Niha Zubair, Arivale Clinical Research Scientist, PhD
An increasing number of people in the United States are suffering from Crohn’s disease, one of the most common types of Inflammatory Bowel Disease (IBD).
A big question is why.
If researchers could only unravel what causes this devastating disease, they would be that much closer to a cure. Fortunately, unprecedented breakthroughs in genomics and gut microbiome analysis may finally provide Crohn’s researchers with some answers they’ve long been seeking.
Your Gut, Your Genes, and Crohn’s Disease
How do genes influence your gut? Two recently published studies in Crohn’s disease patients give clues to the ways our genetics and gut interact to create both health and disease.
Results from these remarkable studies provide powerful insights into what causes Crohn’s disease and also offer hope that microbiome-modulating therapies could hold the key to ending patients’ suffering.
Before we dive into the studies, it’s important to note that through extensive genetic and microbiome research in Crohn’s patients, two things are now widely accepted:
Genetic factors play an important role in Crohn’s disease, and with Crohn’s, the diversity of the gut microbiome is reduced.
With that in mind, let’s discuss the new research.
Designed to gain more insight into how genes and the microbiome interact in Crohn’s disease, our first study consisted of a team of more than thirty researchers from around the world, including the University of Pittsburgh, Cedars-Sinai Medical Center, and the University of California Los Angeles.1 Their goal was to discover whether Crohn’s disease alters the gut bacteria, or whether pre-existing alterations in gut bacteria increase risk for Crohn’s disease.
The study performed genotyping in 10,523 IBD cases and 5726 non-IBD controls. The team identified a close association between Crohn’s disease and a variant (rs13107325) in the SLC39A8 gene—the same variant that has previously been associated with other diseases, including obesity.
Next, they analyzed the gut microbiomes of people with this genetic variant and determined that the variant is directly associated with lower microbial diversity.1
People with this specific variant—whether healthy, overweight, or suffering from Crohn’s disease—all had a reduction in the abundance of hundreds of minor species of gut bacteria. Many of the species may play key roles in protecting the intestines against Crohn’s disease, as well as protecting against obesity.
Although this doesn’t prove causation, it does suggest that this genetic variant may lead to a shift in the gut microbiome that could explain its effects on Crohn’s disease, obesity, and possibly even other diseases.
Arivale does not currently report on this variant in the SLC39A8 gene to Pioneers because the clinical evidence is not yet strong enough to meet our robust standards. However, that time may soon come.
Fortunately, discoveries on the remarkable interactions between the genome and the microbiome such as this are likely to accelerate the research. Arivale scientists and clinicians are currently poring over the recently-published research and, in addition to reporting more genetic and microbiome information to Pioneers, they are in the early stages of making unique and exciting discoveries on the genome/microbiome connection.
The Discoveries Continue
Another recently published study on Crohn’s and the microbiome sheds light on a different, but equally fascinating, aspect: the interactions that occur between specific microbial species in the gut.2
It turns out, it’s not only bacteria that we harbor in our guts, but fungi too. A team made up of scientists from France, Belgium, and the United States made a groundbreaking discovery about a strong fungal-bacterial interaction in those with Crohn’s disease.2
They identified a threesome characterized by two bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis) which takes on a life of its own once joined. This unique trio forms a biofilm—an incredibly sticky, slimy, thin layer that adheres to the intestines and can be incredibly inflammatory, causing damage to tissues and provoking a strong immune response.
Unfortunately, this biofilm is also typically very resistant to the immune system’s attempt to break it up. Crohn’s patients in the study had significantly higher numbers of all three of these interacting microbes. They also had fewer beneficial bacteria—a finding that is consistent with the previously discussed study as well as with additional research.
While Arivale does not currently collect fungal data from Pioneers, if the evidence base for fungal-bacterial interactions grows, Arivale may begin identifying and quantifying the fungi in Pioneer’s gastrointestinal tracts.
Taken together, the groundbreaking findings from these two studies add significant new information to understanding the important interconnections between genes, the gut microbiome, and Crohn’s disease.
It’s important to keep in mind that correlation does not prove causation. As the research base continues to grow, Arivale’s scientists and clinicians look forward to the exciting discoveries on the horizon.
Using a systems approach that takes the genome and microbiome into account, we may soon reach the point where we can better predict and treat Crohn’s disease and other medical conditions.
- Li, Dalin, et al. “A pleiotropic missense variant in SLC39A8 is associated with Crohn’s disease and human gut microbiome composition.” Gastroenterology 151.4 (2016): 724-732.
- Hoarau, G., et al. “Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease.” mBio 7.5 (2016): e01250-16.