Metabolism Of Polyphenols Research Articles

Design strategies of polysaccharide, protein and lipid-based nano-delivery systems in improving the bioavailability of polyphenols and regulating gut homeostasis.

Polyphenols are plant secondary metabolites that have attracted much attention due to their anti-inflammatory, antioxidant, and gut homeostasis promoting effects. However, food matrix interaction, poor solubility, and strong digestion and metabolism of polyphenols cause barriers to their absorption in the gastrointestinal tract, which further reduces bioavailability and limits polyphenols' application in the food industry. Nano-delivery systems composed of biocompatible macromolecules (polysaccharides, proteins and lipids) are an effective way to improve the bioavailability of polyphenols. Therefore, this review introduces the construction of biopolymer-based nano-delivery systems and their application in polyphenols, with emphasis on improving the solubility, stability, sustained release and intestinal targeting of polyphenols. In addition, there are possible positive effects of polyphenol-loaded nano-delivery systems on modulating gut microbiota and gut homeostasis, with particular emphasis on modulating intestinal inflammation, metabolic syndrome, and gut-brain axis. It is worth noting that the safety of bio-based nano-delivery systems still need to be further studied. In summary, the application of the bio-based nano-delivery system to deliver polyphenols provides insights for improving the bioavailability of polyphenols and for the treatment of potential diseases in the future.

Changes in redox status in raspberry (Rubus idaeus L.) fruit during ripening

The knowledge of the mechanisms affecting the process of berry fruit ripening is important, not only to correctly determine the appropriate date of harvest, at which the fruit is most palatable and characterized by adequate shelf-life stability, but also, to develop new strategies of regulating the ripening process before harvesting. It is recognized that berry fruit quality and its post-harvest shelf-life depend on the cellular redox homeostasis. We, therefore, decided to conduct a comprehensive analysis of the level of oxidative stress status in the raspberry fruit proper at different stages of fruit ripening, from green to overripe fruit. We assessed both the level of typical oxidative stress markers, i.e. ROS production, expression of antioxidant enzymes, degree of cell damage, as well as the expression of selected proteins involved in the energy, glutathione, and polyphenols metabolism. We found two stage-related peaks of ROS production. The first - in green fruit, which corresponded to the maximum expression of antioxidant enzymes (MnSOD, CAT), PARP-1, as well as proteins related to glutathione biosynthesis (GS, γ-GC), autophagy (ATG-8) and ubiquitination (UBQ-11). The second one, in the overripe fruit, was responsible for the intensification of oxidative modifications of cell components, i.e. lipids, proteins, and DNA, as well as the loss of low molecular-weight antioxidants. The fruit ripening process, in turn, was manifested by a strong increase in the expression of proteins involved in the biosynthesis of polyphenols (PAL, CHS), cellular respiration (ACO-1, Cyt-C-ox, ATPase), ethylene biosynthesis and signaling (SAMs, EIN-2) and increasing amounts of ABA.

Effects of Resistant-Starch-Encapsulated Probiotic Cocktail on Intestines Damaged by 5-Fluorouracil.

Probiotics and prebiotics have gained attention for their potential health benefits. However, their efficacy hinges on probiotic survival through the harsh gastrointestinal environment. Microencapsulation techniques provide a solution, with resistant starch (RS)-based techniques showing promise in maintaining probiotic viability. Specifically, RS-encapsulated probiotics significantly improved probiotic survival in gastric acid, bile salts, and simulated intestinal conditions. This study investigated the effects of a resistant-starch-encapsulated probiotic cocktail (RS-Pro) in the context of 5-fluorouracil (5-FU) chemotherapy, which frequently induces microbiota dysbiosis and intestinal mucositis. Female BALB/c mice were divided into three groups: a 5-FU group, a 5-FU+Pro group receiving free probiotics, and a 5-FU+RS-Pro group receiving RS-encapsulated probiotics. After 28 days of treatment, analyses were conducted on fecal microbiota, intestinal histology, peripheral blood cell counts, and body and organ weights. It was revealed by 16S rRNA MiSeq sequencing that 5-FU treatment disrupted gut microbiota composition, reduced microbial diversity, and caused dysbiosis. RS-Pro treatment restored microbial diversity and increased the population of beneficial bacteria, such as Muribaculaceae, which play roles in carbohydrate and polyphenol metabolism. Furthermore, 5-FU administration induced moderate intestinal mucositis, characterized by reduced cellularity and shortened villi. However, RS-Pro treatment attenuated 5-FU-induced intestinal damage, preserving villus length. Mild leukopenia observed in the 5-FU-treated mice was partially alleviated in 5-FU+Pro and 5-FU+RS-Pro groups. These findings suggest that RS-Pro may serve as an adjunct to chemotherapy, potentially reducing adverse effects and improving therapeutic outcomes in future clinical applications.

Canopy-Applied Benzothiadiazole (BTH) during the Pre-Harvest Period as a Tool to Increase Polyphenol Accumulation and Color Intensity in Cabernet Gernischt and Cabernet Franc

Despite the wealth of studies on benzothiadiazole (BTH) and its capacity to modulate grape polyphenol metabolism, comprehensive data detailing polyphenol accumulation at various grape growth stages remain scarce. Therefore, the present study utilized pre-harvest (at 21 days after flowering) canopy-applied BTH (50 mg/L) on Cabernet Gernischt and Cabernet Franc grapes to investigate the physicochemical and polyphenolic changes during grape maturation. The results showed that BTH treatment significantly affected the accumulation of total phenols, flavonoids, flavanols, anthocyanins, and tannins. Concurrently, it induced an increase in colorimetric parameters (CIRG, L*, b*, a*, and C*ab), resulting in the treated grapes exhibiting a greater color intensity and enhanced red-bluish colorimetric characteristics. Moreover, the BTH treatment amplified the anthocyanin content in the grapes, with the levels of petunidin-3-O-glucoside and peonidin-3-O-glucoside exhibiting remarkable increases, particularly in the Cabernet Franc grape. Notably, the content of peonidin-3-O-glucoside even surpassed that of malvidin-3-O-glucoside throughout the growth stages, indicating significant advantages in the treated samples. Additionally, the levels of flavanol, flavonols, phenolic acids, and stilbenes experienced a significant boost post-treatment. In conclusion, the application of BTH treatment can effectively enhance the accumulation of polyphenols and intensify the color of Cabernet Gernischt and Cabernet Franc grapes, thereby significantly improving the overall quality of wine grapes and ensuring the production of higher-quality wines. The research findings will serve as a theoretical foundation and provide scientific data for the appropriate utilization of BTH in wine grape cultivation.

Synthesis of plyphenol-containing cationic linear and dendrimeric peptides with anti-oxidant activity

Natural polyphenols are of great interest from the point of view of their use for the pharmacological control of oxidative stress and many diseases. However, the low bioavailability and rapid metabolism of polyphenols in the form of glycosides or aglycones stimulates the search for effective means of delivery into systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides can result in compounds with strong antioxidant activity and the ability to cross biological barriers. Such compounds may be in demand as drugs for antioxidant therapy, including for the treatment of viral, oncological and neurodegenerative diseases due to the diverse range of biological activities inherent in polyphenols and peptides. In this work, cationic linear and dendrimer amphiphilic cationic peptides were synthesized by the solid phase method, and a number of peptides were conjugated to gallic acid (Ga). Ga is a non-toxic natural phenolic acid and an important functional element of many flavonoids with high antioxidant activity. It was shown that the resulting Ga-peptide conjugates exhibited antioxidant (antiradical) activity that was 2-3 times higher than that of ascorbic acid. Other tests indicated that the addition of Ga did not affect the toxicity and hemolytic activity of the conjugates. Ga-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding the luciferase reporter gene; however, the addition of Ga to the N-terminus of the peptide reduced its transfection activity. Some of the resulting compounds had noticeable inhibitory activity against theE. сoli-Dh5α strain.

Decoding polyphenol metabolism in patients with Crohn’s disease: Insights from diet, gut microbiota, and metabolites

Crohn’s disease (CD) is a chronic and progressive inflammatory disease that can involve any part of the gastrointestinal tract. The protective role of dietary polyphenols has been documented in preclinical models of CD. Gut microbiota mediates the metabolism of polyphenols and affects their bioactivity and physiological functions. However, it remains elusive the capacity of microbial polyphenol metabolism in CD patients and healthy controls (HCs) along with its correlation with polyphenols intake and polyphenol-derived metabolites. Thus, we aimed to decode polyphenol metabolism in CD patients through aspects of diet, gut microbiota, and metabolites. Dietary intake analysis revealed that CD patients exhibited decreased intake of polyphenols. Using metagenomic data from two independent clinical cohorts (FAH-SYSU and PRISM), we quantified abundance of polyphenol degradation associated bacteria and functional genes in CD and HCs and observed a lower capacity of flavonoids degradation in gut microbiota residing in CD patients. Furthermore, through analysis of serum metabolites and enterotypes in participants of FAH-SYSU cohort, we observed that CD patients exhibited reduced levels of serum hippuric acid (HA), one of polyphenol-derived metabolites. HA level was higher in healthier enterotypes (characterized by dominance of Ruminococcaceae and Prevotellaceae, dominant by HCs) and positively correlated with multiple polyphenols intake and abundance of bacteria engaged in flavonoids degradation as well as short-chain fatty acid production, which could serve as a biomarker for effective polyphenol metabolism by the gut microbiota and a healthier gut microbial community structure. Overall, our findings provide a foundation for future work exploring the polyphenol-based or microbiota-targeted therapeutic strategies in CD.

Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.

Metabolic changes in tomato plants caused by psychrotolerant Antarctic endophytic bacteria might be implicated in cold stress mitigation.

Climate change is responsible for mild winters and warm springs that can induce premature plant development, increasing the risk of exposure to cold stress with a severe reduction in plant growth. Tomato plants are sensitive to cold stress and beneficial microorganisms can increase their tolerance. However, scarce information is available on mechanisms stimulated by bacterial endophytes in tomato plants against cold stress. This study aimed to clarify metabolic changes stimulated by psychrotolerant endophytic bacteria in tomato plants exposed to cold stress and annotate compounds possibly associated with cold stress mitigation. Tomato seeds were inoculated with two bacterial endophytes isolated from Antarctic Colobanthus quitensis plants (Ewingella sp. S1.OA.A_B6 and Pseudomonas sp. S2.OTC.A_B10) or with Paraburkholderia phytofirmans PsJN, while mock-inoculated seeds were used as control. The metabolic composition of tomato plants was analyzed immediately after cold stress exposure (4°C for seven days) or after two and four days of recovery at 25°C. Under cold stress, the content of malondialdehyde, phenylalanine, ferulic acid, and p-coumaric acid was lower in bacterium-inoculated compared to mock-inoculated plants, indicating a reduction of lipid peroxidation and the stimulation of phenolic compound metabolism. The content of two phenolic compounds, five putative phenylalanine-derived dipeptides, and three further phenylalanine-derived compounds was higher in bacterium-inoculated compared to mock-inoculated samples under cold stress. Thus, psychrotolerant endophytic bacteria can reprogram polyphenol metabolism and stimulate the accumulation of secondary metabolites, like 4-hydroxybenzoic and salicylic acid, which are presumably involved in cold stress mitigation, and phenylalanine-derived dipeptides possibly involved in plant stress responses.

Metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion/Caco-2 cell transport, and their prebiotic effects during colonic fermentation

The health-promoting activities of polyphenols and their metabolites originating from germinated quinoa (GQ) are closely related to their digestive behavior, absorption, and colonic fermentation; however, limited knowledge regarding these properties hinder further development. The aim of this study was to provide metabolomic insights into the profile, bioaccessibility, and transepithelial transport of polyphenols from germinated quinoa during in vitro gastrointestinal digestion and Caco-2 cell transport, whilst also investigating the changes in the major polyphenol metabolites and the effects of prebiotics during colonic fermentation. It was found that germination treatment increased the polyphenol content of quinoa by 21.91%. Compared with RQ group, 23 phenolic differential metabolites were upregulated and 47 phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after simulated digestion, 7 kinds of phenolic differential metabolites were upregulated and 17 kinds of phenolic differential metabolites were downregulated in GQ group. Compared with RQ group after cell transport, 7 kinds of phenolic differential metabolites were upregulated and 9 kinds of phenolic differential metabolites were downregulated in GQ group. In addition, GQ improved the bioaccessibilities and transport rates of various polyphenol metabolites. During colonic fermentation, GQ group can also increase the content of SCFAs, reduce pH value, and adjust gut microbial populations by increasing the abundance of Actinobacteria, Bacteroidetes, Verrucomicrobiota, and Spirochaeota at the phylum level, as well as Bifidobacterium, Megamonas, Bifidobacterium, Brevundimonas, and Bacteroides at the genus level. Furthermore, the GQ have significantly inhibited the activity of α-amylase and α-glucosidase. Based on these results, it was possible to elucidate the underlying mechanisms of polyphenol metabolism in GQ and highlight its beneficial effects on the gut microbiota.

Dietary Polyphenols: Review on Chemistry/Sources, Bioavailability/Metabolism, Antioxidant Effects, and Their Role in Disease Management.

Polyphenols, as secondary metabolites ubiquitous in plant sources, have emerged as pivotal bioactive compounds with far-reaching implications for human health. Plant polyphenols exhibit direct or indirect associations with biomolecules capable of modulating diverse physiological pathways. Due to their inherent abundance and structural diversity, polyphenols have garnered substantial attention from both the scientific and clinical communities. The review begins by providing an in-depth analysis of the chemical intricacies of polyphenols, shedding light on their structural diversity and the implications of such diversity on their biological activities. Subsequently, an exploration of the dietary origins of polyphenols elucidates the natural plant-based sources that contribute to their global availability. The discussion extends to the bioavailability and metabolism of polyphenols within the human body, unraveling the complex journey from ingestion to systemic effects. A central focus of the review is dedicated to unravelling the antioxidant effects of polyphenols, highlighting their role in combating oxidative stress and associated health conditions. The comprehensive analysis encompasses their impact on diverse health concerns such as hypertension, allergies, aging, and chronic diseases like heart stroke and diabetes. Insights into the global beneficial effects of polyphenols further underscore their potential as preventive and therapeutic agents. This review article critically examines the multifaceted aspects of dietary polyphenols, encompassing their chemistry, dietary origins, bioavailability/metabolism dynamics, and profound antioxidant effects. The synthesis of information presented herein aims to provide a valuable resource for researchers, clinicians, and health enthusiasts, fostering a deeper understanding of the intricate relationship between polyphenols and human health.

Changing the polyphenol composition and enhancing the enzyme activity of sorghum grain by solid-state fermentation with different microbial strains.

Solid-state fermentation (SSF) has been widely used in the processing of sorghum grain (SG) because it can produce products with improved sensory characteristics. To clarify the influence of different microbial strains on the SSF of SG, especially on the polyphenols content and composition, Lactiplantibacillus plantarum, Saccharomyces cerevisiae, Rhizopus oryzae, Aspergillus oryzae, and Neurospora sitophila were used separately and together for SSF of SG. Furthermore, the relationship between the dynamic changes in polyphenols and enzyme activity closely related to the metabolism of polyphenols has also been measured and analyzed. Microstructural changes observed after SSF provide a visual representation of the SSF on the SG. After SSF, tannin content (TC) and free phenolic content (FPC) were decreased by 56.36% and 23.48%, respectively. Polyphenol oxidase, β-glucosidase and cellulase activities were increased 5.25, 3.27, and 45.57 times, respectively. TC and FPC were negatively correlated with cellulase activity. A positive correlation between FPC and xylanase activity after 30 h SSF became negative after 48 h SSF. The SG surface was fragmented and porous, reducing the blocking effect of cortex. Cellulase played a crucial role in promoting the degradation of tannin (antinutrient) and phenolic compounds. Xylanase continued to release flavonoids while microbial metabolism consumed them with the extension of SSF time. SSF is an effective way to improve the bioactivity and processing characteristics of SG. © 2024 Society of Chemical Industry.

Sorghum phytonutrients and their health benefits: A systematic review from cell to clinical trials.

Sorghum is key for global food security due to its genetic variability, resilience, and rich phytonutrient content, which are linked to numerous health benefits. A systematic review assessed the health effects of sorghum by analyzing cell (n=22), animal (n=20), and human (n=7) studies across antioxidant, anti-inflammatory, obesity, cancer, cardiovascular, and diabetes outcomes. This review, involving 42 papers and 177 researchers from 12 countries, collected data from sorghum accessions (acc) and significant effects. Studies used 68 identified and 8 unidentified sorghums, 57% red (n=20), brown (n=5), and black (n=17) pericarp colors, and evaluated whole (n=31), brans (n=11), and decorticated grains (n=2). Colored sorghum, richer in phenolic compounds, especially 3-deoxyanthocyanins and tannins, inhibited cancer cell activities, including proliferation, tumor growth, and ROS activity, and promoted cell cycle arrest and apoptosis. Sorghum elevated HO1 and eNOS expression for cardiovascular, health-reduced platelet aggregation, and modulated platelet microparticles. They also suppressed inflammation markers and decreased lipid accumulation. Animal studies indicated sorghum's potential across antioxidant capacity, cancer and inflammation mitigation, and lipid and glucose metabolism. Translating these findings to human scenarios requires caution, especially considering cell studies do not fully represent polyphenol metabolism. Human studies provided mixed results, indicating antioxidant and potential anti-inflammatory benefits and nuanced effects on glucose and lipid metabolism. The main risks of bias highlighted challenges in quantifying phytonutrients, identifying sorghum acc features, and lack of assessors blinding. Nonetheless, sorghum emerges as a promising functional food for countering chronic diseases in Western diets.

De Novo Transcriptome Analysis by PacBio SMRT-Seq and Illumina RNA-Seq Provides New Insights into Polyphenol Biosynthesis in Chinese Olive Fruit

Polyphenols play a crucial role in fruit flavor. To elucidate the mechanism of fruit polyphenol metabolism, we constructed a transcriptome atlas through PacBio single-molecule real-time (SMRT) sequencing and Illumina next-generation sequencing (NGS) using Canarium album (Lour.) Raeusch., which is a fantastic fruit rich in polyphenolic compounds. In this work, PacBio full-length transcriptome assembly generated 135,439 isoforms with an average length of all isoforms of 2687.94 bp and an N50 length of 3224 bp. To gain deeper insights into the molecular mechanisms of polyphenol biosynthesis in C. album, we constructed twelve RNA-Seq libraries from four developmental stages of the fruits. We identified a total of 28,658 differentially expressed genes (DEGs). We found that many DEGs were involved in metabolic pathways, biosynthesis of secondary metabolites, biosynthesis of antibiotics, starch and sucrose metabolism, and plant hormone signal transduction. Here, we report the expression profiles of 215 DEGs encoding 27 enzymes involved in the polyphenol biosynthesis pathway in C. album. In addition, 285 differentially expressed transcription factors (TFs) continuously down-regulated in four developmental periods of C. album fruit, which may indicate their potential role in the response to polyphenol metabolism and phenylpropanoid biosynthesis pathways. This report will help us understand polyphenol biosynthesis’s functions and metabolic mechanism in C. album. The transcriptome data provide a valuable resource for genetic and genomics research. They will facilitate future work exploiting C. album and other fruits used as medicine and food.

Metabolomic analysis of Chinese yam (Dioscorea polystachya Turczaninow) bulbils at different germination stages by UPLC-Q-TOF-MS

Bulbil germination is crucial to the survival of Chinese yam plants, the preservation of germplasm resources and the worldwide supply of food and natural medicine. There are still some unknowns regarding bulbil biochemical variations associated with germination. The metabolic changes during the germination of Chinese yam (Dioscorea polystachya Turczaninow) bulbils were studied using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) at eight-time points covering all four phases of germination. It was determined that 27 metabolites, including organic acids, amino acids, sugars, lipid metabolites, phenolics and steroids, were responsible for the variation in the Chinese yam bulbil groups. A metabolomics pathway was proposed based on the identified metabolites. The main processes affected during germination were those related to carbohydrate metabolism, the TCA cycle, lipid metabolism, nitrogen metabolism, lipid metabolism and polyphenol metabolism. It is one of the earliest reports on the metabolite identification and profiling of Chinese yam bulbils at different germination stages.

High intraspecific variability and previous experience affect polyphenol metabolism in polyphagous Lymantria mathura caterpillars.

Polyphagous insect herbivores feed on multiple host-plant species and face a highly variable chemical landscape. Comparative studies of polyphagous herbivore metabolism across a range of plants is an ideal approach for exploring how intra- and interspecific chemical variation shapes species interactions. We used polyphagous caterpillars of Lymantria mathura (Erebidae, Lepidoptera) to explore mechanisms that may contribute to its ability to feed on various hosts. We focused on intraspecific variation in polyphenol metabolism, the fates of individual polyphenols, and the role of previous feeding experience on polyphenol metabolism and leaf consumption. We collected the caterpillars from Acer amoenum (Sapindaceae), Carpinus cordata (Betulaceae), and Quercus crispula (Fagaceae). We first fed the larvae with the leaves of their original host and characterized the polyphenol profiles in leaves and frass. We then transferred a subset of larvae to a different host species and quantified how host shifting affected their leaf consumption and polyphenol metabolism. There was high intraspecific variation in frass composition, even among caterpillars fed with one host. While polyphenols had various fates when ingested by the caterpillars, most of them were passively excreted. When we transferred the caterpillars to a new host, their previous experience influenced how they metabolized polyphenols. The one-host larvae metabolized a larger quantity of ingested polyphenols than two-host caterpillars. Some of these metabolites could have been sequestered, others were probably activated in the gut. One-host caterpillars retained more of the ingested leaf biomass than transferred caterpillars. The pronounced intraspecific variation in polyphenol metabolism, an ability to excrete ingested metabolites and potential dietary habituation are factors that may contribute to the ability of L. mathura to feed across multiple hosts. Further comparative studies can help identify if these mechanisms are related to differential host-choice and response to host-plant traits in specialist and generalist insect herbivores.

Synthesis and Biological Properties of Polyphenol-Containing Linear and Dendrimeric Cationic Peptides.

Natural polyphenols are promising compounds for the pharmacological control of oxidative stress in various diseases. However, low bioavailability and rapid metabolism of polyphenols in a form of glycosides or aglycones have stimulated the search for the vehicles that would provide their efficient delivery to the systemic circulation. Conjugation of polyphenols with cationic amphiphilic peptides yields compounds with a strong antioxidant activity and ability to pass through biological barriers. Due to a broad range of biological activities characteristic of polyphenols and peptides, their conjugates can be used in the antioxidant therapy, including the treatment of viral, oncological, and neurodegenerative diseases. In this work, we synthesized linear and dendrimeric cationic amphiphilic peptides that were then conjugated with gallic acid (GA). GA is a non-toxic natural phenolic acid and an important functional element of many flavonoids with a high antioxidant activity. The obtained GA-peptide conjugates showed the antioxidant (antiradical) activity that exceeded 2-3 times the antioxidant activity of ascorbic acid. GA attachment had no effect on the toxicity and hemolytic activity of the peptides. GA-modified peptides stimulated the transmembrane transfer of the pGL3 plasmid encoding luciferase reporter gene, although GA attachment at the N-terminus of peptides reduced their transfection activity. Several synthesized conjugates demonstrated the antibacterial activity in the model of Escherichia coli Dh5α growth inhibition.

Metabolic profiling of (poly)phenolic compounds in mouse urine following consumption of hull-less and purple-grain barley.

The present study attempted for the first time to investigate the metabolic fate of (poly)phenolic compounds provided by a hull-less and purple grain barley genotype biofortified in anthocyanins. Balb/c mice were supplemented either with standard purified diet (SD) or whole-grain barley supplemented diet (WGB) for six weeks. Subsequently, (poly)phenolic metabolites were determined in urine samples by UPLC-MS/MS, and the principal metabolic pathways were elucidated. Thirty-nine (poly)phenolics compounds were identified in WGB which were distributed between the free (58%) and bound (42%) fractions, encompassing anthocyanins, phenolic acids, flavan-3-ols and flavones. Upon WGB intake, forty-two (poly)phenolic metabolites were identified, predominantly comprising phase-II sulphate, glucuronide, and/or methylated conjugates, along with colonic catabolites. Noteworthy metabolites included peonidin-3-O-glucuronide, peonidin-3-O-6''-O-malonylglucoside, and peonidin-3-O-glucoside among anthocyanins; hydroxyphenylpropanoic acid-O-sulphate among phenolic acids; and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone-O-sulphate among flavan-3-ols. Metabolites like phenylpropionic, phenylacetic, hydroxybenzoic, and hippuric acids were found in both WGB and SD groups, with higher levels after barley consumption, indicating both endogenous and polyphenolic metabolism origins. Overall, this study offers valuable insights into the metabolism of (poly)phenols in purple barley, setting the stage for future investigations into the health benefits linked to the consumption of purple grain barley.

Interactions between APOE Genotype, the Gut Microbiome and Polyphenol Metabolism

AbstractBackgroundAPOE genotype is the most significant genetic risk factor for the development of Alzheimer’s disease, with 40‐60% of Alzheimer’s patients carrying at least one APOE4 allele. In addition to its pleiotropic effects on ageing and the brain, recent evidence suggests that APOE genotype may also affect the gut microbiome structure and function. Dietary polyphenols ‐ bioactive molecules found in fruits and vegetables ‐ have been reported to slow cognitive decline and to affect gut microbiota speciation and metabolism. However, differences in the metabolism of these bioactive compounds according to APOE genotypes have not been previously explored.MethodTo address this knowledge gap, we ran an animal study using APOE3 and APOE4 targeted replacement (TR) mice. Animals were fed on a low‐fat diet (10 kcal% from fat), a high‐fat diet (45 kcal% from fat) or a high‐fat diet supplemented with a flavan‐3‐ols rich cocoa extract (100 mg/kg body weight) for 16 weeks. This model has been widely used as a physiologically relevant model for age‐related neuroinflammation and cognitive decline in humans, with consistently higher levels in the APOE4‐TR vs. APOE3‐TR mice, particularly if fed a “western type‟ high fat diet.ResultSignificant shifts in microbiome beta diversity were observed in APOE3‐TR mice only under a high fat diet, with these mice acquiring an APOE4‐TR‐like phenotype. Addition of flavan‐3‐ol rich cocoa reversed this shift by increasing rc4_4, Prevotella, Aldercreutzia and Faecalibacterium genera (log LDA score >2; FDR p‐adjusted 0.1) in APOE3‐TR mice. Surprisingly, flavan‐3‐ol rich cocoa did not affect the structure of the APOE 4 mice’s microbiome. Such results were paralleled by an increased urinary excretion of the colon flora‐derived flavan‐3‐ol metabolites 5‐(3’,4’‐dihydroxyohenyl)‐γ‐valerolactone (p<0.05), 5‐(hydroxyphenyl)valeric acid‐4‐sulfate (p<0.01) and 4‐hydroxy‐5‐(hydroxyphenyl)valeric acid sulfate (p<0.01) in APOE4‐TR mice. These preliminary findings were further validated in a human cohort study (COMBAT Study; NCT03679533) following 12‐week consumption of flavan‐3‐ols rich cranberries.ConclusionThe relationship between polyphenols intake and APOE genotype is intriguing, and further work is required to gain a better understanding of the physiological and molecular mechanisms underlying such disparity between the genotypes.

Biochemical investigations of polyphenol degradation enzymes in the phototrophic bacterium Rubrivivax gelatinosus.

Phloroglucinol (1,3,5-trihydroxybenzene) is an important intermediate in the degradation of flavonoids and tannins by anaerobic bacteria. Recent studies have shed light on the enzymatic mechanism of phloroglucinol degradation in butyrate-forming anaerobic bacteria, including environmental and intestinal bacteria such as Clostridium and Flavonifractor sp. Phloroglucinol degradation gene clusters have also been identified in other metabolically diverse bacteria, although the polyphenol metabolism of these microorganisms remain largely unexplored. Here, we describe biochemical studies of polyphenol degradation enzymes found in the purple non-sulfur bacterium Rubrivivax gelatinosus IL144, an anaerobic photoheterotroph reported to utilize diverse organic compounds as carbon sources for growth. In addition to the phloroglucinol reductase and dihydrophloroglucinol cyclohydrolase that catalyze phloroglucinol degradation, we characterize a Mn2+-dependent phloretin hydrolase that catalyzes the cleavage of phloretin into phloroglucinol and phloretic acid. We also report a Mn2+-dependent decarboxylase (DeC) that catalyzes the reversible decarboxylation of 2,4,6-trihydroxybenzoate to form phloroglucinol. A bioinformatics search led to the identification of DeC homologs in diverse soil and gut bacteria, and biochemical studies of a DeC homolog from the human gut bacterium Flavonifractor plautii demonstrated that it is also a 2,4,6-trihydroxybenzoate decarboxylase. Our study expands the range of enzymatic mechanisms for phloroglucinol formation, and provides further biochemical insight into polyphenol metabolism in the anaerobic biosphere.

Phenolic Profile and Bioactivity Changes of Lotus Seedpod and Litchi Pericarp Procyanidins: Effect of Probiotic Bacteria Biotransformation.

Theoretically, lactic acid bacteria (LABs) could degrade polyphenols into small molecular compounds. In this study, the biotransformation of lotus seedpod and litchi pericarp procyanidins by Lactobacillus plantarum 90 (Lp90), Streptococcus thermophilus 81 (ST81), Lactobacillus rhamnosus HN001 (HN001), and Pediococcus pentosus 06 (PP06) were analysed. The growth curve results indicated that procyanidins did not significantly inhibit the proliferation of LABs. Ultra-high-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) revealed that procyanidin B2 and procyanidin B3 in lotus seedpod decreased by 62.85% and 25.45%, respectively, with ST81 metabolised, while kaempferol and syringetin 3-O-glucoside content increased. Although bioconversion did not increase the inhibitory function of procyanidins against glycosylation end-products in vitro, the 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity and ferric reducing antioxidant power of litchi pericarp procyanidins increased by 157.34% and 6.8%, respectively, after ST81 biotransformation. These findings may inspire further studies of biological metabolism of other polyphenols and their effects on biological activity.