Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Increased ultra-processed food consumption is associated with worsening of cardiometabolic risk factors in adults with metabolic syndrome: Longitudinal analysis from a randomized trial.

BACKGROUND AND AIMS: The association between changes in ultra-processed food (UPF) consumption and cardiometabolic risk (CMR) factors remains understudied. We evaluated the association between changes in UPF consumption over 12 months of follow-up and changes in CMR factors in adults diagnosed with metabolic syndrome. METHODS: We analysed data from 5373 adults (aged 55-75 years) participating in the PREDIMED-Plus trial. Diet was evaluated at baseline, 6- and 12-month visits using a validated food frequency questionnaire, and UPF consumption (in grams/day and percentage of total daily dietary intake in grams) was categorized based on NOVA classification. We used mixed-effects linear models with repeated measurements at baseline, 6 and 12 months of follow-up to assess the associations between changes in UPF consumption and changes in CMR factors adjusting for sociodemographic and lifestyles variables. RESULTS: In multivariable-adjusted models, when comparing the highest versus the lowest quartile of UPF consumption, positive associations were found for several CMR factors: weight (kg, ß = 1.09; 95% confidence interval 0.91 to 1.26); BMI (kg/m2, ß = 0.39; 0.33 to 0.46); waist circumference (cm, ß = 1.03; 0.81 to 1.26); diastolic blood pressure (mm Hg, ß = 0.67; 0.29 to 1.06); fasting blood glucose (mg/dl, ß = 1.66; 0.61 to 2.70); HbA1c (%, ß = 0.04; 0.01 to 0.07); triglycerides (mg/dl, ß = 6.79; 3.66 to 9.91) and triglycerides and glucose index (ß = 0.06; 0.04 to 0.08). CONCLUSIONS: Higher UPF consumption was associated with adverse evolution in objectively measured CMR factors after 12 months of follow-up in adults with metabolic syndrome. Further research is needed to explore whether these changes persist for longer periods.

Does Consumption of Ultra-Processed Foods Matter for Liver Health? Prospective Analysis among Older Adults with Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI (ß 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS.

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk.

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001].

Taxonomic and Functional Fecal Microbiota Signatures Associated With Insulin Resistance in Non-Diabetic Subjects With Overweight/Obesity Within the Frame of the PREDIMED-Plus Study.

Objective: An altered gut microbiota has been associated with insulin resistance, a metabolic dysfunction consisting of cellular insulin signaling impairment. The aim of the present study is to determine the taxonomic and functional fecal microbiota signatures associated with HOMA-IR index in a population with high cardiovascular risk. Methods: A total of 279 non-diabetic individuals (55-75 years aged) with overweight/obesity and metabolic syndrome were stratified according to tertiles of HOMA-IR index. Blood biochemical parameters, anthropometric measurements and fecal samples were collected at baseline. Fecal microbial DNA extraction, 16S amplicon sequencing and bioinformatics analysis were performed. Results: Desulfovibrio, Odoribacter and Oscillospiraceae UCG-002 were negatively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to amino acid degradation. Butyricicoccus, Erysipelotrichaceae UCG-003, Faecalibacterium were positively associated with HOMA-IR index, whereas predicted total functional abundances revealed gut metabolic modules mainly linked to saccharide degradation. These bacteria contribute differentially to the gut metabolic modules, being the degree of contribution dependent on insulin resistance. Both taxa and gut metabolic modules negatively associated to HOMA-IR index were linked to mechanisms involving sulfate reducing bacteria, improvement of intestinal gluconeogenesis and production of acetate. Furthermore, both taxa and gut metabolic modules positively associated to HOMA-IR index were linked to production and mechanisms of action of butyrate. Conclusions: Specific taxonomic and functional fecal microbiota signatures associated with insulin resistance were identified in a non-diabetic population with overweight/obesity at high cardiovascular risk. These findings suggest that tailoring therapies based on specific fecal microbiota profiles could be a potential strategy to improve insulin sensitivity.

One-year changes in fruit and vegetable variety intake and cardiometabolic risk factors changes in a middle-aged Mediterranean population at high cardiovascular risk.

BACKGROUND AND AIMS: Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome. METHODS: a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (ß-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors. RESULTS: Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (-0.33 mg/dL (0.58, -0.07)), body weight (-0.07 kg (-0.13, -0.02)) and waist circumference (WC) (-0.08 cm (-0.16, -10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (-0.50 mg/dL (-0.93, -0.08)), glucose (-0.21 mg/dL (-0.32, -0.11)), body weight (-0.11 kg (-0.15, -0.07)) and WC (-0.10 cm (-0.14, -0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (-1.26 mg/dL (-2.09, -0.43)), body weight (-0.40 kg (-0.58, -0.23)) and WC (-0.50 cm (-0.73, -0.28)). CONCLUSION: Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk.

High Fruit and Vegetable Consumption and Moderate Fat Intake Are Associated with Higher Carotenoid Concentration in Human Plasma.

Carotenoids are pigments contained mainly in fruit and vegetables (F&V) that have beneficial effects on cardiometabolic health. Due to their lipophilic nature, co-ingestion of fat appears to increase their bioavailability via facilitating transfer to the aqueous micellar phase during digestion. However, the extent to which high fat intake may contribute to increased carotenoid plasma concentrations is still unclear. The objective was to examine the degree to which the consumption of different amounts of both carotenoid-rich foods and fats is associated with plasma carotenoid concentrations within a Mediterranean lifestyle context (subsample from the PREDIMED-Plus study baseline) where consumption of F&V and fat is high. The study population was categorized into four groups according to their self-reported consumption of F&V and fat. Carotenoids were extracted from plasma samples and analyzed by HPLC-UV-VIS-QqQ-MS/MS. Carotenoid systemic concentrations were greater in high consumers of F&V than in low consumers of these foods (+3.04 µmol/L (95% CI: 0.90, 5.17), p-value = 0.005), but circulating concentrations seemed to decrease when total fat intake was very high (-2.69 µmol/L (-5.54; 0.16), p-value = 0.064). High consumption of F&V is associated with greater systemic levels of total carotenoids, in particular when fat intake is low-to-moderate rather than very high.

Psychological and metabolic risk factors in older adults with a previous history of eating disorder: A cross-sectional study from the Predimed-Plus study.

GOALS: To explore affective and cognitive status, later in life, in individuals with and without previous history of eating disorder (ED), and also its association with higher risk for metabolic syndrome (MetS) symptomatology. METHODS: A cross-sectional analysis of 6756 adults, aged 55-75 years with overweight/obesity and MetS participating in the Predimed-Plus study was conducted. Participants completed self-reported questionnaires to examine lifetime history of ED, according to DSM-5 criteria, and other psychopathological and neurocognitive factors. Anthropometric and metabolic measurements were also collected. RESULTS: Of the whole sample, 24 individuals (0.35%) reported a previous history of ED. In this subsample, there were more women and singles compared to their counterparts, but they also presented higher levels of depressive symptoms and higher cognitive impairment, but also higher body mass index (BMI) and severe obesity, than those without lifetime ED. CONCLUSIONS: This is one of the first studies to analyse the cognitive and metabolic impact of a previous history of ED. The results showed that previous ED was associated with greater affective and cognitive impairment, but also with higher BMI, later in life. No other MetS risk factors were found, after controlling for relevant variables.

Variety in fruits and vegetables, diet quality and lifestyle in an older adult mediterranean population.

BACKGROUND AND AIMS: Previous studies, mainly focused on quantity rather than variety, have shown beneficial associations between the amount of fruit and vegetable consumed, diet quality and healthy lifestyle. The aim is to evaluate the association between fruit and vegetable consumption, diet quality and lifestyle in an elderly Mediterranean population, considering both variety and the combination of quantity and variety (QV). METHODS: A cross-sectional analysis of 6647 participants (51.6% of males) was conducted in the framework of the PREDIMED-Plus study. A variety score was created as the sum of vegetables and/or fruits consumed at least once per month using food frequency questionnaires. Dietary Reference Intakes (EAR and IA values) were used to estimate the prevalence of inadequate intake of dietary fiber and micronutrients. Logistic regression models were performed to examine the association between fruit and vegetable consumption and not meeting the DRIs, by tertiles of fruit and vegetable variety and QV categories. RESULTS: Participants with higher fruit and vegetable variety score reported a significant higher intake of fiber, vitamins, minerals and flavonoids and were significantly more likely to be physically active and non-smoker. Besides, higher variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.13 (0.11-0.16)], two or more [(0.17 (0.14-0.21)], three or more [(0.15 (0.13-0.18)] and four or more [(0.11 (0.10-0.14)] micronutrients in our participants. Higher quantity and variety in fruit and vegetable consumption was associated with lower prevalence of having an inadequate intake of fiber [(0.05 (0.04-0.06)], two or more [(0.08 (0.06-0.10)], three or more [(0.08 (0.06-0.09)] and four or more [(0.06 (0.05-0.07)] micronutrients. CONCLUSION: Greater variety in fruit and vegetable intake was associated with better nutrient adequacy, diet quality and healthier lifestyle in an elderly Mediterranean population.

Differential Microbial Pattern Description in Subjects with Autoimmune-Based Thyroid Diseases: A Pilot Study.

The interaction between genetic susceptibility, epigenetic, endogenous, and environmental factors play a key role in the initiation and progression of autoimmune thyroid diseases (AITDs). Studies have shown that gut microbiota alterations take part in the development of autoimmune diseases. We have investigated the possible relationship between gut microbiota composition and the most frequent AITDs. A total of nine Hashimoto's thyroiditis (HT), nine Graves-Basedow's disease (GD), and 11 otherwise healthy donors (HDs) were evaluated. 16S rRNA pyrosequencing and bioinformatics analysis by Quantitative Insights into Microbial Ecology and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to analyze the gut microbiota. Beta diversity analysis showed that gut microbiota from our groups was different. We observed an increase in bacterial richness in HT and a lower evenness in GD in comparison to the HDs. GD showed a significant increase of Fusobacteriaceae, Fusobacterium and Sutterella compared to HDs and the core microbiome features showed that Prevotellaceae and Prevotella characterized this group. Victivallaceae was increased in HT and was part of their core microbiome. Streptococcaceae, Streptococcus and Rikenellaceae were greater in HT compared to GD. Core microbiome features of HT were represented by Streptococcus, Alistipes, Anaerostipes, Dorea and Haemophilus. Faecalibacterium decreased in both AITDs compared to HDs. PICRUSt analysis demonstrated enrichment in the xenobiotics degradation, metabolism, and the metabolism of cofactors and vitamins in GD patients compared to HDs. Moreover, correlation studies showed that some bacteria were widely correlated with autoimmunity parameters. A prediction model evaluated a possible relationship between predominant concrete bacteria such as an unclassified genus of Ruminococcaceae, Sutterella and Faecalibacterium in AITDs. AITD patients present altered gut microbiota compared to HDs. These alterations could be related to the immune system development in AITD patients and the loss of tolerance to self-antigens.

Coronavirus disease 2019 (COVID-19) and obesity. Impact of obesity and its main comorbidities in the evolution of the disease.

The COVID-19 pandemic is posing a great challenge worldwide. Its rapid progression has caused thousands of deaths worldwide. Although multiple aspects remain to be clarified, some risk factors associated with a worse prognosis have been identified. These include obesity and some of its main complications, such as diabetes and high blood pressure. Furthermore, although the possible long-term complications and psychological effects that may appear in survivors of COVID-19 are not well known yet, there is a concern that those complications may be greater in obese patients. In this manuscript, we review some of the data published so far and the main points that remain to be elucidated are emphasized.