The Mediterranean diet is a well-recognized healthy diet that has shown to induce positive changes in gut microbiota. Lifestyle changes such as diet along with physical activity could aid in weight loss and improve cardiovascular risk factors. To investigate the effect of an intensive lifestyle weight loss intervention on gut microbiota. This is a substudy of the PREDIMED-Plus (Prevención con Dieta Mediterránea-Plus), a randomized controlled trial conducted in overweight/obese men and women (aged 55–75 y) with metabolic syndrome. The intervention group (IG) underwent an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet) and physical activity promotion, and the control group (CG) underwent a non-energy-restricted MedDiet for 1 y. Anthropometric, biochemical, and gut microbial 16S rRNA sequencing data were analyzed at baseline (n = 362) and 1-y follow-up (n = 343). IG participants had a weight loss of 4.2 (IQR, –6.8, –2.5) kg compared with 0.2 (IQR, –2.1, 1.4) kg in the CG (P < 0.001). Reductions in BMI, fasting glucose, glycated hemoglobin, and triglycerides and an increase in HDL cholesterol were greater in IG than in CG participants (P < 0.05). We observed a decrease in Butyricicoccus, Haemophilus, Ruminiclostridium 5, and Eubacterium hallii in the IG compared with the CG. Many genera shifted in the same direction within both intervention groups, indicating an overall effect of the MedDiet. Decreases in Haemophilus, Coprococcus 3, and few other genera were associated with a decrease in adiposity parameters in both intervention groups. Changes in Lachnospiraceae NK4A136 were positively associated with changes in MedDiet adherence. Weight loss induced by an energy-restricted MedDiet and physical activity induce changes in gut microbiota. The role of MedDiet-induced changes on the host might be via short-chain fatty acid producing bacteria, whereas with energy restriction, these changes might be modulated with other mechanisms, which need to be explored in future studies. This trial was registered at http://www.isrctn.com/ISRCTN89898870 as ISRCT 89898870.

The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects (n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55–75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and <40 kg/m²) and metabolic syndrome. Using the information of food frequency questionnaires, the consumption of UPF, expressed as a percentage of total dietary energy intake in kcal/day, was calculated considering those food items classified in group 4 of NOVA system. Population was categorized according to tertiles of UPF consumption. Taxonomic fecal microbiota information, along with blood biochemical parameters, anthropometric measurements and clinical data were obtained. Bioinformatics analysis was performed to study the association between fecal microbiota composition and UPF consumption. We observed that subjects allocated in the highest tertile of UPF consumption (21.4 ± 5.0 % kcal/day) presented lower adherence to MedDiet (p < 0.001) and higher total energy intake (p < 0.001). The taxonomic analysis of the fecal microbiota revealed a significant (Benjamini-Hochberg adjusted p < 0.2) positive association between specific taxa and tertiles (T) of UPF consumption: Alloprevotella (p = 0.041 vs. T2; p = 0.065 vs. T3), Negativibacillus (p = 0.096 vs. T3), Prevotella (p = 0.116 vs. T3), and Sutterella (p = 0.116 vs. T2). UPF consumption was positively associated with lower adherence to MedDiet and higher total energy intake in senior subjects with overweight obesity and metabolic syndrome. In addition, positive association with specific fecal microbiota taxa related to inflammatory gastro-intestinal diseases and low consumption of fruits and vegetables, was observed.

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.

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. Our goal was to investigate the weight loss effects of a 1-year lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared to an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular risk factors METHODS: A total of 400 participants (200 from each study group), aged 55-75 years, and at high cardiovascular risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 year 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. Compared to the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular risk factors. We identified intervention effects on four 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 risk factors. Additionally, 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 year of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular risk factors. 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. ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

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.

Diabetes is a continuously growing global concern affecting >10% of adults, which may be mitigated by modifiable lifestyle factors. Consumption of nuts and their inclusion in dietary patterns has been associated with a range of beneficial health outcomes. Diabetes guidelines recommend dietary patterns that incorporate nuts; however, specific recommendations related to nuts have been limited. This review considers the epidemiological and clinical evidence to date for the role of nut consumption as a dietary strategy for the prevention and management of type 2 diabetes (T2D) and related complications. Findings suggest nut consumption may have a potential role in the prevention and management of T2D, with mechanistic studies assessing nuts and individual nut-related nutritional constituents supporting this possibility. However, limited definitive evidence is available to date, and future studies are needed to elucidate better the impact of nuts on the prevention and management of T2D.