Chen L, Cao H, Xiao J Polyphenols: absorption, bioavailability, and metabolomics. Chapter 2-Polyphenols Prop Recover Appl 45— Cheruku SP, Ramalingayya GV, Chamallamudi MR et al Catechin ameliorates doxorubicin-induced neuronal cytotoxicity in in vitro and episodic memory deficit in in vivo in Wistar rats.

Cytotechnology Choudhary B, Chauhan OP, Mishra A Edible seaweeds: a potential novel source of bioactive metabolites and nutraceuticals with human health benefits.

Front Mar Sci Article Google Scholar. Cueva C, Moreno-Arribas MV, Martín-Álvarez PJ et al Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Res Microbiol — Dawczynski C, Schäfer U, Leiterer M, Jahreis G Nutritional and toxicological importance of macro, trace, and ultra-trace elements in algae food products.

J Agric Food Chem — Delgado L, Fernandes I, González-Manzano S et al Anti-proliferative effects of quercetin and catechin metabolites.

Food Funct — Dong HP, Yang RC, Chunag IC et al Inhibitory effect of hexahydrocurcumin on human platelet aggregation.

Nat Prod Commun — Dueñas M, Muñoz-González I, Cueva C et al A survey of modulation of gut microbiota by dietary polyphenols. Biomed Res Int El-Beltagi HS, Mohamed AA, Mohamed HI et al Phytochemical and potential properties of seaweeds and their recent applications: a review.

Mar Drugs Espín JC, García-Conesa MT, Tomás-Barberán FA Nutraceuticals: facts and fiction. Phytochemistry — Fabris S, Momo F, Ravagnan G, Stevanato R Antioxidant properties of resveratrol and piceid on lipid peroxidation in micelles and monolamellar liposomes.

Biophys Chem — Fan Y, Pedersen O Gut microbiota in human metabolic health and disease. Nat Rev Microbiol — Feng J, Ge C, Li W, Li R 3- 3-Hydroxyphenyl propionic acid, a microbial metabolite of quercetin, inhibits monocyte binding to endothelial cells via modulating E-selectin expression.

Fitoterapia Filosa S, Di Meo F, Crispi S Polyphenols-gut microbiota interplay and brain neuromodulation. Neural Regen Res — Florio P, Folli C, Cianci M et al Transthyretin binding heterogeneity and anti-amyloidogenic activity of natural polyphenols and their metabolites. J Biol Chem — Gan RY, Bin LH, Sui ZQ, Corke H Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate EGCG : An updated review.

Crit Rev Food Sci Nutr — Gaur G, Gänzle MG Conversion of poly phenolic compounds in food fermentations by lactic acid bacteria: novel insights into metabolic pathways and functional metabolites. Curr Res Food Sci Ghosh S, Sarkar T, Pati S et al Novel bioactive compounds from marine sources as a tool for functional food development.

Front Mar Sci 9. Giménez-Bastida JA, Truchado P, Larrosa M et al Urolithins, ellagitannin metabolites produced by colon microbiota, inhibit Quorum Sensing in Yersinia enterocolitica: phenotypic response and associated molecular changes.

Food Chem — Gómez-Guzmán M, Rodríguez-Nogales A, Algieri F, Gálvez J Potential role of seaweed polyphenols in cardiovascular-associated disorders. Identification of novel colonic metabolites. Gong X, Jiang S, Tian H et al Polyphenols in the fermentation liquid of Dendrobiu candidum relieve intestinal inflammation in zebrafish through the intestinal microbiome-mediated immune response.

Front Immunol Gonthier MP, Cheynier V, Donovan JL et al Microbial aromatic acid metabolites formed in the gut account for a major fraction of the polyphenols excreted in urine of rats fed red wine polyphenols.

J Nutr — González-Barrio R, Edwards CA, Crozier A Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies. Drug Metab Dispos — Gutiérrez-Rodríguez AG, Juárez-Portilla C, Olivares-Bañuelos T, Zepeda RC Anticancer activity of seaweeds.

Drug Discov Today — Food Res Int Hanske L, Loh G, Sczesny S et al The bioavailability of apigeninglucoside is influenced by human intestinal microbiota in rats. Hassaninasab A, Hashimoto Y, Tomita-Yokotani K, Kobayashi M Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism.

Proc Natl Acad Sci USA — Hong YJ, Mitchell AE Metabolic profiling of flavonol metabolites in human urine by liquid chromatography and tandem mass spectrometry. Hsiao YH, Hsieh JF The conversion and deglycosylation of isoflavones and anthocyanins in black soymilk process.

Inada KOP, Silva TBR, Lobo LA et al Bioaccessibility of phenolic compounds of jaboticaba Plinia jaboticaba peel and seed after simulated gastrointestinal digestion and gut microbiota fermentation.

J Funct Foods Ito-Nagahata T, Kurihara C, Hasebe M et al Stilbene analogs of resveratrol improve insulin resistance through activation of AMPK. Biosci Biotechnol Biochem — Jaeger BN, Parylak SL, Gage FH Mechanisms of dietary flavonoid action in neuronal function and neuroinflammation.

Mol Aspects Med — Jarosova V, Vesely O, Marsik P et al Metabolism of stilbenoids by human faecal microbiota.

Molecules Keppler K, Humpf HU Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg Med Chem — Kim Ey, Shin Jy, Park Y-J, Kim Ak Equol induces mitochondria-mediated apoptosis of human cervical cancer cells.

Anticancer Res 9. Knockaert G, Pulissery SK, Lemmens L et al Carrot β-carotene degradation and isomerization kinetics during thermal processing in the presence of oil. Eur J Pharmacol — Koudoufio M, Desjardins Y, Feldman F et al Insight into polyphenol and gut microbiota crosstalk: are their metabolites the key to understand protective effects against metabolic disorders?

Antioxidants Basel, Switzerland — Krga I, Monfoulet LE, Konic-Ristic A et al Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations. Arch Biochem Biophys — Kumar S, Sahoo D, Levine I Assessment of nutritional value in a brown seaweed Sargassum wightii and their seasonal variations.

Algal Res C — Antioxidants Larrosa M, Luceri C, Vivoli E et al Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models.

Mol Nutr Food Res — Lee HC, Jenner AM, Low CS, Lee YK Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota. Leser TD, Mølbak L Better living through microbial action: the benefits of the mammalian gastrointestinal microbiota on the host.

Environ Microbiol — Li F, Han Y, Wu X et al Gut microbiota-derived resveratrol metabolites, dihydroresveratrol and lunularin, significantly contribute to the biological activities of resveratrol.

Front Nutr Liang XL, Wang XL, Li Z et al Improved in vitro assays of superoxide anion and 1,1-diphenyl- 2-picrylhydrazyl DPPH radical-scavenging activity of isoflavones and isoflavone metabolites. Lin S, Wang Z, Lam KL et al Role of intestinal microecology in the regulation of energy metabolism by dietary polyphenols and their metabolites.

Food Nutr Res Ludwig IA, Paz de Peña M, Concepción C, Alan C Catabolism of coffee chlorogenic acids by human colonic microbiota. BioFactors — Makarewicz M, Drożdż I, Tarko T, Duda-Chodak A The interactions between polyphenols and microorganisms, especially gut microbiota.

Manach C, Williamson G, Morand C et al Bioavailability and bioefficacy of polyphenols in humans. Review of 97 bioavailability studies. Am J Clin Nutr S. Marchelak A, Owczarek A, Rutkowska M et al New insights into antioxidant activity of Prunus spinosa flowers: extracts, model polyphenols and their phenolic metabolites in plasma towards multiple in vivo-relevant oxidants.

Phytochem Lett — Marhuenda-Muñoz M, Laveriano-Santos EP, Tresserra-Rimbau A et al Microbial phenolic metabolites: which molecules actually have an effect on human health? Marín L, Miguélez EM, Villar CJ, Lombó F Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties.

Martínez-Huélamo M, Vallverdú-Queralt A, Di Lecce G et al Bioavailability of tomato polyphenols is enhanced by processing and fat addition: evidence from a randomized feeding trial. Mcdougall GJ, Conner S, Pereira-Caro G et al Tracking Poly phenol components from raspberries in ileal fluid.

Mekinić IG, Skroza D, Šimat V et al Phenolic content of brown algae Pheophyceae species: extraction, identification, and quantification.

Biomolecules Mele L, Mena P, Piemontese A et al Antiatherogenic effects of ellagic acid and urolithins in vitro. Min SW, Ryu SN, Kim DH Anti-inflammatory effects of black rice, cyanidinO-β-d-glycoside, and its metabolites, cyanidin and protocatechuic acid.

Int Immunopharmacol — Moco S, Martin FPJ, Rezzi S Metabolomics view on gut microbiome modulation by polyphenol-rich foods. J Proteome Res — Monagas M, Urpi-Sarda M, Sánchez-Patán F et al Insights into the metabolism and microbial biotransformation of dietary flavanols and the bioactivity of their metabolites.

The fermentation process makes the polyphenols susceptible to oxidation by enzymes, allowing catechins to be converted into theaflavins and thearubins, which confer the black tea fragrance and color. In summary, the above-mentioned results demonstrate a valuable aspect to the composition, characterization, and bioactivities of natural polyphenols from fruit and traditional plants, in the context of preventing or controlling metabolic syndrome-associated diseases, especially obesity and diabetes.

Polyphenols have a wide range of benefits and pharmacological effects. This reiterates that they serve as promising nutraceuticals or pharmaceuticals in health and food industries. Despite the evidence that has accumulated in relation to this important Research Topic, there are still many aspects that need to be clarified and improved.

For example, low bioavailability of many polyphenols limits their application on food industry or the clinic. There are key techniques that may improve their bioavailability, such as formation of micelles, nanoparticles, liposomes, and phospholipid complexes.

Converting polyphenols into ingredients that can be easily utilized through gut microbiota could be another way to promote the utilization of polyphenols Chen et al.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. This research was supported by National Key Research and Development Program YFF and the National Natural Science Foundation of China and The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep. doi: PubMed Abstract CrossRef Full Text Google Scholar. Engin A. The definition and prevalence of obesity and metabolic syndrome. Adv Exp Med Biol. Gierach M, Gierach J, Ewertowska M, Arndt A, Junik R.

Correlation between body mass index and waist circumference in patients with metabolic syndrome. ISRN Endocrinol. Yang H, Xiao L, Yuan Y, Luo X, Jiang M, Ni J, et al. Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells.

The main site of metabolization of the complex polyphenols to smaller phenolic compounds is the gut through the action of microorganisms, and reciprocally polyphenols and their metabolites can also modulate the microbial populations. In healthy subjects, these modulations generally lead to an increase in Bifidobacterium , Lactobacillus and Akkermansia , therefore suggesting a prebiotic-like effect of the berries or their compounds.

Finally, berries have been demonstrated to alleviate symptoms of gut inflammation through the modulation of pro-inflammatory cytokines and have chemopreventive effects towards colon cancer through the regulation of apoptosis, cell proliferation and angiogenesis. This review recapitulates the knowledge available on the interactions between berries polyphenols, gut microbiota and gut health and identifies knowledge gaps for future research.

Lavefve, L. Howard and F. Carbonero, Food Funct. To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content. Fetching data from CrossRef. This may take some time to load. Loading related content. Jump to main content. Jump to site search.

Editorial on the Research Topic Natural polyphenols and metabolic syndrome. Metabolic syndrome is a chronic disease characterized by hypertension, obesity, diabetes, and hyperlipidemia, as defined by the World Health Organization 1.

Multiple risk factors, including an unhealthy diet, inactivity, and environmental factors, increase the chances of developing metabolic syndrome.

Therefore, intervention does not only involve exploring clinical therapeutic treatment at the point of diagnosis, but it is also crucial to prevent the occurrence of metabolic syndrome and its complications by keeping a healthy lifestyle, such as by doing sports or by adding vegetables, low sugar fruit, and less salt to the diet.

Natural polyphenols, common specialized metabolites from plants, are a class of bioactive compounds widely found in fruits, vegetables, tea, and herbal medicines.

They confer potentially beneficial activity, by regulating gut microbiota and enacting anti-inflammation or antioxidation 4 — 6. A diet rich in polyphenols alleviates the symptoms and risk factors of metabolic syndrome, such as by reducing blood pressure, improving insulin-resistance and modulating lipid metabolism 7 , 8.

Traditional plants are often used as a source of functional food or pharmaceutical in the industry because they are a rich source of bioactive compounds.

For example, sea buckthorn, a hardy deciduous shrub distributed especially in southwest, northeast, and northwest of China, contains a high yield of polyphenols in its leaves and fruit. The phytochemical components of three teas made from sea buckthorn leaves with different processing treatment were studied by high-performance liquid chromatography HPLC , creating a chemophenetic fingerprint that was studied by multivariate statistical analysis Wang et al.

A total of 48 compounds were identified, including four phenolic acids, 11 tannic acids, and 27 flavonoids. Due to the high yield and diversity of polyphenols, the sea buckthorn tea demonstrated inhibition of α-glucosidase activity and also conferred antioxidant effects in vitro Wang et al.

Oolong tea, another traditional Chinese tea made from partially fermented Camellia sinensis leaves, is especially popular in south China, and has also been proven to have potential health benefits. Li et al. Oolong tea also regulated the expression of genes related to lipid metabolism and inflammation.

To explore the biological effects of polyphenols further, a review by Chen et al. systematically reviewed the literature and commented on the potential network interaction mechanism of natural polyphenols in Chinese herbal medicine. The authors focused on the effects of metabolic homeostasis, immunity, and gut microbial regulation on obesity and diabetes.

Indeed, metabolic disorders are strongly linked to immune imbalance, which may lead to chronic systemic inflammation. When pro-inflammatory cytokines are produced by immune cells it disrupts the metabolism of lipids and glucose, leading to insulin-resistance.

Disturbance to gut microbiota increases gut permeability leaky gut , leading to the entry of microbiota or endotoxic substances into intestinal tissues and systemic circulation.

Ordinarily the metabolites of gut microbiota play an important role in regulation of immunometabolism Chen et al. The profile of natural polyphenols and their yield in biota is affected by postharvest treatment and processing technology.

Wei et al. revealed that 0. Moreover, different processing treatment of sea buckthorn leaves were examined phytochemically, including fresh leaves, black tea produced by withering, rolling, fermentation and drying, and green tea produced by rolling, screening and drying process.

Significant differences of polyphenol patterns occurred among the different processing tea Wang et al. The fermentation process makes the polyphenols susceptible to oxidation by enzymes, allowing catechins to be converted into theaflavins and thearubins, which confer the black tea fragrance and color.

In summary, the above-mentioned results demonstrate a valuable aspect to the composition, characterization, and bioactivities of natural polyphenols from fruit and traditional plants, in the context of preventing or controlling metabolic syndrome-associated diseases, especially obesity and diabetes.

Polyphenols have a wide range of benefits and pharmacological effects. This reiterates that they serve as promising nutraceuticals or pharmaceuticals in health and food industries.

Despite the evidence that has accumulated in relation to this important Research Topic, there are still many aspects that need to be clarified and improved. For example, low bioavailability of many polyphenols limits their application on food industry or the clinic.

There are key techniques that may improve their bioavailability, such as formation of micelles, nanoparticles, liposomes, and phospholipid complexes. Converting polyphenols into ingredients that can be easily utilized through gut microbiota could be another way to promote the utilization of polyphenols Chen et al.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. This research was supported by National Key Research and Development Program YFF and the National Natural Science Foundation of China and The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Small intestine compartment models have a higher pH 6. All studies described here reported a large effect of these conditions on anthocyanins, in agreement with the previous assertion that pH impacts the stability of anthocyanins.

However, acylated anthocyanins from blueberry, delphinidin- and malvidin-acetoyl-glucosides, appeared to have a higher stability. Less than 0. This low bioavailability is explained by the unstable ring fraction of the molecules under the conditions present in the small intestine.

Acylated anthocyanins present in the raw blackberry showed a similar bioaccessibility, even though they were detected at lower concentration in the berries. An increase in relative abundance from 18 compounds have been reported after the in vitro gastro-intestinal digestion of mulberry, among which flavonoids myricetin, epicatechin gallate, quercetin derivative and phenolic acids tartaric acid, caffeic acid, ferulic acid predominate.

These candidate metabolites of anthocyanins breakdown could be formed after the B ring fracture of the anthocyanins, generating phenolic molecules or result from the degradation of other molecules present in the mulberry extracts.

After colonic fermentation of blueberry extracts, the presence of new phenolic compounds has been reported: syringic acid, rhamnetin, hippuric acid, cinammic acid, protocatechuic acid, caffeic acid, and kaempferol rhamnoside.

Most of anthocyanins disappear during the first few hours of colonic fermentation, due to metabolization by the gut microbiota. Depending on the composition of the microbiota, different metabolites may be produced from the fermentation of berry anthocyanins Table 1. The conversion of mulberry anthocyanins by probiotic strains has been reported and the highest conversions were exercised by L.

plantarum and S. thermophiles , respectively degrading cyanidinglucoside and cyanidinrutinoside. The recovered metabolites were mainly chlorogenic acid, cryptochlorogenic acid, caffeic acid and ferulic acid. These observations may be explained by the conversion of some compounds into others, such as rutin into quercetin possibly through the metabolism carried by some Bacteroides species.

The digestion of berries anthocyanins has mainly focused on cyanidin derivatives, but the structure of the compounds simple or acylated, structure of aglycone or sugar moiety was found to impact the stability of anthocyanins in the digestive tract.

After the injection of an acute dose of anthocyanins extracts from blackberries directly into the small intestine, only anthocyanins glycosides were detected in the plasma, urine and bile of rats. The low concentration of native and methylated cyanidinglucoside reported in the plasma shows a low bioavailability.

Cyanidinglucoside and metabolites were reported in the bile 25 minutes after the injection, indicating a rapid absorption and metabolism of the anthocyanins. Arabinoside disappeared more quickly from the plasma than glucoside and galactoside, while among anthocyanins with the same sugar attached, delphinidin and cyanidin remained longer in the plasma than petunidin, peonidin or malvidin.

In pigs, the fate of anthocyanins from black raspberries have been studied in the different compartment of the gastrointestinal tract, as well as their excretion.

The other cyanindin derivatives carrying more complex sugars sambubiose and rutinose showed higher recovery in the gut and were identified as parent compounds of the majority of metabolites found in urine. Only traces of cyanidin sophoroside and glucosylrutinoside were recovered in the digestive tract but their level in the plasma increased, while cyanidinglucoside decreased in the intestine but did not increase in plasma or tissue, indicating metabolism in the gastrointestinal tract.

The previous studies all used acute doses of berry extract or direct perfusion in the intestine, which may not reflect accurately the normal consumption of berry anthocyanins.

Long term exposure of rats to blueberry anthocyanins have been conducted to provide more insights on the absorption, metabolism and excretion under more realistic conditions. In the feces, the content remained stable during the study and the profile of anthocyanins detected was composed of acylated forms of anthocyanins.

The authors reported increased contents of some anthocyanins in both urine and feces compared to the berries, that may result from the methylation of anthocyanins during metabolism. Hippuric acid was reported as the main metabolite from the anthocyanins consumption and the ultimate product of their degradation.

The rapid absorption of anthocyanins was also confirmed in this study as no such compounds were identified in plasma, liver or brain after 3—4 hours of last meal consumption. The absorption in the gastro-intestinal tract of anthocyanins in vivo seems to be mainly dictated by the sugar attached to the aglycone, as well as the aglycone structure itself.

The bioavailability and distribution of these polyphenols remains very low and is influenced by the same factors as well as hydrophobicity of the molecule methylated compounds versus compounds carrying free OH groups.

Overall, the absorption and excretion of anthocyanins in vivo do not seem to be associated with extensive metabolism in animal models.

The form under which anthocyanins are absorbed is not fully understood, even though it remains clear that the nature of the sugar moiety and the aglycone are determinant in the absorption and excretion of the molecules.

Cyanidinglucoside and cyanidinsambubioside are very often found in plasma or urine. The low absorption of anthocyanins in the upper gut suggests the availability of these molecules in the gut, where they can be subjected to further degradation. The recovered phenolic compounds in the ileal fluid were associated with the metabolism of native anthocyanins from the fruits.

This indicates a possible metabolism by the enterocytes or could be the products of a metabolism happening in the liver with the products returning to the gastrointestinal tract via biliary excretion.

These results showed that some anthocyanins could be absorbed from the small intestine primarily , with the stomach also being another potential site of absorption. The amount of metabolites was higher in the plasma and urine of the population with an intact gut, suggesting that the absorbed anthocyanins can form degradation products in the plasma.

Absorption of anthocyanins in humans is generally low, confirming findings in vitro and in animal models, with a large amount being able to reach the gut although conflicting reports exist. Their metabolism seems to depend on the native compounds and their structures, the food matrix and the individual ingesting the anthocyanins.

Once in the gut, they can be catabolized by specific genera producing enzymes necessary to the reactions. Most of the studies regarding the metabolism of anthocyanins by the gut microbiota have been conducted in vitro , as the environment and parameters in vivo studies are complicated to control and lead to several confounding factors that could influence the observations.

In Chilean currants previously digested in the gastric compartment, the remaining total flavonoids decreased again in the small intestine. The slight increase in the content of phenolic acids could be due to isomerization reactions among hydroxycinnamic acids under the intestinal conditions.

Van de Velde et al. However, consistent amount of free ellagic acid were recovered in the intestinal tract, suggesting the breakdown of ellagitannins into free ellagic acids in this compartment. The fermentation of ellagitannins by the gut microbiota showed no recovery of lambertianin A and C, indicating the hydrolysis of these compounds in this compartment as well.

Free ellagic acids were not found after the fermentation either, suggesting further metabolization of ellagic acid into urolithin derivatives. The results of an in vitro colonic fermentation with human microbiota of proanthocyanidin from cranberry, but without previous digestion, suggested a metabolization of the proanthocyanidins A found in the fresh cranberry into phenolic acids.

However, a decreased access by the microbiota when the molecules had a higher degree of polymerization was reported. After fermentation, only a few parent compounds were recovered, but most of the molecules were metabolites, derivatives of benzoic, phenylacetic and phenylpropionic acids.

In vitro studies on the digestion of phenolic compounds from berries suggest poor degradation of complex molecules in the stomach.

The availability of these compounds remains low in the intestine; however, they are intensively metabolized by the gut microbiota in vitro. The profile of recovered phenolic acids differ among the berries ingested, due to their initial profile in polyphenols.

Cranberry and blueberry, initially rich in proanthocyanidins, mainly led to the formation of 4-hydroxycinnamic acid for the former and chlorogenic, ferulic and 3,4-dihydroxycinnamic acids for the latter.

Black raspberry, which contains primarily anthocyanins in the form of cyanidins in the fresh fruits, led to the formation of 3-hydroxyphenylpropionic, 3-hydroxybenzoic and 3-hydroxycinnamic acids.

The proanthocyanidins from grape pomace has been recovered in the plasma of rats after 4 hours feeding. Catechin, epicatechin, dimer and trimer were identified, as well as their metabolites, catechin and epicatechin glucuronide, methyl catechin and epicatechin glucuronide and methyl catechin and epicatechin sulphate.

Proanthocyanidins, and more specifically catechin and epicatechin metabolites also include valerolactone derivatives. The study of raspberry ellagitannins fate in the gastrointestinal tract of rats showed that from the two molecules initially present in the fruit juice, lambertianin C and sanguiin H-6, they were not recovered in the entire gastrointestinal tract nor the plasma, urine or feces an hour after ingestion.

The acidic conditions of the pH are probably responsible for the rapid breakdown of these molecules. Ellagic acid were recovered in the stomach 9. Black raspberries, a berry rich in ellagitannins, were fed to mice in order to study the colonic metabolites produced after the berries consumption, as well as the impact of the phytochemicals on the microbial populations.

Ellagitannins metabolites were found in the mice plasma, liver, prostate and colon under the form of urolithin A dominantly , and C, produced by the mice microbiota.

Protocatechuic acid was also recovered in the plasma and indicated as an anthocyanins metabolite. Quercetin from berries have been shown to be bioavailable. After the ingestion of black currant juice, quercetin in plasma was higher than in the control group.

Some of the phenolics even had two absorption peaks, suggesting a reabsorption of the compounds excreted in the bile, or the metabolism of high weight molecules not absorbed in the stomach by the gut microbiota. The role of the large intestine in the metabolism of ellagitannins has been investigated by comparing ileostomists and volunteers with an intact gut.

From the three ellagitannins found in the raspberry sanguiin H-6, sanguiin H and lambertianin C , only sanguiin H-6 was recovered in ileal fluid, representing a fourth of the initial intake. They may originate from the breakdown of ellagitannins. In the urine samples, trace of ellagic acids were found while urolithins were recovered in the urine of healthy subjects.

Ellagic acids are an intermediate to the production of urolithin. The recovery of urolithin seems to depend on the gut microbiota composition as the recovery in urine between subjects varied from 0.

In all human studies, large inter-individual variabilities have been reported, implying the individual's ability to generate specific metabolites. In addition to difference in gender and genetic polymorphism of transporters or metabolizing enzymes, the influence of the gut microbiota composition is becoming evident.

Due to the complexity of the berry matrices as well as the gut microbiota, studies on the role played by specific microorganisms in the metabolism of berry polyphenols are scarce.

The modulation of the gut microbiota at the genus level has also been observed. The antimicrobial effect of cranberry extracts was assessed using fermentation batch culture incubated with human colonic bacteria, but without previous digestion of the berry extracts. Observation with qPCR shows antimicrobial effects towards Bacteroides , Prevotella and Blautia coccoides-Eubacterium rectale populations.

In animal models, blackcurrant extracts have been found to reduce the population of Bacteroides , and the addition of blackcurrant and black raspberry extracts decreased Clostridium spp. in murine models, 88, therefore suggesting that berry compounds can exert antimicrobial effects in vivo as well.

The consumption of honeyberry extracts by mouse fed with high-fat diet reduced the Ruminococcus and Oscillospira populations, and the addition of blackberry extracts impacted the gut microbiota of diet-induced obese rats by increasing Oscillobacter and Sporobacter and decreasing Rumminococcus.

This study also showed a positive association between Musispirillum and the number of plaques. Thus, lingonberry may be beneficial towards vascular conditions.

In human, the consumption of blackcurrant products led to a decrease in Clostridium spp. and Bacteroides. Animal studies have also focused on the effects of berry polyphenols when the gut microbiota is disturbed by a high fat diet or health concerns such as obesity, gut inflammation or other chronic diseases.

These conditions generally lead to a dysbiosis unbalanced gut microbiota. In the following studies, berry extracts were used to evaluate their potential effect in restoring a balanced gut microbiota.

In mice fed with a high-fat diet, the addition of honey berry Lonicera cerula L. led to a decrease in Lactobacillus population. was also decreased by the consumption of blueberries, while no effect as reported on Bifidobacterium.

These bacteria show protective effects against IBD. Supplementation with strawberry helped increase this genus in the diabetic animals. Black raspberry extracts in the diet of rats increased the relative abundance of Akkermensia and butyrate producing bacteria.

Akkermansia have been associated with a generally healthy gut, being found in lower amount in patients with inflammatory bowel diseases and metabolic disorders. This initiates competition for resources rapidly, thus influencing the ecology of the gut.

In conclusion, berry constituents can reach the gut and modulate the microbiota by decreasing the growth of some genera and increasing the populations of others. In a healthy gut, these effects were mainly beneficial.

In challenged microbiota due to health conditions, the supplement with berries or their compounds often resulted in an improvement in terms of the gut composition.

Direct associations between the consumption of berries and the regulation of the gut microbiota are hard to draw due to scarce knowledge on the role of specific genus in health or disease, the interindividual differences between subjects in term of microbiota composition, the diversity of compounds from which the effect could originate and the diversity of methods used in the studies plate count, fingerprinting or sequencing methods.

Black raspberry showed positive effects on induced-colitis in murine models, by suppressing levels of key pro-inflammatory cytokines, and particularly NF-κB. A proposed mechanism is that black raspberry compounds prevent the phosphorylation of Iκβα in the colon, thus resulting in the inhibition of NF-κB and its target genes playing a role in inflammation COX-2, TNF and IL-1b.

After treatment with black raspberry and the decrease in NF-κB expression, the promoter methylation in the Wnt pathway decreased as well, therefore prohibiting its activation.

The ingestion of cranberry also had beneficial effects on MPO activity and production of proinflammatory cytokines, however the results were only significant for the cranberry product containing fibers and not the cranberry polyphenols extracts.

Both products decreased the disease activity index. The authors hypothesized a regulatory effect of the fermented products from the gut microbiota to contribute to the positive effects of cranberry on ulcerative colitis.

Bilberries and anthoycanins also significantly reduced the apoptosis of epithelial cells. In conclusion, ingestion of berries seems to ameliorate the symptoms of colitis in colitis-induced murine models. The main reported effect was the downregulation of proinflammatory cytokines through the inhibition of NF-κB expression.

Bilberry was efficient in improving the conditions of patients with ulcerative colitis, however the disease activity increased again after the end of the treatment.

The active compound and the mechanisms behind these potential effects remain to be elucidated, but the induction of apoptosis in the cancer cells has been reported. Different blueberry extracts tested against HT and Caco-2 cancer cell lines showed that the anthocyanin fractions had the most important antiproliferative effect, while the phenolic acids fraction had little effect.

The anthocyanins fraction also induced cancer cells apoptosis. These observations suggest an association between inflammation, induced by COX-2, and cancer. Of all the berries tested in this study, all showed some pro-apoptotic effects on the HT cells, except cranberry extracts.

More recent studies have looked at the effect of berry extracts on colon cancer lines following the in vitro digestion and fermentation of these extracts. The compounds from raspberries, strawberries and blackcurrants were broken down into metabolites during in vitro digestion and fermentation, but their products retained anti-genotoxic, anti-mutagenic and anti-invasive activities on colon cells.

However, they had an anti-migration effect on the cells tested. Black raspberries show promising action against colon cancer in patients, through modulation of apoptosis, proliferation and angiogenesis in cancerous cells.

However, not all patients responded to the treatments. Similar effects in other berries remain to be studied. View PDF Version Previous Article Next Article. DOI: Received 23rd July , Accepted 12th November Abstract Berries are rich in phenolic compounds such as phenolic acids, flavonols and anthocyanins.

Selma, J. Espín and F. Tomás-Barberán, J. Food Chem. Copyright American Chemical Society. Table 1 Phenolic acid metabolites from the colonic degradation of polyphenols after the consumption of berries. Polyphenol class Berry used in study Type of study Possible gut microbial metabolites Potential microorganisms involved Ref.

In vitro studies. One of the most reported polyphenolic compounds in berries are anthocyanins and their bioavailability in the gastrointestinal tract under in vitro experiments have been studied, using simulated gastrointestinal digestion conditions, and, in some studies, a colonic fermentation model.

In these conditions, the total anthocyanins of chokeberry, mulberry and blueberry remained stable, with no major qualitative nor quantitative changes in their profiles.

Berries anthocyanins appear to be stable and resistant to gastric digestion under strong acidic conditions, but an increase in pH favors the degradation of these compounds in the stomach in vitro.

Animal studies.