Fate of Antioxidants in Gut and Interaction of Gut Metabolites and Gut Microbiota

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 64806

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Guest Editor
Food Science and Technology Program, Department of Life Sciences, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai 519087, China
Interests: phytochemicals; natural products; functional foods; human health
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Special Issue Information

Dear Colleagues,

It is widely accepted that antioxidants can help in disease prevention by effectively quenching free radicals or inhibiting damage caused by oxidative stress. However, the final fate of antioxidants in the gut, how antioxidant metabolites affect gut microbiota, and how gut microbiota affect the metabolism of antioxidants are not fully understood.

We invite you to contribute your latest research findings or a review article to this Special Issue, which will bring together current research concerning and critical thinking on the fate of phytochemical antioxidants in the gut and the role antioxidant gut metabolites play in reducing oxidative stress in various gut diseases and metabolic diseases.

Your contribution can include either in vitro or in vivo studies relating to any of the following topics: fate of antioxidants in the gut; antioxidative activities of phytochemicals in the digestive system; molecular mechanisms of phytochemical antioxidants in maintaining gut health; and interactions of antioxidant metabolites and gut microbiota.

We look forward to your contributions.

Prof. Dr. Baojun Xu
Guest Editor

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Keywords

  • Antioxidants
  • Phytochemicals
  • Phenolic acids
  • Gut metabolites of antioxidants
  • Fate of antioxidants
  • Gut microbiota
  • Gut health

Published Papers (11 papers)

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Research

Jump to: Review

22 pages, 5469 KiB  
Article
Bacillus amyloliquefaciens SC06 Induced AKT–FOXO Signaling Pathway-Mediated Autophagy to Alleviate Oxidative Stress in IPEC-J2 Cells
by Li Tang, Zihan Zeng, Yuanhao Zhou, Baikui Wang, Peng Zou, Qi Wang, Jiafu Ying, Fei Wang, Xiang Li, Shujie Xu, Pengwei Zhao and Weifen Li
Antioxidants 2021, 10(10), 1545; https://doi.org/10.3390/antiox10101545 - 28 Sep 2021
Cited by 23 | Viewed by 2519
Abstract
Autophagy is a conserved proteolytic mechanism, which degrades and recycles damaged organs and proteins in cells to resist external stress. Probiotics could induce autophagy; however, its underlying molecular mechanisms remain elusive. Our previous study has found that BaSC06 could alleviate oxidative stress by [...] Read more.
Autophagy is a conserved proteolytic mechanism, which degrades and recycles damaged organs and proteins in cells to resist external stress. Probiotics could induce autophagy; however, its underlying molecular mechanisms remain elusive. Our previous study has found that BaSC06 could alleviate oxidative stress by inducing autophagy in rats. This research aimed to verify whether Bacillus amyloliquefaciens SC06 can induce autophagy to alleviate oxidative stress in IPEC-J2 cells, as well as explore its mechanisms. IPEC-J2 cells were first pretreated with 108 CFU/mL BaSC06, and then were induced to oxidative stress by the optimal dose of diquat. The results showed that BaSC06 significantly triggered autophagy, indicated by the up-regulation of LC3 and Beclin1 along with downregulation of p62 in IPEC-J2 cells. Further analysis revealed that BaSC06 inhibited the AKT–FOXO signaling pathway by inhibiting the expression of p-AKT and p-FOXO and inducing the expression of SIRT1, resulting in increasing the transcriptional activity of FOXO3 and gene expression of the ATG5–ATG12 complex to induce autophagy, which alleviated oxidative stress and apoptosis. Taken together, BaSC06 can induce AKT–FOXO-mediated autophagy to alleviate oxidative stress-induced apoptosis and cell damage, thus providing novel theoretical support for probiotics in the prevention and treatment of oxidative damage. Full article
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17 pages, 12287 KiB  
Article
Quercetin Ameliorates Insulin Resistance and Restores Gut Microbiome in Mice on High-Fat Diets
by Yuqing Tan, Christina C. Tam, Matt Rolston, Priscila Alves, Ling Chen, Shi Meng, Hui Hong, Sam K. C. Chang and Wallace Yokoyama
Antioxidants 2021, 10(8), 1251; https://doi.org/10.3390/antiox10081251 - 5 Aug 2021
Cited by 37 | Viewed by 5304
Abstract
Quercetin is a flavonoid that has been shown to have health-promoting capacities due to its potent antioxidant activity. However, the effect of chronic intake of quercetin on the gut microbiome and diabetes-related biomarkers remains unclear. Male C57BL/6J mice were fed HF or HF [...] Read more.
Quercetin is a flavonoid that has been shown to have health-promoting capacities due to its potent antioxidant activity. However, the effect of chronic intake of quercetin on the gut microbiome and diabetes-related biomarkers remains unclear. Male C57BL/6J mice were fed HF or HF supplemented with 0.05% quercetin (HFQ) for 6 weeks. Diabetes-related biomarkers in blood were determined in mice fed high-fat (HF) diets supplemented with quercetin. Mice fed the HFQ diet gained less body, liver, and adipose weight, while liver lipid and blood glucose levels were also lowered. Diabetes-related plasma biomarkers insulin, leptin, resistin, and glucagon were significantly reduced by quercetin supplementation. In feces, quercetin supplementation significantly increased the relative abundance of Akkermansia and decreased the Firmicutes/Bacteroidetes ratio. The expression of genes Srebf1, Ppara, Cyp51, Scd1, and Fasn was downregulated by quercetin supplementation. These results indicated that diabetes biomarkers are associated with early metabolic changes accompanying obesity, and quercetin may ameliorate insulin resistance. Full article
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14 pages, 1667 KiB  
Article
Effects of Selenium- and Zinc-Enriched Lactobacillus plantarum SeZi on Antioxidant Capacities and Gut Microbiome in an ICR Mouse Model
by Sini Kang, Rui Li, Hui Jin, Hyun Ju You and Geun Eog Ji
Antioxidants 2020, 9(10), 1028; https://doi.org/10.3390/antiox9101028 - 21 Oct 2020
Cited by 16 | Viewed by 4001
Abstract
Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the [...] Read more.
Selenium and zinc are essential trace minerals for humans with various biological functions. In this study, selenium- and zinc-tolerant lactic acid bacteria (LAB) isolates were screened out from human fecal samples. Amongst three hundred LAB isolates, the Lactobacillus plantarum SeZi strain displayed the tolerance against selenium and zinc with the greatest biomass production and bioaccumulation of selenium and zinc. To further assess the characteristics of this strain, the lyophilized L. plantarum SeZi were prepared and administered to Institute of Cancer Research (ICR) mice. The mice were divided into four groups, provided with normal chow (Con), or normal chow supplemented with Na2SeO3 and ZnSO4∙7H2O (SZ), L. plantarum SeZi (Lp), or selenium- and zinc-enriched L. plantarum SeZi (SZ + Lp), respectively. After 4 weeks of oral administration, the concentrations of selenium and zinc in blood were significantly increased in the SZ + Lp group when compared to the control or SZ group (p < 0.05). The increased selenium level led to an enhanced glutathione peroxidase activity and decreased blood malondialdehyde level in the SZ + Lp group (p < 0.05). Meanwhile, the results of bacterial community and microbial metabolic pathway analysis via 16S rRNA gene amplicon sequencing showed that L. plantarum SeZi significantly promoted the utilization of selenocysteine, seleno-cystathionine and seleno-methionine in the selenocompounds metabolism. Here, the in vivo antioxidant capacities of the selenium- and zinc-enriched lactobacillus strain showed us the utilization of a unique probiotic as a Se/Zn supplement with high availability, low toxicity, and additional probiotic advantages. Full article
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20 pages, 8141 KiB  
Article
Dendropanax morbifera Leaf Extracts Improved Alcohol Liver Injury in Association with Changes in the Gut Microbiota of Rats
by Taekil Eom, Gwangpyo Ko, Kyeoung Cheol Kim, Ju-Sung Kim and Tatsuya Unno
Antioxidants 2020, 9(10), 911; https://doi.org/10.3390/antiox9100911 - 24 Sep 2020
Cited by 13 | Viewed by 4157
Abstract
This study evaluated the protective effects of Dendropanax morbifera leaf (DML) extracts in the liver due to excessive ethanol consumption. Our results showed that the ethanol extract had better antioxidant activity than the water extract, likely due to the higher levels of total [...] Read more.
This study evaluated the protective effects of Dendropanax morbifera leaf (DML) extracts in the liver due to excessive ethanol consumption. Our results showed that the ethanol extract had better antioxidant activity than the water extract, likely due to the higher levels of total flavonoid and phenolic compounds in the former. We found that the main phenolic acid was chlorogenic acid and the major flavonoid was rutin. Results from the animal model experiment showed concentration-dependent liver protection with the distilled water extract showing better liver protection than the ethanol extract. Gut microbiota dysbiosis induced by alcohol consumption was significantly shifted by DML extracts through increasing mainly Bacteroides and Allobaculum. Moreover, predicted metabolic activities of biosynthesis of beneficial monounsaturated fatty acids such as oleate and palmitoleate were enhanced. Our results suggest that these hepatoprotective effects are likely due to the increased activities of antioxidant enzymes and partially promoted by intestinal microbiota shifts. Full article
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18 pages, 2262 KiB  
Article
Beneficial Regulatory Effects of Polymethoxyflavone—Rich Fraction from Ougan (Citrus reticulata cv. Suavissima) Fruit on Gut Microbiota and Identification of Its Intestinal Metabolites in Mice
by Jiebiao Chen, Yue Wang, Tailin Zhu, Sijia Yang, Jinping Cao, Xian Li, Li-Shu Wang and Chongde Sun
Antioxidants 2020, 9(9), 831; https://doi.org/10.3390/antiox9090831 - 6 Sep 2020
Cited by 28 | Viewed by 3356
Abstract
Polymethoxyflavones (PMFs) are special flavonoids in citrus fruits that have been suggested to be beneficial to human health. However, whether PMFs in citrus fruit alter human gut microbiota is not well understood. The aim of the present study was to investigate the effects [...] Read more.
Polymethoxyflavones (PMFs) are special flavonoids in citrus fruits that have been suggested to be beneficial to human health. However, whether PMFs in citrus fruit alter human gut microbiota is not well understood. The aim of the present study was to investigate the effects of PMF-rich fraction from Ougan (Citrus reticulata cv. Suavissima) on gut microbiota and evaluate the intestinal metabolic profile of PMFs in Institute of Cancer Research mice. The main components of the PMF-rich fraction were nobiletin, tangeretin, and 5-demethylnobiletin. The composition of the gut microbiota was analyzed using 16S ribosomal DNA sequencing. The results showed that after oral administration, the composition of mice gut microbiota was significantly altered. The relative abundance of two probiotics, Lactobacillus and Bifidobacterium, were found to increase significantly. A total of 21 metabolites of PMFs were detected in mice intestinal content by high performance liquid chromatography electrospray ionization tandem mass spectrometry, and they were generated through demethylation, demethoxylation, hydroxylation, and glucuronidation. Our results provided evidence that PMFs have potential beneficial regulatory effects on gut microbiota that in turn metabolize PMFs, which warrants further investigation in human clinical trials. Full article
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17 pages, 1380 KiB  
Article
Dietary Lipids Influence Bioaccessibility of Polyphenols from Black Carrots and Affect Microbial Diversity under Simulated Gastrointestinal Digestion
by Chunhe Gu, Hafiz A. R. Suleria, Frank R. Dunshea and Kate Howell
Antioxidants 2020, 9(8), 762; https://doi.org/10.3390/antiox9080762 - 17 Aug 2020
Cited by 35 | Viewed by 4917
Abstract
The bioaccessibility and activity of polyphenols is dependent on their structure and entrapment in the food matrix. While dietary lipids are known to transit into the colon, the impact of different lipids on the microbiome, and their interactions with dietary polyphenols are largely [...] Read more.
The bioaccessibility and activity of polyphenols is dependent on their structure and entrapment in the food matrix. While dietary lipids are known to transit into the colon, the impact of different lipids on the microbiome, and their interactions with dietary polyphenols are largely unknown. Here, we investigated the effect of dietary lipids on the bioaccessibility of polyphenols from purple/black carrots and adaptation of the gut microbiome in a simulated in vitro digestion-fermentation. Coconut oil, sunflower oil, and beef tallow were selected to represent common dietary sources of medium-chain fatty acids (MCFAs), long-chain polyunsaturated fatty acids (PUFAs), and long-chain polysaturated fatty acids (SFAs), respectively. All lipids promoted the bioaccessibility of both anthocyanins and phenolic acids during intestinal digestion with coconut oil exhibiting the greatest protection of anthocyanins. Similar trends were shown in antioxidant assays (2,2-Diphenyl-1-pricrylhydrazyl (DPPH), ferric reducing ability (FRAP), and total phenolic content (TPC)) with higher phytochemical bioactivities observed with the addition of dietary lipids. Most bioactive polyphenols were decomposed during colonic fermentation. Black carrot modulated diversity and composition of a simulated gut microbiome. Dramatic shifts in gut microbiome were caused by coconut oil. Inclusion of sunflower oil improved the production of butyrate, potentially due to the presence of PUFAs. The results show that the impact of polyphenols in the digestive tract should be considered in the context of other components of the diet, particularly lipids. Full article
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16 pages, 1496 KiB  
Article
First-Pass Metabolism of Polyphenols from Selected Berries: A High-Throughput Bioanalytical Approach
by Francisco J. Olivas-Aguirre, Sandra Mendoza, Emilio Alvarez-Parrilla, Gustavo A. Gonzalez-Aguilar, Monica A. Villegas-Ochoa, Jael T.J. Quintero-Vargas and Abraham Wall-Medrano
Antioxidants 2020, 9(4), 311; https://doi.org/10.3390/antiox9040311 - 13 Apr 2020
Cited by 13 | Viewed by 4027
Abstract
Small berries are rich in polyphenols whose first-pass metabolism may alter their ultimate physiological effects. The antioxidant capacity and polyphenol profile of three freeze-dried berries (blackberry, raspberry, Red Globe grape) were measured and their apparent permeability (Papp) and first-pass biotransformation were tracked with [...] Read more.
Small berries are rich in polyphenols whose first-pass metabolism may alter their ultimate physiological effects. The antioxidant capacity and polyphenol profile of three freeze-dried berries (blackberry, raspberry, Red Globe grape) were measured and their apparent permeability (Papp) and first-pass biotransformation were tracked with an ex vivo bioanalytical system [everted gut sac (rat) + three detection methods: spectrophotometry, HPLC-ESI-QTOF-MS, differential pulse voltammetry (DPV)]. Total polyphenol (ratio 0.07-0.14-1.0) and molecular diversity (anthocyanins > flavan-3-ols), antioxidant capacity (DPPH, FRAP), anodic current maxima and Papp (efflux> uptake) were in the following order: blackberry > raspberry > Red Globe grape. Epicatechin, pelargonidin & cyanin (all), callistephin (raspberry/blackberry), catechin (grape), cyanidin glycosides (blackberry) and their derived metabolites [quinic acid, epicatechin, cyanidin/malvidin glucosides, and chlorogenic/caffeic acids] were fruit-specific and concentration-dependent. Time-trend DPV kinetic data revealed concurrent epithelial permeability & biotransformation processes. Regular permeability and high-biotransformation of berry polyphenols suggest fruit-specific health effects apparently at the intestinal level. Full article
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Review

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34 pages, 1556 KiB  
Review
Translational Approaches with Antioxidant Phytochemicals against Alcohol-Mediated Oxidative Stress, Gut Dysbiosis, Intestinal Barrier Dysfunction, and Fatty Liver Disease
by Jacob W. Ballway and Byoung-Joon Song
Antioxidants 2021, 10(3), 384; https://doi.org/10.3390/antiox10030384 - 4 Mar 2021
Cited by 40 | Viewed by 6951
Abstract
Emerging data demonstrate the important roles of altered gut microbiomes (dysbiosis) in many disease states in the peripheral tissues and the central nervous system. Gut dysbiosis with decreased ratios of Bacteroidetes/Firmicutes and other changes are reported to be caused by many disease states [...] Read more.
Emerging data demonstrate the important roles of altered gut microbiomes (dysbiosis) in many disease states in the peripheral tissues and the central nervous system. Gut dysbiosis with decreased ratios of Bacteroidetes/Firmicutes and other changes are reported to be caused by many disease states and various environmental factors, such as ethanol (e.g., alcohol drinking), Western-style high-fat diets, high fructose, etc. It is also caused by genetic factors, including genetic polymorphisms and epigenetic changes in different individuals. Gut dysbiosis, impaired intestinal barrier function, and elevated serum endotoxin levels can be observed in human patients and/or experimental rodent models exposed to these factors or with certain disease states. However, gut dysbiosis and leaky gut can be normalized through lifestyle alterations such as increased consumption of healthy diets with various fruits and vegetables containing many different kinds of antioxidant phytochemicals. In this review, we describe the mechanisms of gut dysbiosis, leaky gut, endotoxemia, and fatty liver disease with a specific focus on the alcohol-associated pathways. We also mention translational approaches by discussing the benefits of many antioxidant phytochemicals and/or their metabolites against alcohol-mediated oxidative stress, gut dysbiosis, intestinal barrier dysfunction, and fatty liver disease. Full article
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70 pages, 6540 KiB  
Review
The Interactions between Polyphenols and Microorganisms, Especially Gut Microbiota
by Małgorzata Makarewicz, Iwona Drożdż, Tomasz Tarko and Aleksandra Duda-Chodak
Antioxidants 2021, 10(2), 188; https://doi.org/10.3390/antiox10020188 - 28 Jan 2021
Cited by 151 | Viewed by 10851
Abstract
This review presents the comprehensive knowledge about the bidirectional relationship between polyphenols and the gut microbiome. The first part is related to polyphenols’ impacts on various microorganisms, especially bacteria, and their influence on intestinal pathogens. The research data on the mechanisms of polyphenol [...] Read more.
This review presents the comprehensive knowledge about the bidirectional relationship between polyphenols and the gut microbiome. The first part is related to polyphenols’ impacts on various microorganisms, especially bacteria, and their influence on intestinal pathogens. The research data on the mechanisms of polyphenol action were collected together and organized. The impact of various polyphenols groups on intestinal bacteria both on the whole “microbiota” and on particular species, including probiotics, are presented. Moreover, the impact of polyphenols present in food (bound to the matrix) was compared with the purified polyphenols (such as in dietary supplements) as well as polyphenols in the form of derivatives (such as glycosides) with those in the form of aglycones. The second part of the paper discusses in detail the mechanisms (pathways) and the role of bacterial biotransformation of the most important groups of polyphenols, including the production of bioactive metabolites with a significant impact on the human organism (both positive and negative). Full article
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50 pages, 2726 KiB  
Review
Insight into Polyphenol and Gut Microbiota Crosstalk: Are Their Metabolites the Key to Understand Protective Effects against Metabolic Disorders?
by Mireille Koudoufio, Yves Desjardins, Francis Feldman, Schohraya Spahis, Edgard Delvin and Emile Levy
Antioxidants 2020, 9(10), 982; https://doi.org/10.3390/antiox9100982 - 13 Oct 2020
Cited by 76 | Viewed by 8351
Abstract
Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given [...] Read more.
Lifestyle factors, especially diet and nutrition, are currently regarded as essential avenues to decrease modern-day cardiometabolic disorders (CMD), including obesity, metabolic syndrome, type 2 diabetes, and atherosclerosis. Many groups around the world attribute these trends, at least partially, to bioactive plant polyphenols given their anti-oxidant and anti-inflammatory actions. In fact, polyphenols can prevent or reverse the progression of disease processes through many distinct mechanisms. In particular, the crosstalk between polyphenols and gut microbiota, recently unveiled thanks to DNA-based tools and next generation sequencing, unravelled the central regulatory role of dietary polyphenols and their intestinal micro-ecology metabolites on the host energy metabolism and related illnesses. The objectives of this review are to: (1) provide an understanding of classification, structure, and bioavailability of dietary polyphenols; (2) underline their metabolism by gut microbiota; (3) highlight their prebiotic effects on microflora; (4) discuss the multifaceted roles of their metabolites in CMD while shedding light on the mechanisms of action; and (5) underscore their ability to initiate host epigenetic regulation. In sum, the review clearly documents whether dietary polyphenols and micro-ecology favorably interact to promote multiple physiological functions on human organism. Full article
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20 pages, 536 KiB  
Review
Interaction of Polyphenols as Antioxidant and Anti-Inflammatory Compounds in Brain–Liver–Gut Axis
by Amritpal Singh, Yu Fung Yau, Kin Sum Leung, Hani El-Nezami and Jetty Chung-Yung Lee
Antioxidants 2020, 9(8), 669; https://doi.org/10.3390/antiox9080669 - 26 Jul 2020
Cited by 40 | Viewed by 8017
Abstract
Oxidative stress plays an important role in the onset as well as the progression of inflammation. Without proper intervention, acute inflammation could progress to chronic inflammation, resulting in the development of inflammatory diseases. Antioxidants, such as polyphenols, have been known to possess anti-oxidative [...] Read more.
Oxidative stress plays an important role in the onset as well as the progression of inflammation. Without proper intervention, acute inflammation could progress to chronic inflammation, resulting in the development of inflammatory diseases. Antioxidants, such as polyphenols, have been known to possess anti-oxidative properties which promote redox homeostasis. This has encouraged research on polyphenols as potential therapeutics for inflammation through anti-oxidative and anti-inflammatory pathways. In this review, the ability of polyphenols to modulate the activation of major pathways of inflammation and oxidative stress, and their potential to regulate the activity of immune cells are examined. In addition, in this review, special emphasis has been placed on the effects of polyphenols on inflammation in the brain–liver–gut axis. The data derived from in vitro cell studies, animal models and human intervention studies are discussed. Full article
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