Relationship Between <scp>FODMAP</scp> Diet and Irritable Bowel Syndrome: A Mendelian Randomization Study

There is some evidence of a link between fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet and irritable bowel syndrome (IBS). However, few studies have analyzed the relationship between specific dietary intakes and IBS using Mendelian randomization (MR). Exposure and outcome datasets were sourced from the IEU Open GWAS project. Genetic variants significantly associated with 28 dietary intakes at a genome-wide level were selected as instrumental variables. Summary statistics for the target outcome of IBS were obtained with a sample of 187,028 European individuals (4605 cases, 182,423 controls). Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after adjustment for genetic liability to intestinal flora. Genetic predispositions to six of 28 dietary intakes were associated with a decreased risk of IBS, including dried fruit, beef, cereal, lobster/crab, cereal, feta, and coffee, while cherry and poultry intake were associated with an increased risk of IBS. Three of eight associations persisted after adjusting for genetically predicted intestinal flora, and multivariable MR analysis identified that salad/raw vegetable intake was associated with a decreased risk of IBS. Twenty of 28 dietary intakes did not remain significantly associated after adjustment for intestinal flora. This study provides MR evidence supporting causal associations between FODMAP dietary intakes and IBS.