Autochthonous cultures to improve the quality of PGI Castellano cheese: Impact on proteolysis, microstructure and texture during ripening.

The aim of this research was to find out the effect of different combinations of starter and non-starter cultures on the proteolysis of Castellano cheese during ripening. Four cheese batches were prepared, each containing autochthonous lactobacilli and or Leuconostoc, and were compared with each other and with a control batch, that used only a commercial starter. To achieve this, nitrogen fractions (pH 4.4-soluble nitrogen and 12 % trichloroacetic acid soluble nitrogen, polypeptide nitrogen and casein nitrogen), levels of free amino acids and biogenic amines were assessed. Texture and microstructure of cheeses were also evaluated. Significant differences in nitrogen fractions were observed between batches at different stages of ripening. The free amino acid content increased throughout the cheese ripening process, with a more significant increase occurring after the first 30 days. Cheeses containing non-starter lactic acid bacteria exhibited the highest values at the end of the ripening period. Among the main amino acids, GABA was particularly abundant, especially in three of the cheese batches at the end of ripening. The autochthonous lactic acid bacteria were previously selected as non-producers of biogenic amines and this resulted in the absence of these compounds in the cheeses. Analysis of the microstructure of the cheese reflected the impact of proteolysis. Additionally, the texture profile analysis demonstrated that the cheese's hardness intensified as the ripening period progressed. The inclusion of autochthonous non-starter lactic acid bacteria in Castellano cheese production accelerated the proteolysis process, increasing significantly the free amino acids levels and improving the sensory quality of the cheeses.

From the gut to the brain: the long journey of phenolic compounds with neurocognitive effects.

The human gut microbiota is a complex community of micro-organisms that play a crucial role in maintaining overall health. Recent research has shown that gut microbes also have a profound impact on brain function and cognition, leading to the concept of the gut-brain axis. One way in which the gut microbiota can influence the brain is through the bioconversion of polyphenols to other bioactive molecules. Phenolic compounds are a group of natural plant metabolites widely available in the human diet, which have anti-inflammatory and other positive effects on health. Recent studies have also suggested that some gut microbiota-derived phenolic metabolites may have neurocognitive effects, such as improving memory and cognitive function. The specific mechanisms involved are still being studied, but it is believed that phenolic metabolites may modulate neurotransmitter signaling, reduce inflammation, and enhance neural plasticity. Therefore, to exert a protective effect on neurocognition, dietary polyphenols or their metabolites must reach the brain, or act indirectly by producing an increase in bioactive molecules such as neurotransmitters. Once ingested, phenolic compounds are subjected to various processes (eg, metabolization by gut microbiota, absorption, distribution) before they cross the blood-brain barrier, perhaps the most challenging stage of their trajectory. Understanding the role of phenolic compounds in the gut-brain axis has important implications for the development of new therapeutic strategies for neurological and psychiatric disorders. By targeting the gut microbiota and its production of phenolic metabolites, it may be possible to improve brain function and prevent cognitive decline. In this article, the current state of knowledge on the endogenous generation of phenolic metabolites by the gut microbiota and how these compounds can reach the brain and exert neurocognitive effects was reviewed.

Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation.

BACKGROUND: The identification of novel therapeutic strategies to overcome resistance to the MEK inhibitor trametinib in mutant KRAS lung adenocarcinoma (LUAD) is a challenge. This study analyzes the effects of trametinib on Id1 protein, a key factor involved in the KRAS oncogenic pathway, and investigates the role of Id1 in the acquired resistance to trametinib as well as the synergistic anticancer effect of trametinib combined with immunotherapy in KRAS-mutant LUAD. METHODS: We evaluated the effects of trametinib on KRAS-mutant LUAD by Western blot, RNA-seq and different syngeneic mouse models. Genetic modulation of Id1 expression was performed in KRAS-mutant LUAD cells by lentiviral or retroviral transductions of specific vectors. Cell viability was assessed by cell proliferation and colony formation assays. PD-L1 expression and apoptosis were measured by flow cytometry. The anti-tumor efficacy of the combined treatment with trametinib and PD-1 blockade was investigated in KRAS-mutant LUAD mouse models, and the effects on the tumor immune infiltrate were analyzed by flow cytometry and immunohistochemistry. RESULTS: We found that trametinib activates the proteasome-ubiquitin system to downregulate Id1 in KRAS-mutant LUAD tumors. Moreover, we found that Id1 plays a major role in the acquired resistance to trametinib treatment in KRAS-mutant LUAD cells. Using two preclinical syngeneic KRAS-mutant LUAD mouse models, we found that trametinib synergizes with PD-1/PD-L1 blockade to hamper lung cancer progression and increase survival. This anti-tumor activity depended on trametinib-mediated Id1 reduction and was associated with a less immunosuppressive tumor microenvironment and increased PD-L1 expression on tumor cells. CONCLUSIONS: Our data demonstrate that Id1 expression is involved in the resistance to trametinib and in the synergistic effect of trametinib with anti-PD-1 therapy in KRAS-mutant LUAD tumors. These findings suggest a potential therapeutic approach for immunotherapy-refractory KRAS-mutant lung cancers.

Real life experience of tafamidis for the treatment of Spanish patients with Val30Met transthyretin amyloidosis with polyneuropathy.

INTRODUCTION: Tafamidis is the only approved transthyretin stabiliser approved for the treatment of variant transthyretin amyloidosis (A-ATTRv) related polyneuropathy (PNP). The aim of this study is to analyse the effectiveness of tafamidis in a real-world setting in Spain. METHODS: This is a national multicenter study in which patients with V30M A-ATTR related PN treated with tafamidis for at least 1 year were included. Clinical, demographic, analytical and neurophysiological variables were analysed. RESULTS: 100 patients were recruited. Overall, 47 patients (47%) were classified as complete responders, 32 (32%) as partial responders and 21 (21%) as non-responders. The median duration of treatment with tafamidis was 35 months. Better treatment response was shown in patients with in polyneuropathy disability score (PND) I, lower neuropathy impairment score (NIS), compound muscle action potential (CMAP) and Norfolk QoL questionnaire. Higher albumin levels and lower NTproBNP levels were also associated with better treatment response. A basal NIS≥15 predicts that the patient could be a non-responder with a 60% probability. CONCLUSIONS: Our results reinforce the tafamidis efficacy to treat A-ATTRv-PNP if started early in the disease course. Patients with the V30M variant, NIS<15 and PND I are the most appropriate subjects for this treatment.

Moderate wine consumption measured using the biomarker urinary tartaric acid concentration decreases inflammatory mediators related to atherosclerosis.

OBJECTIVES: Several studies suggest that moderate wine consumption, particularly red wine, may have benefits for cardiovascular health. Red wine contains a variety of bioactive compounds, including polyphenols like phenolic acids, which have demonstrated anti-inflammatory effects in experimental models. The aim of this study was to assess the anti-inflammatory properties of wine, measured as urinary tartaric acid, a new biomarker of wine consumption. DESIGN, SETTINGS, AND PARTICIPANTS: One-year longitudinal study that included 217 participants from the PREDIMED trial. MEASUREMENTS: Plasma inflammatory biomarkers and urinary tartaric acid were analyzed using xMAP technology and high-performance liquid chromatography, respectively. Multivariable regression analyses were performed to assess the relationship between variations over 1-year in urinary tartaric acid concentrations and 1-year changes in serum inflammatory molecules, including adhesion cell molecules, interleukine-6, tumour necrosis factor alpha, and monocyte chemotactic protein 1. Three categories were built according to tertiles of 1-y changes in urinary tartaric acid. RESULTS: Using a ROC curve, urinary tartaric acid was corroborated as a reliable biomarker of wine consumption (AUC = 0.818 (95% CI: 0.76; 0.87). In the continuous analysis, participants with higher increases in tartaric acid significantly reduced their concentrations in soluble vascular adhesion molecule (sVCAM-1) after 1-year of follow-up (-0.20 (-0.38; -9,93) ng/mL per 1-SD increment, p-value = 0.031). Moreover, tertiles 2 and 3 of 1-year changes in tartaric acid presented a significant reduction in soluble intercellular cell adhesion molecule (sICAM-1) as compared to tertile 1 (-0.31 (-0.52; -0.10) ng/mL, p-value = 0.014 and -0.29 (-0.52; -0.07) ng/mL, p-value = 0.023, respectively). Participants in the third tertile also exhibited a reduced concentration of sVCAM-1 compared to those in the first tertile (-0.31 (-0.55; -0.06) ng/mL, p-value = 0.035). CONCLUSIONS: Our findings suggest that wine consumption is associated with lower levels of inflammation due to the anti-inflammatory properties of wine compounds.

Biomarkers of axonal damage to favor early diagnosis in variant transthyretin amyloidosis (A-ATTRv).

Early identification of ATTRv amyloidosis disease onset is still often delayed due to the lack of validated biomarkers of this disease. Light chain neurofilament (NfL) have shown promising results in early diagnosis in this disease, but data is still needed, including with alternative measuring methods. Our aim was to study the levels of NfL measured by ELISA. Furthermore, interstitial matrix metalloproteinase type 1 (MMP-1) serum levels were measured as a potential new biomarker in ATTRv. Serum NfL and MMP-1 were measured using ELISA assays in 90 participants (29 ATTR-V30M patients, 31 asymptomatic V30M-TTR variant carriers and 30 healthy controls). Median NfL levels among ATTRv amyloidosis patients were significantly higher (116 pg/mL vs 0 pg/mL in both comparison groups). The AUC comparing ATTRv amyloidosis patients and asymptomatic carriers was 0.90 and the NfL concentration of 93.55 pg/mL yielded a sensitivity of 79% and a specificity of 87%. NfL levels had a significant positive correlation with NIS values among patients. We found a negative significant correlation between eGFR and NfL levels. Finally, MMP1 levels were not different between groups. Evidence of NfL use for early diagnosis of ATTR-PN amyloidosis is growing. ELISA seems a reliable and available technique for it quantification. Decreased GFR could influence NfL plasma levels.

Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health.

SCOPE: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. METHODS AND RESULTS: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. CONCLUSIONS: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.

Higher circulating vitamin B12 is associated with lower levels of inflammatory markers in individuals at high cardiovascular risk and in naturally aged mice.

BACKGROUND: Vitamin B12 is an essential nutrient that is involved in numerous physiological processes, and its deficiency can lead to various complications, including neurological and haematological disorders. Some studies have suggested that vitamin B12 may have anti-inflammatory effects, but the mechanisms underlying this relationship are not yet fully understood. We investigated the relationship between circulating vitamin B12 and inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP). The association of peripheral levels of vitamin B12 with IL-6 and CRP was assessed in 136 human samples from a high cardiovascular risk population. To corroborate the results from the human trial, the analysis was replicated in naturally aged mice. RESULTS: Individuals with higher serum levels of vitamin B12 showed lower concentrations of IL-6 and CRP after adjustment for potential confounders, and an inverse association was also found between serum IL-6 and vitamin B12 levels in naturally aged mice. CONCLUSION: Circulating vitamin B12 was inversely associated with IL-6 and CRP in humans and with IL-6 in mice, suggesting that it may exert an anti-inflammatory effect through modulation of these pro-inflammatory molecules. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Occupational practice in patients with hereditary transthyretin amyloidosis, a qualitative study.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disease that negatively affects patients' quality of life through the involvement of various organs and tissues. Despite a large amount of research on medical and psychosocial interventions, the impact of occupational therapy (OT) on patients with ATTRv is not well understood. OBJECTIVE: The aim of this study was to develop an OT programme to improve the daily functioning and quality of life of patients with ATTRv. METHODS: Fourteen patients with ATTRv were interviewed. Together they developed short- and medium-term occupational goals. Patients received the OT intervention for six months. Outcomes were measured using scores for activities of daily living and psychological well-being. RESULTS: The study found that OT can have a positive impact as a complementary intervention to medical and other psychosocial treatments. Of the 14 patients, 12 maintained the same scores in activities of daily living. Two deteriorated and eight improved their psychological scores. CONCLUSION: This study highlights the need for further research in this area and the importance of OT in the management of patients with ATTRv. Early intervention is of paramount importance and further research is needed to evaluate the long-term effects of OT interventions in patients with ATTRv.

Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer.

Drug combinations are key to circumvent resistance mechanisms compromising response to single anti-cancer targeted therapies. The implementation of combinatorial approaches involving MEK1/2 or KRASG12C inhibitors in the context of KRAS-mutated lung cancers focuses fundamentally on targeting KRAS proximal activators or effectors. However, the antitumor effect is highly determined by compensatory mechanisms arising in defined cell types or tumor subgroups. A potential strategy to find drug combinations targeting a larger fraction of KRAS-mutated lung cancers may capitalize on the common, distal gene expression output elicited by oncogenic KRAS. By integrating a signature-driven drug repurposing approach with a pairwise pharmacological screen, here we show synergistic drug combinations consisting of multi-tyrosine kinase PKC inhibitors together with MEK1/2 or KRASG12C inhibitors. Such combinations elicit a cytotoxic response in both in vitro and in vivo models, which in part involves inhibition of the PKC inhibitor target AURKB. Proteome profiling links dysregulation of MYC expression to the effect of both PKC inhibitor-based drug combinations. Furthermore, MYC overexpression appears as a resistance mechanism to MEK1/2 and KRASG12C inhibitors. Our study provides a rational framework for selecting drugs entering combinatorial strategies and unveils MEK1/2- and KRASG12C-based therapies for lung cancer.

A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer.

Background: Harnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [89Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC. Materials and methods: A syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [89Zr]-labeled anti-PD-1 antibody and measured as 89Zr tumor uptake. Results: Conventional [18F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [89Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [89Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001). Conclusion: Our data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC.

A narrative review and expert recommendations on the assessment of the clinical manifestations, follow-up, and management of post-OLT patients with ATTRv amyloidosis.

Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT.

Tomato wastes and by-products: upcoming sources of polyphenols and carotenoids for food, nutraceutical, and pharma applications.

Tomato pomace, a waste product consisting of peels, seeds, rich on fibrous matter, represents an underutilized source of bioactive compounds, such as polyphenols and carotenoids. Here we present a three-pronged review of the circular utilization of tomato waste in line with the United Nations Sustainable Development Goals. First, we explain why tomato waste is important, highlighting the processing techniques that generate it. The bioactive compounds in these by-products are then comprehensively reviewed, focusing especially on phenolic compounds and carotenoids and the methods used for their extraction. Finally, we examine the potential of these bioactive ingredients for application in food systems and pharmaceutical products.

The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer.

BACKGROUND: The discovery of functionally relevant KRAS effectors in lung and pancreatic ductal adenocarcinoma (LUAD and PDAC) may yield novel molecular targets or mechanisms amenable to inhibition strategies. Phospholipids availability has been appreciated as a mechanism to modulate KRAS oncogenic potential. Thus, phospholipid transporters may play a functional role in KRAS-driven oncogenesis. Here, we identified and systematically studied the phospholipid transporter PITPNC1 and its controlled network in LUAD and PDAC. METHODS: Genetic modulation of KRAS expression as well as pharmacological inhibition of canonical effectors was completed. PITPNC1 genetic depletion was performed in in vitro and in vivo LUAD and PDAC models. PITPNC1-deficient cells were RNA sequenced, and Gene Ontology and enrichment analyses were applied to the output data. Protein-based biochemical and subcellular localization assays were run to investigate PITPNC1-regulated pathways. A drug repurposing approach was used to predict surrogate PITPNC1 inhibitors that were tested in combination with KRASG12C inhibitors in 2D, 3D, and in vivo models. RESULTS: PITPNC1 was increased in human LUAD and PDAC, and associated with poor patients' survival. PITPNC1 was regulated by KRAS through MEK1/2 and JNK1/2. Functional experiments showed PITPNC1 requirement for cell proliferation, cell cycle progression and tumour growth. Furthermore, PITPNC1 overexpression enhanced lung colonization and liver metastasis. PITPNC1 regulated a transcriptional signature which highly overlapped with that of KRAS, and controlled mTOR localization via enhanced MYC protein stability to prevent autophagy. JAK2 inhibitors were predicted as putative PITPNC1 inhibitors with antiproliferative effect and their combination with KRASG12C inhibitors elicited a substantial anti-tumour effect in LUAD and PDAC. CONCLUSIONS: Our data highlight the functional and clinical relevance of PITPNC1 in LUAD and PDAC. Moreover, PITPNC1 constitutes a new mechanism linking KRAS to MYC, and controls a druggable transcriptional network for combinatorial treatments.

Total urinary polyphenol excretion: a biomarker of an anti-inflammatory diet and metabolic syndrome status.

BACKGROUND: Chronic inflammation is associated with noncommunicable diseases, including obesity, metabolic syndrome (MetS), and CVDs. The Mediterranean diet has been shown to have strong anti-inflammatory effects, attributed in part to the polyphenol richness of many of its components. OBJECTIVES: This study aimed to assess the value of polyphenols as a urinary biomarker of an anti-inflammatory diet and their influence on MetS status. METHODS: A longitudinal analysis was performed in Spain considering 543 participants with high CVD risk in a PREDIMED study. Approximately 52% of the participants were women and 48% were men with a mean age of 67.5 (5.9) y. Total polyphenol excretion (TPE) in urine was determined at baseline and 5 y of intervention using a validated Folin-Ciocalteu spectrophotometric method, and the dietary inflammatory index (DII) was calculated from a validated 137-item food-frequency questionnaire. Three categories were built according to tertiles of change in the DII score. Multivariable linear regression analyses were performed to assess the association of changes in TPE with changes in the DII scores and with MetS status at 5 y. RESULTS: Tertiles 2 and 3 compared with tertile 1 presented a lower anti-inflammatory potential of the diet and were inversely associated with TPE in women [-0.30 mg gallic acid equivalent (GAE)/g creatinine; 95% CI: -0.46, -0.15; P value = 0.006 and -0.29 mg GAE/g creatinine; 95% CI: -0.43, -0.15; P value = 0.005], respectively. The mean changes in TPE were 7.9 (56.1) mg GAE/g creatinine in women and 7.7 (48.2) mg GAE/g creatinine in men. In addition, TPE was inversely associated with changes in MetS status [-0.06 (-0.09; -0.02), P value = 0.009] in both men and women. CONCLUSIONS: Urinary polyphenols may be a potential biomarker of anti-inflammatory diet consumption in women and are prospectively associated with improvement in MetS.

Urinary metabolomics of phenolic compounds reveals biomarkers of type-2 diabetes within the PREDIMED trial.

BACKGROUND: Phenolic compounds have been associated with protective effects against type-2 diabetes (T2D). We used a metabolomics approach to determine urinary phenolic metabolites associated with T2D and fasting plasma glucose. METHODS: This case-control study within the PREDIMED trial included 200 participants at high cardiovascular risk, 102 of whom were diagnosed with T2D. A panel of urinary phenolic compounds were analysed using a novel method based on liquid chromatography coupled to mass spectrometry. Multivariate statistics and adjusted logistic regressions were applied to determine the most discriminant compounds and their association with T2D. The relationship between the discriminant phenolic compounds and plasma glucose was assessed using multivariable linear regressions. RESULTS: A total of 41 phenolic compounds were modeled in the orthogonal projection to latent structures discriminant analysis, and after applying adjusted logistic regressions two were selected as discriminant: dihydrocaffeic acid (OR = 0.22 (CI 95 %: 0.09; 0.52) per 1-SD, p-value = 0.021) and genistein diglucuronide (OR = 0.72 (CI 95%: 0.59; 0.88) per 1-SD, p-value = 0.021). Both metabolites were associated with a lower risk of suffering from T2D, but only dihydrocaffeic acid was inversely associated with plasma glucose (ß = -17.12 (95 % CI: -29.92; -4.32) mg/dL per 1-SD, p-value = 0.009). CONCLUSIONS: A novel method using a metabolomics approach was developed to analyse a panel of urinary phenolic compounds for potential associations with T2D, and two metabolites, dihydrocaffeic acid and genistein diglucuronide, were found to be associated with a lower risk of this condition.

Association of microbiota polyphenols with cardiovascular health in the context of a Mediterranean diet.

BACKGROUND AND AIMS: The Mediterranean diet (MedDiet) is rich in polyphenols, phytochemicals that are beneficial for cardiovascular health. Phenolic compounds have poor bioavailability but they are extensively metabolized by the gut microbiota. Therefore, we aimed to assess the association of microbial phenolic metabolites (MPM) with adherence to the MedDiet, and their relationship with ideal cardiovascular health (ICVH) and cardiovascular risk factors. METHODS AND RESULTS: This cross-sectional substudy within the PREDIMED trial included 200 participants from the Barcelona-Clinic recruitment center. Five MPM were identified and quantified using a novel method based on liquid chromatography coupled to mass spectrometry: protocatechuic acid (PCA), enterodiol glucuronide (EDG), enterolactone glucuronide (ELG), vanillic acid glucuronide (VAG) and urolithin B glucuronide (UBG). Multivariable-adjusted regressions were used to evaluate the associations between MPM and MedDiet adherence, ICVH score, biochemical parameters, and blood pressure. Additionally, an MPM score was calculated as the weighted sum of MedDiet adherence and ICVH and found to be directly associated. Among individual polyphenols, UBG was inversely associated with LDL-cholesterol. CONCLUSIONS: A score of urinary MPM was associated with higher adherence to the MedDiet and ICVH, and individual MPM were related to better cardiovascular health. These findings suggest that the MedDiet may affect gut microbiota, whose metabolites are linked with cardiovascular health.

Urinary Phenolic Metabolites Associated with Peanut Consumption May Have a Beneficial Impact on Vascular Health Biomarkers.

Phenolic compounds in peanuts may moderate inflammation and endothelial function. Thus, the aim of this study was to evaluate the association of urinary phenolic metabolites (UPMs) with vascular biomarkers after peanut product consumption. A three-arm parallel-group randomized controlled trial was conducted in 63 healthy young adults who consumed 25 g/day of skin roasted peanuts (SRP), 32 g/day of peanut butter (PB), or 32 g/day of a control butter for six months. UPMs were analyzed by liquid chromatography coupled to mass spectrometry. Additionally, urinary eicosanoids, prostacyclin I2 (PGI2), and thromboxane A2 (TXA2) were determined using two competitive enzyme-linked immunosorbent assay kits. Consumers of SRP and PB presented significantly higher excretion of UPMs (enterodiol glucuronide (p = 0.018 and p = 0.031), 3-hydroxybenzoic acid (p = 0.002 and p < 0.001), vanillic acid sulfate (p = 0.048 and p = 0.006), p-coumaric acid (p = 0.046 and p = 0.016), coumaric acid glucuronide I (p = 0.001 and p = 0.030) and II (p = 0.003 and p = 0.036), and isoferulic acid (p = 0.013 and p = 0.015) in comparison with the control group. An improvement in PGI2 (p = 0.037) levels and the TXA2:PGI2 ratio (p = 0.008) was also observed after the peanut interventions compared to the control. Interestingly, UPMs with significantly higher post-intervention levels were correlated with an improvement in vascular biomarkers, lower TXA2 (r from -0.25 to -0.48, p < 0.050) and TXA2:PGI2 ratio (r from -0.25 to -0.43, p < 0.050) and higher PGI2 (r from 0.24 to 0.36, p < 0.050). These findings suggest that the UPMs with higher excretion after peanut product consumption could have a positive impact on vascular health.