Causal effect of smoking status,ruminococcus,IBD:two sample MR study

Smoking influences gut microbiota, particularly Ruminococcus, but its causal role remains unclear. This study investigates the causal effect of smoking on Ruminococcus using Two-sample Mendelian Randomization (MR) and its association with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD).
Methods:
GWAS data were obtained from IEU-GWAS, analyzing a European population (118,419 smokers, 217,605 non-smokers, total N = 336,024, SNPs = 10,894,596). UC cases ranged 208-13,768, controls 935-412,561; CD cases 284-17,897, controls 935-217,852. Ruminococcus data included 8,956 European samples. MR analysis applied IVW as the primary method, with sensitivity analyses (MR Egger, Weighted median, Weighted mode, Leave-one-out).
Results:
1. Smoking and Ruminococcus MR analysis showed a significant causal effect of smoking on Ruminococcus composition:
- Significant associations: 11 (smokers), 15 (ex-smokers), 0 (non-smokers)
- Positive associations: 10 (smokers), 8 (ex-smokers), 0 (non-smokers)
- Negative associations: 1 (smokers), 7 (ex-smokers), 0 (non-smokers)
OTU97_117, TestASV_38, and OTU99_137 significantly increased in smokers (b > 5.0, p < 0.05) but decreased in ex-smokers (b = -1.09, p < 0.05). Further MR analysis showed Ruminococcus reduction was associated with increased UC risk (p = 0.0259), but no significant findings for CD.
Discussion:
These findings align with prior studies suggesting smoking increases CD risk, whereas cessation increases UC risk. The observed increase in Ruminococcus due to smoking may contribute to UC risk upon cessation. Further research using stronger instrumental variables is needed.