults, is the most ambitious survey of the human microbiome to date, providing a reference for future studies investigating the role of the microbiome in human disease.

Heidi Nelson, M.D., director of Mayo Clinic's Microbiome Program, notes that the NIH project and studies like it represent an unprecedented shift in thinking about the microbes that inhabit the human body.

"Historically we've only thought of pathogens, but we now know through sequencing that bacteria cohabitate with us — and encode 100 times more unique genes than our own genome. So we're developing a microbiome program that allows us to not only understand how bacteria cause disease but how they maintain health," she says.

Mayo's Microbiome Program is housed within the Center for Individualized Medicine, which provides infrastructure and resources for researchers interested in studying the role of microbes in a broad range of diseases. Gastrointestinal (GI) disorders under investigation include:

  • Celiac disease
  • Inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis
  • Irritable bowel syndrome (IBS)
  • Esophageal reflux and esophageal cancer
  • Clostridium difficile infection
  • Colorectal cancer
  • Liver and biliary tract diseases

IBS specialist Purna C. Kashyap, MBBS, points out that changes in microbial ecology have been implicated throughout the GI tract, so it makes sense to investigate them all. "Mayo is very proactive in looking at the role of the microbiota in GI diseases," he says. "We have a number of specialty clinics run by people committed to microbiome research."

That research includes replicating human disease in animal models. To facilitate studies involving the transfer of human gut microbiota to mice, Dr. Kashyap is establishing a state-of-the-art, germ-free mouse facility at Mayo Clinic in Rochester, Minn.

Other researchers are comparing the composition of gut microbial communities in people with and without GI disorders. The aim is to better understand how shifts in microbial populations cause disease and whether restoring homeostasis can improve health.

Dr. Kashyap says, "The data are starting to show that there are ways to remedy harmful effects resulting from changes in gut microbes. For example, we have developed a highly successful fecal transplant program for recurring C. difficile infection. By correcting the underlying disturbance in gut microbiology, we've seen life-altering outcomes in our patients. The fecal transplant program at Mayo Clinic in Arizona has had equally successful outcomes." The program was discussed in the October 2012 issue of Digestive Diseases Physician Update e-Edition.

A fecal transplant program is also currently in development at Mayo Clinic in Florida.

Another major area of investigation is the effect of exogenous and endogenous host factors on microbiota composition. "The human genome is inherited, but the microbiome is acquired," Dr. Kashyap says. "So we're trying to understand why one person has a healthy microbiome and another doesn't. A number of factors, including diet, genetics and psychosocial stressors impact the gut microbiota. We need to look at differences in infant feeding, in the way a child is delivered — either vaginally or by cesarean section — and early exposure to antibiotics to determine if they lead to aberrant microbial populations that contribute to adult-onset disease. For example, obesity is associated with a microbiota that is very efficient at extracting calories from food, but was that microbiota present at birth? These are all questions we're trying to answer."

Dr. Kashyap and colleagues recently published a case study in The Journal of Allergy and Immunology in which diet-mediated alterations in gut microbial populations led to remission of symptoms in long-standing ulcerative colitis. They suggest that diet may affect onset, progression and remission of IBD in some patients by enabling or preventing colonization by specific gut microbial groups and that it may therefore be possible to better individualize IBD therapies based on genotype and gut microbial composition.

For more information

Kashyap PC, et al. Role of diet and gut microbiota in the management of inflammatory bowel disease in an Asian migrant. The Journal of Allergy and Clinical Immunology. 2013;132:250.

Quick, inexpensive and a 90 percent cure rate.Mayo Clinic. Digestive Diseases Physician Update e-Edition.