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Green and black tea phenolics - Bioavailability, transformation by colonic microbiota, and modulation of colonic microbiota Zhibin Liu, Marieke E. Bruins, Li Ni, and Jean-Paul Vincken J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b02233 • Publication Date (Web): 18 Jul 2018 Downloaded from http://pubs.acs.org on July 19, 2018

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Journal of Agricultural and Food Chemistry

Green and black tea phenolics - Bioavailability, transformation by colonic microbiota, and modulation of colonic microbiota

Zhibin Liu1,2,3, Marieke Elisabeth Bruins3, Li Ni2*, Jean-Paul Vincken1* 1

Laboratory of Food Chemistry, Wageningen University, P.O. Box 17, 6700 AA Wageningen, The Netherlands 2

3

Institute of Food Science & Technology, Fuzhou University, Fuzhou 350108, P.R. China

Food & Biobased Research, Wageningen University, PO Box 17, 6700 AA Wageningen, The Netherlands

Corresponding author:

Dr. Li Ni Tel: +86-591-22866378 Fax: +86-591-22866378 Email: [email protected]

Dr. Jean-Paul Vincken Tel: +31-317482234

Fax: +31-317482234 Email: [email protected]

1 ACS Paragon Plus Environment


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Abstract:

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Monomeric green tea catechins (GTC) and oligomeric, oxidized black tea phenolics (BTP)

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have shown promising health benefits, although GTC has been more extensively studied than

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BTP. We review the current knowledge on bioavailability, colonic transformation and gut

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microbiota modulatory effects of GTC and BTP. Due to their similar poor bioavailability in

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the small intestine and potentially similar metabolites upon colonic fermentation, it seems as

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if GTC and BTP have similar health effects, although it cannot be excluded that they have

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different gut microbiota modulatory effects, and that BTP gives poorer yield of bioactive

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phenolic metabolites upon colonic fermentation than GTC.

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Keywords: green tea catechins, black tea phenolics, gut microbiota, bioavailability, microbial

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metabolism, health benefits.


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Introduction

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Tea, originating from the leaves of Camellia sinensis, is the most widely consumed beverage

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in the world. The major constituents of tea are flavonoids, including flavonols, flavones,

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flavanols (flavan-3-ols), etc., of which over 60% are flavanols. Based on the processing

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method, tea is generally divided into three forms: green tea, oolong tea and black tea. Among

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them, black tea is the most consumed type, accounting for 78% of tea production worldwide;

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green tea comes next, contributing 20%; the remainder 2% is oolong tea.1 Green tea is

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produced by enzymatic inactivation of the fresh tea leaves, with monomeric flavanols,

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commonly referred to as catechins, as the primary phenolic compounds. Here, we will further

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refer to monomeric green tea catechins as GTC. Black tea differs from green tea by a so-

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called “fermentation” process, during which over 90% of the catechins in fresh tea leaves

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undergo extensive oxidation by endogenous polyphenol oxidases (PPO) and peroxidases

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(POD), resulting in the formation of dimeric and oligomeric compounds, such as theaflavins,

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theasinensins and thearubigins. Here, we will further refer to oligomeric black tea phenolics

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as BTP. Oolong tea is a semi-oxidized, semi-fermented product, comprising a mixture of

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catechins and their oxidation products.

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A considerable number of studies has demonstrated the importance of regular tea

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consumption in human health, as it seems to counteract cardiovascular disease, obesity, and

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type 2 diabetes.2 These pharmaceutical benefits are generally attributed to the phenolic

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compounds in tea because of their potent anti-oxidative, anti-inflammatory, anti-microbial,

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anti-tumour, and anti-aging properties.2 Due to the differences in GTC and BTP, consumers

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might be curious about which tea is the best for promoting health. Green tea is generally

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recommended because of its stronger antioxidant properties, associated with the higher

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concentration of unoxidized flavanols.3 However, it is controversial to link the health benefits 3 ACS Paragon Plus Environment


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of tea solely to antioxidant activity, as other properties may also contribute to their

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pharmaceutical activities. Furthermore, the low bioavailability of phenolics, those from black

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tea in particular, has long been recognized, which does not seem in accordance with their in

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vivo antioxidative activity.

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The interaction of tea phenolics and gut microbiota has long been overlooked and might

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provide clues to understand the health-beneficial effects of tea phenolics. The large intestinal

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lumen is inhabited by a large, diverse population of microorganisms, mainly anaerobic

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bacteria. It is commonly believed that more than 1,000 “species-level” phylotypes, belonging

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to a few phyla, reside in a healthy gut.4 Of these phyla, Bacteroidetes and Firmicutes usually

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dominate the gut microbiota, followed by Actinobacteria, Proteobacteria, Verrucomicrobia,

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etc..4 They play an essential role in the maintenance of intestinal homeostasis and host health,

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via extracting nutrients and energy from the diet and creating a physical and immunologic

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barrier for the host. The unabsorbed phenolics reaching the colon will be subjected to

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enzymatic degradation by gut microbiota, resulting in a series of metabolites, which are

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readily absorbed. Simultaneously, the composition of gut microbiota might be modulated.

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Such reciprocal interactions between phenolics and gut microbiota might eventually exert

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some health benefits to the host. In this review, the bioavailability, degradation pathways, and

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gut microbiota modulatory effects of GTC and BTP were compared, and their potential health

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beneficial properties are discussed based on their interaction with gut microbiota.

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Phenolic compounds in tea and their bioavailability

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According to the United States Department of Agriculture (USDA) flavonoid databases, tea is

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the most important dietary source of flavanols. As indicated before, green tea and black tea

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are the most frequently consumed kinds of tea. The main difference between the two kinds

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resides in the much more extensive oxidation of phenolics in black tea than in green tea, 4 ACS Paragon Plus Environment

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resulting in a distinctive phenolic composition. The phenolic compounds of green tea and

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black tea, together with their bioavailability, are first reviewed here.

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GTC and their bioavailability. Catechins in green tea are characterized by di- or tri-

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hydroxyl group substitution of the B-ring and the meta-5,7-di-hydroxy substitution of the A-

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ring. Furthermore, over 50% of the catechins are esterified with a galloyl moiety.5 There are

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four major catechins: epigallocatechin gallate (EGCg), epigallocatechin (EGC), epicatechin

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gallate (ECg), and epicatechin (EC), of which EGCg is the most abundant one. The chemical

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structures of these catechins are shown in Figure 1. In addition, four corresponding

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stereoisomers, including gallocatechin gallate (GCg), gallocatechin (GC), catechin gallate

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(Cg), and catechin (C), are also found in tea, albeit in much smaller amounts.

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The poor bioavailability of catechins in the small intestine has long been recognized. EC,

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EGC, ECg and EGCg were reported to possess low transepithelial permeability in a human

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intestinal absorption model, whereas their basal-to-apical efflux was reported to be more

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significant, which involved active transport via transporters, such as Multidrug Resistance

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Proteins (MRP).6 Moreover, the galloylated catechins exhibited lower affinity to MRP than

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non-galloylated ones.6 Following administration, approximately 13.7% of EGC, 31.2% of EC

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and 0.1% of EGCg were directly bioavailable.7 The directly absorbed catechins are

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transferred to the liver via the portal vein, where they are metabolized by phase II enzymes,

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resulting in glucuronidated, methylated and sulfated conjugates.8, 9 It was shown that these

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metabolites will enter the systemic circulation, or are eliminated via the bile and returned back

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to the gastrointestinal tract.8 There is evidence indicating that phase II metabolism of EC also

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occurred in enterocytes, the metabolites (mainly sulfated conjugates) of which were

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eliminated by efflux back to the intestinal lumen, which was much higher than the elimination

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via bile.10 Stalmach et al. reported that approximately 70% of the ingested green tea catechins



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were recovered in the large intestine, of which 33% in the form of parent compounds and 37%

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in the form of phase II metabolites, mainly O-linked sulfates and methyl-sulfates.9

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BTP and their bioavailability. In black tea, abundant phenolic compounds are theaflavin

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and theasinensin, and their mono- and di-gallates. Theaflavins, with their characteristic

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benzotropolone moiety, are produced by condensation of a catechol-type B-ring (EC or ECg)

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and a pyrogallol-type B-ring (EGC or EGCg). Theasinensins are formed from condensation of

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two pyrogallol-type B-rings. In addition to theaflavins and theasinensins, various other

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catechin dimers have been identified in black tea, such as theaflagallins, theaflavates,

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theaflavic acids, theacitrins, dehydrodicatechins, etc. (Figure 1).11 These dimeric phenolics are

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not the final products of the oxidation process, as they can be further oxidized and

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oligomerized to form even more complex oxidation products. Collectively, these complex

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oxidation products of catechins are referred to as thearubigins.12

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Given the complexity of oxidized tea phenolics, the knowledge on the bioavailability of

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black tea phenolics is limited. It was recently reported that theaflavins and their phase II

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metabolites were not detected in urine excreted 0−30 h after intake, which suggested their low

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bioavailability.13 Thus, it is speculated that theaflavin-related black tea phenolics, such as

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theaflavic acids, theaflavates, and theaflagallins, exhibit similarly low bioavailability as

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theaflavins. Regarding other black tea phenolics, such as theasinensins, dehydrodicatechins,

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and theacitins, no literature is available yet. It has been reported that B-type procyanidin

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dimers, with two catechin units linked with C4–C8 or C4–C6 bonds between A-ring and C-

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ring, had lower bioavailability than monomeric catechins, which was less than 10% of that of

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catechins.14 Theasinensins have structural similarities with B-type procyanidins in that both

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are formed by catechin dimerization through C-C bonds, but they differ in the position of the

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interflavanic linkage, i.e. they are connected at the B-rings through C2'–C2' bonds. Thus, low


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bioavailability is expected for theasinensins, similar to that of B-type procyanidins. Likewise,

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dehydrodicatechins are expected to have similar low bioavailability.

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In general, monomeric flavan-3-ols are the primary phenolic compounds in green tea,

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whereas in black tea, oxidized dimeric and oligomeric flavan-3-ols are predominant. Given

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their low bioavailability, substantial amounts of GTC and BTP will enter the colon in their

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original form, and be subject of bioconversion by gut microbiota, resulting in the formation of

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low-molecular-weight metabolites which are known to be much more easily absorbed.

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Bioconversion of tea phenolics by gut microbiota

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The diverse microbiota that inhabits the large intestine is equipped with a large set of different

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enzymes capable of transforming various food ingredients that enter the colon, and plays

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essential metabolic functions in digestion by the host. This microbial community can

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hydrolyze glycosides, glucuronides, sulfates, amides, esters and lactones through the action of

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enzymes such as α-rhamnosidase, β-glucuronidase, β-glucosidase, sulfatase and esterases. In

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addition, other catalytic reactions, including non-aromatic ring cleavage, reduction

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(reductases, hydrogenases), decarboxylation (decarboxylase), demethylation (demethylase),

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isomerization (isomerase) and dehydroxylation (dehydroxylase), also extensively occur in the

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colon due to the metabolic activities of intestinal microbes. Hence, the remaining unabsorbed

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green tea catechins and black tea phenolics in the large intestine are expected to undergo

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extensive microbial degradation, subsequently leading to numerous simpler compounds.

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Bioconversion of GTC. A number of studies have been carried out to elucidate the

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degradation pathway of catechins by gut microbiota. In general, the transformations can be

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grouped into three major processes: (i) galloyl ester hydrolysis, (ii) C-ring opening, and (iii)

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further modification of the reaction products by reactions including lactonization,

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decarboxylation, dehydroxylation, and oxidation reactions.8, 15-18 In the case of galloylated 7 ACS Paragon Plus Environment


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catechins (ECg and EGCg), the microbial metabolism usually starts with the galloyl ester

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hydrolysis by microbial esterases, giving rise to gallic acid, which may be further

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decarboxylated to pyrogallol. After degalloylation, the C-ring of the catechin remainder is

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opened, leading to diphenylpropan-2-ol, which is later converted into valerolactone [5-(3',4'-

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dihydroxyphenyl)-γ-valerolactone in the case of EC/ECg or 5-(3',4',5'-trihydroxyphenyl)-γ-

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valerolactone in the case of EGC/EGCg]. The lactone ring later breaks, resulting in

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hydroxyphenylvaleric acids and/or 4-hydroxy-hydroxyphenylvaleric acids. Subsequent

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biotransformations

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hydroxyphenylacetic and hydroxybenzoic acids by successive loss of carbon atoms from the

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side chain. Meanwhile, dehydroxylation of these hydroxylated phenolic acids might also

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occur at C-3', C-4' and/or C-5' of the original B-rings, resulting in various simpler phenolic

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acids. The possible microbial metabolism pathway of catechins is summarized in Figure 2. It

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was also reported that, benzene rings of these phenolic acids can be further opened and

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converted into short chain fatty acids, such as acetate and butyrate.19 However, valerolactone

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and phenolic acids are generally considered to be the primary reaction products from

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catechins for intestinal absorption.

of

hydroxyphenylvaleric

acids lead

to

hydroxyphenylpropionic,

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Besides the native catechins, the glucuronidated, methylated and sulfated conjugates of

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catechins (phase II metabolites) that reach the colon via enterohepatic circulation are also

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susceptible to degradation by the intestinal microbiota.16 Microbial glucuronidase,

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demethylase and sulfatase probably first deconjugate these phase II metabolites, releasing the

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original catechins for further degradation.

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After formation of valerolactones and phenolic acids, these microbial metabolites are

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readily absorbed in the large intestine, and subsequently they undergo phase I and II

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metabolism, distribution and finally excretion, just like the native catechins. Using radio-

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labelled EC, Ottaviani et al. convincingly demonstrated that 82 ± 5% of ingested EC was 8 ACS Paragon Plus Environment

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absorbed and finally excreted via urine.20 Moreover, ca. 70% of the recovered radioactivity

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was in the form of microbial metabolites, 42 ± 5% being O-glucuronidated and sulfated

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derivatives of γ-valerolactone and γ-hydroxyvaleric acid, and 28 ± 3% as derivatives of

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amongst others phenolic acids.20

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Bioconversion of BTP. Regarding the phenolics from black tea, such as theaflavins,

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theasinensins, and thearubigins, the knowledge on their microbial metabolism pathways is

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relatively limited. For theaflavins, it is believed that degalloylation will occur first.13, 21 Then

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after a series of degradation steps, several phenolic catabolites, including 5-(3',4'-

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dihydroxyphenyl)-γ-valerolactone,

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hydroxyphenyl)-γ-hydroxyvaleric acid, 5-(phenyl)-γ-hydroxyvaleric acid, and 3-(3',4'-

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dihydroxyphenyl)propionic acid, which are similar to the metabolites of catechins, will be

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formed.13 Furthermore, 3-phenylpropionic acid and its hydroxylated derivatives were reported

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to be the key metabolites.19 From this, it is evident that the theaflavin skeleton is prone to

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break down after reaching the colon. Because of the identification of 5-(3',4'-

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dihydroxyphenyl)-γ-valerolactone, which contains the complete B-ring of catechin, it is

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reasonable to speculate that the tropolone ring of the benzotropolone moiety of theaflavins

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will be cleaved. The details of the degradation pathways of the benzotropolone moiety are

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unknown yet, especially the fate of tropolone-containing part. We hypothesize that, after the

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opening of the tropolone ring, an intact catechin molecule and a catechin-derived compound

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will be formed first. The catechin part will be further degraded following the pathways

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described earlier, thus forming 3-phenylpropionic acid and its hydroxylated derivatives. The

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fissured tropolone ring might engage in keto-enol tautomerism and pyruvic acid-type

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oxidation to give succinaldehyde derivatives. Such succinaldehyde derivatives are highly

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reactive and are likely to react further with other compounds in the colon. It is therefore likely

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that they will not be found as such. In addition to the degradation of the benzotropolone

5-(3'-hydroxyphenyl)-γ-valerolactone,


5-(3'-


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moiety, the C-rings may also be opened prior to tropolone fission by gut microbiota, followed

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by progressive A-ring cleavage, lactonization and aliphatic chain shortening. In general, these

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progressive degradations are similar to those of catechins, finally resulting in a set of highly

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diverse low molecular weight metabolites, including phenylpropionic, phenylacetic, benzoic

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and short chain fatty acids, as well as some succinaldehyde derivatives. The tentative

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microbial degradation pathway of theaflavins is summarized in Figure 3. It should be noted

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that further study is required to fully elucidate the degradation pathway of theaflavins.

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Currently, there are no reports on the degradation pathways of theasinensins. Considering

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the similarities in interflavanic bonds between theasinensins and B-type procyanidins, it is

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speculated that some features of B-type procyanidin degradation might also apply to that of

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theasinensins. B-type procyanidin dimers are subjected to A-ring (terminal unit) and C-ring

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(extension unit) cleavage leading to 5-(3,4-dihydroxyphenyl)-γ-valerolactone and 2-(3,4-

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dihydroxyphenyl)acetic acid, respectively, as main metabolites when incubated with human

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gut microbiota.22 Similar reactions might occur with theasinensins, besides the degalloylation,

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but it remains unclear whether the C-C bond between the B-rings is prone to degradation.

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Although thearubigins are known to be the major oxidized phenolics in black tea, their

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biotransformation will not be further discussed here, as their highly complex and

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heterogeneous structures have not yet been established. They are likely to contain similar

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structural moieties as theaflavins and theasinensins, and consequently their biotransformation

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might follow similar routes.

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Summarizing, similar sets of phenolic acids with different hydroxylation patterns and side-

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chain lengths are expected to originate from colonic fermentation of both GTC and BTP.

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However, a comprehensive comparison of microbial metabolite profiles of green tea and

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black tea is not yet available.


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Gut microbiota modulatory effects of tea phenolics and their metabolites

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Along with the bioconversion of GTC and BTP by gut microbiota, the composition of the

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intestinal bacterial community may also shift, by means of selective inhibition or promotion

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of certain intestinal bacteria.

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Comparison of the gut microbiota modulatory effects of green and black tea. So far,

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several studies on gut microbiota modulatory effects of green and black tea have been

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conducted with different experimental approaches, including in vitro fermentation with

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human faeces, animal trials and human subject interventions. The reported intestinal bacteria

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that are affected by these two kinds of tea are summarized in Table 1. Some details of these

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studies were listed in Supplementary material Table S1.

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In vitro fermentation studies indicated that green tea can increase the populations of

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beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus,23,

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growth of pathogenic bacteria, such as Clostridium spp..23-25 However, Bifidobacterium spp.

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were reported to be inhibited by black tea phenolics.26 Several animal trials with normal or

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obese mice suggested an increase in the diversity of gut microbiota and a decrease in the ratio

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of Firmicutes/Bacteroidetes by both kinds of tea.27-29 The increase of Akkermansia by both

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green and black tea was also repeatedly reported.26, 28, 30 In addition, the effect on some other

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intestinal bacteria has been documented in various studies (Table 1). Besides these in vitro

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and animal studies, a human intervention study also indicated that 10 days of green tea

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consumption could increase the proportion of the Bifidobacterium spp..31 Hence, green tea

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and black tea exert significant effects on the intestinal environment by modulation of the gut

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microbiota. However, another randomized, single blind, placebo-controlled human trial

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indicated that, after administration of capsules with green tea extract for 12 weeks, no

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significant changes in gut microbiota diversity were found 32. Possibly, the modulatory effect


24

and repress the


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of tea phenolics in that study was concealed by considerable inter-individual variation

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between subjects.

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Due to the variation in intake dose, experimental subjects, duration of the experiment, and

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bacterial analysis methods, it is hard to compare the gut microbiota modulatory effects of

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green and black tea, and draw unambiguous conclusions. Moreover, some are mutually

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contradictory, for example, Bacteroides was reported to be promoted in some papers,27, 33 in

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contrast to some others.25,

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methodological approach may be a more appropriate way for understanding the difference.

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Only one study conducted such comparison, which suggested that under similar intake of

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polyphenols, both green and black tea altered the proportions of a wide range of intestinal

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microbes in obese mice, and exhibited similar gut microbiota profiles, but significantly

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different from the ones without tea intervention.28 Considering the similarity of building

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blocks of GTC and BTP, as well as in their bacterial metabolites in the colon as indicated

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earlier, it is reasonable to speculate that both kinds of tea exhibit consistency in gut

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microbiota modulatory effects. Nevertheless, the effect of degree of polymerization of

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monomeric tea catechins on gut microbiota modulation should be further substantiated, using

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purified compounds.

28

Direct comparison of green and black tea with the same

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The mechanism of the gut microbiota modulatory effects of tea phenolics. The

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stimulation effect of tea phenolics on certain intestinal bacteria might be related to the

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capacity of these microorganisms to metabolize flavonoid compounds. For example, certain

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lactobacilli, such as Lactobacillus plantarum strains, are able to use phenolic compounds as

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substrate to obtain energy.34 Such selective growth stimulation by phenolics on Lactobacillus

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sp. and Bifidobacterium sp. is similar to the stimulation effect of e.g. inulin and

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galactooligosaccharides, which are commonly referred to as prebiotics.


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Regarding the inhibitory effect of tea phenolics, it has long been recognized that

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polyphenols, as secondary plant metabolites, play an important role in plant defence.

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Numerous studies have demonstrated that both GTC and BTP could inhibit the growth of a

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great variety of pathogenic and spoilage bacteria. For example, catechins are considered

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potent antibacterial agents against foodborne and other pathogenic bacteria, besides gut

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microbiota, such as Bacillus cereus, Campylobacter jejuni, Clostridium perfringens,

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Escherichia coli, Helicobacter pylori, Legionella pneumophila, Mycobacterium spp..35

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Furthermore, black tea also exhibits inhibitory effects towards B. subtilis, E. coli, Proteus

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vulgaris, Pseudomonas fluorescens, Salmonella sp., Staphylococcus aureus, etc..3 With regard

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to the mechanism behind the inhibitory effect of tea phenolics on bacteria, the most widely

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accepted one is via their ability to disrupt membranes. EGCg can directly bind the exposed

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peptidoglycan layer of Gram-positive bacteria, resulting in cleavage of cross-links in

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peptidoglycan. Once the peptidoglycan layer is disrupted, its protective effect is reduced and

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permeability is increased, consequently resulting in loss of vitality of the bacteria.36 Gram-

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negative bacteria are less susceptible to EGCg, due to their outer membrane protecting the

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peri-plasmic peptidoglycan layer. Moreover, the outer membrane of Gram-negative bacteria is

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composed of negatively charged lipopolysaccharides, which repel EGCg, also bearing

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negative charge in aqueous solution at around neutral pH.36 However, the postulated

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disruption of the peptidoglycan layer cannot fully explain the modulatory effects of tea

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phenolics, as several Gram-positive bacteria, including Lactobacillus, Bifidobacterium,

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Lachnospiraceae, Oscillospira, do not seem to be susceptible to catechins.

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Apart from damage to the bacterial cell surface by directly binding to the peptidoglycan

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layer, other hypotheses have also been put forward to explain the inhibitory effect of tea

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phenolics. For instance, it was reported that catechins could produce hydrogen peroxide by

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donating one electron to dissolved oxygen,37 and thus further induce indirect cell surface 13 ACS Paragon Plus Environment


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damage and endogenous oxidative stress to both Gram-positive and Gram-negative bacteria.38

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Nevertheless, considering the anaerobic environment of intestinal tract, the significance of

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such hydrogen peroxide formation is debatable. Last but not least, Vandeputte et al.

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documented that catechins reduced the expression of several quorum sensing-related genes

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(lasB, rhlA, lasI, lasR, rhlI, and rhlR), thereby inhibiting the virulence factor production of

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Pseudomonas aeruginosa PAO1.39 Together, these studies provide preliminary explanations

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of the gut microbiota modulatory effect of tea phenolics. Nonetheless, due to the complexity

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of the gut microbial ecosystem, the precise mechanisms are still ambiguous, and require

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further study.

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Gut microbiota related health benefits of green tea and black tea

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A considerable number of scientific publications has demonstrated the bioactivities of tea

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phenolics, most of which are focused on their antioxidant properties and direct effects on host

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or cells. As mentioned above, following ingestion, a large portion of tea phenolics will not be

293

absorbed and reach the colon intact, where they are subsequently converted into phenolic

294

acids or other small bacterial metabolites by gut microbiota. Simultaneously, the composition

295

of gut microbiota will be modulated. Such reciprocal interactions between tea phenolics and

296

gut microbiota may finally confer health benefits to the host.

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Health benefits derived from metabolites of GTC and BTP. Phenolic acids with various

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hydroxylation patterns and side-chain lengths are the main metabolites for absorption of both

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green tea catechins and black tea phenolics after ingestion. Regarding the health beneficial

300

properties of these phenolic acids, Crozier et al. indicated that these compounds might exert

301

modulatory effects on different intracellular signalling components, which were vital for

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cellular functions such as growth, proliferation and apoptosis.40 In addition, Duynhoven et

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al.41 and Chen & Sang18 reviewed their possible bioactivities, including inhibition of platelet 14 ACS Paragon Plus Environment

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aggregation, ACE activity, oxidation of LDL and erythrocytes, and oxidative stress induced

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cytotoxicity, enhancement of vasodilation, anti-inflammatory potential, protection of colon

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fibroblasts, etc.. Thus, these metabolites may potentially exert health benefits to the host,

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rather than their original forms. If so, it is worth noting that part of the health-promoting

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potential of BTP might be lost, as part of BTP is converted to succinaldehyde derivatives,

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rather than to phenolic acids, as shown for theaflavins (Figure 3).

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Health benefits derived from gut microbiota modulation induced by GTC and BTP.

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The reshape of gut microbiota induced by tea phenolics may also exert certain health benefits.

312

The most apparent outcomes are the stimulation of beneficial bacteria, such as Lactobacillus

313

sp., and the inhibition of pathogenic bacteria, such as Clostridium spp.. Beyond these, other

314

profound health benefits may be conferred by tea phenolics through gut microbial ecosystem

315

modulation. For example, Akkermansia, as previously indicated, is promoted by both GTC

316

and BTP.26, 28, 30 This mucin-degrading microorganism resides in the mucus layer and shows

317

reverse correlation with endotoxemia, adipose tissue inflammation, fat body weight gain, and

318

insulin resistance in mice.42 Moreover, GTC were found to stimulate Bacteroidetes and

319

Oscillospira, which were previously linked to the lean phenotype in human and animal

320

studies, and inhibit Peptostreptococcaceae, which were previously linked to colorectal cancer,

321

in an animal trial.27 The increase of gut microbiota diversity and the decrease of the ratio of

322

Firmicutes/Bacteroidetes are commonly found in several studies for both green tea and black

323

tea intake.27-29 Data in human subjects and rodents revealed that obesity was linked to the

324

decrease of gut microbiota diversity and the increase of this ratio, whereas tea intake could

325

restore the balance. In addition, lipopolysaccharides (LPS), which is a constituent of the outer

326

membrane of Gram-negative and able to induce immune responses, is reported to be reduced

327

by tea ingestion in obese mice.43 Summarizing, the modification of intestinal microbiota

328

induced by tea phenolics may further contribute to the integrity of mucus layer, attenuate the 15 ACS Paragon Plus Environment


329

inflammatory process, regulate metabolic disorders, etc., underlining the prebiotic potential of

330

both green and black tea phenolics.

331

With respect to health benefits, green tea has generally received more attention than black

332

tea, and is commonly preferred over black tea because of its higher antioxidant activities.

333

Nevertheless, considering their similar building blocks, their similar poor bioavailability, and

334

their potentially similar colonic metabolites, there is not sufficient evidence that green tea

335

truly has better health-promoting properties than black tea. For obtaining such evidence, it is

336

important to study the interaction between tea phenolics and gut microbiota more extensively.

337

The key questions to be answered are: (i) “What is the phenolic acid recovery from BTP

338

compared to that from GTC upon colonic fermentation, starting from an equal amount of

339

flavan-3-ol equivalents?” and (ii) “Do GTC and BTP differ in their gut microbiota modulatory

340

effects?”

341

342

Abbreviations Used

343

GTC, green tea catechins; BTP, black tea phenolics; PPO, polyphenol oxidases; POD,

344

peroxidases; USDA, United States Department of Agriculture; EGCg, epigallocatechin gallate;

345

EGC, epigallocatechin; ECg, epicatechin gallate; EC, epicatechin; GCg, gallocatechin gallate;

346

GC, gallocatechin; Cg, catechin gallate; C, catechin; MRP, multidrug resistance proteins; LPS,

347

lipopolysaccharides.

348

349

Acknowledgment

350

Zhibin Liu is grateful for the financial support of the China Scholarship Council (CSC).

351


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352

Supporting Information

353

The detailed information of the studies on the gut microbiota modulatory effect of green and

354

black tea.

355

References

356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400

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470



Figure Captions Figure 1. Chemical structures of green tea catechins and primary black tea phenolics. Figure 2. Microbial degradation pathways of green tea catechins by gut microbiota. Figure 3. Speculative representation on microbial degradation pathways of black tea theaflavin by gut microbiota. The red arrows speculate on putative degradation routes, the black arrows represent reactions to confirmed degradation products. The reaction in BOX1 is further explained in BOX2.


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Page 21 of 25


Table 1. The Gut Microbiota Modulatory Effect Of Green And Black Tea. Promoted bacteria Green tea

● Akkermansia

Inhibited bacteria

28, 30

G-

28

● Alistipes Bacteroides 27, 33 Bifidobacterium spp. Escherichia coli 24

GGG+

23, 24, 31, 45

Eubacterium–Clostridium ● Lachnospiraceae 28

GG+ G+

24

30, 45

Lactobacillus Lactobacillus–Enterococcus 23 Oscillospira ● Rikenella 28

27

● Akkermansia ● Alistipes 28 Enterococci Klebsiella 26

28

● Allobaculum Bacillus weihenstephanensis 44

G+ G+ G+

25, 28

● Bacteroides Bacteroides–Prevotella,23 23-25, 33, 45

Clostridium spp. Eubacterium–Clostridium23 28

● Parabacteroides Peptostreptococcaceae 27

GGGG+ G+ G-

G+

Staphylococcus saprophyticus

Black tea

G+ G+

Aerococcus urinaeequi 44

44

28

GG+ GGG+

26

● Lachnospiraceae ● Rikenella 28

GG+

28

G-

28

● Allobaculum Anaeroglobus 26

G+ GGG+

28

● Bacteroides Bifidobacteria 26 26

Blautia coccoides ● Parabacteroides 28 Victivallis

26

Note: the bullet point (●) indicates bacteria that respond similarly towards green and black tea. G- indicates Gram negative bacteria; G+ indicates Gram positive bacteria.


G+ GG-


Figure 1.


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Page 23 of 25


Figure 2.



Figure 3.


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TOC graphic


Green and black tea phenolics - Bioavailability ... - ACS Publications

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