TOPLINE:

Smoking affects the immune system of patients with inflammatory bowel disease (IBD) by modulating gut metabolite profiles and mucosal microbiota, potentially explaining why smoking is harmful in Crohn’s disease (CD) while beneficial in ulcerative colitis (UC).

METHODOLOGY: 

• The underlying mechanisms for why smoking exerts opposing effects on UC and CD remain unclear.
• To investigate, researchers analyzed saliva, fecal, and colonic mucosal microbiota in people with IBDD, categorized by smoking status (never, former, or current smokers), and healthy controls.
• They assessed the effects of smoking-associated bacteria on the gut immune system and colitis using germ-free mice and murine models of UC and CD. 

TAKEAWAY:

• Major short-chain fatty acids, such as acetate and butyrate, which play a key role in preserving the intestinal barrier and exerting anti-inflammatory effects, were increased in feces of UC smokers versus quitters. Similar trends were seen in CD, but the number of patients with CD was small, limiting conclusions.
• Aromatic compounds found in cigarette smoke, including hydroquinone, were significantly elevated in smokers with UC and promoted colonization of oral bacteria such as Streptococcus mitis in the colonic mucosa.
• Colonization of germ-free mice with S mitis increased T helper type 1 and interferon-gamma producing CD8 T cells, attenuated inflammation in UC models, and worsened inflammation in CD models. 

IN PRACTICE:

“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 [UC]. 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,” author Hiroshi Ohno, MD, PhD, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, said in a statement. 

SOURCE:

The study was published online August 25 in Gut. 

LIMITATIONS:

A major limitation is the relatively small number of patients with CD, due to its lower prevalence in Japan, limiting the statistical power for CD-specific analyses. Mouse models only partially recapitulate human IBD, particularly in terms of chronicity and epithelial barrier dysfunction. Medication use and time since disease flare were not comprehensively recorded.

DISCLOSURES:

The study had no commercial funding. The authors declared no relevant conflicts of interest.