Perspective on the Coevolutionary Role of Host and Gut Microbiota in Polyphenol Health Effects: Metabotypes and Precision Health.

"Personalized nutrition" aims to establish nutritional strategies to improve health outcomes for non-responders. However, it is utopian since most people share similar nutritional requirements. "Precision health," encompassing lifestyles, may be more fitting.

Polyphenolic Characterization and Anti-Inflammatory Effect of In Vitro Digested Extracts of L. Plant Parts in an Inflammatory Model of Human Colon Cells.

L. (EP) preparations are globally popular herbal supplements known for their medicinal benefits, including anti-inflammatory activities, partly related to their phenolic composition. However, regarding their use for the management of inflammation-related intestinal diseases, the knowledge about the fate of orally ingested constituents throughout the human gastrointestinal tract and the exposition of in vitro digested extracts in relevant inflammatory models are unknown.

Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, , non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant.

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging.

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice.

(,)-Equol 7-β-D-glucuronide, but not other circulating isoflavone metabolites, modulates migration and tubulogenesis in human aortic endothelial cells targeting the VEGF pathway.

Current knowledge indicates that the consumption of isoflavone-rich foodstuffs can have a beneficial impact on cardiovascular health. To what extent these isoflavones act as the main actors of that benefit is less clear. Genistein (GEN), daidzein (DAZ), and the DAZ-derived microbial metabolite equol (Eq) exhibit antiangiogenic effects , but their low bloodstream concentrations make it difficult to rationalize the effects.

Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs.

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs.

NMR Spectroscopic Identification of Urolithin G, a Novel Trihydroxy Urolithin Produced by Human Intestinal Species.

Urolithins are gut microbiota metabolites of ellagic acid. Here, we have identified and chemically characterized a novel urolithin produced from urolithin D (3,4,8,9-tetrahydroxy urolithin) by in vitro incubation with different human gut species under anaerobic conditions. Urolithin G (3,4,8-trihydroxy urolithin) was identified by H NMR, C NMR, UV, HRMS, and 2D NMR.

Adjuvant pomegranate juice intake improves the inflammatory status of hospitalized COVID-19 patients: A randomized and placebo-controlled trial.

Background: This study aimed to evaluate the effect of pomegranate juice intake on the inflammatory status and complete blood count in hospitalized Covid-19 patients.

Methods: This randomized, double-blinded placebo-controlled trial included 48 patients with two parallel arms. In addition to the standard care provided at the hospital, the patients consumed 500 mL of whole pomegranate juice (PJ) daily or a placebo for 14 days.

Ellagic acid and its metabolites urolithins A/B ameliorate most common disease phenotypes in cellular and mouse models for lysosomal storage disorders by enhancing extracellular vesicle secretion.

Niemann Pick diseases types A (NPDA) and C (NPDC) are lysosomal storage disorders (LSDs) leading to cognitive impairment, neurodegeneration, and early death. NPDA and NPDC have different genetic origins, being caused by mutations in the acid sphingomyelinase (ASM) or the cholesterol transport protein NPC1, respectively. However, they share a common pathological hallmark in the accumulation of lipids in the endolysosomal compartment.

administration of gut bacterial consortia replicates urolithin metabotypes A and B in a non-urolithin-producing rat model.

Urolithin (Uro) production capacity and, consequently, at least partly, the health effects attributed to ellagitannin and ellagic acid consumption vary among individuals. The reason is that not all individuals have the gut bacterial ecology needed to produce the different Uro metabolites. Three human urolithin metabotypes (UM-A, UM-B, and UM-0) based on dissimilar Uro production profiles have been described in populations worldwide.

Gut Bacteria Involved in Ellagic Acid Metabolism To Yield Human Urolithin Metabotypes Revealed.

We aimed to elucidate the gut bacteria that characterize the human urolithin metabotypes A and B (UM-A and UM-B). We report here a new bacterium isolated from the feces of a healthy woman, capable of producing the final metabolites urolithins A and B and different intermediates. Besides, we describe two gut bacterial co-cultures that reproduced the urolithin formation pathways upon in vitro fermentation of both UM-A and UM-B.

Can exosomes transfer the preconditioning effects triggered by (poly)phenol compounds between cells?

Effective strategies in prolonging life- and health span are increasingly recognized as acting as mild stressors. Micronutrients and other dietary compounds such as (poly)phenols may act as moderate stressors and confer protective effects a preconditioning phenomenon. (Poly)phenols and their metabolites may not need to reach their target cells to produce biologically significant responses, so that cells exposed to it at entry points may communicate signals to other cells.

Main Determinants Affecting the Antiproliferative Activity of Stilbenes and Their Gut Microbiota Metabolites in Colon Cancer Cells: A Structure-Activity Relationship Study.

-Resveratrol can be catabolized by the gut microbiota to dihydroresveratrol, 3,4'-dihydroxy-trans-stilbene, lunularin, and 4-hydroxydibenzyl. These metabolites can reach relevant concentrations in the colon. However, not all individuals metabolize RSV equally, as it depends on their RSV gut microbiota metabotype (i.

Effect of Resistant Dextrin on Intestinal Gas Homeostasis and Microbiota.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects ( = 20) were given resistant dextrin (14 g/d NUTRIOSE, Roquette Frères, Lestrem, France) for four weeks.

Exosome-Containing Extracellular Vesicles Contribute to the Transport of Resveratrol Metabolites in the Bloodstream: A Human Pharmacokinetic Study.

Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood-brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs.

Lunularin Producers versus Non-producers: Novel Human Metabotypes Associated with the Metabolism of Resveratrol by the Gut Microbiota.

We describe here for the first time the consistent observation of two metabotypes associated with resveratrol metabolism by the human gut microbiota, that is, lunularin (LUNU)-producers and LUNU non-producers. In healthy volunteers ( = 195), resveratrol was reduced to dihydroresveratrol, which only in the LUNU-producer metabotype was sequentially dehydroxylated at the 5-position to yield LUNU and the 3-position to produce 4-hydroxydibenzyl. These metabolites (also 3,4'-dihydroxy--stilbene in some LUNU-producers) were detected in the urine and (or) feces of 74% of volunteers after consuming resveratrol, while 26% lacked these dehydroxylase activities.

Ellagitannins, urolithins, and neuroprotection: Human evidence and the possible link to the gut microbiota.

Ellagitannins (ETs) and ellagic acid (EA) are dietary polyphenols poorly absorbed but extensively metabolized by the human gut microbiota to produce different urolithins (Uros). Depending on the individuals' microbial signatures, ETs metabolism can yield the Uro metabotypes A, B, or 0, potentially impacting human health after consuming ETs. Human evidence points to improved brain health after consuming ET-rich foods, mainly pomegranate juices and extracts containing punicalagin, punicalin, and different EA-derivatives.

Physiologically relevant curcuminoids inhibit angiogenesis via VEGFR2 in human aortic endothelial cells.

Angiogenesis is a complex process encompassing endothelial cell proliferation, migration, and tube formation. While numerous studies describe that curcumin exerts antitumor properties (e.g.

Effects of red raspberry polyphenols and metabolites on the biomarkers of inflammation and insulin resistance in type 2 diabetes: a pilot study.

Berry fruits are rich in polyphenolic compounds (PCs) and may promote health benefits. Anthocyanin (ACN) concentrations of red raspberry (RR) () extracts were 887.6 ± 262.

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs.

An Integrative Approach to Characterize the Early Phases of Dimethylhydrazine-Induced Colorectal Carcinogenesis in the Rat.

This study aimed to characterize an animal model of colorectal cancer (CRC) in the early stages of disease development. Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2), receiving EDTA-saline injections and two induced groups (CRC1 and CRC2), receiving 1,2-dimethylhydrazine (DMH) injections for seven consecutive weeks. CRC1 and CTRL1 were euthanized at the 11th week, while CRC2 and CTRL2 were euthanized at the 17th week.

Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota.

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin-rich sources (pomegranates, walnuts, strawberries, etc.).

Main drivers of (poly)phenol effects on human health: metabolite production and/or gut microbiota-associated metabotypes?

Despite the high human interindividual variability in response to (poly)phenol consumption, the cause-and-effect relationship between some dietary (poly)phenols (flavanols and olive oil phenolics) and health effects (endothelial function and prevention of LDL oxidation, respectively) has been well established. Most of the variables affecting this interindividual variability have been identified (food matrix, gut microbiota, single-nucleotide-polymorphisms, .).