| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Baldanzi, Gabriel, et al.
(författare)
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Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS.
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.METHODS: In 8416 participants aged 50-65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.FINDINGS: Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.INTERPRETATION: Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.FUNDING: European Research Council, Swedish Heart-Lung Foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation.
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| 3. |
- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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| 4. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 5. |
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| 6. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 7. |
- Ghosh, Nilanjana, et al.
(författare)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1, s. 8933-
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Tidskriftsartikel (refereegranskat)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 8. |
- Ghosh, Nilanjana, et al.
(författare)
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Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.
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| 9. |
- Grahnemo, Louise, et al.
(författare)
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Identification of three bacterial species associated with increased appendicular lean mass : the HUNT study.
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Appendicular lean mass (ALM) associates with mobility and bone mineral density (BMD). While associations between gut microbiota composition and ALM have been reported, previous studies rely on relatively small sample sizes. Here, we determine the associations between prevalent gut microbes and ALM in large discovery and replication cohorts with information on relevant confounders within the population-based Norwegian HUNT cohort (n = 5196, including women and men). We show that the presence of three bacterial species - Coprococcus comes, Dorea longicatena, and Eubacterium ventriosum - are reproducibly associated with higher ALM. When combined into an anabolic species count, participants with all three anabolic species have 0.80 kg higher ALM than those without any. In an exploratory analysis, the anabolic species count is positively associated with femoral neck and total hip BMD. We conclude that the anabolic species count may be used as a marker of ALM and BMD. The therapeutic potential of these anabolic species to prevent sarcopenia and osteoporosis needs to be determined.
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| 10. |
- Kennedy, Beatrice, et al.
(författare)
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Sociodemographic characteristics and COVID-19 testing rates : spatiotemporal patterns and impact of test accessibility in Sweden
- 2024
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Ingår i: European Journal of Public Health. - 1101-1262 .- 1464-360X. ; 34:1, s. 14-21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiagnostic testing is essential for disease surveillance and test–trace–isolate efforts. We aimed to investigate if residential area sociodemographic characteristics and test accessibility were associated with Coronavirus Disease 2019 (COVID-19) testing rates.MethodsWe included 426 224 patient-initiated COVID-19 polymerase chain reaction tests from Uppsala County in Sweden from 24 June 2020 to 9 February 2022. Using Poisson regression analyses, we investigated if postal code area Care Need Index (CNI; median 1.0, IQR 0.8–1.4), a composite measure of sociodemographic factors used in Sweden to allocate primary healthcare resources, was associated with COVID-19 daily testing rates after adjustments for community transmission. We assessed if the distance to testing station influenced testing, and performed a difference-in-difference-analysis of a new testing station targeting a disadvantaged neighbourhood.ResultsWe observed that CNI, i.e. primary healthcare need, was negatively associated with COVID-19 testing rates in inhabitants 5–69 years. More pronounced differences were noted across younger age groups and in Uppsala City, with test rate ratios in children (5–14 years) ranging from 0.56 (95% CI 0.47–0.67) to 0.87 (95% CI 0.80–0.93) across three pandemic waves. Longer distance to the nearest testing station was linked to lower testing rates, e.g. every additional 10 km was associated with a 10–18% decrease in inhabitants 15–29 years in Uppsala County. The opening of the targeted testing station was associated with increased testing, including twice as high testing rates in individuals aged 70–105, supporting an intervention effect.ConclusionsEnsuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.
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| 11. |
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| 12. |
- Lind, Lars, et al.
(författare)
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Metabolic Profiling of Obesity With And Without The Metabolic Syndrome : A Multi-Sample Evaluation
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. 1337-1345
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not.OBJECTIVE: We aimed to compare the plasma metabolome in obese subjects without the metabolic syndrome (MetS) to normal-weight subjects without MetS, as well as to obese subjects with MetS.DESIGN: Cross-sectional.SETTING: Two academic centers in Sweden.PARTICIPANTS: Three population-based samples (EpiHealth, n=2342, SCAPIS-Uppsala, n=4985 and SCAPIS-Malmö, n=3978) in which individuals were divided into groups according to their BMI and presence/absence of MetS (NCEP/consensus criteria).INTERVENTION: None.MAIN OUTCOME MEASURE: 791 annotated endogenous metabolites measured by ultra-performance liquid chromatography tandem mass spectrometry.RESULTS: We observed major differences in metabolite profiles (427 metabolites) between obese (BMI ≥ 30 kg/m 2) and normal-weight (BMI < 25 kg/m 2) subjects without MetS after adjustment for major life-style factors. Pathway enrichment analysis highlighted branch-chained and aromatic amino acid synthesis/metabolism, aminoacyl-tRNA biosynthesis and sphingolipid metabolism. The same pathways, and similar metabolites, were also highlighted when obese subjects with and without MetS were compared despite adjustment for BMI and waist circumference, or when the metabolites were related to BMI and number of MetS components in a continuous fashion. Similar metabolites and pathways were also related to insulin sensitivity (Matsuda index) in a separate study (POEM, n=501).CONCLUSION: Our data suggest a graded derangement of the circulating metabolite profile from lean to obese to the metabolic syndrome, in particular for metabolites involved in amino acid synthesis/metabolism and sphingolipid metabolism. Insulin resistance is a plausible mediator of this gradual metabolic deterioration.
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| 13. |
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| 14. |
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| 15. |
- Lind, Lars, et al.
(författare)
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The metabolomic profile associated with clustering of cardiovascular risk factors-A multi-sample evaluation.
- 2022
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS.791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in five different population-based samples (Discovery samples: EpiHealth, n = 2342 and SCAPIS-Uppsala, n = 4985. Replication sample: SCAPIS-Malmö, n = 3978, Characterization samples: PIVUS, n = 604 and POEM, n = 501). MetS was defined by the NCEP/consensus criteria. Fifteen metabolites were related to all five components of MetS (blood pressure, waist circumference, glucose, HDL-cholesterol and triglycerides) at a false discovery rate of <0.05 with adjustments for BMI and several life-style factors. They represented different metabolic classes, such as amino acids, simple carbohydrates, androgenic steroids, corticosteroids, co-factors and vitamins, ceramides, carnitines, fatty acids, phospholipids and metabolonic lactone sulfate. All 15 metabolites were related to insulin sensitivity (Matsuda index) in POEM, but only Palmitoyl-oleoyl-GPE (16:0/18:1), a glycerophospholipid, was related to incident cardiovascular disease over 8.6 years follow-up in the EpiHealth sample following adjustment for cardiovascular risk factors (HR 1.32 for a SD change, 95%CI 1.07-1.63).A complex metabolic profile was related to all cardiovascular risk factors included in MetS independently of BMI. This profile was also related to insulin sensitivity, which provide further support for the importance of insulin sensitivity as an important underlying mechanism in the clustering of cardiovascular risk factors.
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| 16. |
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| 17. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis and to explore relevant clinical correlates.Methods: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.Results: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10-5). Associations were largely similar across coronary computed tomography angiography-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.Conclusions: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 18. |
- Sayols-Baixeras, Sergi, et al.
(författare)
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Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort
- 2023
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 148:6, s. 459-472
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS: We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of fecal samples, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS: The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed for Streptococcus anginosus and Streptococcus oralis subsp oralis (P<1×10–5). Associations were largely similar across coronary computed tomography angiography–based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations, and 16 with neutrophil counts. Gut microbial species that are commonly found in the oral cavity were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species, including 3 streptococci, correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid β-oxidation, and amino acid degradation were associated with coronary artery calcium score.CONCLUSIONS: This study provides evidence of an association of a gut microbiota composition characterized by increased abundance of Streptococcus spp and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation markers. Further longitudinal and experimental studies are warranted to explore the potential implications of a bacterial component in atherogenesis.
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| 19. |
- Wernroth, Lisa, et al.
(författare)
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Development of gut microbiota during the first 2 years of life
- 2022
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Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Although development of microbiota in childhood has been linked to chronic immune-related conditions, early childhood determinants of microbiota development have not been fully elucidated. We used 16S rRNA sequencing to analyse faecal and saliva samples from 83 children at four time-points during their first 2 years of life and from their mothers. Our findings confirm that gut microbiota in infants have low diversity and highlight that some properties are shared with the oral microbiota, although inter-individual differences are present. A considerable convergence in gut microbiota composition was noted across the first 2 years of life, towards a more diverse adult-like microbiota. Mode of delivery accounted for some of the inter-individual variation in early childhood, but with a pronounced attenuation over time. Our study extends previous research with further characterization of the major shift in gut microbiota composition during the first 2 years of life.
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| 20. |
- Yi-Ting, Lin, 1981-, et al.
(författare)
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Association of the gut microbiome composition with 24-hour blood pressure measurements in 4,459 participants from the SCAPIS cohort
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHypertension is a multifactorial condition affected by genetic and environmental factors. Previous studies have indicated a link between gut microbiome characteristics and blood pressure regulation but studies were limited by small sample size, restriction to office measurements, and/or using amplicon sequencing techniques, limiting taxonomic resolution and functional profiling. This study aims to examine the relationship between the gut microbiome composition measured with deep shotgun metagenomics and blood pressure measured over 24 hours.MethodsWe analyzed data from 4,459 participants without antihypertensive medication from two sites of the Swedish CArdioPulmonary BioImage Study (SCAPIS). In the first step, we assessed the association of each metagenomic species with mean 24-hour systolic and diastolic blood pressure in regression models adjusting for age, sex, country of birth, plate effect and microbiota richness, in 3,480 participants from Uppsala. Species identified in the first step were assessed for replication in the 879 participants from Malmö/Lund. As a second step, we applied models additionally adjusted for smoking, renal function, and diabetes mellitus.ResultsWe found Dorea longicatena to be positively associated with both systolic and diastolic blood pressure in fully adjusted models and Alistipes sp. 6CPBBH3, to be negatively associated. Dorea longicatena and Alistipes family have previously both been linked to metabolic outcomes. Moreover, we found Roseburia faecis and Collinsella aerofaciens to be positively associated with mean systolic blood pressure, and Fusicatenibacter saccharivorans, Coprococcus comes, and Clostridium sp. TM06-18 positively with mean diastolic blood pressure in the fully adjusted analysis. ConclusionsIn the large, well characterized population-based study SCAPIS, we found specific bacterial species associated with blood pressure. Further studies are needed to understand the causal mechanisms.
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