Urolithin

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Chemical structure of urolithin A. Urolithin A.svg
Chemical structure of urolithin A.

Urolithins are microflora metabolites of dietary ellagic acid derivatives, such as ellagitannins. [1] They are produced in the gut, and found in the urine in the form of urolithin B glucuronide after absorption of ellagitannins-containing foods, such as pomegranate. [2] During intestinal metabolism by bacteria, ellagitannins and punicalagins are converted to urolithins, which have unknown biological activity in vivo.[ medical citation needed ]

Contents

Ellagitannins exhibit low bioavailability and are transformed in the gut to ellagic acid and its microbiota metabolites.[ medical citation needed ] Urolithins are found in plasma mostly as glucuronides at low concentrations. [3] Urolithins production is dependent on the gut microbiome enterotype. Individuals producing urolithins show a much higher abundance of the Clostridium leptum group of Firmicutes phylum than Bacteroides or Prevotella .[ medical citation needed ] [4]

Known molecules

catabolic intermediates:

See also

Related Research Articles

Resveratrol Chemical compound

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, and peanuts.

Ellagic acid Natural phenol antioxidant

Ellagic acid is a polyphenol found in numerous fruits and vegetables. It is the dilactone of hexahydroxydiphenic acid.

Punicalagin Chemical compound

Punicalagin is an ellagitannin, a type of phenolic compound. It is found in forms alpha and beta in pomegranates, in Terminalia catappa and Terminalia myriocarpa, and in Combretum molle, the velvet bushwillow, a plant species found in South Africa. These three genera are all Myrtales and the last two are both Combretaceae.

Gut microbiota Community of microorganisms in the gut

Gutmicrobiota are the microorganisms, including bacteria and archaea, that live in the digestive tracts of vertebrates including humans, and of insects. Alternative terms include gutflora and gutmicrobiome. The gastrointestinal metagenome is the aggregate of all the genomes of gut microbiota. In the human, the gut is the main location of human microbiota. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut-brain axis.

Dysbiosis is characterized as a disruption to the microbiota homeostasis caused by an imbalance in the microflora, changes in their functional composition and metabolic activities, or a shift in their local distribution. It is a term for a microbial imbalance or maladaptation on or inside the body, such as an impaired microbiota. For example, a part of the human microbiota, such as the skin flora, gut flora, or vaginal flora, can become deranged, with normally dominating species underrepresented and normally outcompeted or contained species increasing to fill the void. Dysbiosis is most commonly reported as a condition in the gastrointestinal tract, particularly during small intestinal bacterial overgrowth (SIBO) or small intestinal fungal overgrowth (SIFO).

Microbial symbiosis and immunity

Long-term close-knit interactions between symbiotic microbes and their host can alter host immune system responses to other microorganisms, including pathogens, and are required to maintain proper homeostasis. The immune system is a host defense system consisting of anatomical physical barriers as well as physiological and cellular responses, which protect the host against harmful microorganisms while limiting host responses to harmless symbionts. Humans are home to 1013 to 1014 bacteria, roughly equivalent to the number of human cells, and while these bacteria can be pathogenic to their host most of them are mutually beneficial to both the host and bacteria.

The ellagitannins are a diverse class of hydrolyzable tannins, a type of polyphenol formed primarily from the oxidative linkage of galloyl groups in 1,2,3,4,6-pentagalloyl glucose. Ellagitannins differ from gallotannins, in that their galloyl groups are linked through C-C bonds, whereas the galloyl groups in gallotannins are linked by depside bonds.

Grandinin Chemical compound

Grandinin is an ellagitannin. It can be found in Melaleuca quinquenervia leaves and in oaks species like the North American white oak and European red oak. It shows antioxydant activity. It is an astringent compound. It is also found in wine, red or white, aged in oak barrels.

Syringic acid Chemical compound

Syringic acid is a naturally occurring phenolic compound and dimethoxybenzene that is commonly found as a plant metabolite.

Tergallic acids are trimers of gallic acid, often found naturally in the form of glycosides. Tergallic acid O- or C-glucosides that can be found in acorns of several Quercus (oak) species. The dehydrated tergallic acid C-glucoside and tergallic acid O-glucoside can be characterised in the acorns of Quercus macrocarpa. Dehydrated tergallic-C-glucoside can be found in the cork from Quercus suber.

<i>delta</i>-Viniferin Chemical compound

δ-Viniferin is a resveratrol dehydrodimer. It is an isomer of epsilon-viniferin. It can be isolated from stressed grapevine leaves. It is also found in plant cell cultures and wine. It can also be found in Rheum maximowiczii.

Punicalin Chemical compound

Punicalin is an ellagitannin. It can be found in Punica granatum (pomegranate) or in the leaves of Terminalia catappa, a plant used to treat dermatitis and hepatitis. It is also reported in Combretum glutinosum, all three species being Myrtales, the two last being Combretaceae.

Pedunculagin Chemical compound

Pedunculagin is an ellagitannin. It is formed from casuarictin via the loss of a gallate group.

Sanguiin H-6 Chemical compound

Sanguiin H-6 is an ellagitannin.

Gut–brain axis

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system (CNS). The term "gut–brain axis" is occasionally used to refer to the role of the gut microbiota in the interplay as well. The "microbiota–gut–brainaxis" explicitly includes the role of gut microbiota in the biochemical signaling events that take place between the GI tract and the CNS. Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis, sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.

Urolithin A Chemical compound

Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. Its precursors – ellagic acids and ellagitannins – are ubiquitous in nature, including edible plants, such as pomegranates, strawberries, raspberries, and walnuts. Since the 2000s, urolithin A has been the subject of preliminary studies regarding its possible biological effects.

Callistephin Chemical compound

Callistephin is an anthocyanin. It is the 3-O-glucoside of pelargonidin.

Urolithin B Chemical compound

Urolithin B (UB) is an urolithin, a type of phenolic compounds produced in the human gut after absorption of ellagitannins-containing food such as pomegranate, strawberries, red raspberries, walnuts or oak-aged red wine. Urolithin B is found in the urine in the form of urolithin B glucuronide.

3-Indolepropionic acid

3-Indolepropionic acid (IPA), or indole-3-propionic acid, is a potent neuroprotective antioxidant, plant auxin, and natural product in humans that is being studied for therapeutic use in Alzheimer's disease. It is endogenously produced by human microbiota and has only been detected in vivo when the species Clostridium sporogenes is present in the gastrointestinal tract. As of April 2016, C. sporogenes, which uses tryptophan to synthesize IPA, is the only species of bacteria known to synthesize IPA in vivo at levels which are subsequently detectable in the blood plasma of the host.

Indole-3-carboxaldehyde Chemical compound

Indole-3-carboxaldehyde (I3A), also known as indole-3-aldehyde and 3-formylindole, is a metabolite of dietary L-tryptophan which is synthesized by human gastrointestinal bacteria, particularly species of the Lactobacillus genus. I3A is a biologically active metabolite which acts as a receptor agonist at the aryl hydrocarbon receptor in intestinal immune cells, in turn stimulating the production of interleukin-22 which facilitates mucosal reactivity.

References

  1. Larrosa, M; González-Sarrías, A; García-Conesa, MT; Tomás-Barberán, FA; Espín, JC (2006). "Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities". Journal of Agricultural and Food Chemistry. 54 (5): 1611–1620. doi:10.1021/jf0527403. PMID   16506809.
  2. Bialonska D, Kasimsetty SG, Khan SI, Ferreira D (11 November 2009). "Urolithins, intestinal microbial metabolites of Pomegranate ellagitannins, exhibit potent antioxidant activity in a cell-based assay". J Agric Food Chem. 57 (21): 10181–6. doi:10.1021/jf9025794. PMID   19824638.
  3. Giménez-Bastida, Juan A.; González-Sarrías, Antonio; Larrosa, Mar; Tomás-Barberán, Francisco; Espín, Juan C.; García-Conesa, María-Teresa (2012). "Ellagitannin metabolites, urolithin a glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells". Molecular Nutrition & Food Research. 56 (5): 784–796. doi:10.1002/mnfr.201100677. PMID   22648625.
  4. García-Villalba, Rocío; Beltrán, David; Espín, Juan Carlos; Selma, María Victoria; Tomás-Barberán, Francisco A. (2013). "Time Course Production of Urolithins from Ellagic Acid by Human Gut Microbiota". Journal of Agricultural and Food Chemistry. 61 (37): 8797–8806. doi:10.1021/jf402498b. PMID   23984796.