It is well known that cigarette smoking makes Crohn's disease worse. Is it the nicotine or the toxins, or both?

Question

It is well known that smoking increases both the severity and frequency of flares in people with Crohn's disease. What is not clear is whether that is due to the nicotine or the thousands of other toxins in cigarette smoke. A cursory search only returns studies which show that smoking cigarettes makes Crohn's worse. I can't find any studies on the topic of whether alternative nicotine delivery methods (such as e-cigarettes) makes Crohn's worse, but if anyone can find some then that would form part of an ideal answer.

As a side note, we know that nicotine tends to actually improve symptoms in Ulcerative Colitis, the other form of inflammatory bowel disease. We know in this disease that this is due to the nicotine and not the other toxins in cigarette smoke, because there are plenty of studies (for UC only) that can be easily found linking the use of nicotine patches to an improvement in symptoms.

Further reading:

Role of smoking in inflammatory bowel disease: implications for therapy

Nicotine treatment for ulcerative colitis

Note: Even though I have already accepted an answer for this question, new studies are done all the time and I would be highly interested in and upvote any other answers that are added which contain more studies on this topic.

Answer 1

As suggested by one small human study and one study in mice, nicotine might improve Crohn's disease in the colon but aggravate Crohn's disease in the small intestine.

Nicotine Enemas for Active Crohn's Colitis: An Open Pilot Study (Hindawi, 2008)

Thirteen patients with active rectosigmoid Crohn's diseae...were given 6 mg nicotine enemas, each day for 4 weeks... Mean Crohn's disease activity index (CDAI) decreased from 202 to 153—the score was reduced in 6 patients, unchanged in 3, and increased in one. Frequency of bowel movements decreased in 8 patients and the sigmoidoscopy grade was reduced in 7.

In a study in mice (PubMed, 2002) with chemically induced inflammatory bowel disease, nicotine (added into the drinking water) treatment improved inflammation of the colon but aggravated inflammation of the jejunum (a part of small intestine).

This evidence if far too weak to make any conclusions/recommendations but suggests that differences in the nicotine effect might be due to disease location (Effect of smoking on inflammatory bowel disease: Is it disease or organ specific? - PubMed, 2007).