Intestinal Microbial Metabolites Research Articles

Endothelial NLRP3 Inflammasome Activation and Neointima Formation in Mice by Gut Microbial Metabolite Trimethylamine‐N‐Oxide

Recent studies have demonstrated that trimethylamine‐N‐oxide (TMAO), an intestinal microbial metabolite induces atherosclerosis and enhances the risk for cardiovascular disorders. However, the precise mechanisms of action of TMAO in cardiovascular pathophysiology are yet to be elucidated. In the current study, we examined whether TMAO induces inflammasome activation and thereby contributing to endothelial dysfunction and vascular injury. Confocal microscopic analysis demonstrated the formation of Nlrp3 inflammasomes in the intima of the carotid arteries of Nlrp3+/+ mice but not in Nlrp3−/− mice. Correspondingly, TMAO‐induced increases in IL‐1β production in the carotid intima were abolished in Nlrp3−/− mice. The endothelial tight junction protein, ZO‐1 was reduced by TMAO in Nlrp3+/+ mice, but not in Nlrp3−/− mice. It was also found that TMAO significantly increased neointimal formation in partially ligated carotid arteries of Nlrp3+/+ mice, but not in Nlrp3−/− mice. In in vitro studies, we also found that TMAO treatment significantly increased the colocalization of NLRP3 with Asc or NLRP3 with caspase‐1 in endothelial cells compared to control cells. Pretreatment with Nlrp3 siRNA transfection abolished the TMAO‐induced inflammasome formation in these cells. Correspondingly, TMAO treatment significantly increased the caspase‐1 activity (2.2 folds) and IL‐1β production (1.8 folds) compared to control cells but not in Nlrp3 siRNA transfected cells. Furthermore, western blot analysis showed that TMAO treatment significantly decreased tight junction protein ZO‐1 level compared to control cells. In addition, TMAO treatment significantly increased the cell permeability of EOMA cell layers compared to control cells (Control: 1 ± 0.1 vs TMAO: 2 ± 0.07). Prior treatment with Nlrp3 siRNA attenuated the TMAO‐induced cell permeability. Together, these results suggest that TMAO‐induced formation and activation of NLRP3 inflammasomes in vascular endothelium thereby leading to endothelial dysfunction and atherosclerosis in mice.Support or Funding InformationDK104031

Inflammatory Bowel Disease: Effects on Bone and Mechanisms.

Inflammatory bowel disease (IBD) is associated with decreased bone mass and alterations in bone geometry from the time of diagnosis, before anti-inflammatory therapy is instituted. Deficits in bone mass can persist despite absence of symptoms of active IBD. The effects of IBD on the skeleton are complex. Protein-calorie malnutrition, inactivity, hypogonadism, deficits in calcium intake and vitamin D consumption and synthesis, stunted growth in children, decreased skeletal muscle mass, and inflammation all likely play a role. Preliminary studies suggest that the dysbiotic intestinal microbial flora present in IBD may also affect bone at a distance. Several mechanisms are possible. T cells activated by the gut microbiota may serve as "inflammatory shuttles" between the intestine and bone. Microbe-associated molecular patterns leaked into the circulation in IBD may activate immune responses in the bone marrow by immune cells and by osteocytes, osteoblasts, and osteoclasts that lead to decreased bone formation and increased resorption. Finally, intestinal microbial metabolites such as H2S may also affect bone cell function. Uncovering these mechanisms will enable the design of microbial cocktails to help restore bone mass in patients with IBD.

New insights into the role of the porcine intestinal yeast, Kazachstania slooffiae, in intestinal environment of weaned piglets.

Kazachstania slooffiae is a porcine intestinal yeast whose role in the intestinal environment is largely unexplored. Therefore, the impact of K. slooffiae on growth performance, intestinal microbial metabolites and the microbiota of weaned piglets was investigated in this study. Forty-eight German Landrace pigs were weaned at day 27 or 28 of life and grouped into one control and three treatment groups. During the 5-week experiment, piglets had ad libitum access to feed and water. On days 5, 6 and 7 post weaning, pigs were orally supplemented with either placebo or K.slooffiae cells once a day. Faecal samples collected on days 5-8, 14, 21 and 28 post weaning were used for microbiological and chemical analyses. Between groups, there were no significant differences in the incidence of diarrhoea, pH and growth performance. Total yeasts and K.slooffiae correlated positively with total short-chain fatty acids, acetic, propionic, n-butyric, i-valeric and valeric acids, and negatively with pH. Pyrosequencing of the bacterial intestinal community revealed that K.slooffiae significantly affected the composition of the microbiota. The results of this study suggest that K. slooffiae may play an important role in the porcine digestive system, especially in the critical weaning period.

The Liver at the Nexus of Host-Microbial Interactions.

The liver receives blood from the intestine, from the spleen, and directly from the heart and holds a vital position in vertebrate physiology. It plays a role in intermediary metabolism, bile secretion, maintaining blood sterility, serum homeostasis, xenobiotic detoxification, and immunological activity. This article provides our perspective on the liver as a nexus in establishing and maintaining host microbial mutualism. We discuss the role of the liver not only in sanitizing the blood stream from penetrant live microbes, but also in metabolizing xenobiotics that are synthesized or modified by intestinal microbes, and how microbiota modify the signaling potential of bile acids. The combination of bile acids as hormones and the metabolic control from pervasive effects of other absorbed microbial molecules powerfully shape hepatic metabolism. In addition, intestinal microbial metabolites can be sensed by liver-resident immune cells, which may disturb liver homeostasis, leading to fibrosis and liver cancer.

0952 Intestinal microbiota, microbial metabolites and carcass traits are changed in a pig model fed a high-fat/low-fiber or a low-fat/high-fiber diet

0952 Intestinal microbiota, microbial metabolites and carcass traits are changed in a pig model fed a high-fat/low-fiber or a low-fat/high-fiber diet

Intestinal Microbial Metabolites Are Linked to Severity of Myocardial Infarction in Rats.

Intestinal microbiota determine severity of myocardial infarction in rats. We determined whether low molecular weight metabolites derived from intestinal microbiota and transported to the systemic circulation are linked to severity of myocardial infarction. Plasma from rats treated for seven days with the non-absorbed antibiotic vancomycin or a mixture of streptomycin, neomycin, polymyxin B and bacitracin was analyzed using mass spectrometry-based metabolite profiling platforms. Antibiotic-induced changes in the abundance of individual groups of intestinal microbiota dramatically altered the host’s metabolism. Hierarchical clustering of dissimilarities separated the levels of 284 identified metabolites from treated vs. untreated rats; 193 were altered by the antibiotic treatments with a tendency towards decreased metabolite levels. Catabolism of the aromatic amino acids phenylalanine, tryptophan and tyrosine was the most affected pathway comprising 33 affected metabolites. Both antibiotic treatments decreased the severity of an induced myocardial infarction in vivo by 27% and 29%, respectively. We then determined whether microbial metabolites of the amino acids phenylalanine, tryptophan and tyrosine were linked to decreased severity of myocardial infarction. Vancomycin-treated rats were administered amino acid metabolites prior to ischemia/reperfusion studies. Oral or intravenous pretreatment of rats with these amino acid metabolites abolished the decrease in infarct size conferred by vancomycin. Inhibition of JAK-2 (AG-490, 10 μM), Src kinase (PP1, 20 μM), Akt/PI3 kinase (Wortmannin, 100 nM), p44/42 MAPK (PD98059, 10 μM), p38 MAPK (SB203580, 10 μM), or KATP channels (glibenclamide, 3 μM) abolished cardioprotection by vancomycin, indicating microbial metabolites are interacting with cell surface receptors to transduce their signals through Src kinase, cell survival pathways and KATP channels. These inhibitors have no effect on myocardial infarct size in untreated rats. This study links gut microbiota metabolites to severity of myocardial infarction and may provide future opportunities for novel diagnostic tests and interventions for the prevention of cardiovascular disease.

Impact of Prematurity and Perinatal Antibiotics on the Developing Intestinal Microbiota: A Functional Inference Study.

Background: The microbial colonization of the neonatal gut provides a critical stimulus for normal maturation and development. This process of early microbiota establishment, known to be affected by several factors, constitutes an important determinant for later health. Methods: We studied the establishment of the microbiota in preterm and full-term infants and the impact of perinatal antibiotics upon this process in premature babies. To this end, 16S rRNA gene sequence-based microbiota assessment was performed at phylum level and functional inference analyses were conducted. Moreover, the levels of the main intestinal microbial metabolites, the short-chain fatty acids (SCFA) acetate, propionate and butyrate, were measured by Gas-Chromatography Flame ionization/Mass spectrometry detection. Results: Prematurity affects microbiota composition at phylum level, leading to increases of Proteobacteria and reduction of other intestinal microorganisms. Perinatal antibiotic use further affected the microbiota of the preterm infant. These changes involved a concomitant alteration in the levels of intestinal SCFA. Moreover, functional inference analyses allowed for identifying metabolic pathways potentially affected by prematurity and perinatal antibiotics use. Conclusion: A deficiency or delay in the establishment of normal microbiota function seems to be present in preterm infants. Perinatal antibiotic use, such as intrapartum prophylaxis, affected the early life microbiota establishment in preterm newborns, which may have consequences for later health.

Intestinal Microbiota and Microbial Metabolites Are Changed in a Pig Model Fed a High-Fat/Low-Fiber or a Low-Fat/High-Fiber Diet.

The intestinal microbiota and its metabolites appear to be an important factor for gastrointestinal function and health. However, research is still needed to further elaborate potential relationships between nutrition, gut microbiota and host’s health by means of a suitable animal model. The present study examined the effect of two different diets on microbial composition and activity by using the pig as a model for humans. Eight pigs were equally allotted to two treatments, either fed a low-fat/high-fiber (LF), or a high-fat/low-fiber (HF) diet for 7 weeks. Feces were sampled at day 7 of every experimental week. Diet effects on fecal microbiota were assessed using quantitative real-time PCR, DNA fingerprinting and metaproteomics. Furthermore, fecal short-chain fatty acid (SCFA) profiles and ammonia concentrations were determined. Gene copy numbers of lactobacilli, bifidobacteria (P<0.001) and Faecalibacterium prausnitzii (P<0.05) were higher in the LF pigs, while Enterobacteriaceae were more abundant in the HF pigs (P<0.001). Higher numbers of proteins affiliated to Enterobacteriaceae were also present in the HF samples. Proteins for polysaccharide breakdown did almost exclusively originate from Prevotellaceae. Total and individual fecal SCFA concentrations were higher for pigs of the LF treatment (P<0.05), whereas fecal ammonia concentrations did not differ between treatments (P>0.05). Results provide evidence that beginning from the start of the experiment, the LF diet stimulated beneficial bacteria and SCFA production, especially butyrate (P<0.05), while the HF diet fostered those bacterial groups which have been associated with a negative impact on health conditions. These findings correspond to results in humans and might strengthen the hypothesis that the response of the porcine gut microbiota to a specific dietary modulation is in support of using the pig as suitable animal model for humans to assess diet-gut-microbiota interactions.Data are available via ProteomeXchange with identifier PXD003447.

A Prospective Investigation of the Association Between Urinary Excretion of Dietary Lignan Metabolites and Weight Change in US Women.

Results from animal studies have consistently suggested that lignans play a role in the regulation of in body weight, but evidence from human studies has been limited. We examined the associations between urinary excretion of enterolactone and enterodiol, the major intestinal microbial metabolites of dietary lignans, and 10-year prospective weight change using data from 2 well-characterized cohort studies of US women: the Nurses' Health Study (2000-2010) and Nurses' Health Study II (1997-2007). Urinary excretion levels of enterolactone and enterodiol were measured at baseline. Associations with prospective weight change were analyzed using a multivariable-adjusted linear mixed-effects model. We observed that women in the highest quartile of urinary excretion of total lignans had significantly lower baseline body mass indices (weight in kilograms divided by height in meters squared) (mean, 24.6, 95% confidence interval (CI): 23.9, 25.2) than did those in the lowest quartile (mean, 27.7, 95% CI: 27.0, 28.4; P for trend < 0.01). Compared with women in the lowest quartile of enterodiol excretion, those in the highest quartile gained 0.27 kg/year less weight (95% CI: 0.12, 0.41; P for trend < 0.01) during the 10-year follow-up. The association was borderline significant for enterolactone (for the fourth vs. first quartile, least square mean of weight change rate = -0.14 kg/year, 95% CI: -0.29, 0.00). Our data suggest that higher urinary excretion of lignan metabolites, especially enterodiol, is associated with modestly slower weight gain.

A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat

BackgroundDietary intakes of red meat and fat are established risk factors for both colorectal cancer (CRC) and cardiovascular disease (CVDs). Recent studies have shown a mechanistic link between TMAO, an intestinal microbial metabolite of red meat and fat, and risk of CVDs. Data linking TMAO directly to CRC is, however, lacking. Here, we present an unbiased data-driven network-based systems approach to uncover a potential genetic relationship between TMAO and CRC.Materials and methodsWe constructed two different epigenetic interaction networks (EINs) using chemical-gene, disease-gene and protein-protein interaction data from multiple large-scale data resources. We developed a network-based ranking algorithm to ascertain TMAO-related diseases from EINs. We systematically analyzed disease categories among TMAO-related diseases at different ranking cutoffs. We then determined which genetic pathways were associated with both TMAO and CRC.ResultsWe show that CVDs and their major risk factors were ranked highly among TMAO-related diseases, confirming the newly discovered mechanistic link between CVDs and TMAO, and thus validating our algorithms. CRC was ranked highly among TMAO-related disease retrieved from both EINs (top 0.02%, #1 out of 4,372 diseases retrieved based on Mendelian genetics and top 10.9% among 882 diseases based on genome-wide association genetics), providing strong supporting evidence for our hypothesis that TMAO is genetically related to CRC. We have also identified putative genetic pathways that may link TMAO to CRC, which warrants further investigation. Through systematic disease enrichment analysis, we also demonstrated that TMAO is related to metabolic syndromes and cancers in general.ConclusionsOur genome-wide analysis demonstrates that systems approaches to studying the epigenetic interactions among diet, microbiome metabolisms, and disease genetics hold promise for understanding disease pathogenesis. Our results show that TMAO is genetically associated with CRC. This study suggests that TMAO may be an important intermediate marker linking dietary meat and fat and gut microbiota metabolism to risk of CRC, underscoring opportunities for the development of new gut microbiome-dependent diagnostic tests and therapeutics for CRC.

Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4

Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "leaky" gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2(-/-)Tlr4(-/-) mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.

Gut Microbiota Metabolites of Dietary Lignans and Risk of Type 2 Diabetes: A Prospective Investigation in Two Cohorts of U.S. Women

OBJECTIVETo examine urinary levels of enterolactone and enterodiol, intestinal microbial metabolites of dietary lignans, in relation to type 2 diabetes (T2D) risk.RESEARCH DESIGN AND METHODSUrinary concentrations of the lignan metabolites were assayed by liquid chromatography-mass spectrometry among 1,107 T2D and 1,107 control subjects in a nested case-control study conducted in participants from the Nurses’ Health Study (NHS) and NHSII. Subjects were free of diabetes, cardiovascular disease, and cancer at urine sample collection in 1995–2001. Incident self-reported T2D cases identified through 2008 were confirmed with a validated questionnaire.RESULTSIn both cohorts, T2D subjects had significantly lower concentrations of both enterolactone and enterodiol than control subjects. After multivariate adjustment for lifestyle and dietary risk factors of T2D, urinary concentrations of enterolactone were significantly associated with a lower risk of T2D (pooled odds ratio [OR] comparing the extreme quartiles 0.62 [95% CI 0.44, 0.88], P for trend = 0.003). Higher urinary concentrations of enterodiol were also marginally significantly associated with a lower T2D risk (pooled OR comparing extreme quartiles 0.67 [95% CI 0.48, 0.96], P for trend = 0.08). When concentrations of both metabolites were combined to reflect total lignan intake, the OR was 0.70 (95% CI 0.53, 0.92) for each SD increment of total lignan metabolites.CONCLUSIONSThese results indicate that lignan metabolites, especially enterolactone, are associated with a lower risk of T2D in U.S. women. Further studies are needed to replicate these findings and to explore potential mechanisms underlying the observed association.

ChemInform Abstract: Cu(I)‐Mediated Lactone Formation in Subcritical Water: A Benign Synthesis of Benzopyranones and Urolithins A—C.

Benzopyranones were successfully synthesized using Cu(I)-mediated C–O bond formation in subcritical water. A number of benzopyranone derivatives including polymethoxy benzopyranones, benzopyranopyridones, chromenoindolones, and furochromenones were synthesized in satisfactory yield. This methodology was further applied to synthesize the intestinal microbial metabolites, urolithins A, B, and C, which were found to exhibit potent antioxidant activity.

Cu(I)-mediated lactone formation in subcritical water: a benign synthesis of benzopyranones and urolithins A–C

Benzopyranones were successfully synthesized using Cu(I)-mediated C–O bond formation in subcritical water. A number of benzopyranone derivatives including polymethoxy benzopyranones, benzopyranopyridones, chromenoindolones, and furochromenones were synthesized in satisfactory yield. This methodology was further applied to synthesize the intestinal microbial metabolites, urolithins A, B, and C, which were found to exhibit potent antioxidant activity.

Differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior

Feather pecking in laying hens is a serious behavioral problem and is often associated with feather eating. There is some evidence that ingested feathers affect gut function. The aim of the present study was to explore whether differences in intestinal microbial metabolites in laying hens with high and low levels of repetitive feather-pecking behavior exist. Sixty high feather-pecking birds (H) and sixty low feather-pecking birds (L) of the White Leghorn breed were used for behavioral recordings of feather pecking. Feather pecking activity was observed for 5weeks, after which 22 H birds with the highest and 22 L birds with the lowest feather pecking activity were chosen. The number of whole feathers and feather parts in the gizzard and intestinal microbial metabolites in the ileum and ceca of these laying hens was examined. Biogenic amines, short-chain fatty acids, ammonia and lactate were measured as microbial metabolites. A higher number of feather parts and particles were found in H than in L birds. Putrescine and cadaverine concentrations were higher in the ileum of the hens with low pecking activity (P<0.001 and P=0.012). In the cecum the amounts of l-lactate, d-lactate and total lactate and SCFA were higher in H birds (P=0.007, P=0.005, P=0.006, and P<0.001). Acetate, i-butyrate, i-valeriate and n-valeriate all displayed significantly higher molar ratios in the cecal contents of L birds (P=0.001, P=0.003, P=0.001, and P<0.001). Propionate and n-butyrate showed higher molar ratios in H birds (P<0.001 and P=0.034). Ammonia was higher in the ileum and cecum of the L birds (P<0.001 and P=0.004). For the first time, this study shows that birds with high and low numbers of repetitive pecking movements to the plumage of other birds differ in their intestinal microbial metabolism. Further experiments should be conducted to investigate whether these differences alter behavior in H and L feather pecking birds. The present results, however, open new avenues of research into implications of gut bacteria, their metabolites and the polyamine system on brain and behavior in laying hens.

The interplay between fiber and the intestinal microbiome in the inflammatory response.

Fiber intake is critical for optimal health. This review covers the anti-inflammatory roles of fibers using results from human epidemiological observations, clinical trials, and animal studies. Fiber has body weight-related anti-inflammatory activity. With its lower energy density, a diet high in fiber has been linked to lower body weight, alleviating obesity-induced chronic inflammation evidenced by reduced amounts of inflammatory markers in human and animal studies. Body weight-unrelated anti-inflammatory activity of fiber has also been extensively studied in animal models in which the type and amount of fiber intake can be closely monitored. Fermentable fructose-, glucose-, and galactose-based fibers as well as mixed fibers have shown systemic and local intestinal anti-inflammatory activities when plasma inflammatory markers and tissue inflammation were examined. Similar anti-inflammatory activities have also been demonstrated in some human studies that controlled total fiber intake. The anti-inflammatory activities of synbiotics (probiotics plus fiber) were reviewed as well, but there was no convincing evidence indicating higher efficacy of synbiotics compared with that of fiber alone. Adverse effects have not been observed with the amount of fiber intake or supplementation used in studies, although patients with Crohn's disease may be more sensitive to inulin intake. Several possible mechanisms that may mediate the body weight-unrelated anti-inflammatory activity of fibers are discussed based on the in vitro and in vivo evidence. Fermentable fibers are known to affect the intestinal microbiome. The immunomodulatory role of the intestinal microbiome and/or microbial metabolites could contribute to the systemic and local anti-inflammatory activities of fibers.

Erratum to “Dietary inclusion of feathers affects intestinal microbiota and microbial metabolites in growing Leghorn-type chickens” (Poult. Sci. 91:1506–1513)

Erratum to “Dietary inclusion of feathers affects intestinal microbiota and microbial metabolites in growing Leghorn-type chickens” (Poult. Sci. 91:1506–1513)

Dietary inclusion of feathers affects intestinal microbiota and microbial metabolites in growing Leghorn-type chickens

Feather pecking in laying hens is a serious behavioral problem that is often associated with feather eating. The intake of feathers may influence the gut microbiota and its metabolism. The aim of this study was to determine the effect of 2 different diets, with or without 5% ground feathers, on the gut microbiota and the resulting microbial fermentation products and to identify keratin-degrading bacteria in chicken digesta. One-day-old Lohmann-Selected Leghorn chicks were divided into 3 feeding groups: group A (control), B (5% ground feathers in the diet), and C, in which the control diet was fed until wk 12 and then switched to the 5% feather diet to study the effect of time of first feather ingestion. The gut microbiota was analyzed by cultivation and denaturing gradient gel electrophoresis of ileum and cecum digesta. Short-chain fatty acids, ammonia, and lactate concentrations were measured as microbial metabolites. The concentration of keratinolytic bacteria increased after feather ingestion in the ileum (P < 0.001) and cecum (P = 0.033). Bacterial species that hydrolyzed keratin were identified as Enterococcus faecium, Lactobacillus crispatus, Lactobacillus reuteri-like species (97% sequence homology), and Lactobacillus salivarius-like species (97% sequence homology). Molecular analysis of cecal DNA extracts showed that the feather diet lowered the bacterial diversity indicated by a reduced richness (P < 0.001) and shannon (P = 0.012) index. The pattern of microbial metabolites indicated some changes, especially in the cecum. This study showed that feather intake induced an adaptation of the intestinal microbiota in chickens. It remains unclear to what extent the changed metabolism of the microbiota reflects the feather intake and could have an effect on the behavior of the hens.

Metabolites of the Ellagitannin Geraniin and Their Antioxidant Activities

Different types of ellagitannins are reported to have various biological activities, such as antioxidant, antiviral, and antitumor activities. However, there are few definitive studies on the absorption and metabolism of ellagitannins. This review compares the absorption and metabolism of ellagitannins, and the antioxidant properties of their metabolites in rats, with those of intact ellagitannins by means of IN VITRO and IN VIVO assays. We isolated 7 urinary and intestinal microbial metabolites in rats after the ingestion of geraniin, which is a typical ellagitannin isolated from GERANIUM THUNBERGII, an antidiarrheic remedy in Japan. The structures of these metabolites were determined to be dibenzopyran derivatives ( 1- 7), using NMR and mass spectroscopic data. Four major metabolites ( 1- 4) prepared by chemical synthesis were evaluated for their antioxidant activities by using 2,2-diphenyl-1-picrylhydrazyl radical scavenging and oxygen radical absorbance capacity (ORAC) methods. The metabolites exhibited more potent antioxidant activities in the ORAC assay than intact ellagitannins, such as geraniin and corilagin. Furthermore, plasma ORAC scores increased with increases in the plasma concentration of the metabolites after the oral administration of geraniin to rats. These findings suggest that these metabolites may contribute to the health benefits of ellagitannins as antioxidants in the body.

Metabolites of ellagitannins and their antioxidant activity

Various biological activities such as antioxidant, antiviral and antitumor activities were reported for different types of ellagitannins [1,2]. Nevertheless, there are little definitive studies on the absorption and metabolism of ellagitannins. We describe the characterization of urinary and intestinal microbial metabolites in rats after ingestion of geraniin, which is a typical ellagitannin isolated from Geranium thunbergii, an anti-diarrheic in Japan. Seven metabolites (M1-M7) were isolated from the suspension of rat intestinal microflora and rat urine samples. The structures of M1 (urolithin A), M2 (3,8,9-trihydroxy-6H-dibenzo[b,d]pyran-6-one), M3 (3,8-dihydroxy-9-methoxy-6H-dibenzo[b,d]pyran-6-one), M4 (3,9-dihydroxy-8-methoxy-6H-dibenzo[b,d]pyran-6-one), M5 (3,4,8,9,10-pentahydroxy-6H-dibenzo[b,d]pyran-6-one), M6 (3,8,9, 10-tetrahydroxy-6H-dibenzo[b,d]pyran-6-one), and M7 (3,8,10-trihydroxy-6H-dibenzo[b,d]pyran-6-one) were determined based on spectroscopic data. [3]. Furthermore, four major metabolites (M1-M4) were evaluated for antioxidant activity. These metabolites showed more potent antioxidant activity than intact ellagitannins such as geraniin in the ORAC assay, suggesting that the metabolites may contribute to the health benefits of ellagitannins as an antioxidant in the body.