Netherlands Organization for Health Research and Development (ZonMw).

Circulating monocytes of patients with symptomatic, but not asymptomatic, atherosclerosis have a pro-inflammatory phenotype and increased expression of glycolytic enzymes, associated with epigenetic remodeling at the level of histone methylation.

A hallmark of obesity is chronic low-grade inflammation, which plays a major role in the process of atherosclerotic cardiovascular disease (ACVD). Gut microbiota is one of the factors influencing systemic immune responses, and profound changes have been found in its composition and metabolic function in individuals with obesity. This systematic review assesses the association between the gut microbiota and markers of low-grade inflammation in humans. We identified 14 studies which were mostly observational and relatively small (n = 10 to 471). The way in which the microbiome is analysed differed extensively between these studies. Lower gut microbial diversity was associated with higher white blood cell counts and high sensitivity C-reactive protein (hsCRP) levels. The abundance of Bifidobacterium, Faecalibacterium, Ruminococcus and Prevotella were inversely related to different markers of low-grade inflammation such as hsCRP and interleukin (IL)-6. In addition, this review speculates on possible mechanisms through which the gut microbiota can affect low-grade inflammation and thereby ACVD. We discuss the associations between the microbiome and the inflammasome, the innate immune system, bile acids, gut permeability, the endocannabinoid system and TMAO. These data reinforce the importance of human research into the gut microbiota as potential diagnostic and therapeutic strategy to prevent ACVD.

Objectives: To identify parameters at first presentation after mild traumatic brain injury (MTBI) that are predictive of the severity of post-traumatic complaints (PTC) after six months. Early recognition of patients with MTBI who are at risk of developing PTC would be useful because early follow up at the outpatient clinic may help to reduce the severity of these complaints in the long run. Methods: The presence of symptoms in the emergency room (ER) (headache, dizziness, nausea, vomiting, and neck pain) and biochemical markers (neurone specific enolase and S-100B) in serum were assessed as possible predictive variables for the severity of PTC. Outcome variables were the severity of 16 PTC six months after the trauma. Result: After six months, the severity of most complaints had declined to pretrauma levels but medians for headache, dizziness, and drowsiness were still increased. In a series of 79 patients, 22 (28%) reported one or more PTC after six months. After adjustment for baseline variables, an at least twofold increased severity of all PTC subgroups was reported by those patients reporting headache, dizziness, or nausea in the ER. A twofold increased severity of "cognitive" and "vegetative" PTC was also found in those with increased concentrations of biochemical serum markers at first presentation. The prevalence of full recovery after six months increased from 50% in patients with three symptoms to 78% in those with no symptoms in the ER. Inclusion of biochemical markers showed that all 10 patients with no symptoms in the ER and normal markers recovered fully. Conclusions: The presence of headache, dizziness, or nausea in the ER after MTBI is strongly associated with the severity of most PTC after six months. Identifying MTBI patients in the ER without headache, dizziness, nausea, or increased serum marker concentrations may be a promising strategy for predicting a good outcome.

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear. Objectives: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts. Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk. Conclusions: This study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.