Cross-talks Between Gut Microbiota and Tobacco Smoking: A Two-Sample Mendelian Randomization Study

Abstract

Abstract Considerable evidence has been reported that tobacco use could cause alterations in gut microbiota composition. The microbiota-gut-brain axis also in turn hinted at a possible contribution of gut microbiota to smoking. However, population-level studies with a higher evidence level for causality are lacking. This study deployed two-sample bidirectional Mendelian randomization (MR) design to reveal the causal association between gut microbiota and tobacco smoking. The summary-level data of genome-wide association studies (GWAS) for 211 gut microbial taxa and five smoking phenotypes were acquired from meta-analyzed datasets with totally 1.7 million European ancestry-dominated samples. Our MR results confirmed the effects of smoking on three taxa (Intestinimonas, Catenibacterium, and Ruminococcaceae, observed from previous studies) with boosted evidence level and identified another thirteen taxa which may be causally affected by tobacco smoking. As for the other direction, we revealed that smoking behaviors could be potential consequence of taxa abundance. Combining with existing observational evidence, we provided novel insights regarding a positive feedback loop of smoking addiction through Actinobacteria and indicated a potential mechanism for the link between parental smoking and early smoking initiation of their children driven by Bifidobacterium. In summary, the current study suggested a substantial role of the intestinal microbes on the risk for cigarette smoking, and in turn smoking on intestinal microbes. Our findings highlighted the hazards of tobacco use for gut flora dysbiosis and shed light on the potential role of gut microbiota for tobacco control.