Why Smoking Surprisingly Soothes Ulcerative Colitis Symptoms

Few truths are more universally acknowledged than the fact that smoking poses a serious threat to human health. Smoking cigarettes significantly increases a person’s risk of developing cancer, cardiovascular diseases, and respiratory illnesses, killing seven million people worldwide each year.¹ Paradoxically, smoking is beneficial to individuals suffering from ulcerative colitis, a type of inflammatory bowel disease wherein the immune system mistakenly attacks healthy intestinal tissue. This chronic condition causes symptoms such as abdominal pain, diarrhea, weight loss, and fatigue. However, smoking reduces the intensity and frequency of flare-ups.²

“Smoking is, of course, bad. But for ulcerative colitis, somehow smoking helps to improve the disease states,” said Hiroshi Ohno, an intestinal immunologist at the Institute of Physical and Chemical Research, Japan. “It’s an enigma.”

For over 40 years, scientists and clinicians have observed that people who smoke have lower chances of developing ulcerative colitis compared to those who have never smoked in their lives. What’s more, they also noticed that individuals with the disease who gave up smoking experienced worsening of their condition.³ Contrastingly, smoking aggravates Crohn’s disease, another type of inflammatory bowel disease.

“Often, you'll get a story when you talk with [ulcerative colitis] patients that they quit smoking months, or a year ago, and that's when their flare started. We’ve never really been able to explain why that is,” said Gil Kaplan, a gastroenterologist at the University of Calgary who studies the global epidemiology of inflammatory bowel disease.

Now, in a new study, Ohno and his colleagues provided some answers. By examining the intestinal microbiota of people with inflammatory bowel disease, the team showed that smoking produces metabolites that encourage certain bacteria from the oral microbiome to settle in the gut. There, the invaders trigger immune responses that dampen ulcerative colitis, but exacerbate Crohn’s disease.⁴ These findings, published in the journal Gut, could lead to metabolite-based therapies that could mitigate inflammation in patients and reduce their reliance on smoking to keep the disease in check.

“We’ve known that there's something in the microbiome that's different between smokers, non-smokers, and people who quit smoking. But I think this is probably one of the first studies that eloquently does a series of experiments to elucidate how this might happen,” said Kaplan, who was not involved in the study.

One of the more established triggers of inflammatory bowel disease is a change in the gut bacterial composition and the associated metabolites.⁵ Considering that cigarette smoking and its cessation can contribute to this alteration, Ohno and his team speculated that smoking might differentially affect Crohn’s disease and ulcerative colitis through the gut microbiome.⁶

To test this theory, the researchers recruited patients with both conditions, including those who never smoked in their life, quit smoking, or were still smoking during the study. The researchers analyzed the participants’ gut mucosal microbiota—bacteria closely associated with the inner lining of the colon—in colonoscopically collected samples. They observed that certain oral bacterial, such as Streptococcus, populated the gut microbiome of smokers with both ulcerative colitis and Crohn’s disease. The microbiota composition of those who quit smoking did not show this change.

“This was highly surprising,” said Kaplan. “I didn't realize that in individuals who smoke, you actually get the promotion of these oral bacteria in the colon.”

How did the arrival of these unexpected guests alter the gut? To answer this, Ohno and his team examined bacterial metabolites in the patients’ feces. People with ulcerative colitis who smoked had higher abundance of short-chain fatty acids, such as acetate and butyrate, compared to those who quit smoking. Crohn’s disease patients showed a similar trend. Various aromatic compounds, such as hydroquinone and catechol, were also present in higher quantities in the fecal samples of ulcerative colitis patients who smoked, compared to those who stopped.

Since hydroquinone is found in high concentrations in cigarette smoke, the scientists wondered if it helped Streptococcus home to the colon. When they administered the compound to mice, they observed an increase in the abundance of Streptococcus in the gut mucosa. Teasing this apart further, Ohno and his team tested how different strains of the bacteria affected animal models of the two types of inflammatory bowel disease. They reported that inoculating mice with Streptococcus mitis suppressed inflammation in ulcerative colitis and enhanced it in Crohn’s disease, replicating the effects of smoking.

To understand the reason for these contrasting effects, Ohno and his colleagues examined how these bacteria affected the immune system in mice models of inflammatory bowel disease. Colonization of the mice guts with S. mitis triggered the production of the immune cells T helper-1, in both models. These cells are known to cause Crohn’s disease, providing hints about why smoking aggravates the condition’s symptoms. Ulcerative colitis, on the other hand, is caused by T helper-2 cells, which get suppressed by the oral bacteria-induced immune reaction.

Kaplan thinks that these findings lay the foundation for developing new treatments for ulcerative colitis, ranging from diets that promote the secretion of beneficial compounds to creating therapeutic microbiomes, that might allow people to stop smoking in a safe manner.