Wang Congrong, Reimann Brigitte, Nawrot Tim S, Martens Dries S, Wright John, McEachan Rosemary, Lepeule Johanna, Yuan Wenlun, Chatzi Leda, Vafeiadi Marina, Grazuleviciene Regina, Andrusaityte Sandra, Robinson Oliver, Sunyer Jordi, Keun Hector, Lau Chung-Ho E, Siskos Alexandros P, Coen Muireann, Borràs Eva, Sabidó Eduard, González Juan R, Vives-Usano Marta, Estivill Xavier, Carracedo Angel, Ruiz-Arenas Carlos, Quintela Inés, Casas Maribel, Nieuwenhuijsen Mark, Tamayo Ibon, Gutzkow Kristine B, Thomsen Cathrine, Sakhi Amrit K, Bustamante Mariona, Maitre Lea, Vrijheid Martine, Plusquin Michelle, Alfano Rossella
Centre for Environmental Health, Hasselt University, Belgium.
Centre for Environmental Health, Hasselt University, Belgium; Department of Public Health & Primary Care, Leuven University, Leuven, Belgium.
Environ Int. 2025 Aug;202:109630. doi: 10.1016/j.envint.2025.109630. Epub 2025 Jun 23.
Obesity is a multi-cause chronic disease recognized across the lifespan, with childhood obesity prevalence rising over the past decades. Although exposome-wide association studies have identified early-life environmental drivers of child obesity, and explored the multi-omics signatures of the exposome of children, it is understudied whether the combined effects of multiple exposures are potentially mediated by multi-omics.
Within the Human Early Life Exposome (HELIX) project, 1041 mother-child pairs were surveyed for a wide range of environmental exposures including over 354 prenatal and childhood exposures. Multi-omics molecular features were measured during childhood, encompassing the blood methylome and transcriptome, plasma proteins and urinary and serum metabolites. Exposome and multi-omics features were integrated into latent factors by Multi-omics Factor Analysis, based on which structural equation modelling was used to assess whether multi-omics mediated associations between exposome and child body mass index (BMI).
Key findings included: (i) prenatal nutrition, exercise, and passive smoking influencing BMI via DNA methylation of HOXA5 and Tenascin XB; (ii) childhood exposure to PCBs and phenols linked with BMI through inflammation and coagulation pathways; and (iii) childhood PCB and dietary exposures associated with BMI via immune pathways.
This novel untargeted workflow elucidated biological mechanisms linking environmental exposures to child obesity, potentially supporting targeted public health interventions.
肥胖是一种在整个生命周期中都被认可的多病因慢性疾病，在过去几十年里儿童肥胖患病率不断上升。尽管全暴露组关联研究已经确定了儿童肥胖的早期环境驱动因素，并探索了儿童暴露组的多组学特征，但多种暴露的综合影响是否可能由多组学介导仍未得到充分研究。
在人类早期生命暴露组（HELIX）项目中，对1041对母婴进行了广泛的环境暴露调查，包括354种以上的产前和儿童期暴露。在儿童期测量了多组学分子特征，包括血液甲基化组和转录组、血浆蛋白以及尿液和血清代谢物。通过多组学因子分析将暴露组和多组学特征整合为潜在因子，并在此基础上使用结构方程模型来评估多组学是否介导了暴露组与儿童体重指数（BMI）之间的关联。
主要发现包括：（i）产前营养、运动和被动吸烟通过HOXA5和腱生蛋白XB的DNA甲基化影响BMI；（ii）儿童期接触多氯联苯和酚类物质通过炎症和凝血途径与BMI相关；（iii）儿童期多氯联苯暴露和饮食暴露通过免疫途径与BMI相关。
这种新的非靶向工作流程阐明了将环境暴露与儿童肥胖联系起来的生物学机制，可能为有针对性的公共卫生干预提供支持。
