ESPE Yearbook of Paediatric Endocrinology

Sci Rep. 2025 Jun 3;15(1):19427. doi: 10.1038/s41598-025-04343-3

Brief Summary: The authors performed an untargeted lipidomic analysis using liquid chromatography–mass spectrometry in children aged 7–16 years, comparing 10 children in each group: T2D, MetS, and healthy controls. They examined associations with obesity, metabolic risk factors, inflammatory biomarkers, and gut microbiota. Of the 375 annotated plasma lipids identified, differences compared to healthy controls were found in 45 and 47 lipid species in MetS and T2D, respectively. Several lipid species were associated with specific gut microbial taxa, suggesting a potential interplay between lipid metabolism and gut microbiome composition.

Comment: Although lipidomics has been linked to cardiometabolic risk over the past decade, few studies have focused on pediatric populations. This novel study integrated plasma lipidomic profiling with microbiome analysis in children and adolescents with T2D and MetS.

As expected, subjects from both groups showed higher body mass index (BMI), waist-to-height ratio, insulin levels, and insulin resistance (HOMA-IR). Pro-inflammatory cytokines were elevated particularly in individuals with T2D. The study identified distinct lipid profiles associated with T2DM and MetS in children and adolescents. These included increased levels of phosphocholines, phosphoinositols, and sphingomyelins, and decreased levels of ether phospholipids (ePLs) and lysophospholipids (lyso-PLs).

Phosphocholines and phosphoinositols were positively correlated with BMI, waist circumference, HOMA-IR, and pro-inflammatory cytokines; certain sphingomyelins were increased and linked to HOMA-IR suggesting they could play an important role in early signaling of metabolic dysfunction. Ceramides were positively correlated with glucose and insulin levels, making them potential markers for insulin resistance. The elevated levels of phosphocholines, phosphoinositols, sphingomyelins, triglycerides, and ceramides found in MetS and T2DM subjects reveal lipid pathways related to lipotoxicity, membrane remodeling, and disrupted phospholipid metabolism. The observed reduction in ether phospholipids, plasmalogens, and lysophospholipids may reflect impaired antioxidant defenses and dysregulated lipid metabolism, potentially due to reduced activity of enzymes such as lysophosphatidylcholine acyltransferase.

Additionally, lipid species showed correlations with specific gut microbiota. In MetS, lipids were positively correlated with gut microbes from the Enterobacteriaceae family and Pseudomonas aeruginosa, while in T2DM, correlations were observed with Enterobacteriaceae family and Enterococcus casseliflavus. These findings support the idea that there is a significant interaction between lipid metabolism and gut microbiota in metabolic diseases.

By linking lipidomic changes to both metabolic dysfunction and gut microbiota alterations, the study suggests potential avenues for therapeutic interventions, including dietary strategies and microbiome modulation, to address metabolic diseases in pediatricpopulations.

Key message: By demonstrating a link between lipidomic profiles and gut microbiota composition in MetS and T2D, this study highlights potential therapeutic avenues, such as dietary strategies and microbiome modulation, for managing metabolic diseases in children and adolescents.