Microbes: Love Them or Fear Them
My favorite clinical microbiology professor once said, “There may be more bacterial cells in our bodies than human cells, so whether we love them or fear them, they are part of who we are.” This simple statement initiated my conversion from the typical clinical-microbiology-hypochondriac (any cut could get infected with flesh-eating bacteria!) to an enthusiast of the microbes that inhabit our bodies and the world around us.
I am not alone in my fascination with microbes. In the last decade, our understanding of the microbiome has grown immensely, in large part due to the National Institute of Health’s Human Microbiome Project. However, scientific exploration of the human microbiome is still in its infancy and major discoveries are still being made. For example, the exact ratio of microbial to human cells in the body was for decades reputed to be 10:1 and has only recently been refined to a likely more accurate estimate of 1:1.
More importantly for our work to find a cure for Inflammatory Bowel Disease (IBD), researchers do not yet understand how alterations in the microbiome affect, or perhaps cause, debilitating chronic diseases such as Crohn’s or ulcerative colitis. Nonetheless, discoveries in other fields are already influencing how scientists and clinicians investigate treatments for IBD.
Fighting Against & With Microbes
Of all the microbes humans interact with, Clostridium difficile (a.k.a: C. difficile or C. diff) is a bad one to come across. This Gram-negative microbe is found throughout the environment, is often contracted in healthcare settings and causes severe, sometimes life threatening, diarrhea. Thankfully, there is a treatment with an 87-90% cure rate.
The treatment is not a new miracle drug, rather a form of Microbial Restoration Therapy (MRT) known as Fecal Microbiota Transplantation (FMT), the infusion of fecal microbes from a healthy person into the gastrointestinal tract of someone with a C. difficile infection, which restores the gut microbial community and alleviates the symptoms of infection. In a randomized controlled trial there was a 94% overall cure rate with FMT versus a 27% cure rate with antibiotic therapy. Thanks to this research, FMT is now widely considered a safe and effective treatment for C. difficile infections.
As a leading funder of research on IBD, the Rainin Foundation is excited about the benefits MRT, and specifically FMT, could offer the estimated 5 million people worldwide living with IBD.
FMT’s Potential to Treat IBD
Unlike C. difficile infections, the causes of IBD are not yet known. Genetic susceptibility and environmental factors including imbalances in the intestinal microbiota and mucosal immunity are thought to contribute.
Initial studies on the use of FMT in the management of IBD report mixed findings, although systematic reviews of the studies to date report amelioration of IBD symptoms in 62-76% of IBD patients receiving FMT. While these results are promising, a large controlled clinical trial is needed truly understand the benefits and potential risks of FMT for the treatment of IBD, and the Kenneth Rainin Foundation is working to accelerate progress towards this goal.
“We’re inspired by FMT’s enormously positive results in treating C. diff infections,” stated Dr. Jennifer Rainin, CEO of the Kenneth Rainin Foundation. “We need to know whether and how FMT could impact the lives of people living with IBD, and we need a large scale clinical trial to find out.”
The Path to a FMT Clinical Trial
In February 2016, the Foundation convened a panel of academic and industry experts from the field of IBD and MRT/FMT to provide their perspectives and insights on the path to a large-scale clinical trial. OpenBiome, a nonprofit stool bank and FMT information nexus, provided extensive insight on the current research landscape that will be published as a white paper this spring.
The convening was thought provoking, and a great example of an altruistic collaborative brainstorming that occurs too infrequently in science and medicine.
“Our health programs must encourage collaboration to find new and better treatments for IBD,” said Rainin. “So, it was awe-inspiring to witness such brilliant scientists and clinicians working together and asking the big questions and strategizing a path forward for FMT as a potential treatment for IBD.”
- What makes a good donor?
- What is the best way to administer FMT?
- Which IBD patients will respond the best to FMT?
- How will success be measured when using FMT to treat IBD?
We will be working with our panel of experts and our Scientific Advisory Board on next steps, including funding a pilot study to address these questions and forming a consortium of top IBD and MRT/FMT experts to lay the foundation for a properly designed clinical trial. We’re excited to support further exploration of the potential of the human microbiome and MRT/FMT in our efforts to understand and ultimately cure IBD.
Stay tuned for more!