For more than 40 years, doctors have noticed a strange medical mystery: people who smoke are less likely to suffer from ulcerative colitis, a painful disease that causes inflammation in the large intestine.
But scientists haven’t understood why—until now. New research from Japan has uncovered the reason and may lead to safer treatments without the harmful effects of smoking.
The study, led by Hiroshi Ohno from the RIKEN Center for Integrative Medical Sciences and published in the journal Gut, reveals that smoking helps certain bacteria from the mouth move into the intestines, where they help calm the immune system and reduce inflammation in people with ulcerative colitis.
Ulcerative colitis is one of two major types of inflammatory bowel disease (IBD), the other being Crohn’s disease.
Both cause symptoms like stomach pain, diarrhea, and weight loss, but they affect different parts of the digestive system and involve different immune responses.
Interestingly, smoking makes Crohn’s disease worse but seems to protect against ulcerative colitis.
To find out why, researchers studied people with ulcerative colitis who were smokers and non-smokers, as well as mouse models of both ulcerative colitis and Crohn’s disease.
They found that smokers with colitis had bacteria in their intestines that are usually only found in the mouth, such as Streptococcus.
These bacteria were found in the inner lining of the colon, where they don’t usually live. Ex-smokers didn’t have these bacteria in their gut linings, suggesting that smoking somehow allows them to stay in the gut.
The team then looked at the chemicals in the gut called metabolites, which are small substances made when food is digested. They found that smokers with ulcerative colitis had higher levels of certain metabolites, especially one called hydroquinone.
In experiments with mice, hydroquinone helped the Streptococcus bacteria grow and settle in the mucus that lines the intestines.
The researchers also tested whether these mouth bacteria could help treat colitis without smoking. They isolated 10 strains of Streptococcus from the saliva of smokers and gave them to mice with ulcerative colitis or Crohn’s disease.
One strain in particular, called Streptococcus mitis, reduced inflammation in mice with ulcerative colitis. However, it made inflammation worse in mice with Crohn’s disease.
Further testing showed that S. mitis activated special immune cells in the gut called Th1 cells. In Crohn’s disease, these cells already cause too much inflammation, so adding more made things worse. But in ulcerative colitis, Th1 cells fight against the initial inflammation caused by another set of immune cells (Th2), so they help reduce symptoms.
This breakthrough explains why smoking seems to help people with ulcerative colitis—but it also shows why smoking is not a good treatment. Smoking causes cancer, heart disease, and many other serious health problems.
Instead, the researchers suggest that using the helpful bacteria directly, or using hydroquinone as a prebiotic to help those bacteria grow in the gut, could offer the same benefits as smoking without the risks.
“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.
“Logically, direct treatment with this kind of bacteria, or indirect treatment with hydroquinone, is thus likely to mimic the beneficial effects of smoking but avoid all the negative effects.”
The study is published in Gut.
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