Metabolic syndrome is associated with chronic diarrhea but not chronic constipation: evidence from population-based and Mendelian randomization analyses

Metabolic syndrome (MetS) has been linked to gastrointestinal symptoms, but its associations with chronic diarrhea and chronic constipation remain unclear. This study evaluated the associations of MetS with chronic diarrhea and chronic constipation and assessed potential causal relationships. We analyzed 5,455 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Chronic diarrhea and constipation were defined using stool consistency and frequency. Survey-weighted multivariable logistic regression assessed associations of MetS and its individual components with bowel habits. Bidirectional two-sample Mendelian randomization (MR) was performed using genome-wide association study data. Chronic diarrhea and constipation were present in 8.0% and 9.2% of participants, respectively. After multivariable adjustment, MetS was associated with higher odds of chronic diarrhea (OR 1.35; 95% CI 1.07–1.70; P = 0.010), but not chronic constipation (OR 0.81; 95% CI 0.62–1.06; P = 0.122). The sensitivity analysis with additional adjustment for antidiabetic medication use and average dietary intake from two 24-hour recalls yielded similar findings. Among MetS components, elevated triglycerides and elevated blood glucose were positively associated with chronic diarrhea, whereas high waist circumference was inversely associated with chronic constipation; these associations remained significant after FDR correction. MR analyses showed that genetically predicted MetS was associated with increased odds of chronic diarrhea (OR 1.19; 95% CI 1.09–1.30; FDR-adjusted P < 0.001), but not chronic constipation (OR 1.06; 95% CI 0.94–1.19; FDR-adjusted P = 0.688). Reverse MR found no statistically significant associations of chronic diarrhea or chronic constipation with MetS. Metabolic syndrome was associated with chronic diarrhea but not chronic constipation, supporting a potential link between metabolic health and chronic diarrhea. However, the applicability of these findings beyond U.S. and European-ancestry populations requires further validation.