Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome

Abstract Youth-onset type 2 diabetes mellitus (T2DM) has an aggressive clinical course and is usually preceded by obesity and metabolic syndrome (MetS). Lipids have emerged as potential biomarkers for studying metabolic risk factors and predicting disease progression. An untargeted lipidomic analysi...

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Main Authors: Shirley Mora-Godínez, Ana Laura de la Garza, Oscar Tamez-Rivera, Carolina Senés-Guerrero, Ana Karen Carrizales-Sánchez, Gerardo García-Rivas, Carmen Hernández-Brenes
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04343-3
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author Shirley Mora-Godínez
Ana Laura de la Garza
Oscar Tamez-Rivera
Carolina Senés-Guerrero
Ana Karen Carrizales-Sánchez
Gerardo García-Rivas
Carmen Hernández-Brenes
author_facet Shirley Mora-Godínez
Ana Laura de la Garza
Oscar Tamez-Rivera
Carolina Senés-Guerrero
Ana Karen Carrizales-Sánchez
Gerardo García-Rivas
Carmen Hernández-Brenes
author_sort Shirley Mora-Godínez
collection DOAJ
description Abstract Youth-onset type 2 diabetes mellitus (T2DM) has an aggressive clinical course and is usually preceded by obesity and metabolic syndrome (MetS). Lipids have emerged as potential biomarkers for studying metabolic risk factors and predicting disease progression. An untargeted lipidomic analysis by liquid chromatography-mass spectrometry was performed in thirty pediatric subjects with T2DM and MetS and a healthy group. Plasma lipids were associated with obesity, metabolic risk factors, inflammatory biomarkers, and gut microbiota. A total of 375 lipid species were annotated. MetS and T2DM groups had increased levels of phosphocholines (15–18), phosphoinositols (2–3), sphingomyelins (2–3), and triglycerides (1–4), and lower plasmalogens (2–6) and lysophospholipids (1–2). Phosphocholines, phosphoinositols, sphingomyelins, and triglycerides positively correlated with metabolic risk factors such as body mass index (BMI), waist and hip circumference, triglycerides, glucose, insulin, and HOMA-IR. Ceramides were significantly higher in MetS and T2DM in regression analysis, adjusted for BMI, age, and sex, and only increased with higher BMI in the healthy group. Significant positive correlations were observed for phosphocholines and phosphoinositols with species from the phyla Pseudomonadota and Bacillota, like Weissella cibaria and Enterobacter hormaechei, and the latter species with ceramides. This study provides novel evidence on the role of plasma lipids in the pathophysiology of MetS and T2DM in children and adolescents and their associations with gut microbial species. These findings documented opportunities for developing therapeutic strategies, such as dietary interventions and microbiome modulation, to mitigate the burden of metabolic diseases in pediatric populations.
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spelling doaj-art-5b7d3fc389ea45738579dd29a582c4102025-08-20T03:26:44ZengNature PortfolioScientific Reports2045-23222025-06-0115111510.1038/s41598-025-04343-3Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndromeShirley Mora-Godínez0Ana Laura de la Garza1Oscar Tamez-Rivera2Carolina Senés-Guerrero3Ana Karen Carrizales-Sánchez4Gerardo García-Rivas5Carmen Hernández-Brenes6Institute for Obesity Research, Tecnologico de MonterreyFacultad de Salud Pública y Nutrición, Centro de Investigación en Nutrición y Salud Pública, Universidad Autonoma de Nuevo LeonInstitute for Obesity Research, Tecnologico de MonterreyEscuela de Ingenieria y Ciencias, Laboratorio de Sostenibilidad y Cambio Climático, Tecnologico de MonterreyEscuela de Ingeniería y Ciencias, Tecnologico de MonterreyInstitute for Obesity Research, Tecnologico de MonterreyInstitute for Obesity Research, Tecnologico de MonterreyAbstract Youth-onset type 2 diabetes mellitus (T2DM) has an aggressive clinical course and is usually preceded by obesity and metabolic syndrome (MetS). Lipids have emerged as potential biomarkers for studying metabolic risk factors and predicting disease progression. An untargeted lipidomic analysis by liquid chromatography-mass spectrometry was performed in thirty pediatric subjects with T2DM and MetS and a healthy group. Plasma lipids were associated with obesity, metabolic risk factors, inflammatory biomarkers, and gut microbiota. A total of 375 lipid species were annotated. MetS and T2DM groups had increased levels of phosphocholines (15–18), phosphoinositols (2–3), sphingomyelins (2–3), and triglycerides (1–4), and lower plasmalogens (2–6) and lysophospholipids (1–2). Phosphocholines, phosphoinositols, sphingomyelins, and triglycerides positively correlated with metabolic risk factors such as body mass index (BMI), waist and hip circumference, triglycerides, glucose, insulin, and HOMA-IR. Ceramides were significantly higher in MetS and T2DM in regression analysis, adjusted for BMI, age, and sex, and only increased with higher BMI in the healthy group. Significant positive correlations were observed for phosphocholines and phosphoinositols with species from the phyla Pseudomonadota and Bacillota, like Weissella cibaria and Enterobacter hormaechei, and the latter species with ceramides. This study provides novel evidence on the role of plasma lipids in the pathophysiology of MetS and T2DM in children and adolescents and their associations with gut microbial species. These findings documented opportunities for developing therapeutic strategies, such as dietary interventions and microbiome modulation, to mitigate the burden of metabolic diseases in pediatric populations.https://doi.org/10.1038/s41598-025-04343-3ChildrenType 2 diabetes mellitusMetabolic syndromeLipidomicsGut microbiota
spellingShingle Shirley Mora-Godínez
Ana Laura de la Garza
Oscar Tamez-Rivera
Carolina Senés-Guerrero
Ana Karen Carrizales-Sánchez
Gerardo García-Rivas
Carmen Hernández-Brenes
Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
Scientific Reports
Children
Type 2 diabetes mellitus
Metabolic syndrome
Lipidomics
Gut microbiota
title Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
title_full Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
title_fullStr Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
title_full_unstemmed Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
title_short Lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
title_sort lipidomic signatures linked to gut microbiota alterations in children and adolescents with type 2 diabetes mellitus and metabolic syndrome
topic Children
Type 2 diabetes mellitus
Metabolic syndrome
Lipidomics
Gut microbiota
url https://doi.org/10.1038/s41598-025-04343-3
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