Smoking Differentially Alters the Microbiome Depending on the Type of Inflammatory Bowel Disease

Abstract

The gut microbiome plays a pivotal role in the development and progression of inflammatory bowel disease (IBD), with environmental factors such as smoking significantly influencing disease outcomes. Smoking has been shown to have contrasting effects on Crohn’s disease (CD) and ulcerative colitis (UC), exacerbating inflammation and disease severity in CD while appearing to have a protective effect in UC. However, the specific effects of smoking on gut microbial diversity, composition, and its contribution to disease pathogenesis remain poorly understood. Previous studies have highlighted changes in microbial diversity and shifts in specific taxa associated with smoking, but findings are inconsistent, and the regional effects across the gastrointestinal tract are underexplored. This study investigates the impact of smoking on microbial diversity, composition, and inflammation in CD and UC across different gastrointestinal regions. Our analysis revealed no significant effect of smoking or inflammation on overall gut microbial diversity. However, smoking and IBD status significantly influenced microbial beta diversity, with smokers showing distinct shifts in microbial diversity compared to non-smokers. Unique microbes were identified in smokers, with Bacteroidaceae, Peptostreptococcaceae, and Lachnospiraceae uniquely present in UC smokers while Ruminococcaceae was unique to CD smokers. In UC, Tannerellaceae and Peptostreptococcaceae were enriched in smokers, potentially contributing to disease-specific microbial changes, while Oscillospiraceae showed reduced abundance. Regionally, condition-specific microbial diversity patterns were observed. Smokers with CD exhibited higher diversity in the ascending and descending colon but lower diversity in the transverse colon. Conversely, smokers with UC exhibited reduced diversity in the sigmoid colon. These findings provide novel insights into how smoking influences the gut microbiome in IBD, emphasizing the complex interplay between environmental factors, microbial diversity, and disease mechanisms. This work underscores the importance of targeting the microbiome in developing personalized therapeutic strategies for CD and UC.