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Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 34314

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Special Issue Editor

Dr. Elad Tako

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Guest Editor

USDA-ARS, Robert W. Holley Center for Agriculture and Health, Cornell University, Ithaca, NY 14853, USA
Interests: dietary micronutrients; Fe and Zn deficiencies; anemia; Zn status biomarkers; bioactive compounds; prebiotics; microbiome; nutrigenomics; intestinal functionality and development; polyphenols; in vivo models of human nutrition
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Micronutrient malnutrition affects more than half of the global population, primarily in developing regions. Iron (Fe), zinc (Zn), and vitamin A deficiencies are prominent health constraints worldwide. In low-income countries, plants are the significant source of food. In crude cereal and legume foods, the low bioavailability of Fe and Zn leads to metabolic disorders that are associated with these nutritional factors. Hence, increasing the nutritional value of such types of dietary ingredients will contribute to the nutritional status of the target population. Mineral, phosphorous, and phytate content is much higher in bran than whole grain. The main phenolic compounds found in cereal and legumes comprise condensed tannins, flavonoids, and phenolic acids. These phenolic compounds are found specifically in the seed coat and are biosynthesized via the phenylpropanoid pathway, with condensed tannin molecules being responsible for the seed-coat coloring. In dark-colored hulls, tannin and flavonoid compounds are the majority of phenolic compounds; however, in seeds with clear hulls, phenolic acids are the main compounds. Polyphenols in the seed coat present antioxidant and anti-mutagenic activity, shielding the seed from oxidative stress. In field conditions, these compounds also deliver chemical resistance against pathogens and insect pests during the growing process of the plant. Polyphenols in legumes appear mostly as insoluble or bound forms, covalently bonded to structural components of the cell wall such as cellulose, hemicellulose, lignin, and pectin. The polyphenolic composition of peas is predominantly interesting with respect to metabolic health, given their alleged protective properties against oxidative stress. Isoflavone polyphenols are linked with biological pathways in the lessening of osteoporosis and cardiovascular disease, the deterrence of cancer, and treating symptoms related to menopause. Phenolic compounds also display anti-nutritional effects, and related research showed a decrease in the bioavailability of proteins triggered by phenolic compounds. The purpose of the current Special Issue is to expand upon the knowledge related to how dietary polyphenols and flavonoids affect the intestinal morphology, microbiome and the brush border membrane functionality.

Dr. Elad Tako
Guest Editor

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Keywords

Polyphenols
Flavanoids
Minerals
Micronitrients
Dietary biovavailability
Intestine
Brush Border membrane
Morphology
Mucrobiome
Bioactive
Plant
Iron
Zinc
Cereals
Legumes
Beans
Physiology
Metabolism

Published Papers (7 papers)

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Research

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14 pages, 2397 KiB

Open AccessArticle

Quinoa Soluble Fiber and Quercetin Alter the Composition of the Gut Microbiome and Improve Brush Border Membrane Morphology In Vivo (Gallus gallus)

by Nikita Agarwal, Nikolai Kolba, Noa Khen, Carmel Even, Sondra Turjeman, Omry Koren and Elad Tako

Nutrients 2022, 14(3), 448; https://doi.org/10.3390/nu14030448 - 20 Jan 2022

Cited by 11 | Viewed by 3424

Abstract

Quinoa (Chenopodium quinoa Willd.), a gluten-free pseudo-cereal, has gained popularity over the last decade due to its high nutritional value. Quinoa is a rich source of proteins, carbohydrates, fibers, tocopherols (Vitamin E), unsaturated fatty acids and a wide range of polyphenols. The study used Gallus gallus intra-amniotic feeding, a clinically validated method, to assess the effects of quinoa soluble fiber (QSF) and quercetin 3-glucoside (Q3G) versus control. Quercetin is a pharmacologically active polyphenol found in quinoa. Six groups (no injection, 18 Ω H₂O, 5% inulin, 1% Q3G, 5% QSF, 1% Q3G + 5% QSF) were assessed for their effect on the brush border membrane (BBM) functionality, intestinal morphology and cecal bacterial populations. Our results showed a significant (p < 0.05) improvement in BBM morphology, particularly goblet and Paneth cell numbers, in the group administered with quinoa and quercetin. However, there were no significant changes seen in the expression of the genes assessed both in the duodenum and liver between any of the treatment groups. Furthermore, fibrous quinoa increased the concentration of probiotic L. plantarum populations compared to the control (H₂O). In conclusion, quercetin and quinoa fiber consumption has the potential to improve intestinal morphology and modulate the microbiome. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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13 pages, 2627 KiB

Open AccessEditor’s ChoiceArticle

Saffron (Crocus sativus L.) Flower Water Extract Disrupts the Cecal Microbiome, Brush Border Membrane Functionality, and Morphology In Vivo (Gallus gallus)

by Nikita Agarwal, Nikolai Kolba, YeonJin Jung, Jacquelyn Cheng and Elad Tako

Nutrients 2022, 14(1), 220; https://doi.org/10.3390/nu14010220 - 05 Jan 2022

Cited by 14 | Viewed by 3709

Abstract

Saffron (Crocus sativus L.) is known as the most expensive spice. C. sativus dried red stigmas, called threads, are used for culinary, cosmetic, and medicinal purposes. The rest of the flower is often discarded, but is now being used in teas, as coloring agents, and fodder. Previous studies have attributed antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, anti-depressant, and anticancer properties to C. sativus floral bio-residues. The aim of this study is to assess C. sativus flower water extract (CFWE) for its effects on hemoglobin, brush boarder membrane (BBM) functionality, morphology, intestinal gene expression, and cecal microbiome in vivo (Gallus gallus), a clinically validated model. For this, Gallus gallus eggs were divided into six treatment groups (non-injected, 18 Ω H₂O, 1% CFWE, 2% CFWE, 5% CFWE, and 10% CFWE) with n~10 for each group. On day 17 of incubation, 1 mL of the extracts/control were administered in the amnion of the eggs. The amniotic fluid along with the administered extracts are orally consumed by the developing embryo over the course of the next few days. On day 21, the hatchlings were euthanized, the blood, duodenum, and cecum were harvested for assessment. The results showed a significant dose-dependent decrease in hemoglobin concentration, villus surface area, goblet cell number, and diameter. Furthermore, we observed a significant increase in Paneth cell number and Mucin 2 (MUC2) gene expression proportional to the increase in CFWE concentration. Additionally, the cecum microbiome analysis revealed C. sativus flower water extract altered the bacterial populations. There was a significant dose-dependent reduction in Lactobacillus and Clostridium sp., suggesting an antibacterial effect of the extract on the gut in the given model. These results suggest that the dietary consumption of C. sativus flower may have negative effects on BBM functionality, morphology, mineral absorption, microbial populations, and iron status. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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19 pages, 3557 KiB

Open AccessArticle

Modifications in the Intestinal Functionality, Morphology and Microbiome Following Intra-Amniotic Administration (Gallus gallus) of Grape (Vitis vinifera) Stilbenes (Resveratrol and Pterostilbene)

by Mariana Juste Contin Gomes, Nikolai Kolba, Nikita Agarwal, Dean Kim, Adi Eshel, Omry Koren and Elad Tako

Nutrients 2021, 13(9), 3247; https://doi.org/10.3390/nu13093247 - 18 Sep 2021

Cited by 13 | Viewed by 5473

Abstract

This efficacy trial evaluated the effects of two polyphenolic stilbenes, resveratrol and pterostilbene, mostly found in grapes, on the brush border membrane functionality, morphology and gut microbiome. This study applied the validated Gallus gallus intra-amniotic approach to investigate the effects of stilbene administration versus the controls. Three treatment groups (5% resveratrol; 5% pterostilbene; and synergistic: 4.75% resveratrol and 0.25% pterostilbene) and three controls (18 MΩ H₂O; no injection; 5% inulin) were employed. We observed beneficial morphological changes, specifically an increase in the villus length, diameter, depth of crypts and goblet cell diameter in the pterostilbene and synergistic groups, with concomitant increases in the serum iron and zinc concentrations. Further, the alterations in gene expression of the mineral metabolism proteins and pro-inflammatory cytokines indicate a potential improvement in gut health and mineral bioavailability. The cecal microbiota was analyzed using 16S rRNA sequencing. A lower α-diversity was observed in the synergistic group compared with the other treatment groups. However, beneficial compositional and functional alterations in the gut microbiome were detected. Several key microbial metabolic pathways were differentially enriched in the pterostilbene treatment group. These observations demonstrate a significant bacterial–host interaction that contributed to enhancements in intestinal functionality, morphology and physiological status. Our data demonstrate a novel understanding of the nutritional benefits of dietary stilbenes and their effects on intestinal functionality, morphology and gut microbiota in vivo. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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23 pages, 2272 KiB

Open AccessArticle

Flavonoid-Modifying Capabilities of the Human Gut Microbiome—An In Silico Study

by Tobias Goris, Rafael R. C. Cuadrat and Annett Braune

Nutrients 2021, 13(8), 2688; https://doi.org/10.3390/nu13082688 - 03 Aug 2021

Cited by 21 | Viewed by 5181

Abstract

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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16 pages, 2476 KiB

Open AccessArticle

Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype

by Dalanda Wanes, Mohamad Toutounji, Hichem Sebai, Sandra Rizk and Hassan Y. Naim

Nutrients 2021, 13(2), 441; https://doi.org/10.3390/nu13020441 - 29 Jan 2021

Cited by 6 | Viewed by 3106

Abstract

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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Review

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18 pages, 5339 KiB

Open AccessReview

The Pro-Health Benefits of Morusin Administration—An Update Review

by Anita Panek-Krzyśko and Monika Stompor-Gorący

Nutrients 2021, 13(9), 3043; https://doi.org/10.3390/nu13093043 - 30 Aug 2021

Cited by 10 | Viewed by 3469

Abstract

Prenylflavonoids are widespread in nature. Plants are valuable sources of natural polyphenolic compounds with isoprenyl groups, which include flavones, flavanones, chalcones and aurones. They can be found in flowers, bark and stems. One of the most important compounds found in the bark of white mulberry (Morus alba) is morusin, a prenylated flavone with interesting pro-health properties. The research carried out so far revealed that morusin has antioxidant, antitumor, anti-inflammatory and anti-allergic activity. Moreover, its neuroprotective and antihyperglycemic properties have also been confirmed. Morusin suppresses the growth of different types of tumors, including breast cancer, glioblastoma, pancreatic cancer, hepatocarcinoma, prostate cancer, and gastric cancer. It also inhibits the inflammatory response by suppressing COX activity and iNOS expression. Moreover, an antimicrobial effect against Gram-positive bacteria was observed after treatment with morusin. The objective of this review is to summarize the current knowledge about the positive effects of morusin on human health in order to facilitate future study on the development of plant polyphenolic drugs and nutraceutics in the group of prenylflavones. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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20 pages, 1394 KiB

Open AccessReview

Effects of Anthocyanin on Intestinal Health: A Systematic Review

by Thaísa Agrizzi Verediano, Hércia Stampini Duarte Martino, Maria Cristina Dias Paes and Elad Tako

Nutrients 2021, 13(4), 1331; https://doi.org/10.3390/nu13041331 - 17 Apr 2021

Cited by 48 | Viewed by 7889

Abstract

Intestinal health relies on the association between the mucosal immune system, intestinal barrier and gut microbiota. Bioactive components that affect the gut microbiota composition, epithelial physical barrier and intestinal morphology were previously studied. The current systematic review evaluated evidence of anthocyanin effects and the ability to improve gut microbiota composition, their metabolites and parameters of the physical barrier; this was conducted in order to answer the question: “Does food source or extract of anthocyanin promote changes on intestinal parameters?”. The data analysis was conducted following the PRISMA guidelines with the search performed at PubMed, Cochrane and Scopus databases for experimental studies, and the risk of bias was assessed by the SYRCLE tool. Twenty-seven studies performed in animal models were included, and evaluated for limitations in heterogeneity, methodologies, absence of information regarding allocation process and investigators’ blinding. The data were analyzed, and the anthocyanin supplementation demonstrated positive effects on intestinal health. The main results identified were an increase of Bacteroidetes and a decrease of Firmicutes, an increase of short chain fatty acids production, a decrease of intestinal pH and intestinal permeability, an increase of the number of goblet cells and tight junction proteins and villi improvement in length or height. Thus, the anthocyanin supplementation has a potential effect to improve the intestinal health. PROSPERO (CRD42020204835). Full article

(This article belongs to the Special Issue Dietary Polyphenols and Flavonoids, Mineral Bioavailability, Gut Functionality, Morphology and Microbiome)

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