Factors and Exposures Linked to Autoimmune Diseases

Marla Dubinsky, MD: What are patients doing? What does the environment around them look like that actually puts them at risk for developing an IBD [inflammatory bowel disease]? The same would probably apply with other autoimmune diseases. Is there, again, that allusive environmental trigger? We don’t know for sure, but this is what has been proposed: Anything that can sort of impact the integrity of the bowel wall, where the bacteria are able to sneak into the mucosa and create that inflammatory response that goes unchecked when you have a gene. It makes sense to think about things that could impact the permeability or the integrity of the bowel wall. Nonsteroidal anti-inflammatories, for example, have been proposed to be something that changes the lining or the integrity or the mucous layer, which opens up the cells for bacteria to invade. So we always ask patients about their history with nonsteroidal anti-inflammatories.

Antibiotic exposure is probably one of the more exciting things that people are chasing because it will change the microbiome. And again, if you change your flora that you are born with and then sort of settle into within the first 3 years of life, that’s the proposed time frame for which you actually acquire your adult microbiome.

For children with earlier onset of IBD, we often focus on the first 2 years of their life. Did you get antibiotics that can change the flora? The answer is yes. Epidemiology studies have shown that children who have received multiple courses of antibiotics are at risk for getting IBD. In adults, it looks as if antibiotic exposure within the year preceding the diagnosis increases the rate of diagnosis.

The gene had to be there, so it’s not as if it’s a random event. Any of us who took antibiotics, if we don’t have the gene, I don’t think that’s going to be the result. So you have to understand what the susceptibility genes are. In those individuals, should you avoid antibiotics? Obviously if they need antibiotics, they do. But for a random ear infection that is probably viral, in pediatric patients, in particular, it may be helpful to limit the exposure to antibiotics. And so, anything that changes the microbiome could affect the invasion of the microbiome in a genetically acceptable host.

Diet—that’s a big topic. How is diet actually changing the microbiome? There are proposed foods that are high in simple sugars. The idea is that sugar is a food that’s very attractive to bacteria in our gut, and it creates hydrogen and metabolites that may be lacking short-chain fatty acids, which has actually been proposed as a protective barrier in the gut. So foods that are low or that ignite a change in the short-chain fatty acid production may impact, again, the permeability of the gut and the bacteria will thus invade. So there are factors that we believe are involved. But again, without a gene, I’m not sure it’s that relevant. We’re not exactly sure what it’s doing to the microbiome.

Smoking is another possible risk factor, especially for Crohn disease. But in ulcerative colitis, it’s protective. Researchers even looked at using nicotine patches in the role of ulcerative colitis. I am not stating that we’re proposing that everyone should smoke, but there has been this idea that nicotine is actually protective in patients with uncontrolled disease, which is interesting. When people were told, later in life, to stop smoking for cardiac reasons or for other reasons, there was a second peak in ulcerative colitis, which is interesting. But in Crohn disease, it actually causes more severe disease, an increased rate of surgery, and an increased risk of disease.