Asthma (Diagnosis), Cardiovascular Diseases, Chronic Obstructive Airway Disease, Gastrointestinal Cancer, Healthy
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
Karolinska Institutet
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
SMC and COSM * Born between 1914 and 1948 (SMC) or through 1952 (COSM) * Residing in Västmanland and Uppsala counties (SMC) * Residing in Västmanland and Örebro counties (COSM) BAMSE cohort * All children born in certain areas of northern and central Stockholm between Feb 1994 and Nov 1996.
Exclusion criteria
SMC and COSM * Incorrect or missing national registration number * Prevalent disease at baseline (depending on research question) * Implausible energy intake BAMSE cohort * The family planned to move within 1 year of the study start; * Insufficient knowledge of the Swedish language; * The family had a seriously ill child or * an older sister or brother was already included in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal cancers incidence | Through study completion, an average of 25 years | In SIMPLER cohorts |
| Cardiovascular diseases incidence | Through study completion, an average of 25 years | In SIMPLER cohorts |
| Chronic obstructive pulmonary disease incidence | Through study completion, an average of 25 years | In SIMPLER cohorts |
| Differential abundance of gut microbiota sequenced using DNBseq | At baseline (time of sample collection) | 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) |
| Asthma incidence | From birth through young adulthood (up to 24 years of age) | In BAMSE cohort |
| Lung function (FEV1 and FVC) | Assessed every 8 years | 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)) |
| Concentrations of inflammatory biomarkers assessed by Olink Inflammation panel | At 24 years of age | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary bacterial metabolite profiles assessed by non-targeted LC-HRMS | At 24 years of age | 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. |
Countries
Sweden
Outcome results
None listed