Mendelian randomization analyses support causal relationship between gut microbiota and childhood obesity

Abstract

Background: Childhood obesity (CO) is an increasing public health issue. Mounting evidence has shown that gut microbiota (GM) is closely related to CO. However, the causal association needs to be treated with caution due to confounding factors and reverse causation. Methods: Data were obtained from the Microbiome Genome Consortium for GM as well as the Early Growth Genetics Consortium for childhood obesity and childhood body mass index (CBMI). Inverse variance weighted, maximum likelihood, weighted median, and MR.RAPS methods were applied to examine the causal association. Then replication dataset was used to validate the results and reverse Mendelian randomization analysis was performed to confirm the causal direction. Additionally, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy. Results: Our study found suggestive causal relationships between eight bacterial genera and the risk of childhood obesity (five for CO and four for CBMI). After validating the results in the replication dataset, we finally identified three childhood obesity-related GM including the genera Akkermansia, Intestinibacter, and Butyricimonas. Amongst these, the genus Akkermansia was both negatively associated with the risk of CO (OR = 0.574; 95% CI: 0.417, 0.789) and CBMI (β = −0.172; 95% CI: −0.306, −0.039). Conclusions: In this study, we employed the MR approach to investigate the causal relationship between GM and CO, and discovered that the genus Akkermansia has a protective effect on both childhood obesity and BMI. Our findings may provide a potential strategy for preventing and intervening in CO, while also offering novel insights into the pathogenesis of CO from the perspective of GM.