Smoking and IBD

By Wayne Persky

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For decades, physicians have puzzled over the contradictory effects of smoking on inflammatory bowel diseases (IBD). Smoking makes Crohn’s disease worse, but appears to protect against ulcerative colitis (UC). Recent research from RIKEN has uncovered a surprising mechanism: smoking alters the gut environment in a way that allows oral bacteria such as Streptococcus mitis to colonize the colon, where they shape the immune response (Miyauchi et al., 2025).1 These findings may help guide the development of safer therapies for colitis and may also shed light on the inflammation associated with microscopic colitis (MC).​

The study found that:

1. Smoking reshapes the gut microbiome via metabolites.

Smoking produces metabolites such as hydroquinone, which allow oral bacteria, particularly Streptococcus mitis, to take hold in the colonic mucosa. This effect was seen in smokers with UC, but not in ex-smokers, suggesting the change depends on ongoing exposure to smoking compounds.

​2. Oral bacteria influence immune responses.

When S. mitis was introduced into mouse models:
​

• It reduced inflammation in ulcerative colitis.
• It worsened Crohn’s disease, due to the way Th1 immune pathways were activated.
• This explains the long-standing paradox of smoking’s opposite effects in UC and Crohn’s.

​3. Immune modulation is key.

In UC, inflammation is largely driven by Th2 immune responses, so activating Th1 cells creates a balancing effect that reduces inflammation. In Crohn’s, which already involves Th1-driven inflammation, the effect piles on more damage.​

Similar to MC, Crohn’s disease (CD) can affect any part of the gastrointestinal tract, but in practice it shows a fairly typical pattern of distribution. Large cohort studies (including European and North American IBD registries) give us good estimates of how often each region is involved.

​Statistics show that for Crohn's disease (at diagnosis):

• The colon only is involved in about 20–25% of cases.
• Ileocecal/ileocolonic disease involves both the ileum and the colon for 30–40% of cases.
• The ileum (terminal ileitis) is involved in 30–40% of cases.
• Isolated jejunal disease occurs in only 3–5% of cases, but jejunal involvement may occur in up to 15% when combined with ileal disease.
• The duodenum is involved in only 3–5% of cases for adults, but rates are slightly higher for pediatric cases.

UC is very different, because it:
​

• Always starts in the rectum (proctitis).
• Extends proximally in a continuous fashion (no skip lesions, unlike Crohn’s).
• Only affects the colon and rectum (never the small intestine, except for mild “backwash ileitis” in some severe pancolitis cases).

For UC, statistics show that:

• Ulcerative proctitis (rectum only) is present in 30–35% of cases.
  
• ​Symptoms: rectal bleeding, urgency, tenesmus, mucus in stool.
  
• Left-sided colitis (rectum (sigmoid, or escending colon) up to the splenic flexure) is present in 30–40% of cases.
  
• Extensive colitis (beyond splenic flexure, up to transverse colon but not entire colon) is present in 15–20% of cases.
  
• Pancolitis, involving the entire colon from rectum to cecum is involved in 15–20% of cases.

​How does MC compare with these?

Similar to Crohn's disease, MC can affect (cause the inflammation of) any organ in the gastrointestinal tract. Although you won't find many references to small intestinal involvement for MC in recent research, many credible, older pathology-focused studies reported frequent small intestinal involvement, especially involving the terminally ileum.

Most modern reviews incorrectly refer to MC as a disease of the colon. Why is small bowel involvement ignored in most current literature discussing MC? With such biased treatment, it's no wonder gastroenterologists are confused about MC and its treatment.

In 2003, for example, Nature published a research study in its Modern Pathology series, showing that 78% of lymphocytic colitis patients and 50% of collagenous colitis cases (versus 9% of controls) had intraepithelial lymphocytosis (lymphocytic infiltration) of their terminal ileum (Padmanabhan, Callas, Li, and Trainer, 2003).2

That article also mentions duodenal and jejunal changes in subsets of MC patients, and summarizes prior literature describing abnormal duodenal and jejunal findings, including villous atrophy and collagen deposition in some MC patients, again pointing to small bowel immune activation in a fraction of MC cases.

How might this research relate to MC?

• Obviously, MC shares features with both UC and Crohn’s.
• Like UC, MC always involves inflammation of the colon.
• Like Crohn’s, MC may affect any organ in the gastrointestinal tract, and it may involve immune dysregulation triggered by environmental or microbial factors.

Experiences shared by MC patients on our discussion and support forum suggests that bacteria commonly found in the mouth, and sometimes trapped by dental procedures (such as root canals) can contribute to MC flares if they reach the gut. The studies suggest that immune balance between Th1 and Th2 cells is critical. MC has been linked to abnormal T-cell activity, so understanding whether S. mitis–like bacteria can shift this balance is highly relevant.

The bottom line:

The discovery that smoking promotes oral bacteria growth in the gut, altering immune pathways in opposite ways for Crohn’s disease and ulcerative colitis, solves a decades-old puzzle in gastroenterology. For MC patients, these findings highlight the importance of the microbiome-immune connection, and point toward new therapies that could harness microbial modulation—without the dangers of smoking.

However, in the absence of dedicated research data, definite conclusions regarding MC, cannot be drawn. We know that when medical discoveries revealed the extent of the risks associated with smoking, many people who stopped a long-term smoking habit developed MC (almost surely due to the stress that resulted). But the unanswered question remains — “Does MC more closely resemble Chron's, or UC?” The evidence suggests that it more closely resembles Crohn's, than UC, but without compelling evidence, we can't be sure.​

And as we all know as MC patients, what works for some, does not work for all. So there is a possibility that this line of research may well lead to treatments that benefit some of us, but worsen symptoms for others.

References:

1. Miyauchi, E., Taida, T., Uchiyama, K., Nakanishi, Y., Kato, T., Koido, S., . . . Ohno, H. (2025). Smoking affects gut immune system of patients with inflammatory bowel diseases by modulating metabolomic profiles and mucosal microbiota. Gut, Published Online First Retrieved from https://gut.bmj.com/content/early/2025/08/06/gutjnl-2025-33492

2. Padmanabhan, V., Callas, P. W., Li, S.. C., and Trainer, T, D. (2003). Histopathological Features of the Terminal Ileum in Lymphocytic and Collagenous Colitis: A Study of 32 Cases and Review of Literature. Nature Modern Pathology, 16. pp 115–119. Retrieved from https://www.nature.com/articles/3880725