Impacts of smoking on the gut ecosystem and pathogenesis in inflammatory bowel disease

Although smoking is known to be a major risk factor for Crohn’s disease (CD) but not ulcerative colitis (UC), details are uncovered. This study aims to deal with this question.
Metabolome analysis revealed the significant increase in fecal short chain fatty acids (SCFAs) including butyrate and acetate from UC smokers compared to those from UC ex-smokers. Correlation network analysis of metabolites and bacterial OTUs revealed that SCFA-producing bacteria were significantly correlated with butyrate and acetate. We also found that colonic aspirates were enriched with mucosa-associated bacteria. Based on the microbial structures of colonic aspirates, patients were clustered into four groups. Co-abundance groups analysis indicated that one group, Cluster D, had increased abundance of oral bacteria in the colonic aspirates. Compared to non-smokers and ex-smokers, smokers were significantly biased into Cluster D. While the total number of CD4 and CD8 T cells was stable in the small intestine and colon, Th1 and Th17 cells were significantly increased in the colon upon colonization of oral bacteria. Furthermore, the administration of oral bacteria attenuated an UC model oxazolone-induced colitis, whereas exacerbated an CD model TNBS-induced colitis, in mice. These results suggest that smoking might skew intestinal immune responses toward Th1 dominancy by facilitating intestinal colonization of bacteria of oral origin. Our findings may explain the opposite effects of smoking in patients with CD and UC.