Lipoprotein Particle Profiles Associated with Telomere Length and Telomerase Complex Components.

Telomere length (TL) is a well-known marker of age-related diseases. Oxidative stress and inflammation increase the rate of telomere shortening, triggering cellular senescence. Although lipoproteins could have anti-inflammatory and proinflammatory functional properties, the relationship between lipoprotein particles with TL and telomerase activity-related genes has not been investigated much. In this study, we assessed the associations of lipoprotein subfractions with telomere length, TERT, and WRAP53 expression in a total of 54 pre-diabetic subjects from the EPIRDEM study. We regressed TL, TERT, and WRAP53 on 12 lipoprotein subclasses, employing a Gaussian linear regression method with Lasso penalty to determine a lipoprotein profile associated with telomere-related parameters. The covariates included age, sex, body mass index (BMI), dyslipidemia, statin consumption, and physical activity leisure time. We identified a lipoprotein profile composed of four lipoprotein subfractions associated with TL (Pearson r = 0.347, p-value = 0.010), two lipoprotein subfractions associated with TERT expression (Pearson r = 0.316, p-value = 0.020), and five lipoprotein subfractions associated with WRAP53 expression (Pearson r = 0.379, p-value =0.005). After adjusting for known confounding factors, most lipoprotein profiles maintained the association with TL, TERT, and WRAP53. Overall, medium and small-sized HDL particles were associated with shorter telomeres and lower expression of TERT and WRAP53. Large HDL particles were associated with longer telomere and lower expression of WRAP53, but not with TERT. Our results suggest that the lipoprotein profiles are associated with telomere length, TERT, and WRAP53 expression and should be considered when assessing the risk of chronic diseases.

Examining the Interaction of the Gut Microbiome with Host Metabolism and Cardiometabolic Health in Metabolic Syndrome.

(1) Background: The microbiota-host cross-talk has been previously investigated, while its role in health is not yet clear. This study aimed to unravel the network of microbial-host interactions and correlate it with cardiometabolic risk factors. (2) Methods: A total of 47 adults with overweight/obesity and metabolic syndrome from the METADIET study were included in this cross-sectional analysis. Microbiota composition (151 genera) was assessed by 16S rRNA sequencing, fecal (m = 203) and plasma (m = 373) metabolites were profiled. An unsupervised sparse generalized canonical correlation analysis was used to construct a network of microbiota-metabolite interactions. A multi-omics score was derived for each cluster of the network and associated with cardiometabolic risk factors. (3) Results: Five multi-omics clusters were identified. Thirty-one fecal metabolites formed these clusters and were correlated with plasma sphingomyelins, lysophospholipids and medium to long-chain acylcarnitines. Seven genera from Ruminococcaceae and a member from the Desulfovibrionaceae family were correlated with fecal and plasma metabolites. Positive correlations were found between the multi-omics scores from two clusters with cholesterol and triglycerides levels. (4) Conclusions: We identified a correlated network between specific microbial genera and fecal/plasma metabolites in an adult population with metabolic syndrome, suggesting an interplay between gut microbiota and host lipid metabolism on cardiometabolic health.

Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors.

SCOPE: To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS: Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day-1 ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS: Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.

Effects of Mediterranean Diet on plasma metabolites and their relationship with insulin resistance and gut microbiota composition in a crossover randomized clinical trial.

BACKGROUND & AIMS: The Mediterranean Diet (MedDiet) may decrease the cardiometabolic risk through modulation of metabolic pathways. Furthermore, the interplay between MedDiet, metabolites and microbial metabolism may improve our understanding on the metabolic effects of this diet. We aimed to evaluate the effect of the MedDiet compared to nuts supplementation on circulating metabolites and their relationship with cardiometabolic health. We further examined whether changes in the metabolomic profiles were associated with changes in gut microbiota composition in a multi-omics integrative approach. METHODS: Forty-four adults with Metabolic Syndrome (MetS), (aged 37-65) participated in a randomized controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, consuming a MedDiet or a non MedDiet plus nuts (50 g/day). Nutritional data were collected at the beginning and the end of each intervention period using 3-day dietary records, as well as fasting blood and fecal samples. Plasma metabolites (m = 378) were profiled using targeted metabolomics. Associations of these metabolites with the interventions were assessed with elastic net regression analyses. Gut microbiota composition was assessed by 16S rRNA sequencing. A sparse least regression analysis combined with a canonical correlation analysis was conducted between the plasma selected metabolites and genera in order to identify the relevant dual-omics signatures discriminating the dietary interventions. RESULTS: Changes in 65 circulating metabolites were significantly associated with the MedDiet (mainly lipids, acylcarnitines, amino acids, steroids and TCA intermediates). Importantly, these changes were associated with decreases in glucose, insulin and HOMA-IR. The network analysis identified two main clusters of genera with an opposite behaviour towards selected metabolites, mainly PC species, ChoE(20:5), TGs and medium/long-chain acylcarnitines. CONCLUSION: Following a MedDiet, rather than consuming nuts in the context of a non-MedDiet was associated with a specific plasma metabolomic profile, which was also related to metabolic improvements in adults with MetS. The identified correlated network between specific bacteria and metabolites suggests interplay between diet, circulating metabolites and gut microbiota. The trial was registered in the ISRCTN with identifier ISRCTN88780852, https://doi.org/10.1186/ISRCTN88780852.

Chronic pistachio intake modulates circulating microRNAs related to glucose metabolism and insulin resistance in prediabetic subjects.

PURPOSE: To assess the effects of a pistachio-enriched diet on the profile of circulating microRNAs (miRNAs) related to glucose metabolism and insulin resistance (IR). METHODS: Randomized crossover clinical trial in 49 subjects with prediabetes was performed. Subjects consumed a pistachio-supplemented diet (PD, 50 % carbohydrates, 33 % fat, including 57 g/day of pistachios) and an isocaloric control diet (CD, 55 % carbohydrates and 30 % fat) for 4 months each, separated by a 2-week washout period. The plasma profile of a set of seven predefined miRNAs related to glucose and insulin metabolism was analyzed by quantitative RT-PCR. RESULTS: After the PD period, subjects have shown significant lower circulating levels of miR-192 and miR-375 compared to CD period, whereas miR-21 nonsignificantly increased after PD compared with CD (47 vs. 2 %, P = 0.092). Interestingly, changes in circulating miR-192 and miR-375 were positively correlated with plasma glucose, insulin and HOMA-IR. CONCLUSION: Chronic pistachio consumption positively modulates the expression of some miRNA previously implicated on insulin sensitivity.