Metabolomics and Multi-Omics Determination of Potential Plasma Biomarkers in PRV-1-Infected Atlantic Salmon.

Metabolomic analysis has been explored to search for disease biomarkers in humans for some time. The application to animal species, including fish, however, is still at the beginning. In the present study, we have used targeted and untargeted metabolomics to identify metabolites in the plasma of Atlantic salmon (Salmo salar) challenged with Piscine orthoreovirus (PRV-1), aiming to find metabolites associated with the progression of PRV-1 infection into heart and skeletal muscle inflammation (HSMI). The metabolomes of control and PRV-1-infected salmon were compared at three time points during disease development by employing different biostatistical approaches. Targeted metabolomics resulted in the determination of affected metabolites and metabolic pathways, revealing a substantial impact of PRV-1 infection on lipid homeostasis, especially on several (lyso)phosphatidylcholines, ceramides, and triglycerides. Untargeted metabolomics showed a clear separation of the treatment groups at later study time points, mainly due to effects on lipid metabolism pathways. In a subsequent multi-omics approach, we combined both metabolomics datasets with previously reported proteomics data generated from the same salmon plasma samples. Data processing with DIABLO software resulted in the identification of significant metabolites and proteins that were representative of the HSMI development in the salmon.

Fish Skin and Gill Mucus: A Source of Metabolites for Non-Invasive Health Monitoring and Research.

Mucous membranes such as the gill and skin mucosa in fish protect them against a multitude of environmental factors. At the same time, changes in the molecular composition of mucus may provide valuable information about the interaction of the fish with their environment, as well as their health and welfare. In this study, the metabolite profiles of the plasma, skin and gill mucus of freshwater Atlantic salmon (Salmo salar) were compared using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Several normalization procedures aimed to reduce unwanted variation in the untargeted data were tested. In addition, the basal metabolism of skin and gills, and the impact of the anesthetic benzocaine for euthanisation were studied. For targeted metabolomics, the commercial AbsoluteIDQ p400 HR kit was used to evaluate the potential differences in metabolic composition in epidermal mucus as compared to the plasma. The targeted metabolomics data showed a high level of correlation between different types of biological fluids from the same individual, indicating that mucus metabolite composition could be used for fish health monitoring and research.

Milk and Dairy Product Consumption and Inflammatory Biomarkers: An Updated Systematic Review of Randomized Clinical Trials.

Milk and dairy products contribute ≤14% of the caloric intake in developed countries. Recent evidence has shown controversial results with regard to the role of dairy products in deleterious processes such as inflammation. The increasing number of studies on the anti- and proinflammatory effects of milk and dairy products in the past 5 y reflects the growing interest in this area of research. The aim of this systematic review was to evaluate the scientific evidence provided in the past 5 y on the effects of milk and dairy products on inflammatory biomarkers provided by randomized clinical trials. The search strategy was conducted in Medline (via PubMed) and Scopus (which includes EMBASE and the Web of Science) databases and included articles from 1 January 2012 to 30 April 2018. The risk of bias was assessed using the Cochrane methodology. The number of study participants, type of study, doses, and the key results are reported. The following primary outcomes were considered for inclusion: circulating concentrations of C-reactive protein, interleukins, cytokines, and vascular adhesion molecules or expression of proinflammatory genes in peripheral blood mononuclear cells; however, the primary outcomes considered were not limited to these. Sixteen studies (15 articles) included in this systematic review reported on healthy individuals and subjects who were overweight or obese and who had metabolic syndrome or type 2 diabetes. The consumption of milk or dairy products did not show a proinflammatory effect in healthy subjects or individuals with metabolic abnormalities. The majority of studies documented a significant anti-inflammatory effect in both healthy and metabolically abnormal subjects, although not all the articles were of high quality. This review was registered on PROSPERO (International Prospective Register of Systematic Reviews) at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=94535 as CRD42018094535.

Role of Functional Fortified Dairy Products in Cardiometabolic Health: A Systematic Review and Meta-analyses of Randomized Clinical Trials.

There is insufficient evidence on the role of functional fortified dairy products in improving health and in preventing risk factors associated with noncommunicable chronic diseases. This systematic review was conducted to summarize effects of the consumption of fortified dairy products on biomarkers of cardiometabolic risk. MEDLINE and SCOPUS databases were used to perform searches to include studies published up to 30 April 2018. Randomized clinical trials with human subjects consuming dairy products fortified with phytosterols, FAs, vitamins or minerals and relating this consumption with cardiometabolic health were included in this review. Risk of bias assessment according to Cochrane guidelines was performed to determine the quality of the trials. Forty-one studies were finally selected for this synthesis; the selected studies tested dairy products fortified with the following nutrients and bioactive components: phytosterols (n = 31), FAs (n = 8), and vitamin D (n = 2). We found that the consumption of phytosterol-fortified dairy, led to an overall LDL cholesterol reduction of -0.36 (-0.41, -0.31) mmol/L, P < 0.001; this decrease was mainly related to the dosage. Likewise, consumption of ω-3 FA-fortified dairy products resulted in a plasma LDL cholesterol reduction of -0.18 (-0.27, -0.09) mmol/L as well as a decrease of -0.18 (-0.32, -0.05) mmol/L in triacylglycerols (TG). Performing meta-analyses of the consumption of dairy products fortified with vitamin D or FAs other than ω-3 FAs and biomarkers of cardiometabolic risk was not possible because of the few available publications. Our results indicate that consumption of dairy products fortified with phytosterols and ω-3 FAs can lead to a reduction of LDL cholesterol and consumption of fortified dairy products fortified with ω-3 FAs can reduce TG concentration. However, more studies with homogeneous designs are needed to determine the advantages of using dairy products as fortification vehicles to prevent cardiometabolic risk.

Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials.

Context: The increasing number of studies on the effects of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) on health, particularly cognition, in the last 5 years reflects the growing interest in this area of research. Objective: The aim for this systematic review was to evaluate the scientific evidence published in the last 5 years (2012-2017) on the effects of n-3 LC-PUFA intake on cognition, cognitive development, and cognitive decline to determine whether n-3 LC-PUFAs support cognitive development and prevent cognitive decline. Data Sources: The PubMed database was searched. Study Selection: The 51 articles included in this systematic review reported on healthy individuals with mild or moderate cognitive impairment and patients with Alzheimer's disease. Risk of bias was assessed using Cochrane methodology. Data Extraction: The number of study participants, the type of study, the type and dose of n-3 LC-PUFAs, and the key results are reported here. Results: Current evidence indicates that n-3 LC-PUFAs administered during pregnancy or breastfeeding have no effect on the skills or cognitive development of children in later stages of development. Evidence regarding the improvement of cognitive function during childhood and youth or in attention deficit/hyperactivity disorder is inconclusive. Moreover, it is still unclear if n-3 LC-PUFAs can improve cognitive development or prevent cognitive decline in young or older adults.

Omega 3 fatty acids in cardiovascular disease risk factors: An updated systematic review of randomised clinical trials.

Several studies and reviews regarding the supplementation of omega-3 LC-PUFAs have been developed during the last years. Indeed, the evidence states that high doses omega-3 LC-PUFAs produce a small but significant decrease in blood pressure in older and hypertensive subjects. Due to the increasing interest in the benefits of LC-PUFAs, we aimed to evaluate the scientific evidence provided in the past five years (2012-2016) on the effects of the intake of omega-3 LC-PUFAs on cardiovascular risk factors such as inflammation and oxidative stress, through a systematic review in PubMed database. Twenty-eight articles were related to cardiovascular disease (CVD) and are included in this systematic review. The studies included healthy subjects and CVD patients; we included the number of subjects, type of study, type and doses of omega-3 LC-PUFAs, primary outcomes, and results. The use of omega-3 LC-PUFAs for ameliorating CVD risk factors can be recommended. However, the administration of omega-3 does not seem to show any benefit for the management of CVD or associated complications.

A serum metabolomics-driven approach predicts orange juice consumption and its impact on oxidative stress and inflammation in subjects from the BIONAOS study.

SCOPE: To identify biomarkers of orange juice (OJ) consumption containing different doses of polyphenols and to determine its impact on oxidative stress and inflammation using an untargeted metabolomics analysis. METHODS AND RESULTS: Thirty subjects aged 22-63 years from the BIONAOS study consumed a normal-polyphenol OJ (NPJ) or a high-polyphenol OJ (HPJ) (299 or 745 mg/L, respectively) for 12 weeks in a randomized, parallel, double-blind study. UHPLC-MS, univariate and multivariate statistical analysis and ROC curves were used to design biomarkers of consumption in serum. We propose betonicine, stachydrine, methyl glucopyranoside (alpha+beta), dihydroferulic acid and galactonate as a new metabolic signature to distinguish the intake of OJ with a different polyphenol content. Changes in metabolites related to OJ, oxidative stress and inflammation were observed. After HPJ consumption, the serum levels of hydroxyoctadecadienoic acid (9-HODE+13-HODE) and dihydroxyoctadecanoic acid (12,13-DiHOME and 9,10-DiHOME) decreased, whereas levels of 12-hydroxyeicosatetraenoic acid (12-HETE) increased. 5-HETE increased after the NPJ intervention exclusively. CONCLUSION: We designed a new panel of biomarkers to differentiate the intake of OJs containing different doses of polyphenols. On the other hand, the consumption of an OJ with a high content of flavanones improved oxidative stress and inflammatory biomarkers.

Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults.

BACKGROUND: The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system. OBJECTIVE: The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese. METHODS: A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions. RESULTS: The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2'-deoxyguanosine (NPJ: 935 ± 134 to 298 ± 19 ng/mg creatinine; HPJ: 749 ± 84 to 285 ± 17 ng/mg creatinine), 8-iso-prostaglandin F2α (NPJ: 437 ± 68 to 156 ± 14 ng/mg creatinine; HPJ: 347 ± 43 to 154 ± 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 ± 1 to 124 ± 2 mm Hg; diastolic blood pressure: 79 ± 1 to 76 ± 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 ± 1.5 to 23.1 ± 1.7 U/mg hemoglobin). CONCLUSIONS: Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250.

A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Phenolic Compounds.

The prevalence of cardiovascular diseases (CVD) is rising and is the prime cause of death in all developed countries. Bioactive compounds (BAC) can have a role in CVD prevention and treatment. The aim of this work was to examine the scientific evidence supporting phenolic BAC efficacy in CVD prevention and treatment by a systematic review. Databases utilized were Medline, LILACS and EMBASE, and all randomized controlled trials (RCTs) with prospective, parallel or crossover designs in humans in which the effects of BAC were compared with that of placebo/control were included. Vascular homeostasis, blood pressure, endothelial function, oxidative stress and inflammatory biomarkers were considered as primary outcomes. Cohort, ecological or case-control studies were not included. We selected 72 articles and verified their quality based on the Scottish Intercollegiate Guidelines Network, establishing diverse quality levels of scientific evidence according to two features: the design and bias risk of a study. Moreover, a grade of recommendation was included, depending on evidence strength of antecedents. Evidence shows that certain polyphenols, such as flavonols can be helpful in decreasing CVD risk factors. However, further rigorous evidence is necessary to support the BAC effect on CVD prevention and treatment.

A Systematic Review of the Efficacy of Bioactive Compounds in Cardiovascular Disease: Carbohydrates, Active Lipids and Nitrogen Compounds.

BACKGROUND/AIMS: The prevalence of cardiovascular diseases (CVD) is rising and it is the prime cause of death in all developed countries. Bioactive compounds (BACs) can play a role in CVD prevention and treatment. To examine the scientific evidence supporting BACs groups' efficacy in CVD prevention and treatment, we conducted a systematized review. METHODS: All available information on Medline, LILACS and EMBASE; all randomized controlled trials (RCTs) with prospective, parallel or crossover designs in humans in which the BACs effect was compared with that of placebo/control. Vascular homeostasis, blood pressure, endothelial function, oxidative stress and inflammatory biomarkers were considered primary outcomes. RESULTS: We selected 26 articles, verifying their quality based on the Scottish Intercollegiate Guidelines Network, establishing diverse quality levels of scientific evidence according to the design and bias risk of a study. Grades of recommendation were included, depending on the evidence strength of antecedents. CONCLUSIONS: Evidence shows that certain BACs' derivative from active lipids and nitrogen compounds, mainly from horse chestnut seed extract, sterol plants, allium derivatives, and certain doses of beta-glucans, can be helpful in decreasing the prevalence of CVD risk factors. However, further rigorous evidence is necessary to support and prove BACs' effect on CVD prevention and treatment.

Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials.

Inflammation is part of the normal host response to infection and injury. Eicosanoids, cytokines, chemokines, adhesion molecules and other inflammatory molecules are frequently produced during this process. Numerous studies in humans have documented the inflammation-limiting properties of omega-3 fatty acids, but only a few have been randomised clinical trials. The aim of this study was to perform a systematic search of randomised clinical trials on omega-3 fatty acids and inflammatory biomarkers in all subjects including healthy and ill persons up to February 2011 using PubMed and LILACS databases, defined by a specific equation using MeSH terms and limited to randomised clinical trials; there was no any a priori decision to include some diseases and not others. The quality of each publication was validated by using the JADAD scale and the CONSORT checklist. Inflammatory biomarkers were considered as primary outcomes. Twenty-six publications of the last 10 years were selected. Studies included healthy subjects and patients with cardiovascular disease and other chronic and acute diseases; all reported the number of subjects, type of study, type and doses of omega-3 fatty acids, main outcomes and major inflammatory biomarkers. Dietary omega-3 fatty acids are associated with plasma biomarker levels, reflecting lower levels of inflammation and endothelial activation in cardiovascular disease and other chronic and acute diseases, including chronic renal disease, sepsis and acute pancreatitis. However, further research is required before definitive recommendations can be made about the routine use of omega-3 fatty acids in critically ill patients or with neurodegenerative or chronic renal disease.