Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS.

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.

Sociodemographic characteristics and COVID-19 testing rates: spatiotemporal patterns and impact of test accessibility in Sweden.

BACKGROUND: Diagnostic 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Ensuring accessible testing across all residential areas constitutes a promising tool to decrease inequalities in testing.

OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study.

BACKGROUND: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, 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 BP and glucose metabolism. RESEARCH QUESTION: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age 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, onsite 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. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, 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. Finally, 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.

Spatio-temporal predictions of COVID-19 test positivity in Uppsala County, Sweden: a comparative approach.

Previous spatio-temporal COVID-19 prediction models have focused on the prediction of subsequent number of cases, and have shown varying accuracy and lack of high geographical resolution. We aimed to predict trends in COVID-19 test positivity, an important marker for planning local testing capacity and accessibility. We included a full year of information (June 29, 2020-July 4, 2021) with both direct and indirect indicators of transmission, e.g. mobility data, number of calls to the national healthcare advice line and vaccination coverage from Uppsala County, Sweden, as potential predictors. We developed four models for a 1-week-window, based on gradient boosting (GB), random forest (RF), autoregressive integrated moving average (ARIMA) and integrated nested laplace approximations (INLA). Three of the models (GB, RF and INLA) outperformed the naïve baseline model after data from a full pandemic wave became available and demonstrated moderate accuracy. An ensemble model of these three models slightly improved the average root mean square error to 0.039 compared to 0.040 for GB, RF and INLA, 0.055 for ARIMA and 0.046 for the naïve model. Our findings indicate that the collection of a wide variety of data can contribute to spatio-temporal predictions of COVID-19 test positivity.

Development of gut microbiota during the first 2 years of life.

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.

App-based COVID-19 syndromic surveillance and prediction of hospital admissions in COVID Symptom Study Sweden.

The app-based COVID Symptom Study was launched in Sweden in April 2020 to contribute to real-time COVID-19 surveillance. We enrolled 143,531 study participants (≥18 years) who contributed 10.6 million daily symptom reports between April 29, 2020 and February 10, 2021. Here, we include data from 19,161 self-reported PCR tests to create a symptom-based model to estimate the individual probability of symptomatic COVID-19, with an AUC of 0.78 (95% CI 0.74-0.83) in an external dataset. These individual probabilities are employed to estimate daily regional COVID-19 prevalence, which are in turn used together with current hospital data to predict next week COVID-19 hospital admissions. We show that this hospital prediction model demonstrates a lower median absolute percentage error (MdAPE: 25.9%) across the five most populated regions in Sweden during the first pandemic wave than a model based on case notifications (MdAPE: 30.3%). During the second wave, the error rates are similar. When we apply the same model to an English dataset, not including local COVID-19 test data, we observe MdAPEs of 22.3% and 19.0% during the first and second pandemic waves, respectively, highlighting the transferability of the prediction model.

Adverse childhood experiences and resilience among adult women: A population-based study.

Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear. Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18-69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders. Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (ß = -0.14; 95% CI-0.15,-0.13) and lower psychiatric resilience (ß = -0.28; 95% CI-0.29,-0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood. Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood. Funding: This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund.

Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multicohort Nontargeted Metabolomics Observational and Mendelian Randomization Study.

Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity and circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data were generated with nontargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N = 1,135), PIVUS (N = 970), and TwinGene (N = 2,059). We assessed associations of general adiposity measured as BMI and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We used MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N = 7,373), the CHARGE Consortium (N = 8,631), the Framingham Heart Study (N = 2,076), and the DIRECT Consortium (N = 3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (P value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid, and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The results of the replication effort provided support for a causal association of adiposity with reduced levels of arachidonic acid (P value = 0.03). Adiposity is associated with variation of large parts of the circulating metabolome; however, further investigation of causality is required in well-powered cohorts.

The shared risk of diabetes between dog and cat owners and their pets: register based cohort study.

OBJECTIVE: To investigate whether dog and cat owners and their pets share a risk of developing diabetes. DESIGN: Cohort study. SETTING: Register based longitudinal study, Sweden. PARTICIPANTS: 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006). MAIN OUTCOME MEASURES: Type 2 diabetes events in dog and cat owners and diabetes events in their pets, including date of diagnosis during the follow-up period (1 January 2007 to 31 December 2012). Owners with type 2 diabetes were identified by combining information from the National Patient Register, the Cause of Death Register, and the Swedish Prescribed Drug Register. Information on diabetes in the pets was extracted from veterinary care insurance data. Multi-state models were used to assess the hazard ratios with 95% confidence intervals and to adjust for possible shared risk factors, including personal and socioeconomic circumstances. RESULTS: The incidence of type 2 diabetes during follow-up was 7.7 cases per 1000 person years at risk in dog owners and 7.9 cases per 1000 person years at risk in cat owners. The incidence of diabetes in the pets was 1.3 cases per 1000 dog years at risk and 2.2 cases per 1000 cat years at risk. The crude hazard ratio for type 2 diabetes in owners of a dog with diabetes compared with owners of a dog without diabetes was 1.38 (95% confidence interval 1.10 to 1.74), with a multivariable adjusted hazard ratio of 1.32 (1.04 to 1.68). Having an owner with type 2 diabetes was associated with an increased hazard of diabetes in the dog (crude hazard ratio 1.28, 1.01 to 1.63), which was attenuated after adjusting for owner's age, with the confidence interval crossing the null (1.11, 0.87 to 1.42). No association was found between type 2 diabetes in cat owners and diabetes in their cats (crude hazard ratio 0.99, 0.74 to 1.34, and 1.00, 0.78 to 1.28, respectively). CONCLUSIONS: Data indicated that owners of a dog with diabetes were more likely to develop type 2 diabetes during follow-up than owners of a dog without diabetes. It is possible that dogs with diabetes could serve as a sentinel for shared diabetogenic health behaviours and environmental exposures.

Oral Microbiota Development in Early Childhood.

Early life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement regression models adjusted for potential confounders confirmed and expanded previous knowledge about the profound shift of oral microbiota composition in early life. These alterations included increased alpha diversity, decreased beta diversity and alteration of bacterial composition with changes in relative abundance of 14 of the 20 most common operational taxonomic units (OTUs). We also found that birth characteristics, breastfeeding and antibiotic use were associated with overall phyla distribution and/or with the relative abundance of specific OTUs. Further, we detected a novel link between morning salivary cortisol level, a physiological marker of neuroendocrine activity and stress, and overall phyla distribution as well as with decreased abundance of the most common OTU mapped to the Streptococcaceae family. In conclusion, a major part of the maturation of the oral microbiome occurs during the first two years of life, and this development may be influenced by early life circumstances.

Low stress resilience in late adolescence and risk of smoking, high alcohol consumption and drug use later in life.

BACKGROUND: While compromised stress resilience constitutes a recognised risk factor for somatic and psychiatric disease development in general, the knowledge about how individual variation in vulnerability to stress may specifically influence the long-term risks of disadvantageous health behaviours is limited. METHODS: In this Swedish cohort study, we aimed to investigate the association between stress resilience in late adolescence and adult use of addictive substances. We included 9381 men with information on psychological stress resilience measured during military conscription examinations, who later responded to an extensive health survey (mean age 34.0±7.2 years) including detailed information on substance use. We modelled continuous outcomes using linear regression, binary outcomes with logistic regression and other categorical outcomes with multinomial logistic regression. RESULTS: We found that low stress resilience in adolescence conferred increased risks of all studied measures of addictive behaviour. After adjusting for childhood socioeconomic information, low stress resilience was associated with adult current regular smoking (relative risk ratio: 5.85, 95% CI 4.32 to 7.93), higher nicotine dependence scores (beta: 0.76, 95% CI 0.29 to 1.23), hazardous use of alcohol (>14 alcoholic drink-equivalents per week, OR: 1.72, 95% CI 1.37 to 2.16), DSM-IV criteria for alcohol dependence (OR: 1.74, 95% CI 1.35 to 2.25), and drug use (OR: 1.77, 95% CI 1.51 to 2.08). The results remained largely unchanged after further adjustments for adult educational attainment and occupation as well as for additional conscription covariates. CONCLUSION: Low stress resilience in late adolescence appears to be associated with an increased risk of disadvantageous and addictive health behaviours in adulthood.

Impact of parental cancer on IQ, stress resilience, and physical fitness in young men.

BACKGROUND: A parental cancer diagnosis is a stressful life event, potentially leading to increased risks of mental and physical problems among children. This study aimed to investigate the associations of parental cancer with IQ, stress resilience, and physical fitness of the affected men during early adulthood. MATERIALS AND METHODS: In this Swedish population-based study, we included 465,249 men born during 1973-1983 who underwent the military conscription examination around the age of 18 years. We identified cancer diagnoses among the parents of these men from the Cancer Register. IQ, stress resilience, and physical fitness of the men were assessed at the time of conscription and categorized into three levels: low, moderate, and high (reference category). We used multinomial logistic regression to assess the studied associations. RESULTS: Overall, parental cancer was associated with higher risks of low stress resilience (relative risk ratio [RRR]: 1.09 [95% confidence interval (CI) 1.04-1.15]) and low physical fitness (RRR: 1.12 [95% CI 1.05-1.19]). Stronger associations were observed for parental cancer with a poor expected prognosis (low stress resilience: RRR: 1.59 [95% CI 1.31-1.94]; low physical fitness: RRR: 1.45 [95% CI 1.14-1.85]) and for parental death after cancer diagnosis (low stress resilience: RRR: 1.29 [95% CI 1.16-1.43]; low physical fitness: RRR: 1.40 [95% CI 1.23-1.59]). Although there was no overall association between parental cancer and IQ, parental death after cancer diagnosis was associated with a higher risk of low IQ (RRR: 1.11 [95% CI 1.01-1.24]). CONCLUSION: Parental cancer, particularly severe and fatal type, is associated with higher risks of low stress resilience and low physical fitness among men during early adulthood. Men who experienced parental death after cancer diagnosis also have a higher risk of low IQ.

Childhood Bereavement and Lower Stress Resilience in Late Adolescence.

PURPOSE: Although childhood traumatic experiences are recognized as important determinants for adolescent psychiatric health in general, our objective was to explore the specific influence of childhood bereavement on the stress resilience development trajectory. METHODS: In this national register-based cohort study, we identified 407,639 men born in Sweden between 1973 and 1983, who underwent compulsory military enlistment examinations in late adolescence, including measures of psychological stress resilience. We defined exposure as loss of a first-degree family member in childhood, and estimated relative risk ratios (RRRs) for reduced (moderate or low), compared with high, stress resilience with 95% confidence intervals (CIs) using multinomial logistic regression. RESULTS: Loss of a parent or sibling in childhood conferred a 49% increased risk of subsequent low stress resilience (RRR, 1.49, 95% CI, 1.41-1.57) and an 8% increased risk of moderate stress resilience (RRR, 1.08, 95% CI, 1.03-1.13) in late adolescence. There was also a graded increase in risk with increasing age at loss; teenagers were at higher risk for low resilience (RRR, 1.64, 95% CI, 1.52-1.77) than children aged 7-12 (RRR, 1.47, 95% CI, 1.34-1.61) and ≤6 years (RRR, 1.16 95% CI, 1.02-1.32). The excess risk was observed for all causes of death, including suicide and unexpected deaths as well as deaths due to other illnesses. The associations remained after exclusion of parents with a history of hospitalization for psychiatric diagnoses. CONCLUSIONS: The long-term consequences of childhood bereavement may include lower stress resilience in late adolescence.

Stress resilience and cancer risk: a nationwide cohort study.

BACKGROUND: Stress resilience is recognised as a determinant of both psychiatric and somatic health, but the potential link between stress resilience and cancer development has not been explored. METHODS: In this nationwide cohort study, we examined the association between stress resilience in adolescence and subsequent cancer risk. We identified a cohort of 284 257 Swedish men, born 1952-1956, who underwent compulsory military enlistment examinations including measures of psychological stress resilience (median age 18 years). The resulting score was categorised as low, moderate and high stress resilience. Individuals diagnosed with cancer during the follow-up time were identified through data linkage to the Swedish Cancer Register. RESULTS: Lowest stress resilience, compared with the highest, was associated with increased risks of liver (HR: 4.73, 95% CI 2.73 to 8.19) and lung (HR: 2.75, 95% CI 2.02 to 3.74) cancer after adjusting for markers of socioeconomic circumstances in childhood (p for trend <0.001 for both cancer types). Further adjustment for cognitive and physical fitness at conscription assessment had a marginal influence. In contrast, men with low stress resilience had a decreased risk of being diagnosed with prostate cancer (HR: 0.65, 95% CI 0.56 to 0.76) and malignant melanoma (HR: 0.65, 95% CI 0.55 to 0.76). CONCLUSION: We conclude that adolescent stress resilience, plausibly by influencing behavioural choices and social patterns, constitutes an important determinant of adult cancer occurrence. Increased awareness of long-term consequences in susceptible individuals may help direct future efforts to reduce cancer burden in adults.

Loss of a parent and the risk of cancer in early life: a nationwide cohort study.

BACKGROUND: While early-life exposure to stress has been associated with subsequent psychiatric and cardiovascular morbidity, little is known regarding its potential role in cancer development. We hypothesized that severe emotional stress, such as the loss of a parent through death during childhood, may increase the risk of cancer in early life. METHOD: Based on the Swedish Multi-Generation Register, we identified a cohort of 4,219,691 individuals who had both parents identifiable in the same register and followed the cohort from birth to the age of 40 years between 1961 and 2006. Through information retrieved from the Swedish Causes of Death and Cancer Registers, we ascertained death among the parents and cancer diagnosis among the cohort individuals. We used Poisson regression to calculate the relative risks (RRs) and 95 % confidence intervals (CIs). RESULTS: Parental death was not associated with total cancer risk. However, parental death during childhood was associated with a higher risk of human papillomavirus (HPV) infection-related cancers (RR 1.4; 95 % CI 1.2-1.7), and loss during early adulthood (>18 years) entailed a higher risk of cancers of the stomach (RR 1.8; 95 % CI 1.3-2.6), lung (RR 1.7; 95 % CI 1.1-2.4), rectum (RR 1.4; 95 % CI 1.0-2.0), and breast (RR 1.1; 95 % CI 1.0-1.3). A significant association was observed for pancreatic cancer for both loss during childhood (RR 2.6; 95 % CI 1.6-4.2) and afterward (RR 2.8; 95 % CI 1.9-4.3). CONCLUSION: Our results suggest that severe psychological stress in early life may be associated with premature development of certain malignancies, particularly cancers related to smoking and HPV infection.