Pathophysiology of Autoimmune Diseases and Inflammation

Marla Dubinsky, MD: There’s a proposed hypothesis about IBD [inflammatory bowel disease] that there is genetic susceptibility, meaning that you can’t get IBD or these immune diseases without underlying genetic susceptibility. It’s thought that in these genetically susceptible hosts, there is somewhat of an abnormal immune reaction to what we believe is our own gut flora. So as in other immune diseases, such as diabetes, it’s an immune reaction against the pancreas or the thyroid—for low or high thyroid disease. So there is an organ that is the target.

What’s interesting here is that we’re saying that it’s specifically the bacteria that occupy our microbiome, where there are trillions of bacteria. We believe that there’s an environmental trigger that somehow changes the way our genes view our host bacteria.

There are a lot of theories about the role of the microbiome, which has really become very important in the research space. There are a lot of initiatives that are targeting the microbiome with the idea that the past decade was all about the human genome and finding genetic susceptibility. There are over 250 genes that have now been shown to be associated with IBD, which makes it more complicated. If you have trillions of bacteria and hundreds of genes, and we don’t know what the environmental factor is, it really lends itself to be complicated to focus on cure. That’s why a cure has been difficult to land on. But I think an understanding of all these factors will help us choose better treatment options once we start individualizing therapy based on someone’s underlying genes and microbiome patterns. Maybe if we understand the environmental trigger, we can even think about prevention of disease.