Smoking has well-established detrimental effects on CD, but the biological mechanisms for this association are not clear. This study showed that gut microbial gene richness, genus diversity and species diversity were reduced in smokers with CD as compared with nonsmokers with CD. The microbial profile also differed between these groups regarding the relative abundance of bacterial taxa, including decreased proportions of the genera Collinsella, Enterorhabdus, and Gordonibacter among smoking patients. These findings indicate that an altered gut microbiota may underlie the association between smoking and CD.
Phylogenetic diversity and gene richness of the intestinal microbiome are consistently linked to human health and disease.9,11,30,31 An overall decrease in these ecological measures has been associated with a variety of disorders, including IBD and CD in particular.9,32–35 The observed reduction in gut microbial diversity among smokers in our study is in line with the general perception that this feature is related to an unhealthy state. Accordingly, a greater perturbed microbiota in smoking patients with CD could possibly more readily predispose to the development of disease activity in comparison with nonsmoking patients with CD.
Although not reaching statistical significance after correction for multiple testing, a difference was also observed in the relative abundance of microbes previously implicated in CD. This included a consistent decrease in proportions of A. muciniphila,49,50B. pullicaecorum,51 and F. prausnitzii among smoking patients.52,53 As studies have shown that these bacteria can exert anti-inflammatory effects, this could further support the hypothesis of microbes mediating the adverse effects of smoking in CD.
Previous studies examining the impact of smoking on the gut microbiota are limited, especially in patients with CD. An elegant, interventional study, in which healthy smoking individuals underwent controlled smoking cessation, showed significant alterations in the fecal microbiota, including an increase in Actinobacteria (high guanine and cytosine content bacteria and Bifidobacteria) and a decrease in Bacteroidetes (Prevotella spp. and Bacteroides spp.).16,17 A higher number of Prevotella spp. and Bacteroides spp. (combined) was also found to be associated with smoking in a study reporting on the effects of smoking in patients with active CD.18 Using a whole-metagenome shotgun sequencing, we were able to assess the relative abundance of these bacterial taxa separately, finding a reduced proportion of the Bacteroides genus (unadjusted P = 0.01), but not the Prevotella genus (unadjusted P = 0.59). A few studies also documented associations for F. prausnitzii and the genus Anaerostipes with smoking in CD.18,54,55 Collectively, our data partly confirm and expand on previous studies. Although it remains to be established how smoking might affect the composition of intestinal microbes, these results emphasize that differences in the gut microbiome may be involved in the deleterious effects of smoking in CD.
A significant advantage of this study over previous studies was the metagenomic approach, which allowed us to evaluate the whole gut microbial community rather than targeting (specific) 16S rRNA sequences. Moreover, this technique offered a full quantitative assessment of the gut microbiome. To minimize the influence of disease activity, we only included patients who were either in endoscopic remission or had low fecal calprotectin levels.
This study was limited by the relatively small sample size, which might have resulted in a lack of statistical power to identify more minor but potentially biologically relevant microbial differences. However, the use of a matched design does result in a more powerful study and reduces the risk of identifying confounding variables, although data on diet or other lifestyle factors possibly associated with smoking were not at our disposal. Furthermore, the smoking status of patients was not extensively evaluated. Self-administered questionnaires may carry a risk of misclassification, but previous studies showed that self-reported data on smoking behavior were fairly accurate.56,57
To conclude, we demonstrated that gut microbial gene richness, genus diversity, and species diversity were decreased in smokers with CD as compared with nonsmokers with CD. This was accompanied by differences in the relative abundance of bacterial taxa, including reduced proportions of the genera Collinsella, Enterorhabdus, and Gordonibacter. In future, larger studies need to evaluate whether intestinal microbes mediate the adverse effects of smoking in CD.
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