Understanding how environmental exposures in our early life affect our health

A new study provides a unique resource for understanding how environmental exposures in our early life affect our health.

The collaborative research, published in Nature Communications, is the first exposome study to systematically associate over 100 environmental exposures during vulnerable early life periods with molecular signatures in childhood. 

The international study, supported by Imperial's Professor Hector Keun and led by the Barcelona Institute for Global Health (ISGlobal), systematically documented all associations between a wide range of early life exposures and molecular profiles at different levels, from the genome to the metabolome, creating a unique resource for identifying new biomarkers of environmental exposures in early life and understanding their health effects. 

"Knowing about these effects can help scientists and governments devise ways to reduce the risk of negative outcomes in children." Professor Hector Keun Professor of Biochemistry

Our health depends greatly on the environment we live in. In fact, 70 -90% of the risk of developing a disease is determined by our exposome: a multitude of environmental factors (i.e. non-genetic factors) to which we are exposed throughout our life. And yet, we still have limited knowledge on which are these environmental hazards, how they interact, and what biological processes they trigger.

“Early life is a particularly important period, since exposures during these developmentally vulnerable periods may have pronounced effects at the molecular level, which may not be clinically detectable until adulthood,” explains Martine Vrijheid, Head of the Childhood and Environment Programme at ISGlobal.

In this study, the research team led by Vrijheid aimed to associate multiple chemical, outdoor, social and lifestyle exposures (92 in pregnancy and 116 when the children were 6-11 years old), with molecular profiles in the same children (DNA methylation and gene transcription in blood, plasma proteins, and metabolites in serum and urine). The study included 1,301 mother-child pairs of the Human Early Life Exposome (HELIX) project, a longitudinal cohort study in six European countries (Spain, UK, France, Lithuania, Norway and Greece).

The analysis identified 1,170 significant associations (249 in pregnancy and 921 in childhood) which provide insights into potential biological responses and sources of exposure. Pregnancy exposures, such as maternal smoking, the heavy metal cadmium, or the trace mineral molybdenum, were mostly associated with changes in DNA methylation. In contrast, childhood exposures were associated with signatures at all molecular levels, most particularly with metabolites in serum. The findings revealed, for example, that children are exposed to chemical pollutants through their diet.

 “We identified novel multi-omics associations with childhood exposure to essential trace elements, weather conditions, indoor air quality, and phtalates and parabens,” says Lea Maitre, first author.

“By visualizing these associations as networks, we can better understand if a given molecular profile is connected to several exposures or vice versa, and thereby identify potential biological pathways,” adds Maitre. Indeed, the findings provide plausible mechanisms that could lead to disease for six groups of exposures: copper, tobacco smoke, indoor air quality during childhood, persistent organic pollutants, phthalates and parabens, and weather conditions.

“With the rich exposome and molecular information available in our catalogue, we provide a valuable resource to the scientific community for finding exposure biomarkers, identifying exposure sources, improving the understanding of disease mechanisms, and, ultimately, promoting public health policies,” concludes Vrijheid.

Speaking about the study, Professor Keun, Professor of Biochemistry in the Department of Surgery and Cancer, said: "Our team's involvement was to measure the levels of metabolites in blood and urine samples from children across Europe and then to link changes in this to levels of exposures (some chemical, but also dietary and the lived environment) that can influence health and development.

"The findings give us important information about the route of exposure to potentially harmful chemicals, for example, if they come through the diet, and also clues about the biological changes that they cause in growing children. Knowing about these effects can help scientists and governments devise ways to reduce the risk of negative outcomes in children."

Léa Maitre, Mariona Bustamante, Carles Hernández-Ferrer, Denise Thiel, Chung-Ho E. Lau, Alexandros P. Siskos, Marta Vives-Usano, Carlos Ruiz-Arenas, Dolors Pelegrí-Sisó, Oliver Robinson, Dan Mason, John Wright, Solène Cadiou, Rémy Slama, Barbara Heude, Maribel Casas, Jordi Sunyer, Eleni Z. Papadopoulou, Kristine B. Gutzkow, Sandra Andrusaityte, Regina Grazuleviciene, Marina Vafeiadi, Leda Chatzi, Amrit K. Sakhi, Cathrine Thomsen, Ibon Tamayo, Mark Nieuwenhuijsen, Jose Urquiza, Eva Borràs, Eduard Sabidó, Inés Quintela, Ángel Carracedo, Xavier Estivill, Muireann Coen, Juan R. González, Hector C. Keun & Martine Vrijheid. Multi-omics signatures of the human early life exposome. Nat Commun 13, 7024 (2022). https://doi.org/10.1038/s41467-022-34422-2