Leaving No Microbe Unturned

The Trust and the Crohn's & Colitis Foundation of America work together to unlock the secrets of the human microbiome.

Within every human body, trillions of microorganisms, viruses and bacterial cells – both good and bad –influence the state of our health and illnesses. This vast community of microbes comprises one collective organ: the human microbiome.

In a relatively new but rapidly expanding field of study, researchers aim to decipher which of these microbial players are key to certain diseases, and which can be targeted to develop new therapies for patients.

Through its IBD and Crohn’s Disease Program, the Helmsley Charitable Trust supports the Crohn’s & Colitis Foundation of America (CCFA) to better understand how microorganisms in the gut contribute to this recurring inflammatory condition. IBD is a chronic malady that affects millions worldwide and consists of two disorders: Crohn’s disease and ulcerative colitis. While science has told us that intestinal microbes in the gut are intimately linked to the cause of IBD, only a limited number of these enormously complex microbial agents have been identified and their functions have remained largely unknown.

CCFA has been responsible for many of the most advanced IBD studies conducted by major medical institutions since its founding nearly 50 years ago. The Trust’s partnership with CCFA paved the way for the advancement of CCFA’s multi-phase Microbiome Initiative, a project designed specifically to ensure that investigators receive the nurturing and funding necessary to strengthen microbiome-focused endeavors to cure IBD.

For this important project, CCFA competitively selected seven teams spanning 15 institutions in the U.S. and Canada to apply complementary study designs and analytic approaches to uncover the composition, function and host-interactions of disease-associated microbes. Since Helmsley’s initial support in 2010, the Microbiome Initiative’s multidisciplinary research consortium has discovered that the enzymes produced by microbes are the molecular basis for some manifestations of IBD. In addition, the effort has already identified 20 different types of bacteria that are present in the gut of Crohn’s patients. This work raises promising new possibilities for IBD investigators and patients alike. The ability to discern which microbial products in the gut provoke IBD – and which are activated in conjunction with other factors like diet or genetics – will offer new hope to uncover novel therapies.

“The exciting thing in our work is that we’ve been able to figure out what the organisms produce and how they affect our bodies,” said Jonathan Braun, director of the CCFA Microbiome Initiative’s research consortium. “That changes the game because now rather than looking at organisms, we’re looking at functions that can be targeted by diet or by drugs.”

The Microbiome Initiative aims to undertake the critical scientific challenges at hand, namely finding a way for modern medicine to translate basic biological and chemical studies into microbiome-targeted interventions to treat IBD. With Helmsley funding, CCFA’s research consortium is now looking to identify potential therapies for development by pharmaceutical companies while also conducting a rigorous investigation of the effect of diet on the microbiome and how that might allow patients to alter the course of their illness without taking medications.

We now have a sense of what the bugs within us are doing, and scientists are starting to unravel whether our genes change our bugs or our bugs change our genes.

Jim O'Sullivan, IBD and Crohn's Disease Program Director

“CCFA is our biggest single partnership in the IBD and Crohn’s Disease Program and it is one that has helped inform all the work that we do,” said Jim O’Sullivan, Program Director of the Trust’s IBD portfolio.

On the path to a cure, the Trust continues to fuel preeminent international investigators performing results-oriented studies that transform the ability to diagnose, treat and prevent IBD. The next phase of the Microbiome Initiative will apply a translational approach to established concepts to yield a productive pipeline of microbial targets and initial lead molecules suitable for entry into preclinical therapeutic development.

“The microbiome is an important lead-in to better understanding what might be happening to people with Crohn’s disease and colitis. We now have a sense of what the bugs within us are doing, and scientists are starting to unravel whether our genes change our bugs or our bugs change our genes,” O’Sullivan said. “Understanding that complexity in diseases like IBD is going to get us to the answers we want, the treatments we want and even the cures we want faster than we would without it.”