Abstract
Background: Whether a gluten-free diet (GFD) is a cause of irritable bowel syndrome (IBS) remains controversial. We aim at exploring the causal relationship between gluten intake and IBS within Mendelian randomization (MR) design. Methods: We conducted a two-sample MR and selected single-nucleotide polymorphisms (SNPs) associated with GFD as instrumental variables (IVs). SNPs and genetic associations with GFD and IBS were obtained from the latest genome-wide association studies (GWAS) in Europeans (GFD: cases: 1,376; controls: 63,573; IBS: cases:1,121; controls: 360,073). We performed inverse variance weighting (IVW) as the primary method with several sensitivity analyses like MR-Egger and MR-PRESSO for quality control. The above analyses were re-run using another large dataset of IBS, as well as changing the p-value threshold when screening IVs, to verify the stability of the results. Results: The final estimate indicated significant causal association [per one copy of effect allele predicted log odds ratio (OR) change in GFD intake: OR = 0.97, 95% confidence interval (CI) 0.96 to 0.99, p < 0.01] without heterogeneity statistically (Q = 2.48, p = 0.78) nor horizontal pleiotropy biasing the causality (p = 0.92). Consistent results were found in validation analyses. Results of MR Steiger directionality test indicated the accuracy of our estimate of the causal direction (Steiger p < 0.001). Conclusion: GFD might be a protective factor of IBS. Therefore, we suggest taking a diet of lower gluten intake into account in IBS prevention and clinical practice.
Highlights
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with recurrent abdominal pain associated with defecation and bowel habit change (Ford et al, 2020)
In this Mendelian randomization (MR) analysis, we extracted genetic variants that are strongly associated with gluten-free diet (GFD) from open genome-wide association studies (GWAS) as instrumental variables (IVs) and used IVs to replace GFD as new exposures to investigate the causal relationship between GFD and irritable bowel syndrome (IBS)
We found that GFD was associated with a lower risk of IBS, and this causal effect provided evidence for IBS prevention and was valuable for future investigations and clinical practice
Summary
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder with recurrent abdominal pain associated with defecation and bowel habit change (Ford et al, 2020). Dietary modification like a gluten-free diet (GFD) was recommended to relieve their symptoms because of the overlap between IBS and gluten sensitivity (Lahner et al, 2013; De Giorgio et al, 2016); Verdu et al, 2009; Biesiekierski et al, 2011). There is little high-quality evidence exploring the effect of specific diets on IBS (Ford et al, 2020), and whether a causal association between GFD and the development of IBS exists remains unanswered. Whether a gluten-free diet (GFD) is a cause of irritable bowel syndrome (IBS) remains controversial. We aim at exploring the causal relationship between gluten intake and IBS within Mendelian randomization (MR) design
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