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Aims Gut microbiota have been linked to blood lipid levels and cardiovascular diseases (CVDs). The composition and abundance of gut microbiota trophic networks differ between ethnicities. We aim to evaluate the relationship between gut microbiotal trophic networks and CVD phenotypes. Methods and results We included cross-sectional data from 3860 individuals without CVD history from 6 ethnicities living in the Amsterdam region participating in the prospective Healthy Life in Urban Setting (HELIUS) study. Genetic variants were genotyped, faecal gut microbiota were profiled, and blood and anthropometric parameters were measured. A machine learning approach was used to assess the relationship between CVD risk (Framingham score) and gut microbiota stratified by ethnicity. Potential causal relationships between gut microbiota composition and CVD were inferred by performing two-sample Mendelian randomization with hard CVD events from the Pan-UK Biobank and microbiome genome-wide association studies summary data from a subset of the HELIUS cohort (n = 4117). Microbial taxa identified to be associated with CVD by machine learning and Mendelian randomization were often ethnic-specific, but some concordance across ethnicities was found. The microbes Akkermansia muciniphila and Ruminococcaceae UCG-002 were protective against ischaemic heart disease in African-Surinamese and Moroccans, respectively. We identified a strong inverse association between blood lipids, CVD risk, and the combined abundance of the correlated microbes Christensenellaceae–Methanobrevibacter–Ruminococcaceae (CMR). The CMR cluster was also identified in two independent cohorts and the association with triglycerides was replicated. Conclusion Certain gut microbes can have a potentially causal relationship with CVD events, with possible ethnic-specific effects. We identified a trophic network centred around Christensenellaceae , Methanobrevibacter, and various Ruminococcaceae , frequently lacking in South-Asian Surinamese, to be protective against CVD risk and associated with low triglyceride levels. [ABSTRACT FROM AUTHOR]

Background: During the course of history, various important lifestyle changes have caused profound transitions of the gut microbiome. These include the introduction of agriculture and animal husbandry, a shift from a nomadic to a more sedentary lifestyle, and recently increased levels of urbanization and a transition towards a more Western lifestyle. The latter is linked with shifts in the gut microbiome that have a reduced fermentative capability and which are commonly associated with diseases of affluence. In this study, in which 5193 subjects are included, we investigated the direction of microbiome shifts that occur in various ethnicities living in Amsterdam by comparing 1st and 2nd generation participants. We furthermore validated part of these findings with a cohort of subjects that moved from rural Thailand to the USA. Results: The abundance of the Prevotella cluster, which includes P. copri and the P. stercorea trophic network, diminished in the 2nd generation Moroccans and Turks but also in younger Dutch, whilst the Western-associated Bacteroides/Blautia/Bifidobacterium (BBB) cluster, which has an inverse correlation with α-diversity, increased. At the same time, the Christensenellaceae/Methanobrevibacter/Oscillibacter trophic network, which is positively associated with α-diversity and a healthy BMI, decreased in younger Turks and Dutch. Large compositional shifts were not observed in South-Asian and African Surinamese, in whom the BBB cluster is already dominant in the 1st generation, but ASV-level shifts towards certain species, associated amongst others with obesity, were observed. Conclusion: The Moroccan and Turkish populations, but also the Dutch population are transitioning towards a less complex and fermentative less capable configuration of the gut microbiota, which includes a higher abundance of the Western-associated BBB cluster. The Surinamese, whom have the highest prevalence of diabetes and other diseases of affluence, are already dominated by the BBB cluster. Given the continuous increase in diseases of affluence, this devolution towards low-diversity and fermentatively less capable gut microbiome compositions in urban environments is a worrying development. 9koSLJh1fDbsjUtu7rD1NM Video Abstract [ABSTRACT FROM AUTHOR]

Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO 2 max <80%) at 18 months were analyzed. A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function. [Display omitted] [ABSTRACT FROM AUTHOR]