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OBJECTIVE: Meat intake is suggested to affect gut microbiome composition and the risk of chronic diseases. We aimed to identify meat-associated gut microbiome features and their association with host factors.

DESIGN: Gut microbiota species were profiled by deep shotgun metagenomics sequencing in 9669 individuals. Intake of white meat, unprocessed red meat, and processed red meat was assessed using a food frequency questionnaire. The associations of meat intake with alpha-diversity and relative abundance of gut microbiota species were tested using linear regression models with adjustment for dietary fiber intake, body mass index, and other potential confounders. Meat-associated species were further assessed for association with enrichment of microbial gene function, meat-associated plasma metabolites, and clinical biomarkers.

RESULTS: Higher intake of processed red meat was associated with reduced alpha microbial diversity. White meat, unprocessed, and processed red meat intakes were associated with 36, 14, and 322 microbiota species, respectively. Species associated with processed red meat were enriched for bacterial pathways like amino acid degradation, while those negatively linked were enriched for pathways like homoacetogenesis. Furthermore, species positively associated with processed red meat were to a large extent associated with reduced trimethylamine N-oxide and glutamine levels but increased creatine and carnitine metabolites, fasting insulin and glucose, C-reactive protein, apolipoprotein A1, and triglyceride levels and higher blood pressure.

CONCLUSION: This largest to date population-based study on meat and gut microbiota suggests that meat intake, particularly processed red meat, may modify the gut microbiota composition, functional capacity, and health-related biomarkers.

Background

Higher meat intake has been associated with adverse health outcomes, including cardiovascular disease (CVD). This study investigated plasma metabolites associated with meat intake and their relation with cardiometabolic biomarkers, subclinical CVD markers, and incident CVD.

Methods

Associations between self-reported meat intake and 1272 plasma metabolites were investigated in the SCAPIS cohort (n = 8,819; ages 50–64). Meat-associated metabolites were further examined for relation with subclinical CVD markers in the POEM cohort (n = 502; age 50) and incident CVD in the EpiHealth cohort (n = 2,278; ages 45–75; 107 incident cases over 9.6 years follow-up). Meat intake was categorized into white, unprocessed red, and processed red meat. Linear regression analyzed associations between meat intake, metabolites and cardiometabolic biomarkers, and subclinical CVD markers, while Cox models evaluated association between meat-associated metabolites and incident CVD.

Results

After correction for multiple testing, 458, 368, and 403 metabolites were associated with white, unprocessed red, and processed red meat, respectively. Processed red meat-associated metabolites were associated with higher levels of fasting insulin, hemoglobin A1c, and lipoprotein(a), and were inversely associated with maximal oxygen consumption. Two metabolites, 1-palmitoyl-2-linoleoyl-GPE (16:0/18:2) (hazard ratios (HR: 1.32; 95 % CI: 1.08, 1.62)) and glutamine degradant (HR: 1.35; 95 % CI: 1.07, 1.72), that were inversely associated with intake of all meat types, were also associated with a higher risk of incident CVD.

Conclusions

This study provides comprehensive analysis of self-reported meat intake and plasma metabolites. The findings may enhance our understanding of the relationship between meat intake and CVD, and provide insights into underlying mechanisms.

BACKGROUND: The urinary microbiome, or urobiome, is a novel area of research that has been gaining attention recently, as urine was thought to be sterile for years. There is limited information about the composition of the urobiome in health and disease. The urobiome may be affected by several factors and diseases such as diabetes, a disease that often leads to kidney damage. Thus, we need to understand the role of the urobiome to assess and monitor kidney disease related to diabetes over time.

METHODS: We conducted a systematic review to summarize knowledge about the urobiome in association with diabetes mellitus and diabetic kidney disease. The search was conducted in several electronic databases until November 2024.

RESULTS: Eighteen studies were selected including cross-sectional case-control studies, cross-sectional surveys and one prospective longitudinal study. In total, the urobiome of 1,571 people was sequenced, of which 662 people had diabetes, and of these 36 had confirmed diabetic kidney disease; 609 were healthy individuals, 179 had prediabetes or were at risk of type 2 diabetes mellitus and 121 did not have diabetes but had other comorbidities. Eight studies analysed data from females, one was focused on male data, and the other nine had mixed female-male data. Most of the studies had a small sample size, used voided midstream urine, and used 16S rRNA sequencing.

CONCLUSION: This systematic review summarizes trends seen throughout published data available to have a first baseline knowledge of the urinary microbiome, and its microbiota, in association with diabetes including the decreased richness and α-diversity in urinary microbiota in individuals with diabetes compared to healthy controls and the decreased α-diversity with the evolution of kidney disease independently of the cause.

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.

Importance Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited. Objectives To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction. Design, Setting, and Participants This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information. Baseline data included self-reported demographics and a validated food-frequency questionnaire. The data collection period was from April 1993 to January 1996, and data analysis took place from June 2018 to November 2023. Exposures Mediterranean diet score (range, 0-9) was computed based on 9 dietary components. Main Outcome and Measures Thirty-three blood biomarkers, including traditional and novel lipid, lipoprotein, apolipoprotein, inflammation, insulin resistance, and metabolism measurements, were evaluated at baseline using standard assays and nuclear magnetic resonance spectroscopy. Mortality and cause of death were determined from medical and death records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for Mediterranean diet adherence and mortality risk, and mediation analyses were used to calculate the mediated effect of different biomarkers in understanding this association. Results Among 25 315 participants, the mean (SD) baseline age was 54.6 (7.1) years, with 329 (1.3%) Asian women, 406 (1.6%) Black women, 240 (0.9%) Hispanic women, 24 036 (94.9%) White women, and 95 (0.4%) women with other race and ethnicity; the median (IQR) Mediterranean diet adherence score was 4.0 (3.0-5.0). Over a mean (SD) of 24.7 (4.8) years of follow-up, 3879 deaths occurred. Compared with low Mediterranean diet adherence (score 0-3), adjusted risk reductions were observed for middle (score 4-5) and upper (score 6-9) groups, with HRs of 0.84 (95% CI, 0.78-0.90) and 0.77 (95% CI, 0.70-0.84), respectively (P for trend < .001). Further adjusting for lifestyle factors attenuated the risk reductions, but they remained statistically significant (middle adherence group: HR, 0.92 [95% CI, 0.85-0.99]; upper adherence group: HR, 0.89 [95% CI, 0.82-0.98]; P for trend = .001). Of the biomarkers examined, small molecule metabolites and inflammatory biomarkers contributed most to the lower mortality risk (explaining 14.8% and 13.0%, respectively, of the association), followed by triglyceride-rich lipoproteins (10.2%), body mass index (10.2%), and insulin resistance (7.4%). Other pathways, including branched-chain amino acids, high-density lipoproteins, low-density lipoproteins, glycemic measures, and hypertension, had smaller contributions (<3%). Conclusions and Relevance In this cohort study, higher adherence to the Mediterranean diet was associated with 23% lower risk of all-cause mortality. This inverse association was partially explained by multiple cardiometabolic factors.

Genetic variants associated with increased liver fat and volume have been reported, but whether physical activity (PA) can attenuate the impact of genetic susceptibility to these traits is poorly understood. We aimed to investigate whether higher PA modify genetic impact on liver-related traits in the UK Biobank cohort. PA was self-reported, while magnetic resonance images were used to estimate liver fat (n = 27,243) and liver volume (n = 24,752). Metabolic dysfunction-associated liver disease (MASLD) and chronic liver disease (CLD) were diagnosed using ICD-9 and ICD-10 codes. Ten liver fat and eleven liver volume-associated genetic variants were selected and unweighted genetic-risk scores for liver fat (GRS_LF) and liver volume (GRS_LV) were computed. Linear regression analyses were performed to explore interactions between GRS_LF/ GRS_LV and PA in relation to liver-related traits. Association between GRS_LF and liver fat was not different among lower (β = 0.063, 95% CI 0.041-0.084) versus higher PA individuals (β = 0.065, 95% CI 0.054-0.077, p_interaction = 0.62). The association between the GRS_LV and liver volume was not different across different PA groups (p_interaction = 0.71). Similarly, PA did not modify the effect of GRS_LF and GRS_LV on MASLD or CLD. Our findings show that physical activity and genetic susceptibility to liver-related phenotypes seem to act independently, benefiting all individuals regardless of genetic risk.

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.

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.

BACKGROUND: The genetic background of general obesity and fat distribution is different, pointing to separate underlying physiology. Here, we searched for metabolites and lipoprotein particles associated with fat distribution, measured as waist/hip ratio adjusted for fat mass (WHRadjfatmass), and general adiposity measured as percentage fat mass.

METHOD: The sex-stratified association of 791 metabolites detected by liquid chromatography-mass spectrometry (LC-MS) and 91 lipoprotein particles measured by nuclear magnetic spectroscopy (NMR) with WHRadjfatmass and fat mass were assessed using three population-based cohorts: EpiHealth (n = 2350) as discovery cohort, with PIVUS (n = 603) and POEM (n = 502) as replication cohorts.

RESULTS: Of the 193 LC-MS-metabolites being associated with WHRadjfatmass in EpiHealth (false discovery rate (FDR) <5%), 52 were replicated in a meta-analysis of PIVUS and POEM. Nine metabolites, including ceramides, sphingomyelins or glycerophosphatidylcholines, were inversely associated with WHRadjfatmass in both sexes. Two of the sphingomyelins (d18:2/24:1, d18:1/24:2 and d18:2/24:2) were not associated with fat mass (p>0.50). Out of 91, 82 lipoprotein particles were associated with WHRadjfatmass in EpiHealth and 42 were replicated. Fourteen of those were associated in both sexes and belonged to very-large or large HDL particles, all being inversely associated with both WHRadjfatmass and fat mass.

CONCLUSION: Two sphingomyelins were inversely linked to body fat distribution in both men and women without being associated with fat mass, while very-large and large HDL particles were inversely associated with both fat distribution and fat mass. If these metabolites represent a link between an impaired fat distribution and cardiometabolic diseases remains to be established.

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.