The gut microbiota plays a crucial role in the conversion of dietary flavonoids and thereby affects their health-promoting effects in the human host. The identification of the bacteria involved in intestinal flavonoid conversion has gained increasing interest. This review summarizes available information on the so far identified human intestinal flavonoid-converting bacterial species and strains as well as their enzymes catalyzing the underlying reactions. The majority of described species involved in flavonoid transformation are capable of carrying out the O-deglycosylation of flavonoids. Other bacteria cleave the less common flavonoid-C-glucosides and/or further degrade the aglycones of flavonols, flavanonols, flavones, flavanones, dihydrochalcones, isoflavones and monomeric flavan-3-ols. To increase the currently limited knowledge in this field, identification of flavonoid-converting bacteria should be continued using culture-dependent screening or isolation procedures and molecular approaches based on sequence information of the involved enzymes.

An anaerobic, quercetin-degrading bacterium was isolated from human feces and identified as Clostridium orbiscindens by comparative 16S rRNA gene sequence analysis. The organism was tested for its ability to transform several flavonoids. The isolated C. orbiscindens strain converted quercetin and taxifolin to 3,4-dihydroxyphenylacetic acid; luteolin and eriodictyol to 3-(3,4-dihydroxyphenyl)propionic acid; and apigenin, naringenin, and phloretin to 3-(4-hydroxyphenyl)propionic acid, respectively. Genistein and daidzein were not utilized. The glycosidic bonds of luteolin-3-glucoside, luteolin-5-glucoside, naringenin-7-neohesperidoside (naringin), quercetin-3-glucoside, quercetin-3-rutinoside (rutin), and phloretin-2-glucoside were not cleaved. Based on the intermediates and products detected, pathways for the degradation of the flavonol quercetin and the flavones apigenin and luteolin are proposed. To investigate the numerical importance of C. orbiscindens in the human intestinal tract, a species-specific oligonucleotide probe was designed and tested for its specificity. Application of the probe to fecal samples from 10 human subjects proved the presence of C. orbiscindens in 8 out of the 10 samples tested. The numbers ranged from 1.87 ؋ 10 8 to 2.50 ؋ 10 9 cells g of fecal dry mass ؊1 , corresponding to a mean count of 4.40 ؋ 10 8 cells g of dry feces ؊1 .Flavonoids are widely distributed in plants and are ingested in considerable amounts with food. More than 5,000 different naturally occurring flavonoids have been described so far. They have been proposed to have beneficial effects on human health based on their anti-inflammatory, antioxidant, vasodilatory, anticancerigenic, and antibacterial properties (for reviews, see references 3, 12, and 21). Although it is known that human intestinal bacteria play a significant role in the degradation of flavonoids (22), there is a paucity of information on the species involved, their distribution in humans, and the mechanisms of degradation. So far, Clostridium scindens (30), Clostridium orbiscindens (30, 31), Eubacterium desmolans (30), and Eubacterium ramulus (24), all isolated from human fecal samples, are known to convert flavonoids. However, only E. ramulus (24) was further characterized with respect to its potential to degrade flavonoids, the pathways of conversion of flavonoids, and the organism's distribution in humans.In this study, quercetin-degrading fecal isolates were identified as C. orbiscindens, whose ability to degrade flavonoids was first described by Winter et al. (30,31) but not analyzed in detail. Therefore, the C. orbiscindens strains isolated were tested for their range of flavonoids converted and the degradation pathways that were employed. Population levels of C. orbiscindens in 10 human subjects were determined. MATERIALS AND METHODSMedia and growth conditions. For cultivation of C. orbiscindens strains I1 to I6, which were isolated in our study, the anoxic techniques of Hungate (14) and Bryant (7) were applied. Cultures were grown under strictl...

The degradation of the flavonol quercetin and the flavone luteolin by Eubacterium ramulus, a strict anaerobe of the human intestinal tract, was studied. Resting cells converted these flavonoids to 3,4-dihydroxyphenylacetic acid and 3-(3,4-dihydroxyphenyl)propionic acid, respectively. The conversion of quercetin was accompanied by the transient formation of two intermediates, one of which was identified as taxifolin based on its specific retention time and UV and mass spectra. The structure of the second intermediate, alphitonin, was additionally elucidated by 1 H and 13 C nuclear magnetic resonance analysis. In resting-cell experiments, taxifolin in turn was converted via alphitonin to 3,4-dihydroxyphenylacetic acid. Alphitonin, which was prepared by enzymatic conversion of taxifolin and subsequent purification, was also transformed to 3,4-dihydroxyphenylacetic acid. The coenzyme-independent isomerization of taxifolin to alphitonin was catalyzed by cell extract or a partially purified enzyme preparation of E. ramulus. The degradation of luteolin by resting cells of E. ramulus resulted in the formation of the intermediate eriodictyol, which was identified by high-performance liquid chromatography and mass spectrometry analysis. The observed intermediates of quercetin and luteolin conversion suggest that the degradation pathways in E. ramulus start with an analogous reduction step followed by different enzymatic reactions depending on the additional 3-hydroxyl group present in the flavonol structure.Flavonoids are polyphenolic compounds which are present in foods and beverages of plant origin. The daily intake of flavonoids calculated on the basis of the aglycones was estimated to range from approximately 3 to 70 mg in different countries, and it may well exceed these values in regions with a very high intake of tea and vegetables (5, 10, 13). In vivo data on absorption and metabolism after oral intake are contradictory. However, a major part of ingested flavonoids are not absorbed and are largely degraded by the intestinal microflora.It was shown in vitro that flavonoids are potent antioxidants and inhibitors of ubiquitous enzymes, and their anticarcinogenic properties were demonstrated with different cell lines (for a review, see reference 8). Due to these properties, flavonoids are reported to protect against cancer, coronary heart disease, and stroke. In order to judge the potential beneficial health effects of flavonoids in humans, studies on their fate in the gastrointestinal tract, including transformation by bacteria, are necessary. Intestinal bacteria play important roles not only in deconjugation of flavonoids but also in their further degradation. The bacterial metabolites, which possibly exert biological activities different from those of the original flavonoids, may be absorbed and further metabolized in the human body. Therefore, it is essential to study their conversion by intestinal bacteria and to identify and characterize the fermentation products formed. Although some flavonoid-degrading species...

Aims:  To isolate and characterize bacteria from the human intestine that are involved in the conversion of catechins, a class of bioactive polyphenols abundant in the human diet. Methods and Results:  Two bacterial strains, rK3 and aK2, were isolated from an epicatechin‐converting human faecal suspension. The isolates catalysed individual steps in the degradation of (−)‐epicatechin and (+)‐catechin. Based on their phenotypic characteristics and 16S rRNA gene sequences, the isolates were identified as Eggerthella lenta and Flavonifractor plautii (formerly Clostridium orbiscindens). Eggerthella lenta rK3 reductively cleaved the heterocyclic C‐ring of both (−)‐epicatechin and (+)‐catechin giving rise to 1‐(3,4‐dihydroxyphenyl)‐3‐(2,4,6‐trihydroxyphenyl)propan‐2‐ol. The conversion of catechin proceeded five times faster than that of epicatechin. Higher (epi)catechin concentrations led to an accelerated formation of the ring fission product without affecting the growth of Eg. lenta rK3. Flavonifractor plautii aK2 further converted 1‐(3,4‐dihydroxyphenyl)‐3‐(2,4,6‐trihydroxyphenyl)propan‐2‐ol to 5‐(3,4‐dihydroxyphenyl)‐γ‐valerolactone and 4‐hydroxy‐5‐(3,4‐dihydroxyphenyl)valeric acid. Flavonifractor plautii DSM 6740 catalysed the identical reaction indicating it is not strain specific. Conclusions:  The conversion of dietary catechins by the isolated Eg. lenta and F. plautii strains in the human intestine may affect their bioavailability. Significance and Impact of the Study:  The majority of catechin metabolites are generated by the intestinal microbiota. The identification of catechin‐converting gut bacteria therefore contributes to the elucidation of the bioactivation and the health effects of catechins.

Flavonoids may play an important role for adjunct nutritional therapy of chronic intestinal inflammation. In this study, we characterized the molecular mechanisms by which quercetin and its enteric bacterial metabolites, taxifolin, alphitonin, and 3, 4-dihydroxy-phenylacetic acid, inhibit tumor necrosis factor alpha (TNF)-induced proinflammatory gene expression in the murine small intestinal epithelial cell (IEC) line Mode-K as well as in heterozygous TNFDeltaARE/WT mice, a murine model of experimental ileitis. Quercetin inhibited TNF-induced interferon-gamma-inducible protein 10 (IP-10) and macrophage inflammatory protein 2 (MIP-2) gene expression in Mode-K cells with effective inhibitory concentration of 40 and 44 micromol/L, respectively. Interestingly, taxifolin, alphitonin, and 3,4-dihydroxy-phenylacetic acid did not inhibit TNF responses in IEC, suggesting that microbial transformation of quercetin completely abolished its anti-inflammatory effect. At the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit TNF-induced RelA/I-kappaB phosphorylation and IkappaB degradation or TNF-alpha-induced nuclear factor-kappaB transcriptional activity. Most important for understanding the mechanism involved, chromatin immunoprecipitation analysis revealed inhibitory effects of quercetin on phospho-RelA recruitment to the IP-10 and MIP-2 gene promoters. In addition, and consistent with the lack of cAMP response element binding protein (CBP)/p300 recruitment and phosphorylation/acetylation of histone 3 at the promoter binding site, quercetin inhibited histone acetyl transferase activity. The oral application of quercetin to heterozygous TNFDeltaARE/WT mice [10 mg/(d x kg body wt)] significantly inhibited IP-10 and MIP-2 gene expression in primary ileal epithelial cells but did not affect tissue pathology. These studies support an anti-inflammatory effect of quercetin in epithelial cells through mechanisms that inhibit cofactor recruitment at the chromatin of proinflammatory genes.