Association of trimethylamine-N-oxide levels with risk of cardiovascular disease and mortality among elderly subjects: a systematic review and meta-analysis

Background: Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that has been linked to cardiovascular and renal function. This study has reviewed and analyzed the relationship between TMAO and all-cause mortality and adverse cardiovascular events in the elderly subjects. Methods: We determined whether this association was modified in the presence of CKD, heart failure and diabetes. Based on the criteria, systematic review and meta-analysis were conducted and performed. Results: A total of 27 prospective cohort studies were retrieved finally to examine the associations. The high TMAO was positively associated with all-cause mortality [HR: 1.38 (95% CI: 1.306 to 1.460)] as well as adverse cardiovascular events. [HR: 1.032 (95% CI: 1.014 to 1.051)]. The association remained upon subgroup analysis for patients with CKD and heart failure but no association for patients with diabetes [HR: 1.15 (95% CI, 0.81–1.64)]. Conclusions: The findings of this review revealed that the TMAO level is associated with all-cause mortality and adverse cardiovascular events.

Exploring Genotype-by-Environment Interactions of Chemical Composition of Raspberry by Using a Metabolomics Approach

Promoting the consumption of fruits is a key objective of nutrition policy campaigns due to their associated health benefits. Raspberries are well appreciated for their remarkable flavor and nutritional value attributable to their antioxidant properties. Consequently, one of the objectives of present-day raspberry breeding programs is to improve the fruit’s sensory and nutritive characteristics. However, developing new genotypes with enhanced quality traits is a complex task due to the intricate impacts genetic and environmental factors have on these attributes, and the difficulty to phenotype them. We used a multi-platform metabolomic approach to compare flavor- and nutritional-related metabolite profiles of four raspberry cultivars (‘Glen Ample’, ‘Schönemann’, ‘Tulameen’ and ‘Veten’) grown in different European climates. Although the cultivars appear to be better adapted to high latitudes, for their content in soluble solids and acidity, multivariate statistical analyses allowed us to underscore important genotypic differences based on the profiles of important metabolites. ‘Schönemann’ and ‘Veten’ were characterized by high levels of anthocyanins and ellagitannins, respectively, ‘Tulameen’ by its acidity, and ‘Glen Ample’ for its content of sucrose and β-ionone, two main flavor contributors. Our results confirmed the value of metabolomic-driven approaches, which may foster the development of cultivars with enhanced health properties and flavor.

Dairy consumption, plasma metabolites, and risk of type 2 diabetes

ABSTRACT Background Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. Objectives We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. Methods The discovery population included 1833 participants from the Prevención con Dieta Mediterránea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses’ Health Studies (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow-Up Study US-based cohorts. Dairy consumption was assessed using validated FFQs. Plasma metabolites (n = 385) were profiled using LC-MS. We identified the dairy-related metabolite profiles using elastic net regularized regressions with a 10-fold cross-validation procedure. We evaluated the associations between the metabolite profiles and incident T2D in the discovery and the confirmatory cohorts. Results Total dairy intake was associated with 38 metabolites. C14:0 sphingomyelin (positive coefficient), C34:0 phosphatidylethanolamine (positive coefficient), and γ-butyrobetaine (negative coefficient) were associated in a directionally similar fashion with total and specific (milk, yogurt, cheese) dairy consumption. The Pearson correlation coefficients between self-reported total dairy intake and predicted total dairy intake based on the corresponding multi-metabolite profile were 0.37 (95% CI, 0.33–0.40) in the discovery cohort and 0.16 (95% CI, 0.13–0.19) in the US confirmatory cohort. After adjusting for T2D risk factors, a higher total dairy intake–related metabolite profile score was associated with a lower T2D risk [HR per 1 SD; discovery cohort: 0.76 (95% CI, 0.63–0.90); US confirmatory cohort: 0.88 (95% CI, 0.78–0.99)]. Conclusions Total dairy intake was associated with 38 metabolites, including 3 consistently associated with dairy subtypes (C14:0 sphingomyelin, C34:0 phosphatidylethanolamine, γ-butyrobetaine). A score based on the 38 identified metabolites showed an inverse association with T2D risk in Spanish and US populations.

Integrated metabolic profiling and transcriptome analysis of pigment accumulation in diverse petal tissues in the lily cultivar ‘Vivian’

Background Petals are the colorful region of many ornamental plants. Quality traits of petal color directly affect the value of ornamental plants. Although the regulatory mechanism of flower color has been widely studied in many plants, that of lily flower color is still worth further exploration. Results In this study, the pigmentation regulatory network in different regions of the petal of lily cultivar ‘Vivian’ was analyzed through tissue structure, metabolites biosynthesis, and gene expression. We found that cell morphology of the petal in un-pigmented region differed from that in pigmented region. The cell morphology tends to flatten in un-pigmented region where the color is lighter. Moreover, high level anthocyanin was found in the pigmented regions by metabonomic analysis, especially cyanidin derivatives. However, flavanones were accumulated, contrast with anthocyanin in the un-pigmented regions of lily petal. To understand the relationship of these different metabolites and lily flower color, RNA-Seq was used to analyze the differentially expressed genes-related metabolite biosynthesis. Among these genes, the expression levels of several genes-related cyanidin derivatives biosynthesis were significantly different between the pigmented and un-pigmented regions, such as LvMYB5, LvMYB7, LvF3’H, LvDFR, LvANS and Lv3GT. Conclusions This data will help us to further understand the regulation network of lily petal pigmentation and create different unique color species.

MetaboAge DB: a repository of known ageing-related changes in the human metabolome

Accumulating metabolomics data is starting to become extremely useful in understanding the ageing process, by providing a snapshot into the metabolic state of tissues and organs, at different ages. Molecular studies of such metabolic variations during “normal” ageing can hence guide lifestyle changes and/or medical interventions aimed at improving healthspan and perhaps even lifespan. In this work, we present MetaboAge, a freely accessible database which hosts ageing-related metabolite changes, occurring in healthy individuals. Data is automatically filtered and then manually curated from scientific articles reporting statistically significant associations of human metabolite variations or correlations with ageing. Up to date, MetaboAge contains 408 metabolites annotated with their biological and chemical information, and more than 1515 ageing-related variations, graphically represented on the website grouped by validation methods, sex and age-groups. The MetaboAge database aims to continually structure the expanding information from the field of metabolomics in relation to ageing, thus making it more accessible for further research in gerontology.

Integrated Metabolic Profiling and Transcriptome Analysis of Pigment Accumulation in Diverse Petal Tissues in the Lily Cultivar 'Vivian'

Background: Petals are the colorful region of many ornamental plants. Quality traits of petal color directly affect the value of ornamental plants. Although the regulatory mechanism of flower color has been widely studied in many plants, that of lily flower color is still worth further exploration.Results: In this study, the pigmentation regulatory network in different regions of the petal of lily cultivar ‘Vivian’ was analyzed through tissue structure, metabolites biosynthesis, and gene expression. We found that cell morphology of the petal in un-pigmented region was differed with in pigmented region. The cell morphology tends to flatten in un-pigmented region where the color is lighter. Moreover, high level anthocyanin was found in the pigmented regions by metabonomic analysis, especially cyanidin derivatives. However, flavanones were accumulated, contrast with anthocyanin in the un-pigmented regions of lily petal. To understand the relationship of these different metabolites and lily flower color, RNA-Seq was used to analyze the differentially expressed genes-related metabolite biosynthesis. Among these genes, the expression levels of several genes-related cyanidin derivatives biosynthesis were significantly different between the pigmented and un-pigmented regions, such as LvMYB5, LvMYB7, LvF3'H, LvDFR, LvANS and Lv3GT.Conclusions: This data will help us to further understand the regulation network of lily petal pigmentation and create different unique color species.

Gelatin-Based Hydrogels for the Controlled Release of 5,6-Dihydroxyindole-2-Carboxylic Acid, a Melanin-Related Metabolite with Potent Antioxidant Activity

The ability of gelatin-based hydrogels of incorporating and releasing under controlled conditions 5,6-dihydroxyindole-2-carboxylic acid (DHICA), a melanin-related metabolite endowed with marked antioxidant properties was investigated. The methyl ester of DHICA, MeDHICA, was also tested in view of its higher stability, and different solubility profile. Three types of gelatin-based hydrogels were prepared: pristine porcine skin type A gelatin (HGel-A), a pristine gelatin cross-linked by amide coupling of lysines and glutamic/aspartic acids (HGel-B), and a gelatin/chitosan blend (HGel-C). HGel-B and HGel-C differed in the swelling behavior, showed satisfactorily high mechanical strength at physiological temperatures and well-defined morphology. The extent of incorporation into all the gelatins tested using a 10% w/w indole to gelatin ratio was very satisfactory ranging from 60 to 90% for either indoles. The kinetics of indole release under conditions of physiological relevance was evaluated up to 72 h. The highest values were obtained with HGel-B and HGel-C for MeDHICA (90% after 6 h), and an appreciable release was observed for DHICA reaching 30% and 40% at 6 h for HGel-B and HGel-C, respectively. At 72 h, DHICA and MeDHICA were released at around 30% from HGel-A at pH 7.4, with an increase up to 40% at pH 5.5 in the case of DHICA. DHICA incorporated into HGel-B proved fairly stable over 6 h whereas the free compound at the same concentration was almost completely oxidized. The antioxidant power of the indole loaded gelatins was monitored by chemical assays and proved unaltered even after prolonged storage in air, suggesting that the materials could be prepared in advance with respect to their use without alteration of their efficacy.