Genetically Predicted Blood Metabolites Mediate the Association Between Gut Microbiota and Childhood Obesity: A Mendelian Randomization Study
Author(s):
Min Zhang and Wenjuan Yan
Background: Childhood obesity is characterized by metabolic dysregulation and unique gut microbiota profiles. Nevertheless, the comprehensive understanding of gut microbiota and metabolic dysregulation of childhood obesity remains unclear. Objectives: This study aimed to investigate the causal relationship of gut microbiota and childhood obesity and identify the blood metabolites as potential mediators.
Methods: The exposure genome-wide association studies (GWAS) data were sourced from the GWAS Catalog, while the outcome GWAS data were obtained from the Early Growth Genetics (EGG) Consortium. The study used 473 types of gut microbiota, 233 types of blood metabolites, and childhood obesity from GWAS. We then performed two-sample Mendelian randomization (TSMR) and bidirectional Mendelian randomization (BDMR) analyses to explore the causal relationships between gut microbiota, blood metabolites, and childhood obesity. Additionally, we conducted multivariable Mendelian randomization (MVMR) and two-step Mendelian randomization (2SMR) to identify potential mediating blood metabolites in this process.
Results: MR analysis identified 13 types of gut microbiota and 12 types of blood metabolites that were causally associated with childhood obesity. Furthermore, there was no strong evidence that genetically predicted childhood obesity had an effect on these gut microbiota and blood metabolites. Further, 2SMR analysis revealed that the association between K10 sp001941205 and childhood obesity was mediated by the Total cholesterol to total lipids ratio in medium VLDL, accounting for 2.53% (95%CI; 2.14%-2.92%) of the association. Similarly, the relationship between SM23-33 and childhood obesity was mediated by the Ratio of 22:6 docosahexaenoic acid to total fatty acids, which accounted for 4.07% (95%CI; 2.70%-5.44%) of the association.
Conclusion: The present study is the first to investigate the causal relationships among 473 gut microbiota phenotypes, 233 blood metabolites, and childhood obesity through Mendelian randomization analysis, identifying 13 gut microbiota types with potential causal links to childhood obesity and suggesting that 2 blood metabolites may mediate these associations, thereby providing valuable insights for future intervention strategies aimed at addressing childhood obesity.