Causal relationship between gut microbiota and childhood obesity: a Mendelian randomization study and case–control study

Background Gut microbiota and obesity are deeply interconnected. However, the causality in the relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between gut microbiota and childhood obesity. Methods Genetic summary statistics for the gut microbiota were obtained from the MiBioGen consortium. Genome-wide association studies (GWAS) summary data for childhood obesity were obtained from North American, Australian, and European collaborative genome-wide meta-analyses. Mendelian randomization (MR) analyses were performed using the inverse variance weighting method. 16 children with obesity and 16 without obesity were included for clinical observation, and their weight, body mass index, blood lipid levels, and gut microbiology were assessed. Paired t-test was the primary method of data analysis, and statistical significance was set at P < 0.05. Results MR identified 16 causal relationships between the gut microbiome and childhood obesity. In the case–control study, we found that five gut microorganisms differed between children with and without obesity, whereas three gut microorganisms changed after weight loss in children with obesity. Conclusion Our study provides new insights into the genetic mechanisms underlying gut microbiota and childhood obesity. Trial registration number ChiCTR2300072179 Name of registry Change of intestinal flora and plasma metabolome in obese children and their weight loss intervention: a randomized controlled tria URL of registry https://www.chictr.org.cn/showproj.html Date of registration 2023-06-06 Date of enrolment of the first participant to the trial 2023-06-07