Nitrate, nitrite, and phosphate (NO3, NO2, P) are at all age stages ubiquitous in our everyday foods, including naturally occurring and as food additives, and in our drinking water. These compounds are essential in maintaining human well-being and health, but they have also been linked to detrimental health effects including contribution to cancer initiation and artery calcification, making it difficult to evaluate their overall health impact. Therefore, the overarching aim of this project is to shed light on the potential dual effect of these compounds on a variety of chronic diseases (cardiovascular and respiratory diseases, gastrointestinal cancers) at different life stages and to further elucidate on the molecular mechanisms suggested to underly the pathogenesis of these disease outcomes. This will be achieved by using prospective, longitudinal population-based cohorts linked to comprehensive databases of NO3 and NO2 and using a biomarker of P while also integrating omics data on inflammatory and cardiometabolic biomarkers as well as the microbiome and urine bacterial metabolites. The project will be led by the PI and conducted by a team of PhD students and postdoc in close collaboration with relevant experts. It will be initiated early on and continued throughout a 4-year study period. With this research, the investigators attempt to provide the strongest scientific evidence with etiologically more relevant exposure-disease associations and to shape future health risk assessments.
Study Type
OBSERVATIONAL
Enrollment
86,000
Karolinska Institutet
Stockholm, Sweden
Gastrointestinal cancers incidence
In SIMPLER cohorts
Time frame: Through study completion, an average of 25 years
Cardiovascular diseases incidence
In SIMPLER cohorts
Time frame: Through study completion, an average of 25 years
Chronic obstructive pulmonary disease incidence
In SIMPLER cohorts
Time frame: Through study completion, an average of 25 years
Differential abundance of gut microbiota sequenced using DNBseq
In SIMPLER cohorts and sequenced using DNBseq technology (BGI) and computationally analysed using both MetaPhlAn4 and CHAMP (CM HumAn Microbiome Profiler 2.0, Clinical Microbiomics)
Time frame: At baseline (time of sample collection)
Asthma incidence
In BAMSE cohort
Time frame: From birth through young adulthood (up to 24 years of age)
Lung function (FEV1 and FVC)
In BAMSE cohort and measured using spirometry according to the ATS/ERS spirometry criteria (at age 8 years using a 2200 Pulmonary Function Laboratory (SensorMedics), at 16 years of age using a Jaeger MasterScreen-IOS system (CareFusion Technologies), and at 24 years using a Vyaire Vyntus system (Vyaire Medical))
Time frame: Assessed every 8 years
Concentrations of inflammatory biomarkers assessed by Olink Inflammation panel
In BAMSE cohort, using the Olink Target 96 Inflammation panel, which measures relative protein levels reported as Normalized Protein eXpression (NPX) values on a log2 scale. All proteins included in the panel (approximately 92) will be analyzed individually in an exploratory manner.
Time frame: At 24 years of age
Urinary bacterial metabolite profiles assessed by non-targeted LC-HRMS
In BAMSE cohort, urinary metabolites will be assessed using non-targeted screening by liquid chromatography high-resolution mass spectrometry (LC-HRMS) and reported as relative peak intensities (arbitrary units) for detected metabolic features, including bacterial-derived metabolites, in an exploratory manner.
Time frame: At 24 years of age
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