Autoimmune diseases are poorly understood. The elevator pitch explanation is that your immune system gets confused and overactive, and then attacks your body—a very particular part of your body. Targets range from the intestines (ulcerative colitis and Crohn’s disease) to the pancreas or thyroid and even the melanin complexes in the skin (vitiligo).
But what confuses the immune system?
Genetics plays a role. We saw this first in a family tendency towards certain autoimmune conditions. More recently we’ve connected some autoimmune conditions to specific pieces of genetic code.
There also appear to be various biological triggers: foods, stress, chemicals. Singularly, or in combination, these activate some of the body’s more obscure immune programming, and set it onto a course of self-harm. While some autoimmune processes seem fairly straightforward, what presents as a single autoimmune disorder (say, primary sclerosing cholangitis, which attacks the bile ducts in the liver) appears capable of arising from a wide range of environments.
To me some of the more intriguing evidence for a singular and peculiar role for nightshades in autoimmunity is the complex relationship between tobacco use and the autoimmune diseases ulcerative colitis and Crohn’s disease. Inflammatory bowel disease (IBD) is the umbrella term for ulcerative colitis and Crohn’s disease. While there are rare cases of patients suffering from both disease, typically a person will get one or the other.
Tobacco is a nightshade, and its chemical payload contains multiple chemicals found in other nightshades. And while tobacco use seems to have a protective effect in ulcerative colitis, it appears to exacerbate Crohn’s.
If that observation is true, that means tobacco—a nightshade—is implicated as a variable that helps determine where on the IBD spectrum a patient lands. It may be a trigger, or it may be more complex. “Crohn’s disease (CD) is associated, in some studies, with smoking. Smoking may also have detrimental effects on the clinical course of the disease. In contrast, ulcerative colitis (UC) is largely a disease of nonsmokers or former smokers.”1 This trend is seen in large populations, but the most intriguing data comes from twin studies. These look at twins who have identical genetics, but made different choices when it came to smoking. The unexpected difference in their chances of developing the Crohn’s or ulcerative colitis is what makes tobacco look so interesting.2
Scientists are struggling with results that don’t align perfectly. That’s where meta-analysis comes in. Bundle a bunch of different studies on a related subject and you can sometimes use statistical tools to draw deeper conclusions. A 2006 meta-analysis of 22 studies confirmed that smoking is protective against ulcerative colitis and might even decrease the risk of colectomy after onset. But smoking raises the risk of developing Crohn’s and also worsens its course. Stopping smoking will aggravate ulcerative colitis and improve Crohn’s. The kicker? The data isn’t completely conclusive, and “the potential mechanisms involved in this dual relationship are still unknown.”3
Nicotine is assumed to be the active player, but this is confounded because the same effects are not seen with oral tobacco use. Nicotine might work through a variety of avenues: It may change the immune activity within cells, and/or change the molecular messages between cells. It could change the speed of transit through your intestines, and the permeability of the intestinal barrier.1 Smoking also modifies mucus production in the GI tract and can alter mucosal repair.4 We’ve also learned that smoking can flip multiple genetic switches that affect IBD, what scientists call “strong evidence for a complex modifying role.”5
Other nightshades are implicated in autoimmune conditions such as ulcerative colitis and arthritic pain. And smoking is also implicated in other autoimmune conditions: Graves’ disease, the related Graves’ ophthalmopathy, and rheumatoid arthritis.6
All of this not, ahem, a smoking gun. It’s suggestive science. If there were no other reports of nightshades and autoimmunity, it would remain a complex problem. The possibility that nightshades may be more deeply entwined with some immune processes is an intriguing clue. Interpreting all of this is a job for scientists with the proper tools and training.
NEXT: The Chemical Complexity and Relatedness of Other Nightshades
- “Effect of smoking on inflammatory bowel disease: Is it disease or organ specific?” [↩] [↩]
- “Concordance of Inflammatory Bowel Disease among Danish Twins” [↩]
- “Smoking and inflammatory bowel disease: a meta-analysis.” [↩]
- “Impact of Cigarette Smoking on the Gastrointestinal Tract Inflammation: Opposing Effects in Crohn’s Disease and Ulcerative Colitis” [↩]
- “Genetic Factors Interact With Tobacco Smoke to Modify Risk for Inflammatory Bowel Disease in Humans and Mice” [↩]
- “Lessons learned from twins in autoimmune and chronic inflammatory diseases” [↩]
