Integrative metagenomic and lipidomic analyses reveal alterations in children with obesity and after lifestyle intervention

Background: Despite emerging evidence linking alterations in gut microbiota to childhood obesity, the metabolic mechanisms linking gut microbiota to the lipid profile during childhood obesity and weight loss remain poorly understood. Methodology: In this study, children with obesity were treated with lifestyle weight loss therapy. Metagenomics association studies and serum untargeted lipidomics analyses were performed in children with obesity and healthy controls before and after weight loss. Main findings: We identified alterations in gut microbiota associated with childhood obesity, as well as variations in circulating metabolite concentrations. Children with obesity showed significant decreases in the levels of s-Rothia_kristinae and s-Enterobacter_roggenkampii, alongsige elevated levels of s-Clostridiales_bacterium_Marseille-P5551. Following weight loss, the levels of s-Streptococcus_infantarius and s-Leuconostoc_citreum increased by factors of 3.354 and 1.505, respectively, in comparison to their pre-weight loss levels. Correlation analyses indicated a significant positive relationship between ChE(2:0) levels and both with s-Lachnospiraceae_bacterium_TF09-5 and fasting glucose levels. CoQ8 levels were significantly negatively correlated with s-Rothia_kristinae and HOMA-IR. Conclusion: We linked altered gut microbiota and serum lipid levels in children with obesity to clinical indicators, indicating a potential impact on glucose metabolism via lipids. This study contributes to understanding the mechanistic relationship between altered gut microbiota and childhood obesity and weight loss, suggesting gut microbiome as a promising target for intervention. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=178971, ChiCTR2300072179.