Causal relationship between gut microbiota and constipation: a two-sample Mendelian randomization study

Abstract

Background As one of the most common gastrointestinal disorders, recent study has shown that dysfunction in the gut microbiota might lead to constipation. However, the causality between the gut microbiota and constipation is unclear. Methods Genome-Wide Association Studies (GWAS) used to obtain the summary-level data of constipation through IEU OpenGWAS database, and constipation was used as outcome. In addition, MiBioGen was used to gain the summary data of gut microbiota, including Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella, which were used as exposure factors. Univariable Mendelian randomization (MR) analysis was used to evaluate the causality of gut microbiota on constipation. In briefly, Inverse-variance weighted (IVW) method was regarded as a main method to estimate the causality of gut microbiota and constipation, and supplemented by other four methods, including MR-egger, Weighted median, Simple mode and Weighted mode. Finally, funnel plot, heterogeneity test, horizontal pleiotropy test and leave-one-out test were used to evaluate the reliability of MR results. Results Ruminiclostridium 9 and Intestinibacter were causally associated with constipation and were the protective factors for constipation based on the MR analysis of IVW. The causal odds ratio (OR) values of Ruminiclostridium 9 and Intestinibacter were 0.75 (95% confidence interval (CI) 0.73–0.78; P < 0.001) and 0.89 (95% CI 0.86–0.93; P < 0.001) for constipation. Moreover, Anaerotruncus, Butyricimonas and Hungatella were also causally associated with constipation but were the risk factors for constipation. The OR values of Anaerotruncus, Butyricimonas and Hungatella were 1.08 (95% CI 1.02–1.13; P = 0.007), 1.07 (95% CI 1.01–1.13; P = 0.015), 1.03 (95% CI 1.00-1.06; P = 0.037) respectively. Furthermore, validation by funnel plot, heterogeneity test and horizontal pleiotropy test showed that MR results were reliable. Conclusion Ruminiclostridium 9, Intestinibacter, Anaerotruncus, Butyricimonas and Hungatella were identified as causalities of constipation, which provided a basis for understanding pathology of constipation and new insights into prevention and treatment.

Blood metabolomic shift links diet and gut microbiota to multiple health outcomes among Hispanic/Latino immigrants in the U.S.

“…Veillonella plays a significant role in using lactic acid for primary carbohydrate metabolism in the human small intestine [45]. Intestinibacter, although known as a protective microbe for constipation, lacks clear insight into its metabolic functions [46]. Butyrivibrio, extensively studied for its Carbohydrate-Active enZYmes (CAZymes) that break down plant-derived polymers, also produces health-promoting compounds like conjugated linoleic acid and vitamins [47].…”