The development of the human immune system starts in the womb and continues after birth once the child is exposed to bacteria, viruses and other environmental factors. This exposure is important for immune system development, but this stage is not without risks.
“The first few months and years are a very delicate and vulnerable time. We already know that the development of the human immune system in early life is connected to the risks of several diseases later on, particularly allergies, asthma and autoimmune diseases, such as type 1 diabetes. Yet, the mechanisms of immune imprinting in early life are still poorly understood,” says Professor Orešič.
In a collaboration between ten universities, the INITIALISE project (Inflammation in human early life: targeting impacts on life-course health) will investigate which factors impact the development of the human immune system and its significance for people’s health throughout the course of their lives.
A key question is if the immune system can be modified to decrease the risks for different diseases. “Our shared view is that effective early life interventions targeting the immune system will have a positive impact on life-course health,” says Orešič.
INITIALISE researchers are also interested in maternal diet, chemical exposures and stress during pregnancy. After birth, the intricate interplay of environmental factors and genetics begins, and their impact on the development of the immune cells is not yet well understood. In addition, the gut bacteria developed at the beginning of life can impact people's health throughout their lives. Finally, children face the chemical load in their environment while their immune system is still developing.
“We are going to study how chemicals impact the immune system. Even a small exposure to chemicals can have significant consequences, and this also applies to other factors that shape our immune system. This is due to the fact that in our first few years, we develop and change quickly and constantly,” Orešič explains.
In this context, LLNEXT has much to contribute. “The big advantage of the LLNEXT cohort is the availability extensive information for all participants. Parents who have been participating in the main Lifelines study have recorded their lifestyle, diet and health information for up to 10 years before pregnancy, which is truly unique information. Further, mothers are extensively followed during pregnancy via multiple questionnaires and biological measurements. For babies, information on growth, diseases, extensive feeding data, gut health and socio-emotional development is being recorded at several timepoints during the first year of life. Longitudinal collection of stool and oral microbiome allows accurate annotation of the development of the microbial ecosystem and analysis of its role in babies’ health. In the INITIALISE project, the UMCG team will work on the analysis of microbiome in combination with environmental factors, genetics and other omics data to understand their effect on short- and long-term health in children,” says Zhernakova.
Altogether, INITIALISE mobilises clinicians and scientists with diverse and complimentary expertise in immunology, paediatrics, microbiology and metabolism, as well as experts in metabolomics and lipidomics, proteomics, genetics, exposome, psychiatry, systems medicine and bioinformatics.
INITIALISE includes eight prospective and longitudinal birth cohort studies where the researchers follow groups of children for a long period of time to observe the development of immune-mediated diseases. Towards the end of the project, the researchers will conduct a clinical pilot study that aims to discover whether the immune system can be “altered” to prevent the development of diseases.
“The clinical trial will target the gut microbiome in at-risk children. Our aim is to improve immune status and reduce disease risk,” says Orešič.
The INITIALISE project starts at the beginning of 2023 and lasts 6 years. In addition to the University of Turku and the UMCG, member organisations include Örebro University (SE), University of Naples Federico II (IT), Karolinska Institute (SE), Linköping University (SE), University of Helsinki (FI), University of Florida (US), Spanish National Research Council (ES) and University of Aberdeen (associated partner, UK).
