Chronic cigarette smoke exposure induces microbial and inflammatory shifts and mucin changes in the murine gut

Abstract

Inflammatory bowel diseases (IBD) are complex multifactorial diseases characterized by an inappropriate host response to an altered commensal microbiome and dysfunctional mucus barrier. Cigarette smoking is the best known environmental risk factor in IBD. Here, we studied the influence of chronic smoke exposure on the gut microbiome, mucus layer composition and immune factors in conventional mice. We compared smoke-exposed with air-exposed mice (n = 12) after a smoke exposure of 24 weeks. Both Illumina sequencing (n = 6) and denaturing gradient gel electrophoresis (n = 12) showed that bacterial activity and community structure were significantly altered in the colon due to smoke exposure. Interestingly, an increase of Lachnospiraceae sp. activity in the colon was observed. Also, the mRNA expression of Muc2 and Muc3 increased in the ileum, whereas Muc4 increased in the distal colon of smoke-exposed mice (n = 6). Furthermore, we observed increased Cxcl2 and decreased Ifn-γ in the ileum, and increased Il-6 and decreased Tgf-β in the proximal colon. Tight junction gene expression remained unchanged. We infer that the modulating role of chronic smoke exposure as a latently present risk factor in the gut may be driven by the altered epithelial mucus profiles and changes in microbiome composition and immune factors.

Chronic cigarette smoke exposure induces systemic hypoxia that drives intestinal dysfunction

“…We have observed substantial changes in microbial populations in the gut with CS exposure and the development of experimental COPD (unpublished data). Others have shown that chronic CS exposure of mice altered microbial gut populations and the expression of mucus genes in the colon (45).…”

Transient Receptor Potential Channels in Intestinal Inflammation: What Is the Impact of Cigarette Smoking?

“…The effect of CS on the colon is ambiguous, even though epidemiological evidence clearly shows a protective effect of CS on UC. The most important effect of CS on the colon is a prominent shift in microbiome composition and activity [138]. To date, the exact mechanisms which underlie the differential effects of CS on CD and UC remain a matter of debate.…”

“…Furthermore, CS alters the production of immune factors in the mouse ileum (increased CXCL2, an IL-8 homolog) and in the proximal colon (increased IL-6) [138]. Therefore, it is likely that CS exerts its effect on gut inflammation via mechanisms similar to the lung, with the levels of similar cytokines (IL-6 and IL-8), chemokines (MCP-1) and receptors (CCR6) being increased by CS [119,143].…”

“…Finally, differences in microbial composition between distinct gut regions and the potential interaction of bacterial components with TRP channels could play a role. CS differentially affects CD and UC, and prominent effects of CS on the microbial composition in the colon have been reported [138,145]. This is particularly interesting as LPS (a component of the microbial cell wall)-TLR4 interactions are able to sensitize e.g.…”

The respiratory microbiome of HIV-infected individuals

“…Smoking has been shown to modulate the microbial composition of the gut mucosa [78, 79]. Given that cigarette smoking has a direct impact on lung mucosal cells, it is likely that smoking could also alter the lung microbiome.…”