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

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Green and Black Tea Phenolics: Bioavailability, Transformation by Colonic Microbiota, and Modulation of Colonic Microbiota Zhibin Liu,†,‡,§ Marieke Elisabeth Bruins,§ Li Ni,*,‡ and Jean-Paul Vincken*,† †

Laboratory of Food Chemistry and §Food & Biobased Research, Wageningen University, Post Office Box 17, 6700 AA Wageningen, Netherlands ‡ Institute of Food Science and Technology, Fuzhou University, Fuzhou, Fujian 350108, People’s Republic of China

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S Supporting Information *

ABSTRACT: Monomeric green tea catechin (GTC) and oligomeric, oxidized black tea phenolic (BTP) have shown promising health benefits, although GTC has been more extensively studied than BTP. We review the current knowledge on bioavailability, colonic transformation, and gut microbiota modulatory effects of GTC and BTP. As a result of their similar poor bioavailability in the small intestine and potentially similar metabolites upon colonic fermentation, it seems as if GTC and BTP have similar health effects, although it cannot be excluded that they have different gut microbiota modulatory effects and that BTP gives a poorer yield of bioactive phenolic metabolites upon colonic fermentation than GTC. KEYWORDS: green tea catechins, black tea phenolics, gut microbiota, bioavailability, microbial metabolism, health benefits

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INTRODUCTION Tea, originating from the leaves of Camellia sinensis, is the most widely consumed beverage in the world. The major constituents of tea are flavonoids, including flavonols, flavones, flavanols (flavan-3-ols), etc., of which over 60% are flavanols. On the basis of the processing method, tea is generally divided into three forms: green tea, oolong tea, and black tea. Among them, black tea is the most consumed type, accounting for 78% of tea production worldwide; green tea comes next, contributing 20%; and the remainder 2% is oolong tea.1 Green tea is produced by enzymatic inactivation of the fresh tea leaves, with monomeric flavanols, commonly referred to as catechins, as the primary phenolic compounds. Here, we will further refer to monomeric green tea catechin as GTC. Black tea differs from green tea by a so-called “fermentation” process, during which over 90% of the catechins in fresh tea leaves undergo extensive oxidation by endogenous polyphenol oxidase (PPO) and peroxidase (POD), resulting in the formation of dimeric and oligomeric compounds, such as theaflavins, theasinensins, and thearubigins. Here, we will further refer to oligomeric black tea phenolic as BTP. Oolong tea is a semi-oxidized, semi-fermented product, comprising a mixture of catechins and their oxidation products. A considerable number of studies has demonstrated the importance of regular tea consumption in human health, because it seems to counteract cardiovascular disease, obesity, and type 2 diabetes.2 These pharmaceutical benefits are generally attributed to the phenolic compounds in tea because of their potent antioxidative, anti-inflammatory, antimicrobial, antitumor, and antiaging properties.2 As a result of the differences in GTC and BTP, consumers might be curious about which tea is the best for promoting health. Green tea is generally recommended because of its stronger antioxidant properties, associated with the higher concentration of unoxidized flavanols.3 However, it is controversial to link the health benefits of tea solely to antioxidant activity, because other properties may also contribute to their pharmaceutical activities. © 2018 American Chemical Society

Furthermore, the low bioavailability of phenolics, those from black tea in particular, has long been recognized, which does not seem in accordance with their in vivo antioxidative activity. The interaction of tea phenolics and gut microbiota has long been overlooked and might provide clues to understand the health-beneficial effects of tea phenolics. The large intestinal lumen is inhabited by a large, diverse population of microorganisms, mainly anaerobic bacteria. It is commonly believed that more than 1000 “species-level” phylotypes, belonging to a few phyla, reside in a healthy gut.4 Of these phyla, Bacteroidetes and Firmicutes usually dominate the gut microbiota, followed by Actinobacteria, Proteobacteria, Verrucomicrobia, etc.4 They play an essential role in the maintenance of intestinal homeostasis and host health, via extracting nutrients and energy from the diet and creating a physical and immunologic barrier for the host. The unabsorbed phenolics reaching the colon will be subjected to enzymatic degradation by gut microbiota, resulting in a series of metabolites, which are readily absorbed. Simultaneously, the composition of gut microbiota might be modulated. Such reciprocal interactions between phenolics and gut microbiota might eventually exert some health benefits to the host. In this perspective, the bioavailability, degradation pathways, and gut microbiota modulatory effects of GTC and BTP were compared and their potential health beneficial properties are discussed on the basis of their interaction with gut microbiota. Received: Revised: Accepted: Published: 8469

April 27, 2018 July 18, 2018 July 18, 2018 July 18, 2018 DOI: 10.1021/acs.jafc.8b02233 J. Agric. Food Chem. 2018, 66, 8469−8477

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Journal of Agricultural and Food Chemistry

Figure 1. Chemical structures of GTC and primary BTP.

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PHENOLIC COMPOUNDS IN TEA AND THEIR BIOAVAILABILITY According to the United States Department of Agriculture (USDA) flavonoid databases, tea is the most important dietary source of flavanols. As indicated before, green and black tea are the most frequently consumed kinds of tea. The main difference

between the two kinds resides in the much more extensive oxidation of phenolics in black tea than in green tea, resulting in a distinctive phenolic composition. The phenolic compounds of green and black tea, together with their bioavailability, are first reviewed here. 8470

DOI: 10.1021/acs.jafc.8b02233 J. Agric. Food Chem. 2018, 66, 8469−8477

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Figure 2. Microbial degradation pathways of GTC by gut microbiota.

GTC and Their Bioavailability. Catechins in green tea are characterized by di- or trihydroxyl group substitution of the B ring and the meta-5,7-dihydroxy substitution of the A ring. Furthermore, over 50% of the catechins is esterified with a galloyl moiety.5 There are four major catechins: epigallocatechin gallate (EGCg), epigallocatechin (EGC), epicatechin gallate (ECg), and epicatechin (EC), of which EGCg is the most abundant catechin. The chemical structures of these catechins are shown in Figure 1. In addition, four corresponding

stereoisomers, including gallocatechin gallate (GCg), gallocatechin (GC), catechin gallate (Cg), and catechin (C), are also found in tea, albeit in much smaller amounts. The poor bioavailability of catechins in the small intestine has long been recognized. EC, EGC, ECg, and EGCg were reported to possess low transepithelial permeability in a human intestinal absorption model, whereas their basal-to-apical efflux was reported to be more significant, which involved active transport via transporters, such as multidrug resistance protein (MRP).6 8471



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BIOCONVERSION OF TEA PHENOLICS BY GUT MICROBIOTA The diverse microbiota that inhabits the large intestine is equipped with a large set of different enzymes capable of transforming various food ingredients that enter the colon and plays essential metabolic functions in digestion by the host. This microbial community can hydrolyze glycosides, glucuronides, sulfates, amides, esters, and lactones through the action of enzymes, such as α-rhamnosidase, β-glucuronidase, β-glucosidase, sulfatase, and esterase. In addition, other catalytic reactions, including non-aromatic ring cleavage, reduction (reductase and hydrogenase), decarboxylation (decarboxylase), demethylation (demethylase), isomerization (isomerase), and dehydroxylation (dehydroxylase), also extensively occur in the colon as a result of the metabolic activities of intestinal microbes. Hence, the remaining unabsorbed GTC and BTP in the large intestine are expected to undergo extensive microbial degradation, subsequently leading to numerous simpler compounds. Bioconversion of GTC. A number of studies have been carried out to elucidate the degradation pathway of catechins by gut microbiota. In general, the transformations can be grouped into three major processes: (i) galloyl ester hydrolysis, (ii) Cring opening, and (iii) further modification of the reaction products by reactions, including lactonization, decarboxylation, dehydroxylation, and oxidation reactions.8,15−18 In the case of galloylated catechins (ECg and EGCg), the microbial metabolism usually starts with the galloyl ester hydrolysis by microbial esterases, giving rise to gallic acid, which may be further decarboxylated to pyrogallol. After degalloylation, the C ring of the catechin remainder is opened, leading to diphenylpropan-2-ol, which is later converted into valerolactone [5-(3′,4′-dihydroxyphenyl)-γ-valerolactone in the case of EC/ ECg or 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone in the case of EGC/EGCg]. The lactone ring later breaks, resulting in hydroxyphenylvaleric acids and/or 4-hydroxy-hydroxyphenylvaleric acids. Subsequent biotransformations of hydroxyphenylvaleric acids lead to hydroxyphenylpropionic, hydroxyphenylacetic, and hydroxybenzoic acids by successive loss of carbon atoms from the side chain. Meanwhile, dehydroxylation of these hydroxylated phenolic acids might also occur at C3′, C4′, and/ or C5′ of the original B rings, resulting in various simpler phenolic acids. The possible microbial metabolism pathway of catechins is summarized in Figure 2. It was also reported that, benzene rings of these phenolic acids can be further opened and converted into short-chain fatty acids, such as acetate and butyrate.19 However, valerolactone and phenolic acids are generally considered to be the primary reaction products from catechins for intestinal absorption. Besides the native catechins, the glucuronidated, methylated, and sulfated conjugates of catechins (phase II metabolites) that reach the colon via enterohepatic circulation are also susceptible to degradation by the intestinal microbiota.16 Microbial glucuronidase, demethylase, and sulfatase probably first deconjugate these phase II metabolites, releasing the original catechins for further degradation. After formation of valerolactones and phenolic acids, these microbial metabolites are readily absorbed in the large intestine, and subsequently, they undergo phase I and II metabolism, distribution, and finally excretion, just like the native catechins. Using radiolabeled EC, Ottaviani et al. convincingly demonstrated that 82 ± 5% of ingested EC was absorbed and finally excreted via urine.20 Moreover, ca. 70% of the recovered

Moreover, the galloylated catechins exhibited lower affinity to MRP than non-galloylated catechins.6 Following administration, approximately 13.7% of EGC, 31.2% of EC, and 0.1% of EGCg were directly bioavailable.7 The directly absorbed catechins are transferred to the liver via the portal vein, where they are metabolized by phase II enzymes, resulting in glucuronidated, methylated, and sulfated conjugates.8,9 It was shown that these metabolites will enter the systemic circulation or are eliminated via the bile and returned back to the gastrointestinal tract.8 There is evidence indicating that phase II metabolism of EC also occurred in enterocytes, the metabolites (mainly sulfated conjugates) of which were eliminated by efflux back to the intestinal lumen, which was much higher than the elimination via bile.10 Stalmach et al. reported that approximately 70% of the ingested GTC was recovered in the large intestine, of which 33% in the form of parent compounds and 37% in the form of phase II metabolites, mainly o-linked sulfates and methyl sulfates.9 BTP and Their Bioavailability. In black tea, abundant phenolic compounds are theaflavin and theasinensin and their mono- and digallates. Theaflavins, with their characteristic benzotropolone moiety, are produced by condensation of a catechol-type B ring (EC or ECg) and a pyrogallol-type B ring (EGC or EGCg). Theasinensins are formed from condensation of two pyrogallol-type B rings. In addition to theaflavins and theasinensins, various other catechin dimers have been identified in black tea, such as theaflagallins, theaflavates, theaflavic acids, theacitrins, dehydrodicatechins, etc. (Figure 1).11 These dimeric phenolics are not the final products of the oxidation process, because they can be further oxidized and oligomerized to form even more complex oxidation products. Collectively, these complex oxidation products of catechins are referred to as thearubigins.12 Given the complexity of oxidized tea phenolics, the knowledge on the bioavailability of black tea phenolics is limited. It was recently reported that theaflavins and their phase II metabolites were not detected in urine excreted 0−30 h after intake, which suggested their low bioavailability.13 Thus, it is speculated that theaflavin-related black tea phenolics, such as theaflavic acids, theaflavates, and theaflagallins, exhibit similarly low bioavailability as theaflavins. With regard to other black tea phenolics, such as theasinensins, dehydrodicatechins, and theacitins, no literature is yet available. It has been reported that B-type procyanidin dimers, with two catechin units linked with C4−C8 or C4−C6 bonds between A and C rings, had lower bioavailability than monomeric catechins, which was less than 10% of that of catechins.14 Theasinensins have structural similarities with B-type procyanidins in that both are formed by catechin dimerization through C−C bonds but differ in the position of the interflavanic linkage; i.e., they are connected at the B rings through C2′−C2′ bonds. Thus, low bioavailability is expected for theasinensins, similar to that of B-type procyanidins. Likewise, dehydrodicatechins are expected to have similarly low bioavailability. In general, monomeric flavan-3-ols are the primary phenolic compounds in green tea, whereas in black tea, oxidized dimeric and oligomeric flavan-3-ols are predominant. Given their low bioavailability, substantial amounts of GTC and BTP will enter the colon in their original form and be the subject of bioconversion by gut microbiota, resulting in the formation of low-molecular-weight metabolites, which are known to be much more easily absorbed. 8472


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Figure 3. Speculative representation on microbial degradation pathways of black tea theaflavin by gut microbiota. The red arrows speculate on putative degradation routes, and the black arrows represent reactions to confirmed degradation products. The reaction in BOX1 is further explained in BOX2.

radioactivity was in the form of microbial metabolites, with 42 ±

Bioconversion of BTP. With regard to the phenolics from black tea, such as theaflavins, theasinensins, and thearubigins, the knowledge on their microbial metabolism pathways is relatively limited. For theaflavins, it is believed that degalloylation will occur first.13,21 Then after a series of degradation steps,

5% being o-glucuronidated and sulfated derivatives of γvalerolactone and γ-hydroxyvaleric acid and 28 ± 3% as derivatives of, among others, phenolic acids.20 8473


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Journal of Agricultural and Food Chemistry Table 1. Gut Microbiota Modulatory Effect of Green and Black Teaa promoted bacteria green tea

● ●

●

● black tea

● ●

● ●

Akkermansia28,30 Alistipes28 Bacteroides27,33 Bifidobacterium spp.23,24,31,45 Escherichia coli24 Eubacterium−Clostridium24 Lachnospiraceae28 Lactobacillus30,45 Lactobacillus−Enterococcus23 Oscillospira27 Rikenella28 Staphylococcus saprophyticus44 Akkermansia28 Alistipes28 Enterococci26 Klebsiella26 Lachnospiraceae28 Rikenella28

inhibited bacteria G− G− G− G+ G− G+ G+ G+ G+ G+ G− G+ G− G− G+ G− G+ G−

● ●

●

● ●

●

Aerococcus urinaeequi44 Allobaculum28 Bacillus weihenstephanensis44 Bacteroides25,28 Bacteroides−Prevotella23 Clostridium spp.23−25,33,45 Eubacterium−Clostridium23 Parabacteroides28 Peptostreptococcaceae27

G+ G+ G+ G− G− G− G+ G+ G−

Allobaculum28 Anaeroglobus26 Bacteroides28 Bifidobacteria26 Blautia coccoides26 Parabacteroides28 Victivallis26

G+ G− G− G+ G+ G− G−

a

The bullet points (●) indicate bacteria that respond similarly toward green and black tea. G− indicates Gram-negative bacteria, and G+ indicates Gram-positive bacteria.

several phenolic catabolites, including 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, 5-(3′-hydroxyphenyl)-γ-valerolactone, 5(3′-hydroxyphenyl)-γ-hydroxyvaleric acid, 5-(phenyl)-γ-hydroxyvaleric acid, and 3-(3′,4′-dihydroxyphenyl)propionic acid, which are similar to the metabolites of catechins, will be formed.13 Furthermore, 3-phenylpropionic acid and its hydroxylated derivatives were reported to be the key metabolites.19 From this, it is evident that the theaflavin skeleton is prone to break down after reaching the colon. Because of the identification of 5-(3′,4′-dihydroxyphenyl)-γvalerolactone, which contains the complete B ring of catechin, it is reasonable to speculate that the tropolone ring of the benzotropolone moiety of theaflavins will be cleaved. The details of the degradation pathways of the benzotropolone moiety are yet unknown, especially the fate of the tropolone-containing part. We hypothesize that, after the opening of the tropolone ring, an intact catechin molecule and a catechin-derived compound will be formed first. The catechin part will be further degraded following the pathways described earlier, thus forming 3-phenylpropionic acid and its hydroxylated derivatives. The fissured tropolone ring might engage in keto−enol tautomerism and pyruvic-acid-type oxidation to give succinaldehyde derivatives. Such succinaldehyde derivatives are highly reactive and are likely to react further with other compounds in the colon. It is therefore likely that they will not be found as such. In addition to the degradation of the benzotropolone moiety, the C rings may also be opened prior to tropolone fission by gut microbiota, followed by progressive A-ring cleavage, lactonization, and aliphatic chain shortening. In general, these progressive degradations are similar to those of catechins, finally resulting in a set of highly diverse low-molecular-weight metabolites, including phenylpropionic, phenylacetic, benzoic, and shortchain fatty acids, as well as some succinaldehyde derivatives. The tentative microbial degradation pathway of theaflavins is summarized in Figure 3. It should be noted that further study is required to fully elucidate the degradation pathway of theaflavins.

Currently, there are no reports on the degradation pathways of theasinensins. Considering the similarities in interflavanic bonds between theasinensins and B-type procyanidins, it is speculated that some features of B-type procyanidin degradation might also apply to that of theasinensins. B-type procyanidin dimers are subjected to A-ring (terminal unit) and C-ring (extension unit) cleavage, leading to 5-(3,4-dihydroxyphenyl)γ-valerolactone and 2-(3,4-dihydroxyphenyl)acetic acid, respectively, as the main metabolites when incubated with human gut microbiota.22 Similar reactions might occur with theasinensins, besides the degalloylation, but it remains unclear whether the C−C bond between the B rings is prone to degradation. Although thearubigins are known to be the major oxidized phenolics in black tea, their biotransformation will not be further discussed here, because their highly complex and heterogeneous structures have not yet been established. They are likely to contain structural moieties similar to theaflavins and theasinensins, and consequently, their biotransformation might follow similar routes. Summarizing, similar sets of phenolic acids with different hydroxylation patterns and side-chain lengths are expected to originate from colonic fermentation of both GTC and BTP. However, a comprehensive comparison of microbial metabolite profiles of green and black tea is not yet available.

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GUT MICROBIOTA MODULATORY EFFECTS OF TEA PHENOLICS AND THEIR METABOLITES Along with the bioconversion of GTC and BTP by gut microbiota, the composition of the intestinal bacterial community may also shift, by means of selective inhibition or promotion of certain intestinal bacteria. Comparison of the Gut Microbiota Modulatory Effects of Green and Black Tea. Thus far, several studies on gut microbiota modulatory effects of green and black tea have been conducted with different experimental approaches, including in vitro fermentation with human feces, animal trials, and human subject interventions. The reported intestinal bacteria that are affected by these two kinds of tea are summarized in Table 1. 8474


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bacteria, besides gut microbiota, such as Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia coli, Helicobacter pylori, Legionella pneumophila, and Mycobacterium spp.35 Furthermore, black tea also exhibits inhibitory effects toward Bacillus subtilis, E. coli, Proteus vulgaris, Pseudomonas fluorescens, Salmonella sp., Staphylococcus aureus, etc.3 With regard to the mechanism behind the inhibitory effect of tea phenolics on bacteria, the most widely accepted mechanism is via their ability to disrupt membranes. EGCg can directly bind the exposed peptidoglycan layer of Gram-positive bacteria, resulting in cleavage of cross-links in peptidoglycan. Once the peptidoglycan layer is disrupted, its protective effect is reduced and permeability is increased, consequently resulting in the loss of vitality of the bacteria.36 Gram-negative bacteria are less susceptible to EGCg as a result of their outer membrane protecting the periplasmic peptidoglycan layer. Moreover, the outer membrane of Gram-negative bacteria is composed of negatively charged lipopolysaccharides, which repel EGCg, also bearing a negative charge in aqueous solution at around neutral pH.36 However, the postulated disruption of the peptidoglycan layer cannot fully explain the modulatory effects of tea phenolics, because several Gram-positive bacteria, including Lactobacillus, Bifidobacterium, Lachnospiraceae, and Oscillospira, do not seem to be susceptible to catechins. Apart from damage to the bacterial cell surface by directly binding to the peptidoglycan layer, other hypotheses have also been put forward to explain the inhibitory effect of tea phenolics. For instance, it was reported that catechins could produce hydrogen peroxide by donating one electron to dissolved oxygen37 and, thus, further induce indirect cell surface damage and endogenous oxidative stress to both Gram-positive and Gram-negative bacteria.38 Nevertheless, considering the anaerobic environment of the intestinal tract, the significance of such hydrogen peroxide formation is debatable. Last but not least, Vandeputte et al. documented that catechins reduced the expression of several quorum-sensing-related genes (lasB, rhlA, lasI, lasR, rhlI, and rhlR), thereby inhibiting the virulence factor production of Pseudomonas aeruginosa PAO1.39 Together, these studies provide preliminary explanations of the gut microbiota modulatory effect of tea phenolics. Nonetheless, as a result of the complexity of the gut microbial ecosystem, the precise mechanisms are still ambiguous and require further study.

Some details of these studies were listed in Table S1 of the Supporting Information. In vitro fermentation studies indicated that green tea can increase the populations of beneficial bacteria, such as Bifidobacterium spp. and Lactobacillus,23,24 and repress the growth of pathogenic bacteria, such as Clostridium spp.23−25 However, Bifidobacterium spp. were reported to be inhibited by black tea phenolics.26 Several animal trials with normal or obese mice suggested an increase in the diversity of gut microbiota and a decrease in the ratio of Firmicutes/Bacteroidetes by both kinds of tea.27−29 The increase of Akkermansia by both green and black tea was also repeatedly reported.26,28,30 In addition, the effect on some other intestinal bacteria has been documented in various studies (Table 1). Besides these in vitro and animal studies, a human intervention study also indicated that 10 days of green tea consumption could increase the proportion of the Bifidobacterium spp.31 Hence, green and black tea exert significant effects on the intestinal environment by modulation of the gut microbiota. However, another randomized, singleblind, placebo-controlled human trial indicated that, after administration of capsules with green tea extract for 12 weeks, no significant changes in gut microbiota diversity were found.32 Possibly, the modulatory effect of tea phenolics in that study was concealed by considerable interindividual variation between subjects. As a result of the variation in intake dose, experimental subjects, duration of the experiment, and bacterial analysis methods, it is hard to compare the gut microbiota modulatory effects of green and black tea and draw unambiguous conclusions. Moreover, some are mutually contradictory, for example, Bacteroides was reported to be promoted in some papers,27,33 in contrast to some others.25,28 Direct comparison of green and black tea with the same methodological approach may be a more appropriate way for understanding the difference. Only one study conducted such a comparison, which suggested that, under a similar intake of polyphenols, both green and black tea altered the proportions of a wide range of intestinal microbes in obese mice and exhibited similar gut microbiota profiles but significantly different gut microbiota profiles without tea intervention.28 Considering the similarity of building blocks of GTC and BTP as well as in their bacterial metabolites in the colon, as indicated earlier, it is reasonable to speculate that both kinds of tea exhibit consistency in gut microbiota modulatory effects. Nevertheless, the effect of the degree of polymerization of monomeric tea catechins on gut microbiota modulation should be further substantiated, using purified compounds. Mechanism of the Gut Microbiota Modulatory Effects of Tea Phenolics. The stimulation effect of tea phenolics on certain intestinal bacteria might be related to the capacity of these microorganisms to metabolize flavonoid compounds. For example, certain lactobacilli, such as Lactobacillus plantarum strains, are able to use phenolic compounds as a substrate to obtain energy.34 Such selective growth stimulation by phenolics on Lactobacillus sp. and Bifidobacterium sp. is similar to the stimulation effect of, e.g., inulin and galactooligosaccharides, which are commonly referred to as prebiotics. With regard to the inhibitory effect of tea phenolics, it has long been recognized that polyphenols, as secondary plant metabolites, play an important role in plant defense. Numerous studies have demonstrated that both GTC and BTP could inhibit the growth of a great variety of pathogenic and spoilage bacteria. For example, catechins are considered potent antibacterial agents against foodborne and other pathogenic

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GUT-MICROBIOTA-RELATED HEALTH BENEFITS OF GREEN AND BLACK TEA A considerable number of scientific publications has demonstrated the bioactivities of tea phenolics, most of which are focused on their antioxidant properties and direct effects on the host or cells. As mentioned above, following ingestion, a large portion of tea phenolics will not be absorbed and reach the colon intact, where they are subsequently converted into phenolic acids or other small bacterial metabolites by gut microbiota. Simultaneously, the composition of gut microbiota will be modulated. Such reciprocal interactions between tea phenolics and gut microbiota may finally confer health benefits to the host. Health Benefits Derived from Metabolites of GTC and BTP. Phenolic acids with various hydroxylation patterns and side-chain lengths are the main metabolites for absorption of both GTC and BTP after ingestion. With regard to the health beneficial properties of these phenolic acids, Crozier et al. indicated that these compounds might exert modulatory effects on different intracellular signaling components, which were vital for cellular functions, such as growth, proliferation, and 8475


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Journal of Agricultural and Food Chemistry apoptosis.40 In addition, Duynhoven et al.41 and Chen and Sang18 reviewed their possible bioactivities, including inhibition of platelet aggregation, angiotensin-converting enzyme (ACE) activity, oxidation of low-density lipoprotein (LDL) and erythrocytes, oxidative-stress-induced cytotoxicity, enhancement of vasodilation, anti-inflammatory potential, protection of colon fibroblasts, etc. Thus, these metabolites may potentially exert health benefits to the host rather than their original forms. If so, it is worth noting that part of the health-promoting potential of BTP might be lost, because part of BTP is converted to succinaldehyde derivatives rather than to phenolic acids, as shown for theaflavins (Figure 3). Health Benefits Derived from Gut Microbiota Modulation Induced by GTC and BTP. The reshape of gut microbiota induced by tea phenolics may also exert certain health benefits. The most apparent outcomes are the stimulation of beneficial bacteria, such as Lactobacillus sp., and the inhibition of pathogenic bacteria, such as Clostridium spp. Beyond these, other profound health benefits may be conferred by tea phenolics through gut microbial ecosystem modulation. For example, Akkermansia, as previously indicated, is promoted by both GTC and BTP.26,28,30 This mucin-degrading microorganism resides in the mucus layer and shows reverse correlation with endotoxemia, adipose tissue inflammation, fat body weight gain, and insulin resistance in mice.42 Moreover, GTC were found to stimulate Bacteroidetes and Oscillospira, which were previously linked to the lean phenotype in human and animal studies, and inhibit Peptostreptococcaceae, which were previously linked to colorectal cancer, in an animal trial.27 The increase of gut microbiota diversity and the decrease of the ratio of Firmicutes/Bacteroidetes are commonly found in several studies for both green and black tea intake.27−29 Data in human subjects and rodents revealed that obesity was linked to the decrease of gut microbiota diversity and the increase of this ratio, whereas tea intake could restore the balance. In addition, lipopolysaccharide (LPS), which is a constituent of the outer membrane of Gram-negative bacteria and able to induce immune responses, is reported to be reduced by tea ingestion in obese mice.43 In summary, the modification of intestinal microbiota induced by tea phenolics may further contribute to the integrity of the mucus layer, attenuate the inflammatory process, regulate metabolic disorders, etc., underlining the prebiotic potential of both green and black tea phenolics. With respect to health benefits, green tea has generally received more attention than black tea and is commonly preferred over black tea because of its higher antioxidant activities. Nevertheless, considering their similar building blocks, their similarly poor bioavailability, and their potentially similar colonic metabolites, there is not sufficient evidence that green tea truly has better health-promoting properties than black tea. To obtain such evidence, it is important to study the interaction between tea phenolics and gut microbiota more extensively. The key questions to be answered are (i) “What is the phenolic acid recovery from BTP compared to that from GTC upon colonic fermentation, starting from an equal amount of flavan-3-ol equivalents?” and (ii) “Do GTC and BTP differ in their gut microbiota modulatory effects?”

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Detailed information on the studies on the gut microbiota modulatory effect of green and black tea (Table S1) (PDF)

AUTHOR INFORMATION

Corresponding Authors

*Telephone/Fax: +86-591-22866378. E-mail: [email protected]. *Telephone/Fax: +31-317482234. E-mail: jean-paul.vincken@ wur.nl. ORCID

Marieke Elisabeth Bruins: 0000-0003-4307-6091 Li Ni: 0000-0002-8584-2682 Jean-Paul Vincken: 0000-0001-8540-4327 Funding

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

The authors declare no competing financial interest.

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ABBREVIATIONS USED GTC, green tea catechin; BTP, black tea phenolic; PPO, polyphenol oxidase; POD, peroxidase; USDA, United States Department of Agriculture; EGCg, epigallocatechin gallate; EGC, epigallocatechin; ECg, epicatechin gallate; EC, epicatechin; GCg, gallocatechin gallate; GC, gallocatechin; Cg, catechin gallate; C, catechin; MRP, multidrug resistance protein; LPS, lipopolysaccharide

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