The Impact of Omega-3 Fatty Acids on SM23-33 Abundance in Stool and Children with Obesity A Mendelian Randomization Analysis

Background: Children with obesity may be associated with gut microbiota and omega-3 fatty acids. However, the understanding of children with obesity, gut microbiota, and omega-3 fatty acids remains unclear. Objectives: This study aimed to examine the relationships between omega-3 fatty acids, SM23-33 abundance in stool, and children with obesity. Methods: We conducted LDSC to assess the genetic correlation between SM23-33 abundance in stool, Omega-3 fatty acids, and children with obesity. Subsequently, bidirectional MR analyses were performed to investigate the causal connections between SM23-33 abundance in stool and children with obesity, while a two-step MR analysis was employed to identify any potential mediation by Omega-3 fatty acids in this relationship. All statistical analyses were carried out using R software, and the STROBE-MR checklist was followed for reporting MR studies. Results: There was no significant genetic correlation among SM23-33 abundance in stool, Omega-3 fatty acids, and children with obesity (rg_p>0.05). MR analysis identified SM23-33 abundance in stool causally associated with children with obesity (OR=0.747, 95%CI: 0.584-0.957, P=0.021). Furthermore, there was no strong evidence that genetically predicted children with obesity affected SM23-33 abundance in stool. Further, two-step MR analysis found the associations between SM23-33 abundance in stool and children with obesity were mediated by Docosahexaenoic Acid (DHA) of Omega-3 fatty acids with proportions of 3.56% (95%CI: 3.43%, 3.69.0%). Conclusions: The present study provides evidence supporting the causal relationships between SM23-33 Abundance in Stool and Children with Obesity, with a potential effect mediated by Docosahexaenoic Acid (DHA). KEYWORDS SM23-33 abundance in stool, omega-3 fatty acids, mendelian randomization, docosahexaenoic acid, children with obesity