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1
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Williamson G, Clifford MN. A critical examination of human data for the biological activity of phenolic acids and their phase-2 conjugates derived from dietary (poly)phenols, phenylalanine, tyrosine and catecholamines. Crit Rev Food Sci Nutr 2024:1-60. [PMID: 39383187 DOI: 10.1080/10408398.2024.2410874] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2024]
Abstract
Free or conjugated aromatic/phenolic acids arise from the diet, endogenous metabolism of catecholamines (adrenaline, noradrenaline, dopamine), protein (phenylalanine, tyrosine), pharmaceuticals (aspirin, metaprolol) plus gut microbiota metabolism of dietary (poly)phenols and undigested protein. Quantitative data obtained with authentic calibrants for 112 aromatic/phenolic acids including phase-2 conjugates in human plasma, urine, ileal fluid, feces and tissues have been collated and mean/median values compared with in vitro bioactivity data in cultured cells. Ca 30% of publications report bioactivity at ≤1 μmol/L. With support from clinical studies, it appears that the greatest benefit might be produced in vascular tissues by C6-C3 metabolites, including some of gut microbiota origin and some phase-2 conjugates, 15 of which are 3',4'-disubstituted with multiple sources including caffeic acid and hesperetin, plus one unsubstituted and two mono-substituted examples which can originate from protein. There is an unexamined potential for synergy. Free-living and washout plasma data are scarce. Some metabolites have been overlooked, notably phenyl-lactic, phenyl-hydracrylic and phenyl-propanoic acids, especially those from amino acids plus glycine, hydroxy-glycine and glutamine conjugates. Phenolic acids and conjugates from multiple sources exhibit biological activities, some of which are likely relevant in vivo and link to biomarkers of health. Further targeted studies are justified.
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Affiliation(s)
- Gary Williamson
- Department of Nutrition, Dietetics and Food, Victorian Heart Institute, Faculty of Medicine Nursing and Health Sciences, Monash University, Victoria Heart Hospital, Clayton, Australia
| | - Michael N Clifford
- Department of Nutrition, Dietetics and Food, Victorian Heart Institute, Faculty of Medicine Nursing and Health Sciences, Monash University, Victoria Heart Hospital, Clayton, Australia
- School of Bioscience and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
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2
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Xu L, Liao J, Li X, Zhu L, Wang X, Xu B, Li L, Ze X, Sun H, Li J. Exploring the mechanism of probiotics in enhancing the utilization of chemical components (or polyphenols) of grape seed extract. Food Chem 2024; 438:137982. [PMID: 37979272 DOI: 10.1016/j.foodchem.2023.137982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 10/18/2023] [Accepted: 11/11/2023] [Indexed: 11/20/2023]
Abstract
Fecal samples from 20 healthy adults were collected for in vitro fermentation experiments to investigate the effects of combined probiotics on the utilization of grape seed extract in humans. After fermenting for 24 h, short-chain fatty acids, metabolites, and gut microbiota composition were analyzed. Short-chain fatty acids in the grape seed extract probiotics group were significantly higher than those in the grape seed extract group. Probiotics significantly enhanced the conversion and utilization of catechins and epicatechins in grape seed extract group and increased the production of 3-hydroxyphenylacetic acid. The 16S rRNA sequencing results revealed that compound probiotics significantly increased the relative abundance of Lacticaseibacillus, HT002, Bifidobacterium, and Lactobacillus and reduced that of Escherichia-Shigella. Our findings showed considerable individual variability in the metabolic utilization of grape seed extract in humans. The consumption of probiotics appears to significantly enhance the utilization.
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Affiliation(s)
- Lei Xu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China; Department of Orthopedics, The First Hospital of Shanxi Medical University, Taiyuan 030000, China
| | - Jiahao Liao
- College of Animal Science, Shanxi Agricultural University, Taigu 030801, China
| | - Xiaoqiong Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Liying Zhu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Xin Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Benhong Xu
- BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China
| | - Liang Li
- BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China
| | - Xiaolei Ze
- BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China.
| | - Haibiao Sun
- Department of Orthopedics, The First Hospital of Shanxi Medical University, Taiyuan 030000, China.
| | - Jinjun Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
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Beloborodova N, Fadeev R, Fedotcheva N. Influence of Microbiota-Related Metabolites Associated with Inflammation and Sepsis on the Peroxidase Activity of Cyclooxygenase in Healthy Human Monocytes and Acute Monocytic Leukemia Cells. Int J Mol Sci 2023; 24:16244. [PMID: 38003440 PMCID: PMC10671350 DOI: 10.3390/ijms242216244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/31/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
The human microbiota produces metabolites that can enter the bloodstream and exert systemic effects on various functions in both healthy and pathological states. We have studied the participation of microbiota-related metabolites in bacterial infection by examining their influence on the activity of cyclooxygenase (COX) as a key enzyme of inflammation. The influence of aromatic microbial metabolites, derivatives of phenylalanine (phenylpropionic acid, PPA), tyrosine (4-hydroxyphenyllactic acid, HPLA), and tryptophan (indolacetic acids, IAA), the concentrations of which in the blood change notably during sepsis, was evaluated. Also, the effect of itaconic acid (ITA) was studied, which is formed in macrophages under the action of bacterial lipopolysaccharides (LPS) and appears in the blood in the early stages of infection. Metabiotic acetyl phosphate (AcP) as a strong acetylating agent was also tested. The activity of COX was measured via the TMPD oxidation colorimetric assay using the commercial pure enzyme, cultured healthy monocytes, and the human acute monocytic leukemia cell line THP-1. All metabolites in the concentration range of 100-500 μM lowered the activity of COX. The most pronounced inhibition was observed on the commercial pure enzyme, reaching up to 40% in the presence of AcP and 20-30% in the presence of the other metabolites. On cell lysates, the effect of metabolites was preserved, although it significantly decreased, probably due to their interaction with other targets subject to redox-dependent and acetylation processes. The possible contribution of the redox-dependent action of microbial metabolites was confirmed by assessing the activity of the enzyme in the presence of thiol reagents and in model conditions, when the COX-formed peroxy intermediate was replaced with tert-butyl hydroperoxide (TBH). The data show the involvement of the microbial metabolites in the regulation of COX activity, probably due to their influence on the peroxidase activity of the enzyme.
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Affiliation(s)
- Natalia Beloborodova
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka St., 107031 Moscow, Russia;
| | - Roman Fadeev
- Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 3, Institutskaya St., 142290 Pushchino, Russia;
| | - Nadezhda Fedotcheva
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka St., 107031 Moscow, Russia;
- Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 3, Institutskaya St., 142290 Pushchino, Russia;
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4
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Cattivelli A, Conte A, Tagliazucchi D. Quercetins, Chlorogenic Acids and Their Colon Metabolites Inhibit Colon Cancer Cell Proliferation at Physiologically Relevant Concentrations. Int J Mol Sci 2023; 24:12265. [PMID: 37569640 PMCID: PMC10418599 DOI: 10.3390/ijms241512265] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/28/2023] [Accepted: 07/29/2023] [Indexed: 08/13/2023] Open
Abstract
Several studies have suggested that a phenolic-rich diet may be protective against colon cancer. Most phenolic compounds are not absorbed in the small intestine and reach the colon where they are metabolized by gut microbiota in simple phenolic acids. In this study, the anti-proliferative activity of quercetins, chlorogenic acids, their colon metabolites and mixtures of parent compounds/metabolites was assessed by using two colon cancer cell lines (Caco-2 and SW480) at physiologically relevant concentrations. Chlorogenic acids, quercetin and the metabolite 3-(3',4'-dihydroxyphenyl)acetic acid exerted remarkable anti-proliferative activity against Caco-2, whereas quercetin derivatives and metabolites were the most active against SW480. Tested compounds arrested the cell cycle at the S phase in both the cell lines. The mixtures of parent compounds/metabolites, which mimic the colon human metabotypes that slowly or rapidly metabolize the parent compounds, similarly inhibited cell growth. SW480 cells metabolized parent phenolic compounds more rapidly and extensively than Caco-2, whereas colon metabolites were more stable. These results suggest that dietary phenolic compounds exert an anti-proliferative effect against human colon cancer cells that can be further sustained by the colon metabolites. Therefore, gut microbiota metabolism of phenolic compounds may be of paramount importance in explaining the protective effect of phenolic-rich foods against colon cancer.
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Affiliation(s)
| | | | - Davide Tagliazucchi
- Department of Life Sciences, University of Modena and Reggio Emilia, Via Amendola, 2-Pad. Besta, 42100 Reggio Emilia, Italy; (A.C.); (A.C.)
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Zhang Y, Chen R, Zhang D, Qi S, Liu Y. Metabolite interactions between host and microbiota during health and disease: Which feeds the other? Biomed Pharmacother 2023; 160:114295. [PMID: 36709600 DOI: 10.1016/j.biopha.2023.114295] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/20/2023] [Accepted: 01/20/2023] [Indexed: 01/30/2023] Open
Abstract
Metabolites produced by the host and microbiota play a crucial role in how human bodies develop and remain healthy. Most of these metabolites are produced by microbiota and hosts in the digestive tract. Metabolites in the gut have important roles in energy metabolism, cellular communication, and host immunity, among other physiological activities. Although numerous host metabolites, such as free fatty acids, amino acids, and vitamins, are found in the intestine, metabolites generated by gut microbiota are equally vital for intestinal homeostasis. Furthermore, microbiota in the gut is the sole source of some metabolites, including short-chain fatty acids (SCFAs). Metabolites produced by microbiota, such as neurotransmitters and hormones, may modulate and significantly affect host metabolism. The gut microbiota is becoming recognized as a second endocrine system. A variety of chronic inflammatory disorders have been linked to aberrant host-microbiota interplays, but the precise mechanisms underpinning these disturbances and how they might lead to diseases remain to be fully elucidated. Microbiome-modulated metabolites are promising targets for new drug discovery due to their endocrine function in various complex disorders. In humans, metabolotherapy for the prevention or treatment of various disorders will be possible if we better understand the metabolic preferences of bacteria and the host in specific tissues and organs. Better disease treatments may be possible with the help of novel complementary therapies that target host or bacterial metabolism. The metabolites, their physiological consequences, and functional mechanisms of the host-microbiota interplays will be highlighted, summarized, and discussed in this overview.
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Affiliation(s)
- Yan Zhang
- Department of Anethesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
| | - Rui Chen
- Department of Pediatrics, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
| | - DuoDuo Zhang
- Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin Province 130021, People's Republic of China.
| | - Shuang Qi
- Department of Anethesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
| | - Yan Liu
- Department of Hand and Foot Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People's Republic of China.
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Moreno-Jiménez M, Rocha-Guzmán N, Larrosa M, Bressa C, Segura-Sánchez C, Macías-Salas A, Díaz-Rivas J, Flores-Rodríguez P. Constituents of Quercus eduardii leaf infusion: Their interaction with gut microbiota communities and therapeutic role in colorectal cancer. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022] Open
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7
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Chen Y, Wang J, Zou L, Cao H, Ni X, Xiao J. Dietary proanthocyanidins on gastrointestinal health and the interactions with gut microbiota. Crit Rev Food Sci Nutr 2022; 63:6285-6308. [PMID: 35114875 DOI: 10.1080/10408398.2022.2030296] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Many epidemiological and experimental studies have consistently reported the beneficial effects of dietary proanthocyanidins (PAC) on improving gastrointestinal physiological functions. This review aims to present a comprehensive perspective by focusing on structural properties, interactions and gastrointestinal protection of PAC. In brief, the main findings of this review are summarized as follows: (1) Structural features are critical factors in determining the bioavailability and subsequent pharmacology of PAC; (2) PAC and/or their bacterial metabolites can play a direct role in the gastrointestinal tract through their antioxidant, antibacterial, anti-inflammatory, and anti-proliferative properties; (3) PAC can reduce the digestion, absorption, and bioavailability of carbohydrates, proteins, and lipids by interacting with them or their according enzymes and transporters in the gastrointestinal tract; (4). PAC showed a prebiotic-like effect by interacting with the microflora in the intestinal tract, and the enhancement of PAC on a variety of probiotics, such as Bifidobacterium spp. and Lactobacillus spp. could be associated with potential benefits to human health. In conclusion, the potential effects of PAC in prevention and alleviation of gastrointestinal diseases are remarkable but clinical evidence is urgently needed.
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Affiliation(s)
- Yong Chen
- Laboratory of Food Oral Processing, School of Food Science & Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, China
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jing Wang
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China
- Ningbo Research Institute, Zhejiang University, Ningbo, Zhejiang, China
| | - Liang Zou
- Key Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Sichuan Engineering & Technology Research Center of Coarse Cereal Industralization, School of Food and Biological Engineering, Chengdu University, Chengdu, Sichuan, China
| | - Hui Cao
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Faculty of Sciences, Universidade de Vigo, Ourense, Spain
| | - Xiaoling Ni
- Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianbo Xiao
- Institute of Food Safety and Nutrition, Jinan University, Guangzhou, China
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8
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Dias P, Pourová J, Vopršalová M, Nejmanová I, Mladěnka P. 3-Hydroxyphenylacetic Acid: A Blood Pressure-Reducing Flavonoid Metabolite. Nutrients 2022; 14:nu14020328. [PMID: 35057508 PMCID: PMC8781193 DOI: 10.3390/nu14020328] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/06/2022] [Accepted: 01/11/2022] [Indexed: 12/11/2022] Open
Abstract
Regular intake of polyphenol-rich food has been associated with a wide variety of beneficial health effects, including the prevention of cardiovascular diseases. However, the parent flavonoids have mostly low bioavailability and, hence, their metabolites have been hypothesized to be bioactive. One of these metabolites, 3-hydroxyphenylacetic acid (3-HPAA), formed by the gut microbiota, was previously reported to exert vasorelaxant effects ex vivo. The aim of this study was to shed more light on this effect in vivo, and to elucidate the mechanism of action. 3-HPAA gave rise to a dose-dependent decrease in arterial blood pressure when administered i.v. both as a bolus and infusion to spontaneously hypertensive rats. In contrast, no significant changes in heart rate were observed. In ex vivo experiments, where porcine hearts from a slaughterhouse were used to decrease the need for laboratory animals, 3-HPAA relaxed precontracted porcine coronary artery segments via a mechanism partially dependent on endothelium integrity. This relaxation was significantly impaired after endothelial nitric oxide synthase inhibition. In contrast, the blockade of SKCa or IKCa channels, or muscarinic receptors, did not affect 3-HPAA relaxation. Similarly, no effects of 3-HPAA on cyclooxygenase nor L-type calcium channels were observed. Thus, 3-HPAA decreases blood pressure in vivo via vessel relaxation, and this mechanism might be based on the release of nitric oxide by the endothelial layer.
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Affiliation(s)
- Patrícia Dias
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; (P.D.); (M.V.); (P.M.)
| | - Jana Pourová
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; (P.D.); (M.V.); (P.M.)
- Correspondence: ; Tel.: +420-495-067-295; Fax: +420-495-067-170
| | - Marie Vopršalová
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; (P.D.); (M.V.); (P.M.)
| | - Iveta Nejmanová
- Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic;
| | - Přemysl Mladěnka
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; (P.D.); (M.V.); (P.M.)
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9
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Nannini G, Meoni G, Tenori L, Ringressi MN, Taddei A, Niccolai E, Baldi S, Russo E, Luchinat C, Amedei A. Fecal metabolomic profiles: A comparative study of patients with colorectal cancer vs adenomatous polyps. World J Gastroenterol 2021; 27:6430-6441. [PMID: 34720532 PMCID: PMC8517777 DOI: 10.3748/wjg.v27.i38.6430] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/17/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC), the third most common cause of death in both males and females worldwide, shows a positive response to therapy and usually a better prognosis when detected at an early stage. However, the survival rate declines when the diagnosis is late and the tumor spreads to other organs. Currently, the measures widely used in the clinic are fecal occult blood test and evaluation of serum tumor markers, but the lack of sensitivity and specificity of these markers restricts their use for CRC diagnosis. Due to its high sensitivity and precision, colonoscopy is currently the gold-standard screening technique for CRC, but it is a costly and invasive procedure. Therefore, the implementation of custom-made methodologies including those with minimal invasiveness, protection, and reproducibility is highly desirable. With regard to other screening methods, the screening of fecal samples has several benefits, and metabolomics is a successful method to classify the metabolite shift in living systems as a reaction to pathophysiological influences, genetic modifications, and environmental factors. AIM To characterize the variation groups and potentially recognize some diagnostic markers, we compared with healthy controls (HCs) the fecal nuclear magnetic resonance (NMR) metabolomic profiles of patients with CRC or adenomatous polyposis (AP). METHODS Proton nuclear magnetic resonance spectroscopy was used in combination with multivariate and univariate statistical approaches, to define the fecal metabolic profiles of 32 CRC patients, 16 AP patients, and 38 HCs well matched in age, sex, and body mass index. RESULTS NMR metabolomic analyses revealed that fecal sample profiles differed among CRC patients, AP patients, and HCs, and some discriminatory metabolites including acetate, butyrate, propionate, 3-hydroxyphenylacetic acid, valine, tyrosine and leucine were identified. CONCLUSION In conclusion, we are confident that our data can be a forerunner for future studies on CRC management, especially the diagnosis and evaluation of the effectiveness of treatments.
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Affiliation(s)
- Giulia Nannini
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Gaia Meoni
- Department of Chemistry “Ugo Schiff”, University of Florence, Florence 50134, Italy
| | - Leonardo Tenori
- Department of Chemistry “Ugo Schiff”, University of Florence, Florence 50134, Italy
| | - Maria Novella Ringressi
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Antonio Taddei
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Elena Niccolai
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Simone Baldi
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Edda Russo
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
| | - Claudio Luchinat
- Department of Chemistry & Magnetic Resonance Center (CERM), University of Florence, Florence 50134, Italy
| | - Amedeo Amedei
- Department of Clinical and Experimental Medicine, University of Florence, Florence 50134, Italy
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10
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Magaña AA, Kamimura N, Soumyanath A, Stevens JF, Maier CS. Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity. THE PLANT JOURNAL : FOR CELL AND MOLECULAR BIOLOGY 2021; 107:1299-1319. [PMID: 34171156 PMCID: PMC9084498 DOI: 10.1111/tpj.15390] [Citation(s) in RCA: 111] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/15/2021] [Accepted: 06/19/2021] [Indexed: 05/02/2023]
Abstract
Caffeoylquinic acids (CQAs) are specialized plant metabolites we encounter in our daily life. Humans consume CQAs in mg-to-gram quantities through dietary consumption of plant products. CQAs are considered beneficial for human health, mainly due to their anti-inflammatory and antioxidant properties. Recently, new biosynthetic pathways via a peroxidase-type p-coumaric acid 3-hydroxylase enzyme were discovered. More recently, a new GDSL lipase-like enzyme able to transform monoCQAs into diCQA was identified in Ipomoea batatas. CQAs were recently linked to memory improvement; they seem to be strong indirect antioxidants via Nrf2 activation. However, there is a prevalent confusion in the designation and nomenclature of different CQA isomers. Such inconsistencies are critical and complicate bioactivity assessment since different isomers differ in bioactivity and potency. A detailed explanation regarding the origin of such confusion is provided, and a recommendation to unify nomenclature is suggested. Furthermore, for studies on CQA bioactivity, plant-based laboratory animal diets contain CQAs, which makes it difficult to include proper control groups for comparison. Therefore, a synthetic diet free of CQAs is advised to avoid interferences since some CQAs may produce bioactivity even at nanomolar levels. Biotransformation of CQAs by gut microbiota, the discovery of new enzymatic biosynthetic and metabolic pathways, dietary assessment, and assessment of biological properties with potential for drug development are areas of active, ongoing research. This review is focused on the chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity recently reported for mono-, di-, tri-, and tetraCQAs.
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Affiliation(s)
- Armando Alcázar Magaña
- Department of Chemistry, Oregon State University, Corvallis, OR, USA
- Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
- BENFRA Botanical Dietary Supplements Research Center, Oregon Health and Science University, Portland, OR, USA
| | - Naofumi Kamimura
- Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Niigata, Japan
| | - Amala Soumyanath
- BENFRA Botanical Dietary Supplements Research Center, Oregon Health and Science University, Portland, OR, USA
- Department of Neurology, Oregon Health and Science University, Portland, OR, USA
| | - Jan F. Stevens
- Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
- BENFRA Botanical Dietary Supplements Research Center, Oregon Health and Science University, Portland, OR, USA
- Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA
| | - Claudia S. Maier
- Department of Chemistry, Oregon State University, Corvallis, OR, USA
- Linus Pauling Institute, Oregon State University, Corvallis, OR, USA
- BENFRA Botanical Dietary Supplements Research Center, Oregon Health and Science University, Portland, OR, USA
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11
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Sova M, Saso L. Natural Sources, Pharmacokinetics, Biological Activities and Health Benefits of Hydroxycinnamic Acids and Their Metabolites. Nutrients 2020; 12:E2190. [PMID: 32717940 PMCID: PMC7468728 DOI: 10.3390/nu12082190] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/19/2020] [Accepted: 07/22/2020] [Indexed: 12/14/2022] Open
Abstract
Hydroxycinnamic acids (HCAs) are important natural phenolic compounds present in high concentrations in fruits, vegetables, cereals, coffee, tea and wine. Many health beneficial effects have been acknowledged in food products rich in HCAs; however, food processing, dietary intake, bioaccessibility and pharmacokinetics have a high impact on HCAs to reach the target tissue in order to exert their biological activities. In particular, metabolism is of high importance since HCAs' metabolites could either lose the activity or be even more potent compared to the parent compounds. In this review, natural sources and pharmacokinetic properties of HCAs and their esters are presented and discussed. The main focus is on their metabolism along with biological activities and health benefits. Special emphasis is given on specific effects of HCAs' metabolites in comparison with their parent compounds.
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Affiliation(s)
- Matej Sova
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
| | - Luciano Saso
- Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy;
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12
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Nazzaro F, Fratianni F, De Feo V, Battistelli A, Da Cruz AG, Coppola R. Polyphenols, the new frontiers of prebiotics. ADVANCES IN FOOD AND NUTRITION RESEARCH 2020; 94:35-89. [PMID: 32892838 DOI: 10.1016/bs.afnr.2020.06.002] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
There is a growing interest in the identification of molecules capable to promote health and with a concurrent potential for technological applications. Prebiotics are functional ingredients naturally occurring in some plant and animal foods that since many decades stimulated considerable attention from the pharmaceutical and food industries due to their positive health effects. Together the well-known biomolecules with ascertained prebiotic effect, in last year new molecules were finally recognized as prebiotics, so capable to improve the health of an organism, also through the positive effect exerted on host microbiota. Among the so-called prebiotics, a special mention should be given to polyphenols, probably the most important, or at least among the most important secondary metabolites produced by the vegetal kingdom. This short chapter wants to emphasize polyphenols and, after briefly describing the individual microbiome, to illustrate how polyphenols can, through their influence on the microbiome, have a positive effect on the health of the individual in general, and on some pathologies in particular, for which the role of a bad status of the individual microbiome has been definitively established.
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Affiliation(s)
| | | | - Vincenzo De Feo
- Department of Pharmacy, University of Salerno, Fisciano, Salerno, Italy
| | | | - Adriano Gomes Da Cruz
- Food Department, Federal Institute of Education, Science and Technology of Rio de Janeiro, Brazil
| | - Raffaele Coppola
- Department of Agricultural, Environmental and Food Sciences, DiAAA-University of Molise, Campobasso, Italy
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13
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Tsvetikova SA, Koshel EI. Microbiota and cancer: host cellular mechanisms activated by gut microbial metabolites. Int J Med Microbiol 2020; 310:151425. [PMID: 32423739 DOI: 10.1016/j.ijmm.2020.151425] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 03/25/2020] [Accepted: 04/13/2020] [Indexed: 12/13/2022] Open
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14
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Phan ADT, Williams BA, Netzel G, Mikkelsen D, D'Arcy BR, Gidley MJ. Independent fermentation and metabolism of dietary polyphenols associated with a plant cell wall model. Food Funct 2020; 11:2218-2230. [DOI: 10.1039/c9fo02987g] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The metabolic pathways of polyphenol degradation are not influenced by the presence of plant cell walls during in vitro fermentation, but co-fermentation of cell walls may lead to faster microbial metabolism of polyphenols.
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Affiliation(s)
- A. D. T. Phan
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
| | - B. A. Williams
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
| | - G. Netzel
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
| | - D. Mikkelsen
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
| | - B. R. D'Arcy
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
| | - M. J. Gidley
- Centre for Nutrition and Food Sciences
- Queensland Alliance for Agriculture and Food Innovation
- The University of Queensland
- St. Lucia
- Australia
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Applová L, Karlíčková J, Warncke P, Macáková K, Hrubša M, Macháček M, Tvrdý V, Fischer D, Mladěnka P. 4-Methylcatechol, a Flavonoid Metabolite with Potent Antiplatelet Effects. Mol Nutr Food Res 2019; 63:e1900261. [PMID: 31343835 DOI: 10.1002/mnfr.201900261] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Revised: 06/12/2019] [Indexed: 12/11/2022]
Abstract
SCOPE Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids. In this study, a series of 29 known flavonoid metabolites is tested for antiplatelet potential. METHODS AND RESULTS Four compounds appear to have a biologically relevant antiplatelet effect using whole human blood. 4-Methylcatechol (4-MC) is clearly the most efficient being about 10× times more active than clinically used acetylsalicylic acid. This ex vivo effect is also confirmed using a potentially novel in-vivo-like ex ovo hen's egg model of thrombosis, where 4-MC significantly increases the survival of the eggs. The mechanism of action is studied and it seems that it is mainly based on the influence on intracellular calcium signaling. CONCLUSION This study shows that some flavonoid metabolites formed by human microflora have a strong antiplatelet effect. This information can help to explain the antiplatelet potential of orally given flavonoids.
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Affiliation(s)
- Lenka Applová
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Jana Karlíčková
- Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Paul Warncke
- Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Friedrich-Schiller-University Jena, Lessingstr. 8, 07743, Jena, Germany
| | - Kateřina Macáková
- Department of Pharmaceutical Botany, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Marcel Hrubša
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Miloslav Macháček
- Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Václav Tvrdý
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
| | - Dagmar Fischer
- Department of Pharmaceutical Technology and Biopharmacy, Institute of Pharmacy, Friedrich-Schiller-University Jena, Lessingstr. 8, 07743, Jena, Germany
| | - Přemysl Mladěnka
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05, Hradec Králové, Czech Republic
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16
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In vitro impact of amino acid-derived bacterial metabolites on colonocyte mitochondrial activity, oxidative stress response and DNA integrity. Biochim Biophys Acta Gen Subj 2019; 1863:1292-1301. [PMID: 31034912 DOI: 10.1016/j.bbagen.2019.04.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 04/11/2019] [Accepted: 04/25/2019] [Indexed: 01/13/2023]
Abstract
BACKGROUND 4-hydroxyphenylacetic acid (HO-PAA) is produced by intestinal microbiota from L-tyrosine. High concentrations in human fecal water have been associated with cytotoxicity, urging us to test HO-PAA's effects on human colonocytes. We compared these effects with those of phenylacetic acid (PAA), phenol and acetaldehyde, also issued from amino acids fermentation. METHODS HT-29 Glc-/+ human colonocytes were exposed for 24 h to metabolites at concentrations between 350 and 1000 μM for HO-PAA and PAA, 250-1500 μM for phenol and 25-500 μM for acetaldehyde. We evaluated metabolites'cytotoxicity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and DNA quantification assays, reactive oxygen species (ROS) production with H2DCF-DA, and DNA damage with the comet assay. We measured cell oxygen consumption and mitochondrial complexes activity by polarography. RESULTS Although HO-PAA displayed no cytotoxic effect on colonocytes, it decreased mitochondrial complex I activity and oxygen consumption. This was paralleled by an increase in ROS production and DNA alteration. Cells pretreatment with N-acetylcysteine, a ROS scavenger, decreased genotoxic effects of HO-PAA, indicating implication of oxidative stress in HO-PAA's genotoxicity. PAA and phenol did not reproduce these effects, but were cytotoxic towards colonocytes. Last, acetaldehyde displayed no effect in terms of cytotoxicity and mitochondrial metabolic activity, but increased DNA damage. CONCLUSIONS Several bacterial metabolites produced from amino acids displayed deleterious effects on human colonocytes, in terms of genotoxicity (HO-PAA and acetaldehyde) or cytotoxicity (PAA and phenol). GENERAL SIGNIFICANCE This study helps understanding the consequences of intestinal microbiota's metabolic activity on the host since amino acids fermentation can lead to the formation of compounds toxic towards colonic epithelial cells.
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17
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Le Bourvellec C, Bagano Vilas Boas P, Lepercq P, Comtet-Marre S, Auffret P, Ruiz P, Bott R, Renard CMGC, Dufour C, Chatel JM, Mosoni P. Procyanidin-Cell Wall Interactions within Apple Matrices Decrease the Metabolization of Procyanidins by the Human Gut Microbiota and the Anti-Inflammatory Effect of the Resulting Microbial Metabolome In Vitro. Nutrients 2019; 11:E664. [PMID: 30893845 PMCID: PMC6471247 DOI: 10.3390/nu11030664] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 03/08/2019] [Accepted: 03/15/2019] [Indexed: 12/23/2022] Open
Abstract
B-type oligomeric procyanidins in apples constitute an important source of polyphenols in the human diet. Their role in health is not known, although it is suggested that they generate beneficial bioactive compounds upon metabolization by the gut microbiota. During apple processing, procyanidins interact with cell-wall polysaccharides and form stable complexes. These interactions need to be taken into consideration in order to better assess the biological effects of fruit constituents. Our objectives were to evaluate the impact of these interactions on the microbial metabolization of cell walls and procyanidins, and to investigate the potential anti-inflammatory activity of the resulting metabolome, in addition to analyzing the taxonomical changes which the microbiota undergo. In vitro fermentation of three model apple matrices with microbiota from 4 healthy donors showed that the binding of procyanidins to cell-wall polysaccharides, whether covalently or non-covalently, substantially reduced procyanidin degradation. Although cell wall-unbound procyanidins negatively affected carbohydrate fermentation, they generated more hydroxyphenylvaleric acid than bound procyanidins, and increased the abundance of Adlercreutzia and Gordonibacter genera. The best results in terms of production of anti-inflammatory bioactive metabolites were observed from the apple matrix with no bonds between procyanidins and cell wall polysaccharides, although the matrix with non-covalent bonds was not far behind.
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Affiliation(s)
- Carine Le Bourvellec
- UMR408 SQPOV «Sécurité et Qualité des Produits d'Origine Végétale», INRA, Avignon Université, F-84000 Avignon, France.
| | | | - Pascale Lepercq
- Université Clermont Auvergne, INRA, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France.
| | - Sophie Comtet-Marre
- Université Clermont Auvergne, INRA, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France.
| | - Pauline Auffret
- Université Clermont Auvergne, INRA, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France.
- Ifremer, UMR 241 EIO, F-98702 Tahiti, French Polynesia.
| | - Philippe Ruiz
- Université Clermont Auvergne, INRA, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France.
| | - Romain Bott
- UMR408 SQPOV «Sécurité et Qualité des Produits d'Origine Végétale», INRA, Avignon Université, F-84000 Avignon, France.
| | - Catherine M G C Renard
- UMR408 SQPOV «Sécurité et Qualité des Produits d'Origine Végétale», INRA, Avignon Université, F-84000 Avignon, France.
| | - Claire Dufour
- UMR408 SQPOV «Sécurité et Qualité des Produits d'Origine Végétale», INRA, Avignon Université, F-84000 Avignon, France.
| | - Jean-Marc Chatel
- Micalis, INRA, AgroParisTech, Université Paris-Saclay, F-7800 Jouy-en-Josas, France.
| | - Pascale Mosoni
- Université Clermont Auvergne, INRA, UMR 0454 MEDIS, F-63000 Clermont-Ferrand, France.
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Contreras-Jodar A, Nayan NH, Hamzaoui S, Caja G, Salama AAK. Heat stress modifies the lactational performances and the urinary metabolomic profile related to gastrointestinal microbiota of dairy goats. PLoS One 2019; 14:e0202457. [PMID: 30735497 PMCID: PMC6368375 DOI: 10.1371/journal.pone.0202457] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 01/16/2019] [Indexed: 01/02/2023] Open
Abstract
The aim of the study is to identify the candidate biomarkers of heat stress (HS) in the urine of lactating dairy goats through the application of proton Nuclear Magnetic Resonance (1H NMR)-based metabolomic analysis. Dairy does (n = 16) in mid-lactation were submitted to thermal neutral (TN; indoors; 15 to 20°C; 40 to 45% humidity) or HS (climatic chamber; 37°C day, 30°C night; 40% humidity) conditions according to a crossover design (2 periods of 21 days). Thermophysiological traits and lactational performances were recorded and milk composition analyzed during each period. Urine samples were collected at day 15 of each period for 1H NMR spectroscopy analysis. Principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA) assessment with cross validation were used to identify the goat urinary metabolome from the Human Metabolome Data Base. HS increased rectal temperature (1.2°C), respiratory rate (3.5-fold) and water intake (74%), but decreased feed intake (35%) and body weight (5%) of the lactating does. No differences were detected in milk yield, but HS decreased the milk contents of fat (9%), protein (16%) and lactose (5%). Metabolomics allowed separating TN and HS urinary clusters by PLS-DA. Most discriminating metabolites were hippurate and other phenylalanine (Phe) derivative compounds, which increased in HS vs. TN does. The greater excretion of these gut-derived toxic compounds indicated that HS induced a harmful gastrointestinal microbiota overgrowth, which should have sequestered aromatic amino acids for their metabolism and decreased the synthesis of neurotransmitters and thyroid hormones, with a negative impact on milk yield and composition. In conclusion, HS markedly changed the thermophysiological traits and lactational performances of dairy goats, which were translated into their urinary metabolomic profile through the presence of gut-derived toxic compounds. Hippurate and other Phe-derivative compounds are suggested as urinary biomarkers to detect heat-stressed dairy animals in practice.
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Affiliation(s)
- Alexandra Contreras-Jodar
- Group of Research in Ruminants (G2R), Department of Animal and Food Sciences, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
| | - Nazri Hj. Nayan
- Department of Animal Science, Faculty of Agriculture, University Putra Malaysia, Serdang, Selangor, Malaysia
| | - Soufiane Hamzaoui
- Group of Research in Ruminants (G2R), Department of Animal and Food Sciences, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
| | - Gerardo Caja
- Group of Research in Ruminants (G2R), Department of Animal and Food Sciences, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
- * E-mail: (GC); (AAKS)
| | - Ahmed A. K. Salama
- Group of Research in Ruminants (G2R), Department of Animal and Food Sciences, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
- * E-mail: (GC); (AAKS)
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de Almeida Alvarenga L, Borges NA, Moreira LDSG, Resende Teixeira KT, Carraro-Eduardo JC, Dai L, Stenvinkel P, Lindholm B, Mafra D. Cranberries – potential benefits in patients with chronic kidney disease. Food Funct 2019; 10:3103-3112. [DOI: 10.1039/c9fo00375d] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Patients with chronic kidney disease (CKD) present many complications that potentially could be linked to increased cardiovascular mortality such as inflammation, oxidative stress, cellular senescence and gut dysbiosis.
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Affiliation(s)
| | - Natália Alvarenga Borges
- Graduate Program in Nutrition Sciences
- Fluminense Federal University (UFF)
- Niterói
- Brazil
- Graduate Program in Cardiovascular Sciences
| | | | | | | | - Lu Dai
- Division of Renal Medicine and Baxter Novum
- Department of Clinical Science
- Technology and Intervention
- Karolinska Institutet
- Stockholm
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum
- Department of Clinical Science
- Technology and Intervention
- Karolinska Institutet
- Stockholm
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum
- Department of Clinical Science
- Technology and Intervention
- Karolinska Institutet
- Stockholm
| | - Denise Mafra
- Graduate Program in Medical Sciences
- Fluminense Federal University (UFF)
- Niterói
- Brazil
- Graduate Program in Nutrition Sciences
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20
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Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells. Int J Mol Sci 2018; 19:ijms19030723. [PMID: 29510500 PMCID: PMC5877584 DOI: 10.3390/ijms19030723] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 02/23/2018] [Accepted: 02/27/2018] [Indexed: 12/11/2022] Open
Abstract
Chlorogenic acid (CGA) decreases colon cancer-cell proliferation but the combined anti-cancer effects of CGA with its major colonic microbial metabolites, caffeic acid (CA), 3-phenylpropionic acid (3-PPA) and benzoic acid (BA), needs elucidation as they occur together in colonic digesta. Caco-2 cancer cells were treated for 24 h with the four compounds individually (50–1000 µM) and as an equimolar ratio (1:1:1:1; MIX). The effective concentration to decrease cell proliferation by 50% (EC50) was lower for MIX (431 ± 51.84 µM) and CA (460 ± 21.88) versus CGA (758 ± 19.09 µM). The EC50 for cytotoxicity measured by lactate dehydrogenase release in MIX (527 ± 75.34 µM) showed more potency than CA (740 ± 38.68 µM). Cell proliferation was decreased by 3-PPA and BA at 1000 µM with no cytotoxicity. Cell-cycle arrest was induced at the S-phase by CA (100 µM), MIX (100 µM), CGA (250 µM) and 3-PPA (500 µM) with activation of caspase-3 by CGA, CA, MIX (500 and 1000 µM). Mitochondrial DNA content was reduced by 3-PPA (1000 µM). The anti-cancer effects occurred at markedly lower concentrations of each compound within MIX than when provided singly, indicating that they function together to enhance anti-colon cancer activities.
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Jung ES, Park HM, Hyun SM, Shon JC, Singh D, Liu KH, Whon TW, Bae JW, Hwang JS, Lee CH. The green tea modulates large intestinal microbiome and exo/endogenous metabolome altered through chronic UVB-exposure. PLoS One 2017; 12:e0187154. [PMID: 29117187 PMCID: PMC5695601 DOI: 10.1371/journal.pone.0187154] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Accepted: 10/13/2017] [Indexed: 01/22/2023] Open
Abstract
The attenuating effects of green tea supplements (GTS) against the ultraviolet (UV) radiation induced skin damages are distinguished. However, the concomitant effects of GTS on the large intestinal microbiomes and associated metabolomes are largely unclear. Herein, we performed an integrated microbiome-metabolome analysis to uncover the esoteric links between gut microbiome and exo/endogenous metabolome maneuvered in the large intestine of UVB-exposed mice subjected to dietary GTS. In UVB-exposed mice groups (UVB), class Bacilli and order Bifidobacteriales were observed as discriminant taxa with decreased lysophospholipid levels compared to the unexposed mice groups subjected to normal diet (NOR). Conversely, in GTS fed UVB-exposed mice (U+GTS), the gut-microbiome diversity was greatly enhanced with enrichment in the classes, Clostridia and Erysipelotrichia, as well as genera, Allobaculum and Lachnoclostridium. Additionally, the gut endogenous metabolomes changed with an increase in amino acids, fatty acids, lipids, and bile acids contents coupled with a decrease in nucleobases and carbohydrate levels. The altered metabolomes exhibited high correlations with GTS enriched intestinal microflora. Intriguingly, the various conjugates of green tea catechins viz., sulfated, glucuronided, and methylated ones including their exogenous derivatives were detected from large intestinal contents and liver samples. Hence, we conjecture that the metabolic conversions for the molecular components in GTS strongly influenced the gut micro-environment in UVB-exposed mice groups, ergo modulate their gut-microbiome as well as exo/endogenous metabolomes.
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Affiliation(s)
- Eun Sung Jung
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
| | - Hye Min Park
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
| | - Seung Min Hyun
- Department of Genetic Engineering & Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of Korea
| | - Jong Cheol Shon
- College of Pharmacy and Research Institute of Pharmaceutical Science, Kyungpook National University, Daegu, Republic of Korea
| | - Digar Singh
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
| | - Kwang-Hyeon Liu
- College of Pharmacy and Research Institute of Pharmaceutical Science, Kyungpook National University, Daegu, Republic of Korea
| | - Tae Woong Whon
- Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, Republic of Korea
| | - Jin-Woo Bae
- Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul, Republic of Korea
| | - Jae Sung Hwang
- Department of Genetic Engineering & Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of Korea
- * E-mail: (JSH); (CHL)
| | - Choong Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea
- * E-mail: (JSH); (CHL)
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Liu W, Zhao S, Wang J, Shi J, Sun Y, Wang W, Ning G, Hong J, Liu R. Grape seed proanthocyanidin extract ameliorates inflammation and adiposity by modulating gut microbiota in high-fat diet mice. Mol Nutr Food Res 2017; 61. [PMID: 28500724 DOI: 10.1002/mnfr.201601082] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2016] [Revised: 04/16/2017] [Accepted: 04/18/2017] [Indexed: 12/12/2022]
Abstract
SCOPE Obesity and associated metabolic complications is a worldwide public health issue. Gut microbiota have been recently linked to obesity and its related inflammation. In this study, we have explored the anti-inflammatory effect of grape seed proanthocyanindin extract (GSPE) in the high-fat diet (HFD)-induced obesity and identified the contribution of the gut microbiota to GSPE effects on metabolism. METHODS AND RESULTS Mice were fed a normal diet and a high-fat diet with or without GSPE (300 mg/kg body weight/day) by oral gavage for 7 weeks. Supplementation with GSPE significantly decreased plasma levels of inflammatory factors such as TNF-α, IL-6 and MCP-1, companied with ameliorated macrophage infiltration in epidydimal fat and liver tissues. Furthermore, GSPE also reduced epidydimal fat mass and improved insulin sensitivity. 16S rDNA analyses revealed that GSPE supplementation modulated the gut microbiota composition and certain bacteria including Clostridium XIVa, Roseburia and Prevotella. More importantly, depleting gut microbiota by antibiotics treatment abolished the beneficial effects of GSPE on inflammation and adiposity. CONCLUSION Our study identifies the novel links between gut microbiota alterations and metabolic benefits by GSPE supplementation, providing possibilities for the prevention and treatment of metabolic disorders by targeting gut microbiota through a potential prebiotic agent GSPE.
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Affiliation(s)
- Wen Liu
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shaoqian Zhao
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiqiu Wang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Juan Shi
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingkai Sun
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guang Ning
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China
| | - Jie Hong
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruixin Liu
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Disease, Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Amić A, Marković Z, Marković JMD, Jeremić S, Lučić B, Amić D. Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach. Comput Biol Chem 2016; 65:45-53. [DOI: 10.1016/j.compbiolchem.2016.09.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 08/07/2016] [Accepted: 09/22/2016] [Indexed: 12/14/2022]
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Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity. Nutr Res Rev 2016; 29:234-248. [PMID: 27841104 DOI: 10.1017/s0954422416000159] [Citation(s) in RCA: 160] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.
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Wong X, Carrasco-Pozo C, Escobar E, Navarrete P, Blachier F, Andriamihaja M, Lan A, Tomé D, Cires MJ, Pastene E, Gotteland M. Deleterious Effect of p-Cresol on Human Colonic Epithelial Cells Prevented by Proanthocyanidin-Containing Polyphenol Extracts from Fruits and Proanthocyanidin Bacterial Metabolites. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:3574-3583. [PMID: 27039931 DOI: 10.1021/acs.jafc.6b00656] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The protective effect of proanthocyanidin-containing polyphenol extracts from apples, avocados, cranberries, grapes, or proanthocyanidin microbial metabolites was evaluated in colonic epithelial cells exposed to p-cresol, a deleterious compound produced by the colonic microbiota from l-tyrosine. In HT29 Glc(-/+) cells, p-cresol significantly increased LDH leakage and decreased ATP contents, whereas in Caco-2 cell monolayers, it significantly decreased the transepithelial electrical resistance and increased the paracellular transport of FITC-dextran. The alterations induced by p-cresol in HT29 Glc(-/+) cells were prevented by the extracts from cranberries and avocados, whereas they became worse by extracts from apples and grapes. The proanthocyanidin bacterial metabolites decreased LDH leakage, ameliorating cell viability without improving intracellular ATP. All of the polyphenol extracts and proanthocyanidin bacterial metabolites prevented the p-cresol-induced alterations of barrier function. These results suggest that proanthocyanidin-containing polyphenol extracts and proanthocyanidin metabolites likely contribute to the protection of the colonic mucosa against the deleterious effects of p-cresol.
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Affiliation(s)
- Ximena Wong
- Department of Nutrition, Faculty of Medicine, University of Chile , Independencia 1027, Independencia, Santiago, Chile
| | - Catalina Carrasco-Pozo
- Department of Nutrition, Faculty of Medicine, University of Chile , Independencia 1027, Independencia, Santiago, Chile
| | - Elizabeth Escobar
- Department of Nutrition, Faculty of Medicine, University of Chile , Independencia 1027, Independencia, Santiago, Chile
| | - Paola Navarrete
- Institute of Nutrition and Food Technology (INTA), University of Chile , Santiago, Chile
| | - Franςois Blachier
- INRA/AGROPARISTECH , UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France
| | - Mireille Andriamihaja
- INRA/AGROPARISTECH , UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France
| | - Annaig Lan
- INRA/AGROPARISTECH , UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France
| | - Daniel Tomé
- INRA/AGROPARISTECH , UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France
| | - Marı́a José Cires
- Department of Nutrition, Faculty of Medicine, University of Chile , Independencia 1027, Independencia, Santiago, Chile
| | - Edgar Pastene
- Laboratory of Pharmacognosy, Faculty of Pharmacy, University of Concepción , Concepción, Chile
| | - Martin Gotteland
- Department of Nutrition, Faculty of Medicine, University of Chile , Independencia 1027, Independencia, Santiago, Chile
- Institute of Nutrition and Food Technology (INTA), University of Chile , Santiago, Chile
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Mosele JI, Gosalbes MJ, Macià A, Rubió L, Vázquez-Castellanos JF, Jiménez Hernández N, Moya A, Latorre A, Motilva MJ. Effect of daily intake of pomegranate juice on fecal microbiota and feces metabolites from healthy volunteers. Mol Nutr Food Res 2015; 59:1942-1953. [PMID: 26228065 DOI: 10.1002/mnfr.201500227] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 07/15/2015] [Accepted: 07/16/2015] [Indexed: 02/05/2023]
Abstract
SCOPE The purpose of the study was to evaluate the effect, regarding the metabolic and microbial profile of feces, of diet supplementation of healthy adults with pomegranate juice (PJ). METHODS AND RESULTS Twelve healthy adults were recruited to the study, which consisted of the intake of 200 mL/day of PJ during 4 weeks. Feces were collected before and after the supplementation with PJ. Metabolites (phenolic catabolites, short-chain fatty acids, and fecal steroids) and microbial profile were analyzed at baseline and at 4 weeks. Fecal phenolic metabolites, 3-phenylpropionic acid, catechol, hydroxytyrosol, and urolithin A, showed a significant increase in their concentration after supplementation with PJ. Among fecal steroids, parallel to the significant increase of cholesterol concentration, a significant decrease of coprostanol was observed. Although no significant changes in the microbiota profile were observed, different relationships between initial microbiota and the metabolites produced were found. Catechol showed positive and negative correlation with Oscillospora and Paraprevotella genera, respectively, and 3-phenylpropionic acid was positively correlated with Odoribacter genus. CONCLUSION Inclusion of PJ in the diet did not significantly alter the gut microbiota composition in healthy adults, but the individual bacterial composition could contribute to the generation of potential health-promoting phenolic metabolites.
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Affiliation(s)
- Juana I Mosele
- Food Technology Department, Agrotecnio Center, University of Lleida, Lleida, Spain
| | - María-José Gosalbes
- Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO-Salud Pública) y del Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universitat de València), València, Spain
- CIBERESP (Consorcio de Investigación Biomédica de Epidemiología y Salud Pública), Madrid, Spain
| | - Alba Macià
- Food Technology Department, Agrotecnio Center, University of Lleida, Lleida, Spain
| | - Laura Rubió
- Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
| | - Jorge F Vázquez-Castellanos
- Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO-Salud Pública) y del Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universitat de València), València, Spain
- CIBERESP (Consorcio de Investigación Biomédica de Epidemiología y Salud Pública), Madrid, Spain
| | - Nuria Jiménez Hernández
- Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO-Salud Pública) y del Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universitat de València), València, Spain
- CIBERESP (Consorcio de Investigación Biomédica de Epidemiología y Salud Pública), Madrid, Spain
| | - Andrés Moya
- Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO-Salud Pública) y del Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universitat de València), València, Spain
- CIBERESP (Consorcio de Investigación Biomédica de Epidemiología y Salud Pública), Madrid, Spain
| | - Amparo Latorre
- Unidad Mixta de Investigación en Genómica y Salud de la Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO-Salud Pública) y del Instituto Cavanilles de Biodiversidad y Biología Evolutiva (Universitat de València), València, Spain
- CIBERESP (Consorcio de Investigación Biomédica de Epidemiología y Salud Pública), Madrid, Spain
| | - María-José Motilva
- Food Technology Department, Agrotecnio Center, University of Lleida, Lleida, Spain
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Verbeke KA, Boobis AR, Chiodini A, Edwards CA, Franck A, Kleerebezem M, Nauta A, Raes J, van Tol EAF, Tuohy KM, on behalf of the ILSI Europe Prebiotics Task Force Expert Group ‘Microbial metabolism and fermentation’. Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev 2015; 28:42-66. [PMID: 26156216 PMCID: PMC4501371 DOI: 10.1017/s0954422415000037] [Citation(s) in RCA: 225] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p-cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.
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Affiliation(s)
- Kristin A. Verbeke
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven and Leuven Food Science and Nutrition Research Center (LFoRCe), Leuven, Belgium
| | - Alan R. Boobis
- Department of Medicine, Imperial College London, London, UK
| | - Alessandro Chiodini
- Formerly ILSI Europe, Box 6, Avenue Emmanuel Mounier 83, BE-1200, Brussels, Belgium; now European Commission, Research Executive Agency (REA) Unit B2, Brussels, Belgium
| | - Christine A. Edwards
- Human Nutrition School of Medicine, College of MVLS, University of Glasgow, Glasgow, Scotland
| | | | - Michiel Kleerebezem
- Host Microbe Interactomics, Wageningen University, Wageningen, The Netherlands
| | - Arjen Nauta
- FrieslandCampina, Amersfoort, The Netherlands
| | - Jeroen Raes
- Microbiology and Immunology, Rega Institute, KU Leuven, Leuven; VIB, Leuven; DBIT, Vrije Universiteit Brussel, Brussels, Belgium
| | | | - Kieran M. Tuohy
- Nutrition and Nutrigenomics, Research and Innovation Centre-Fondazione Edmund Mach, Trento, Italy
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Moroz VV, Beloborodova NV, Bedova AY, Revel’skii AI, Getsina ML, Osipov AA, Sarshor YN, Buchinskaya AA, Olenin AY. Development of methods of the gas chromatographic determination of phenylcarboxylic acids in blood serum and their adaptation to clinical laboratory conditions. JOURNAL OF ANALYTICAL CHEMISTRY 2015. [DOI: 10.1134/s1061934815040103] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Pilot dietary intervention with heat-stabilized rice bran modulates stool microbiota and metabolites in healthy adults. Nutrients 2015; 7:1282-300. [PMID: 25690418 PMCID: PMC4344588 DOI: 10.3390/nu7021282] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Accepted: 01/15/2015] [Indexed: 01/01/2023] Open
Abstract
Heat-stabilized rice bran (SRB) has been shown to regulate blood lipids and glucose, modulate gut mucosal immunity and inhibit colorectal cancer in animal and human studies. However, SRB’s effects on gut microbial composition and metabolism and the resulting implications for health remain largely unknown. A pilot, randomized-controlled trial was developed to investigate the effects of eating 30 g/day SRB on the stool microbiome and metabolome. Seven healthy participants consumed a study meal and snack daily for 28 days. The microbiome and metabolome were characterized using 454 pyrosequencing and gas chromatography-mass spectrometry (GC-MS) at baseline, two and four weeks post-intervention. Increases in eight operational taxonomic units (OTUs), including three from Bifidobacterium and Ruminococcus genera, were observed after two and four weeks of SRB consumption (p < 0.01). Branched chain fatty acids, secondary bile acids and eleven other putative microbial metabolites were significantly elevated in the SRB group after four weeks. The largest metabolite change was a rice bran component, indole-2-carboxylic acid, which showed a mean 12% increase with SRB consumption. These data support the feasibility of dietary SRB intervention in adults and support that SRB consumption can affect gut microbial metabolism. These findings warrant future investigations of larger cohorts evaluating SRB’s effects on intestinal health.
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Kalinowska M, Bielawska A, Lewandowska-Siwkiewicz H, Priebe W, Lewandowski W. Apples: content of phenolic compounds vs. variety, part of apple and cultivation model, extraction of phenolic compounds, biological properties. PLANT PHYSIOLOGY AND BIOCHEMISTRY : PPB 2014; 84:169-188. [PMID: 25282014 DOI: 10.1016/j.plaphy.2014.09.006] [Citation(s) in RCA: 147] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Accepted: 09/15/2014] [Indexed: 06/03/2023]
Abstract
Apples are among the most popular fruits in the world. They are rich in phenolic compounds, pectin, sugar, macro- and microelements. Applying different extraction techniques it is possible to isolate a particular group of compounds or individual chemicals and then test their biological properties. Many reports point to the antioxidant, antimicrobial, anticancer and many other beneficial effects of apple components that may have potential applications in food, pharmaceutical and cosmetic industries. This paper summarizes and compiles information about apple phenolic compounds, their biological properties with particular emphasis on health-related aspects. The data are reviewed with regard to different apple varieties, part of apple, cultivation model and methods of extraction.
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Affiliation(s)
- Monika Kalinowska
- Division of Chemistry, Bialystok University of Technology, 29 Zamenhofa Str., 15-435 Bialystok, Poland.
| | - Aleksandra Bielawska
- Department of Physical Chemistry, Medical University of Bialystok, 2B Mickiewicza Str., 15-089 Bialystok, Poland
| | - Hanna Lewandowska-Siwkiewicz
- Institute of Nuclear Chemistry and Technology, Centre for Radiobiology and Biological Dosimetry, 16 Dorodna Str., 03-195 Warsaw, Poland
| | - Waldemar Priebe
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
| | - Włodzimierz Lewandowski
- Division of Chemistry, Bialystok University of Technology, 29 Zamenhofa Str., 15-435 Bialystok, Poland
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Ou K, Sarnoski P, Schneider KR, Song K, Khoo C, Gu L. Microbial catabolism of procyanidins by human gut microbiota. Mol Nutr Food Res 2014; 58:2196-205. [PMID: 25045165 DOI: 10.1002/mnfr.201400243] [Citation(s) in RCA: 90] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 07/11/2014] [Accepted: 07/11/2014] [Indexed: 11/12/2022]
Abstract
SCOPE A major portion of ingested procyanidins is degraded by human microbiota in the colon into various phenolic compounds. These microbial metabolites are thought to contribute to the health benefits of procyanidins in vivo. The objective of this study was to identify and quantify the microbial metabolites of procyanidins after anaerobic fermentation with human microbiota. METHODS AND RESULTS (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially purified apple and cranberry procyanidins were incubated with human microbiota at a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid, 3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid, 2-(4'-hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactones and 5-(3'-hydroxyphenyl)-γ-valerolactones were identified as the microbial metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'-Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial metabolites range from 20.0 to 56.9% for the six substrates after 24 h of fermentation. CONCLUSION Procyanidins, both B-type and A-type can be degraded by human gut microbiota. The microbial metabolites may contribute to the bioactivities of procyanidins.
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Affiliation(s)
- Keqin Ou
- Department of Food Science and Human Nutrition, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, USA
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Chiou YS, Wu JC, Huang Q, Shahidi F, Wang YJ, Ho CT, Pan MH. Metabolic and colonic microbiota transformation may enhance the bioactivities of dietary polyphenols. J Funct Foods 2014. [DOI: 10.1016/j.jff.2013.08.006] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
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Strömstedt AA, Felth J, Bohlin L. Bioassays in natural product research - strategies and methods in the search for anti-inflammatory and antimicrobial activity. PHYTOCHEMICAL ANALYSIS : PCA 2014; 25:13-28. [PMID: 24019222 DOI: 10.1002/pca.2468] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Revised: 06/24/2013] [Accepted: 06/24/2013] [Indexed: 06/02/2023]
Abstract
INTRODUCTION Identifying bioactive molecules from complex biomasses requires careful selection and execution of relevant bioassays in the various stages of the discovery process of potential leads and targets. OBJECTIVE The aim of this review is to share our long-term experience in bioassay-guided isolation, and mechanistic studies, of bioactive compounds from different organisms in nature with emphasis on anti-inflammatory and antimicrobial activity. METHODS In the search for anti-inflammatory activity, in vivo and in vitro model combinations with enzymes and cells involved in the inflammatory process have been used, such as cyclooxygenases, human neutrophils and human cancer cell lines. Methods concerning adsorption and perforation of bacteria, fungi, human cells and model membranes, have been developed and optimised, with emphasis on antimicrobial peptides and their interaction with the membrane target, in particular their ability to distinguish host from pathogen. RESULTS A long-term research has provided experience of selection and combination of bioassay models, which has led to an increased understanding of ethnopharmacological and ecological observations, together with in-depth knowledge of mode of action of isolated compounds. CONCLUSION A more multidisciplinary approach and a higher degree of fundamental research in development of bioassays are often necessary to identify and to fully understand the mode of action of bioactive molecules with novel structure-activity relationships from natural sources.
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Affiliation(s)
- Adam A Strömstedt
- Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Center, Uppsala University, Box 574, 751 23, Uppsala, Sweden
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Muñoz-González I, Jiménez-Girón A, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV. Profiling of microbial-derived phenolic metabolites in human feces after moderate red wine intake. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2013; 61:9470-9479. [PMID: 24010549 DOI: 10.1021/jf4025135] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
A controlled and randomized trial study involving 41 healthy volunteers (33 intervention and 8 control subjects) was performed in order to establish changes in the microbial-derived phenolic metabolite profile of feces after moderate consumption of red wine (250 mL/day, 4 weeks). Out of the 35 phenolic metabolites identified, 10 compounds (mainly benzoic and 4-hydroxyvaleric acids) showed statistically significant increases (P < 0.05) after the wine intake. Also, the total phenolic metabolites content was significantly (P < 0.05) higher in the samples after the wine intake (625 ± 380 μg/g feces) in comparison to the samples before (358 ± 270 μg/g feces), and a tentative distribution of the volunteers into three groups could be established: <500, 500-1000, and >1000 μg/g feces. These results suggest that a different gut microbial capacity to metabolize wine polyphenols exists among the human population, as observed for polyphenols from other sources.
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Affiliation(s)
- Irene Muñoz-González
- Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, CEI UAM+CSIC , c/Nicolás Cabrera 9, 28049 Madrid, Spain
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Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects. Nutr Res Rev 2013; 26:118-29. [PMID: 23930641 DOI: 10.1017/s0954422413000097] [Citation(s) in RCA: 165] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Current research on dietary antioxidants misses the so-called non-extractable polyphenols (NEPP), which are not significantly released from the food matrix either by mastication, acid pH in the stomach or action of digestive enzymes, reaching the colon nearly intact. NEPP, not detected by the usual analytical procedures, are made up of macromolecules and single phenolic compounds associated with macromolecules. Therefore, NEPP are not included in food and dietary intake data nor in bioavailability, intervention or observational studies. The present paper aims to provide an overview of dietary NEPP - nature, occurrence in diet, metabolic fate and possible health effects. NEPP are a relevant fraction of dietary polyphenols exerting their main biological action in the colon, where they are extensively fermented by the action of microbiota, giving place to absorbable metabolites. NEPP exhibit different potential health-related properties, in particular in relation to gastrointestinal health, such as increases in antioxidant and antiproliferative capacities, reduction of intestinal tumorigenesis and modification of gene expression, as observed in different animal models. Further research into NEPP may provide a better understanding of the health effects of dietary antioxidants.
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Bennett L, Abeywardena M, Burnard S, Forsyth S, Head R, King K, Patten G, Watkins P, Williams R, Zabaras D, Lockett T. Molecular Size Fractions of Bay Leaf(Laurus nobilis)Exhibit Differentiated Regulation of Colorectal Cancer Cell Growth In Vitro. Nutr Cancer 2013; 65:746-64. [DOI: 10.1080/01635581.2013.796999] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Beloborodova N, Bairamov I, Olenin A, Shubina V, Teplova V, Fedotcheva N. Effect of phenolic acids of microbial origin on production of reactive oxygen species in mitochondria and neutrophils. J Biomed Sci 2012; 19:89. [PMID: 23061754 PMCID: PMC3503878 DOI: 10.1186/1423-0127-19-89] [Citation(s) in RCA: 115] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Accepted: 10/11/2012] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Several low-molecular-weight phenolic acids are present in the blood of septic patients at high levels. The microbial origin of the most of phenolic acids in the human body was shown previously, but pathophysiological role of the phenolic acids is not clear. Sepsis is associated with the excessive production of reactive oxygen species (ROS) in both the circulation and the affected organs. In this work the influence of phenolic acids on ROS production in mitochondria and neutrophils was investigated. METHODS ROS production in mitochondria and neutrophils was determined by MCLA- and luminol-dependent chemiluminescence. The rate of oxygen consumption by mitochondria was determined polarographically. The difference of electric potentials on the inner mitochondrial membrane was registered using a TPP+-selective electrode. The formation of phenolic metabolites in monocultures by the members of the main groups of the anaerobic human microflora and aerobic pathogenic bacteria was investigated by the method of gas chromatography-mass spectrometry. RESULTS All phenolic acids had impact on mitochondria and neutrophils, the main producers of ROS in tissues and circulation. Phenolic acids (benzoic and cinnamic acids) producing the pro-oxidant effect on mitochondria inhibited ROS formation in neutrophils. Their effect on mitochondria was abolished by dithiothreitol (DTT). Phenyllactate and p-hydroxyphenyllactate decreased ROS production in both mitochondria and neutrophils. Bifidobacteria and lactobacilli produced in vitro considerable amounts of phenyllactic and p-hydroxyphenyllactic acids, Clostridia s. produced great quantities of phenylpropionic and p-hydroxyphenylpropionic acids, p-hydroxyphenylacetic acid was produced by Pseudomonas aeruginosa and Acinetobacter baumanii; and benzoic acid, by Serratia marcescens. CONCLUSIONS The most potent activators of ROS production in mitochondria are phenolic acids whose effect is mediated via the interaction with thiol groups. Among these are benzoic and cinnamic acids. Some phenolic acids, in particular phenyllactate and p-hydroxyphenyllactate, which decrease ROS production in mitochondria and neutrophils, can play a role of natural antioxidants. The results indicate that low-molecular weight phenolic acids of microbial origin participate in the regulation of the ROS production in both the circulation and tissues, thereby affecting the level of oxidative stress in sepsis.
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Affiliation(s)
- Natalia Beloborodova
- Negovsky Research Institute of General Reanimatology Russian Academy of Medical Sciences, Laboratory of Metabolism of Critical State, Moscow, Russia
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Seo S, Lee S, Hong Y, Kim Y. Phospholipase A2 inhibitors synthesized by two entomopathogenic bacteria, Xenorhabdus nematophila and Photorhabdus temperata subsp. temperata. Appl Environ Microbiol 2012; 78:3816-23. [PMID: 22447611 PMCID: PMC3346408 DOI: 10.1128/aem.00301-12] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2012] [Accepted: 03/12/2012] [Indexed: 11/20/2022] Open
Abstract
The entomopathogenic bacteria Xenorhabdus nematophila and Photorhabdus temperata subsp. temperata suppress insect immune responses by inhibiting the catalytic activity of phospholipase A(2) (PLA(2)), which results in preventing biosynthesis of immune-mediating eicosanoids. This study identified PLA(2) inhibitors derived from culture broths of these two bacteria. Both X. nematophila and P. temperata subsp. temperata culture broths possessed significant PLA(2)-inhibitory activities. Fractionation of these bacterial metabolites in the culture broths using organic solvent and subsequent chromatography purified seven potent PLA(2) inhibitors, three of which (benzylideneacetone [BZA], proline-tyrosine [PY], and acetylated phenylalanine-glycine-valine [FGV]) were reported in a previous study. Four other compounds (indole, oxindole, cis-cyclo-PY, and p-hydroxyphenyl propionic acid) were identified and shown to significantly inhibit PLA(2). X. nematophila culture broth contained these seven compounds, while P. temperata subsp. temperata culture broth contained three compounds (BZA, acetylated FGV, and cis-cyclo-PY). BZA was detected in the largest amount among these PLA(2) compounds in both bacterial culture broths. All seven bacterial metabolites also showed significant inhibitory activities against immune responses, such as phenoloxidase activity and hemocytic nodulation; BZA was the most potent. Finally, this study characterized these seven compounds for their insecticidal activities against the diamondback moth, Plutella xylostella. Even though these compounds showed relatively low toxicities to larvae, they significantly enhanced the pathogenicity of Bacillus thuringiensis. This study reports bacterial-origin PLA(2) inhibitors, which would be applicable for developing novel insecticides.
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Affiliation(s)
- Samyeol Seo
- Department of Bioresource Sciences, Andong National University, Andong, Republic of Korea
| | - Sunghong Lee
- Department of Applied Chemistry, Andong National University, Andong, Republic of Korea
| | - Yongpyo Hong
- Department of Applied Chemistry, Andong National University, Andong, Republic of Korea
| | - Yonggyun Kim
- Department of Bioresource Sciences, Andong National University, Andong, Republic of Korea
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40
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Mateo Anson N, Hemery YM, Bast A, Haenen GRMM. Optimizing the bioactive potential of wheat bran by processing. Food Funct 2012; 3:362-75. [PMID: 22336890 DOI: 10.1039/c2fo10241b] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Nuria Mateo Anson
- University of Maastricht, PO Box 616, 6200 MD, Maastricht, The Netherlands
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41
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Miene C, Weise A, Glei M. Impact of polyphenol metabolites produced by colonic microbiota on expression of COX-2 and GSTT2 in human colon cells (LT97). Nutr Cancer 2011; 63:653-62. [PMID: 21598179 DOI: 10.1080/01635581.2011.552157] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Polyphenols may play an important role in colon cancer prevention. After entering the colon, they are subjected to metabolism by the human gut microbiota. The objective of the present study was to analyze the impact of selected intestinal metabolites on modulation of enzymes involved in detoxification and inflammation in human adenoma cells LT97. LT97 cells were incubated with 3,4-dihydroxyphenylacetic acid (ES) and 3-(3,4-dihydroxyphenyl)-propionic acid (PS), metabolites of quercetin and chlorogenic acid/caffeic acid, respectively. The effect on cell number was analyzed using 4'- 6-diamino-2-phenylindole-dihydrochloride (DAPI)-staining. Modulation of glutathione S-transferase T2 (GSTT2) and cyclooxygenase-2 (COX-2) was measured by real-time PCR and Western blot. Comet assay was performed to assess the impact on DNA damage caused by the GSTT2 substrate cumene hydroperoxide (CumOOH). Polyphenol metabolites did not affect cell number but significantly upregulated GSTT2 expression and decreased COX-2. The latter was confirmed via Western blot. CumOOH-induced DNA damage was significantly reduced compared to the control. An upregulation of GSTT2 and downregulation of COX-2 could possibly contribute to the chemopreventive potential of polyphenols after degradation in the gut. Working with polyphenol metabolites is an important prerequisite to better understand the in vivo effects of pure polyphenols.
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Affiliation(s)
- Claudia Miene
- Institute for Nutrition, Department of Nutritional Toxicology, Friedrich-Schiller-University Jena, Jena, Germany.
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42
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Lai KK, Stogios PJ, Vu C, Xu X, Cui H, Molloy S, Savchenko A, Yakunin A, Gonzalez CF. An inserted α/β subdomain shapes the catalytic pocket of Lactobacillus johnsonii cinnamoyl esterase. PLoS One 2011; 6:e23269. [PMID: 21876742 PMCID: PMC3158066 DOI: 10.1371/journal.pone.0023269] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Accepted: 07/14/2011] [Indexed: 11/18/2022] Open
Abstract
Background Microbial enzymes produced in the gastrointestinal tract are primarily responsible for the release and biochemical transformation of absorbable bioactive monophenols. In the present work we described the crystal structure of LJ0536, a serine cinnamoyl esterase produced by the probiotic bacterium Lactobacillus johnsonii N6.2. Methodology/Principal Findings We crystallized LJ0536 in the apo form and in three substrate-bound complexes. The structure showed a canonical α/β fold characteristic of esterases, and the enzyme is dimeric. Two classical serine esterase motifs (GlyXSerXGly) can be recognized from the amino acid sequence, and the structure revealed that the catalytic triad of the enzyme is formed by Ser106, His225, and Asp197, while the other motif is non-functional. In all substrate-bound complexes, the aromatic acyl group of the ester compound was bound in the deepest part of the catalytic pocket. The binding pocket also contained an unoccupied area that could accommodate larger ligands. The structure revealed a prominent inserted α/β subdomain of 54 amino acids, from which multiple contacts to the aromatic acyl groups of the substrates are made. Inserts of this size are seen in other esterases, but the secondary structure topology of this subdomain of LJ0536 is unique to this enzyme and its closest homolog (Est1E) in the Protein Databank. Conclusions The binding mechanism characterized (involving the inserted α/β subdomain) clearly differentiates LJ0536 from enzymes with similar activity of a fungal origin. The structural features herein described together with the activity profile of LJ0536 suggest that this enzyme should be clustered in a new group of bacterial cinnamoyl esterases.
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Affiliation(s)
- Kin-Kwan Lai
- Department of Microbiology and Cell Science, Genetics Institute, University of Florida, Gainesville, Florida, United States of America
| | - Peter J. Stogios
- Banting and Best Department of Medical Research, Structural Proteomics in Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Clara Vu
- Department of Microbiology and Cell Science, Genetics Institute, University of Florida, Gainesville, Florida, United States of America
- UF Undergraduate Research Program MCB4905, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America
| | - Xiaohui Xu
- Banting and Best Department of Medical Research, Structural Proteomics in Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Hong Cui
- Banting and Best Department of Medical Research, Structural Proteomics in Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Sara Molloy
- Department of Microbiology and Cell Science, Genetics Institute, University of Florida, Gainesville, Florida, United States of America
- UF Undergraduate Research Program MCB4905, Department of Microbiology and Cell Science, University of Florida, Gainesville, Florida, United States of America
| | - Alexei Savchenko
- Banting and Best Department of Medical Research, Structural Proteomics in Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Alexander Yakunin
- Banting and Best Department of Medical Research, Structural Proteomics in Toronto, University of Toronto, Toronto, Ontario, Canada
| | - Claudio F. Gonzalez
- Department of Microbiology and Cell Science, Genetics Institute, University of Florida, Gainesville, Florida, United States of America
- * E-mail:
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Miene C, Weise A, Glei M. Impact of Polyphenol Metabolites Produced by Colonic Microbiota on Expression of COX-2 and GSTT2 in Human Colon Cells (LT97). Nutr Cancer 2011. [DOI: 10.1080/01635581.2011.552157 pmid: 21598179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2022]
Affiliation(s)
- Claudia Miene
- a Institute for Nutrition, Department of Nutritional Toxicology , Friedrich-Schiller-University Jena , Jena, Germany
| | - Anja Weise
- b Institute of Human Genetics and Anthropology , Friedrich-Schiller-University Jena , Jena, Germany
| | - Michael Glei
- a Institute for Nutrition, Department of Nutritional Toxicology , Friedrich-Schiller-University Jena , Jena, Germany
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Mullen W, Nemzer B, Ou B, Stalmach A, Hunter J, Clifford MN, Combet E. The antioxidant and chlorogenic acid profiles of whole coffee fruits are influenced by the extraction procedures. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:3754-3762. [PMID: 21401105 DOI: 10.1021/jf200122m] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Commercial whole coffee fruit extracts and powder samples were analyzed for chlorogenic acids (CGA), caffeine and antioxidant activities. CGA and caffeine were characterized by LC-MS(n) and HPLC accordingly, and quantified by UV absorbance. ORAC, HORAC, NORAC, SORAC and SOAC (antioxidant capacities) were assessed. Three caffeoylquinic acids, three feruloylquinic acids, three dicaffeoylquinic acids, one p-coumaroylquinic acid, two caffeoylferuloylquinic acids and three putative chlorogenic lactones were quantified, along with a methyl ester of 5-caffeoylquinic acid (detected in one sample, the first such report in any coffee material). Multistep whole coffee fruit extracts displayed higher CGA content than single-step extracts, freeze-dried, or air-dried whole raw fruits. Caffeine in multistep extracts was lower than in the single-step extracts and powders. Antioxidant activity in whole coffee fruit extracts was up to 25-fold higher than in powders dependent upon the radical. Total antioxidant activity of samples displayed strong correlation to CGA content.
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Affiliation(s)
- W Mullen
- College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
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45
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Ktsoyan ZA, Beloborodova NV, Sedrakyan AM, Osipov GA, Khachatryan ZA, Kelly D, Manukyan GP, Arakelova KA, Hovhannisyan AI, Olenin AY, Arakelyan AA, Ghazaryan KA, Aminov RI. Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific. Front Microbiol 2011; 1:148. [PMID: 21687748 PMCID: PMC3109323 DOI: 10.3389/fmicb.2010.00148] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2010] [Accepted: 12/27/2010] [Indexed: 12/16/2022] Open
Abstract
The human gastrointestinal tract is inhabited by a diverse and dense symbiotic microbiota, the composition of which is the result of host-microbe co-evolution and co-adaptation. This tight integration creates intense cross-talk and signaling between the host and microbiota at the cellular and metabolic levels. In many genetic or infectious diseases the balance between host and microbiota may be compromised resulting in erroneous communication. Consequently, the composition of the human metabolome, which includes the gut metabolome, may be different in health and disease states in terms of microbial products and metabolites entering systemic circulation. To test this hypothesis, we measured the level of hydroxy, branched, cyclopropyl and unsaturated fatty acids, aldehydes, and phenyl derivatives in blood of patients with a hereditary autoinflammatory disorder, familial Mediterranean fever (FMF), and in patients with peptic ulceration (PU) resulting from Helicobacter pylori infection. Discriminant function analysis of a data matrix consisting of 94 cases as statistical units (37 FMF patients, 14 PU patients, and 43 healthy controls) and the concentration of 35 microbial products in the blood as statistical variables revealed a high accuracy of the proposed model (all cases were correctly classified). This suggests that the profile of microbial products and metabolites in the human metabolome is specific for a given disease and may potentially serve as a biomarker for disease.
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Affiliation(s)
- Zhanna A Ktsoyan
- Institute of Molecular Biology, National Academy of Sciences of Republic of Armenia Yerevan, Republic of Armenia
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46
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Garcia EDF, de Oliveira MA, Godin AM, Ferreira WC, Bastos LFS, Coelho MDM, Braga FC. Antiedematogenic activity and phytochemical composition of preparations from Echinodorus grandiflorus leaves. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2010; 18:80-86. [PMID: 20637578 DOI: 10.1016/j.phymed.2010.05.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2010] [Revised: 04/06/2010] [Accepted: 05/25/2010] [Indexed: 05/29/2023]
Abstract
The leaves of Echinodorus grandiflorus (Alismataceae) are traditionally used in Brazil to treat inflammatory conditions. The aim of the present study was to evaluate the antidematogenic activity of crude aqueous, dichloromethane and hydroethanolic extracts from E. grandiflorus leaves using the carrageenan-induced paw edema model in mice, along with of fractions enriched in diterpenes, flavonoids and hydroxycinnamoyltartaric acids (HCTA). Significant inhibitions of paw edema were elicited by the 50% and 70% EtOH extracts (1000 mg/kg, p.o.), as well as by the fractions enriched in diterpenes (70-420 mg/kg, p.o.) and flavonoids (7.2-36 mg/kg, p.o.). Isovitexin, isoorientin, trans-aconitic and chicoric acids were identified in all extracts by HPLC analysis. Trans-aconitic acid itself exhibited significant antiedematogenic effect (270 mg/kg, p.o.). The biological activity correlated positively with the contents of flavonoids and diterpenes, but negatively with HCTA concentrations, demonstrating the participation of the two classes of compounds in the antiedematogenic activity of E. grandiflorus.
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Affiliation(s)
- Eliana de Faria Garcia
- Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
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Monagas M, Urpi-Sarda M, Sánchez-Patán F, Llorach R, Garrido I, Gómez-Cordovés C, Andres-Lacueva C, Bartolomé B. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct 2010; 1:233-53. [PMID: 21776473 DOI: 10.1039/c0fo00132e] [Citation(s) in RCA: 454] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity. Studies performed with synthesized or isolated phase II conjugated metabolites have revealed that they could have an effect beyond their antioxidant properties, by interacting with signalling pathways implicated in important processes involved in the development of diseases, among other bioactivities. However, the biological properties of microbe-derived metabolites in their actual conjugated forms remain largely unknown. Currently, there is an increasing interest in their effects on intestinal infections, inflammatory intestinal diseases and overall gut health. The present review will give an insight into the metabolism and microbial biotransformation of flavan-3-ols, including tentative catabolic pathways and aspects related to the identification of bacteria with the ability to catabolize these kinds of polyphenols. Also, the in vitro bioactivities of phase II and microbial phenolic metabolites will be covered in detail.
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Affiliation(s)
- Maria Monagas
- Institute of Industrial Fermentations (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
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Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients. J Nutr Metab 2010; 2010:862569. [PMID: 21052495 PMCID: PMC2967835 DOI: 10.1155/2010/862569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2009] [Revised: 08/19/2010] [Accepted: 09/20/2010] [Indexed: 02/07/2023] Open
Abstract
A few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids. We report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids, and relate this to the proportions of fatty acids and levels of cyclooxygenase mRNA expression in duodenal biopsies, levels of serum lipoproteins, and diet. In the ileostomy group separately (n = 12), the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies. Total serum-cholesterol was negatively correlated to the fecal content of saturates and monounsaturates. The fecal palmitoleic acid/palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.In the ileal-pouch-anal anastomosis group separately (n = 17), significant correlations were found between the fecal contents of oleic acid, linoleic acid, and alpha-linolenic acid, and the proportions of myristic acid, oleic acid and eicosaenoic acid in duodenal biopsies. Dietary monounsaturates were positively correlated to different fecal fatty acids. Future studies should focus on molecular mechanisms relevant to fatty acid metabolism, inflammation, and angiogenesis, in addition to nutrition.
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49
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Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 2010; 104 Suppl 3:S48-66. [DOI: 10.1017/s0007114510003946] [Citation(s) in RCA: 312] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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50
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Gill CIR, McDougall GJ, Glidewell S, Stewart D, Shen Q, Tuohy K, Dobbin A, Boyd A, Brown E, Haldar S, Rowland IR. Profiling of phenols in human fecal water after raspberry supplementation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2010; 58:10389-10395. [PMID: 20809621 DOI: 10.1021/jf1017143] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
The phenolic compositions of fecal water samples from ten free-living human subjects without marked dietary restrictions were monitored before and after intake of raspberry puree (200 g/day, 4 days) using gas chromatography-mass spectrometry. No single phenolic component was increased in all subjects after intake, but a majority of subjects had significant elevations in phenylacetic acid (7/10), 4-hydroxyphenylacetic acid (6/10), 3-hydroxyphenylacetic acid (5/10), 3-phenylpropionic acid and 3-(4-hydroxyphenyl)propionic acid. The levels of 3,4-dihydroxbenzoic acid were elevated in 8/10 subjects, significantly for 6 subjects (p < 0.05), and not significantly reduced in the other 2 subjects. In addition, unlike most other fecal metabolites, the increase was always >2-fold. This metabolite may be representative of the increased colonic dose of cyanidin anthocyanins. The colonic microbiota varied greatly between individuals, and supplementation with raspberries did not produce any statistically significant alterations in the profile of colonic bacteria, nor was a common pattern revealed to account for the interindividual variations observed in the fecal water phenolic profiles.
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Affiliation(s)
- Chris I R Gill
- Northern Ireland Centre for Food and Health, Centre for Molecular Biosciences, University of Ulster, Cromore Road, Coleraine, N Ireland BT52 1SA, UK.
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