Why Smoking Helps Ulcerative Colitis but Harms Crohn’s Disease

A strange paradox has baffled doctors for decades. Smoking increases the risk of Crohn’s disease, yet it protects people with ulcerative colitis. Now, researchers at the RIKEN Center for Integrative Medical Sciences in Japan have discovered why. The study, published August 25 in Gut, shows that tobacco metabolites allow bacteria from the mouth to migrate and thrive in the gut lining, where they trigger an immune shift that eases colitis inflammation. The findings open a path to safer treatments that mimic the effect of smoking without its deadly risks. For more background, see this overview of smoking and inflammatory bowel disease.

From Mystery to Mechanism

Ulcerative colitis and Crohn’s disease are both forms of inflammatory bowel disease, but their immune profiles differ. Ulcerative colitis is driven by an overactive Th2 immune response in the colon, while Crohn’s is linked to Th1-mediated inflammation. For decades, clinicians observed that smoking made Crohn’s worse but paradoxically improved ulcerative colitis symptoms.

The RIKEN team, led by Hiroshi Ohno, combined patient samples and mouse experiments to explain this contradiction. They found that smokers with ulcerative colitis carried unusual populations of oral bacteria, such as Streptococcus mitis, living in the colonic mucosa. Ex-smokers did not. For a broader perspective on smoking’s contrasting effects in Crohn’s disease and ulcerative colitis, see this review in Frontiers in Immunology.

How Smoking Changes the Gut

To understand why these bacteria colonized the gut lining, the researchers analyzed metabolites in the intestinal environment. They identified hydroquinone, a smoking-related aromatic compound, as a key factor. In mice, hydroquinone promoted the growth of Streptococcus in the gut mucosa.

This bacterial presence shifted the immune response. Instead of an unchecked Th2 reaction, the colon recruited Th1 helper cells in response to S. mitis. That immune shift helped suppress colitis inflammation but aggravated Crohn’s disease, where Th1 cells already dominate.

“Our results indicate the relocation of bacteria from the mouth to the gut, particularly those of the Streptococcus genus, and the subsequent immune response in the gut, is the mechanism through which smoking helps protect against the disease,” says Ohno.

Recreating the Effect Without Cigarettes

Because tobacco smoke carries enormous risks for cancer, cardiovascular disease, and premature death, the researchers stress that smoking itself cannot be a therapy. Instead, their work suggests alternatives:

• Prebiotics or supplements that mimic hydroquinone’s ability to foster beneficial Streptococcus growth in the gut
• Probiotic therapies using live S. mitis to induce protective Th1 activity in ulcerative colitis patients
• Personalized microbiome interventions that account for the contrasting effects in Crohn’s versus colitis

Key Findings

• Sample: Human ulcerative colitis patients and mouse models studied
• Location: RIKEN Center for Integrative Medical Sciences, Japan
• Mechanism: Smoking-derived hydroquinone promoted oral Streptococcus colonization in the colon
• Immune Effect: S. mitis activated Th1 cells, suppressing colitis-linked Th2 responses but worsening Crohn’s
• Therapeutic Potential: Hydroquinone-like prebiotics or S. mitis probiotics could replicate benefits without smoking

Takeaway

Smoking protects against ulcerative colitis by enabling oral Streptococcus bacteria to colonize the colon and trigger an immune shift that reduces inflammation. The discovery opens the door to prebiotic or probiotic treatments that capture this benefit without the lethal harms of tobacco.

Journal: Gut
DOI: 10.1136/gutjnl-2025-334922