Digestion and Fermentation in the Lower GI Tract

Lead Research Organisation: Institute of Food Research
Department Name: Contracts

Abstract

There has been much research on the colonic microbiota in the last decade. The major thrust of this research has been comparative studies between different population groups based upon 16S profiling of the microbiota from stool samples, and associated studies seeking functional analyses of human microbiota within mouse models. Human faecal samples are also commonly used to ‘seed’ in vitro colonic models to investigate metabolic derivatives of foods. These studies have provided evidence for the physiological role that gut microbiota play in the fermentation of food entering the colon as well as the multiple means by which resident intestinal bacteria provide immunological, metabolic and neurological benefits to the host, and contribute to well-being. However, the translation of studies from mouse and in vitro models, based upon faecal samples, which may not represent the resident bacteria at the site of fermentation in vivo, to normal digestive processes in humans is open to challenge. From birth, host and dietary carbohydrates are the main drivers influencing gut bacteria composition. A low-fibre diet characteristic of industrialized countries has long been hypothesized to contribute to ‘Western’ diseases such as inflammatory bowel disease. Enabling an effective communication between the gut microbiota and the host via the provision of microbiota-accessible carbohydrates adapted to the physiological state of the host is paramount to optimise human health throughout life. Many phytochemicals are present in plant foods as glycosides or other conjugates which can be hydrolysed and metabolised by gut bacteria, and influence the growth of beneficial bacteria, exerting prebiotic-like effects. For example, supplementing the diets of experimental animals or human subjects with polyphenol-rich foods or extracts has been reported to increase the prevalence of commensal bacteria groups, such as Bifidobacteria and Lactobacilli, that generate significant quantities of potentially beneficial short chain fatty acids, and the decrease in the prevalence of bacterial groups considered potentially detrimental. However, there is little understanding of how polyphenols cause these pre-biotic like effects. It is also increasingly recognised that the intestinal microbiota play a critical role in the metabolism of polyphenols, glucosinolates and other sulphur containing phytochemicals and significantly affect the amount of ingested phytochemical derivatives. This theme will consider how the gut microbiota generate novel metabolites from macronutrients and phytochemicals that are delivered via the upper GI tract, and the mechanisms by which these metabolites may influence nutrient signalling, hormone release and satiety. Moreover, building upon our combined expertise in dietary carbohydrates and phytochemicals we propose to address the impact of the interaction between these plant-derived components on the GI microbiota composition and function, host barrier function and metabolism.

We will adopt approaches developed at Imperial College London to intubate and sample luminal and mucus associated microbiota from the ileum and ascending colon. We will explore how foods that differ in their chemical and physical composition (as developed in Theme 1, and used in studies in Theme 2) can result in acute and long-term changes in gut microbiota and the nature of fermentation. We have an emphasis on starch degrading microbiota, and how they modulate the fermentation of ‘resistant’ starch entering the colon, their influence on the chemical and biophysical properties of the gut mucosa and intestinal barrier function, and how they stimulate the differentiation and functioning of enteroendocrine L-cells. Additionally, we will quantify the biotransformation of dietary phytochemicals by the gut microbiota, and the effect of phytochemicals on gut microbiota diversity and metabolism. We have an emphasis on sulphur-containing phytochemicals and complex polyphenols.

Publications

10 25 50
 
Description Objective 3.1: In vitro fermentation experiments have been completed using 11 different starches with a wide range of amylose contents and crystallinities and stool from 4 volunteers. Metabolite analysis from these experiments has been carried out and is currently being analysed. The preliminary findings from this analysis indicate that there is a strong effect of amylose content on SCFA production, particularly in propionate and acetate production, which is inversely correlated with amylose content. 16S and nanopore based metagenomic sequencing is currently being undertaken on samples from these experiments. This will contribute to the identification of novel starch degrading species/mechanisms.

Objective 3.2:Impact of colonic metabolites on the epithelium and enteroendocrine L cell signalling, differentiation and proliferation
We have established human organoid cultures and demonstrated that the cell assembly aligns the original human tissue. We are currently developing new assays with relate to organoid swelling in the present on a nutrient
Informed by the outcomes of Objective 3.1 we are currently working on the design of a dietary study using humanized mouse experiments with the view to start the experiment in April 2019.

Objective 3.3 Interaction between dietary phytochemicals and the gut microbiota
Using the human-faecal inoculated colon model, we have shown for the first time that the initial breakdown of anthocyanins into an A-ring and a B-ring product is partly spontaneous and partly driven by the gut microbiota. We have identified and quantified multiple metabolites from colonic fermentations and preliminary data indicates multiple initial metabolic routes evidenced by different B-ring products. These findings have informed our targeted analysis of over 120 putative anthocyanin metabolites in tissue samples from a human dietary intervention study with similar anthocyanins which has confirmed the in vitro findings and facilitated the discovery of previously unknown anthocyanin metabolites.

Objective 3.4: Ileum and colonic human intubation studies
We have successfully developed the intubation technology for sampling of the human ileum and ascending colon. The study protocol has recently been published, https://f1000research.com/articles/8-258/v1. The initial studies using this technology have been very encouraging. We have compared the impact of food structure in 8 volunteers. Using three diets which contain the same foods but processed to different degrees.
Exploitation Route The results of Objective 3.1 are being shared with colleagues at the John Innes Centre, where they can inform future breeding programmes aiming to develop healthier options for starchy foods.

Through Objective 3.4 We have developed a safe methodology to access the human ileum and colon for use in further studies.
Sectors Agriculture, Food and Drink,Healthcare

 
Description Fermented seaweed based novel feed additives - SEAFEED
Amount € 490,000 (EUR)
Organisation European Institute of Innovation and Technology (EIT) 
Sector Public
Country Hungary
Start 01/2019 
End 01/2020
 
Description John Innes Centre KEC fund
Amount £50,000 (GBP)
Organisation John Innes Centre 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2019 
End 11/2019
 
Description Training interdisciplinary glycoscientists to get a molecular- level grip on glycocodes at the human mucosa-microbiota
Amount £466,300 (GBP)
Funding ID 814102 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2019 
End 12/2022
 
Description Wellcome Nutrition Award: Applying food science to inform diet choices and improve health
Amount £50,000 (GBP)
Funding ID 215853/Z/19/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2019 
End 01/2020
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Barcelona
Country Spain 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description Bespoke synthesis of polyphenol human metabolites 
Organisation University of Perth
Country Australia 
Sector Academic/University 
PI Contribution We used synthetic organic chemistry routes to make phase-2 conjugates of various dietary flavonoids and phenolic acids and supplied these to various collaborators for testing of biological activity. These compounds are not available commercially and for many of them they are unique to our lab.
Collaborator Contribution Partners have used these physiologically relevant metabolites to test their biological activity using in vitro models such as cultured mammalian cell models, etc... They have also used them as authentic standards to facilitate identification and quantification of metabolites in human and animal tissues including blood, urine and faeces.
Impact Petri N, Tannergen C, Holst B, Mellon FA, Bao Y, Plumb GW, Bacon J, O'Leary KA, Kroon PA, Knutson L, Forsell P, Eriksson T, Lennernas H & Williamson G (2003) "Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejenum in vivo". Drug Metab Disposition 31, 805-813.Nemeth K, Plumb GW, Berrin J-G, Juge N, Jacob R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) "Deglycosylation by small intestinal epithelial cell ? glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42, 29-42.Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C & Williamson G (2004). How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80, 15-21. Dupont MS, Day AJ, Bennett RN, Mellon FA & Kroon PA (2004) "Absorption of kaempferol-3-glucuronide from endive in humans". Eur J Clin Nutr 58, 947-954. Needs PW, Kroon PA (2006) Convenient syntheses of metabolically important quercetin glucuronides and sulfates. Tetrahedron 62, 6862-6868. Davis BD, Needs PW, Kroon PA & Brodbelt (2006) Identification of isomeric flavonoid glucuronides in urine and plasma by metal complexation and liquid chromatography/tandem mass spectrometry. J Mass Spectrom 41, 911-920. Tribolo S, Lodi F, Connor C, Suri S, Wilson V, Taylor M, Needs PW, Kroon PA, Hughes DA (2008). Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 197, 50-56. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: Lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 75, 1045-1053. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA, Hodgson JM & Croft KD (2008). Quercetin and its in vivo metabolites inhibit neutrophil-mediated low-density lipoprotein oxidation. J Agric Food Chem 56, 3609-3615. Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett, RN & Kroon PA (2008). Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108, 869-878. Suri S, Taylor MA, Verity A, Tribolo S, Kroon PA, Hughes DA, Wilson VG (2008). A comparative study of the effects of quercetin and its glucuronide and sulphate metabolites on human neutrophil function in vitro. Biochem Pharmacol 76, 645-673. Barrington R, Williamson G, Bennett RN, Davis BD, Brodbelt JS, Kroon PA (2009). Absorption, conjugation and efflux of the flavonoids, kaempferol and galangin, using the intestinal CaCo-2/TC7 cell model. J Functional Foods 1, 74-97. Brett GM, Hollands W, Needs PW, Teucher B, Dainty JR, Bennett RN, Davis BD, Brodbelt JS & Kroon PA (2009). Absorption, metabolism and excretion of flavanones from single portions of orange fruit and juice and effects of anthropometric variables and contraceptive pill use on flavanone excretion. Br J Nutr 101, 664-675. http://journals.cambridge.org/repo_A44rP6ra (Personal author link) Winterbone MS, Tribolo S, Needs PW, Kroon PA & Hughes DA (2009). Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells. Atherosclerosis 202, 431-438. Kay CD, Kroon PA, Cassidy A (2009). The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products. Mol Nutr Food Res 53 Suppl 1:S92-101. Lodi F, Jiménez R, Moreno L, Kroon PA, Needs PW, Hughes DA, Santos-Buelga C, González-Paramás A, Cogolludo A, Duarte J, Perez-Vizcaino F (2009). Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasodilator effects in rat aorta. Atherosclerosis 204, 34-39. Radreau P, Rhodes JD, Mithen RF, Kroon PA, Sanderson J (2009) Hypoxia-inducible factor-1 (HIF-1) pathway activation by quercetin in human lens epithelial cells. Exp Eye Res 89, 995-1002. Curtis PJ, Kroon PA, Hollands WJ, Walls R, Jenkins G, Kay CD, Cassidy A (2009). Cardiovascular disease risk biomarkers and liver function are not altered following twelve week ingestion of an elderberry extract rich in anthocyanins. J Nutr 139, 2266-2271. Soler A, Romero MP, Saha S, Furniss CSM, Kroon PA, Motilva MJ (2010). Digestion stability and evaluation of the metabolism and transport of olive oil phenols in human small intestinal epithelial Caco2/TC7 cell line. Food Chem, 119, 703-714. Suri S, Liu XH, Rayment S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2010). Quercetin and its major metabolites selectively modulate cyclic GMP-dependent relaxations and associated tolerance in pig isolated coronary artery. Br J Pharmacol 159, 566-575. Bartholomé R, Haenen G, Hollman PCH, Bast A, Dagnelie PC, Roos D, Keijer J, Kroon PA, Needs PW, Arts ICW (2010). Deconjugation kinetics of glucuronidated phase-II flavonoid metabolites by ß-glucuronidase from neutrophils. Drug Metab Pharmacokinet 25, 379-387. Pereira-Caro G, Mateos R, Saha S, Madrona A, Espartero JL, Bravo L, Kroon PA (2010). Trans-epithelial transport and metabolism of new lipopohilic ether derivatives of hydroxytyrosol by enterocyte-like CaCo-2/TC7 cells. J Agric Food Chem 58, 11501-11509. Al-Shalmani S, Suri S, Hughes DA, Kroon PA, Needs PW, Taylor MA, Tribolo S, Wilson VG (2011). Quercetin and its principal metabolites, but not myricetin, oppose LPS-induced hyporesponsiveness of the porcine isolated coronary artery. Br J Pharmacol 162, 1485-1497. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy A (2012). Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a one year double-blind randomized controlled trial. Diabetes Care 35, 226-232. Saha S, Hollands W, Needs PW, Ostertag LM, de Roos B, Duthie GG, Kroon PA (2012). Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: Implications for studies concerned with quantifying epicatechin bioavailability. Pharmacol Res 65, 592-602. Lodi F, Tribolo S, Winterbone MS, Needs PW, Hughes DA, Kroon PA (2012). Human quercetin conjugated metabolites attenuate TNF-a-induced changes in vasomodulatory molecules in a HUASMCs/HUVECs co-culture model. Planta Med 78, 1571-1573. Hollands WJ, Hart D, Dainty JR, Hasselwander O, Tiihonen K, Wood R, Kroon PA (2013). Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol-rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo controlled, crossover trial. Mol Nutr Food Res 57, 1209-1217. Tribolo S, Lodi F, Winterbone MS, Saha S, Needs PW, Suri S, Taylor MA, Wilson VG, Walls R, Cassidy A, Hughes DA, Kroon PA (2013). Human metabolic transformation of quercetin blocks its capacity to decrease eNOS expression and endothelin-1 secretion by human endothelial cells. J Agric Food Chem 61, 8589-8596. Czank C, Cassidy A, Zhang Q, Morrison DJ, Preston T, Kroon PA, Botting NP, Kay CD (2013). Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study. Am J Clin Nutr 97, 995-1003. Konic-Ristic A, Srdic-Rajica T, Kardum N, Kroon PA, Hollands WJ, Hayran O, Boyko N, Jorjadze M, Glibetic M (2013). Effects of bioactive-rich extracts of pomegranate, persimmon, nettle, dill, kale and Sideritis and isolated bioactives on arachidonic acid induced markers of platelet activation and platelet-leucocyte aggregation. J Sci Food Agric 93, 3581-3587. De Ferrars RM, Czank C, Zhang Q, Botting NP, Kroon PA, Cassidy A, Kay CD (2014). The pharmacokinetics of anthocyanins and their metabolites in humans. Br J Pharmacol 171, 3268-3282. De Ferrars R, Czank C, Saha S, Needs PW, Zhang Q, Raheem KS, Kroon PA, Kay CD (2014). Methods for isolating, identifying and quantifying anthocyanin metabolites in clinical samples. Anal Chem 86, 10052-10058. Danesi F, Kroon PA, Saha S, de Biase D, D'Antuono LF, Bordoni A (2014). Mixed pro- and anti-oxidative effects of pomegranate polyphenols in cultured cells. Int J Mol Sci 15, 19458-19471. Barrington RD, Needs PW, Williamson G, Kroon PA. MK571 inhibits phase-2 conjugation of flavonols by Caco-2/TC7 cells, but does not specifically inhibit their apical efflux. Biochem Pharmacol 95, 193-200. Cerezo AB, Winterbone MS, Moyle CW, Needs PW, Kroon PA (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res. 59, 2119-2131. doi: 10.1002/mnfr.201500407. Gornas P, Redenkovs V, Pugacheva I, Soliven A, Needs PW, Kroon PA (2016). Varied composition of tocochromanols in different types of bran: Rye, wheat, oat, spelt, buckwheat, corn and rice. Int J Food Properties 19, 1757-1764. Dower JI, Geleijnse JM, Kroon PA, Philo M, Mensink M, Kromhout D, Hollman PCH (2016). Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomised, crossover study. Mol Nutr Food Res 60, 2379-2386. Poór M, Boda G, Needs PW, Kroon PA, Lemli B, Bencsik T (2017). Interaction of quercetin and its metabolites with warfarin: displacement of warfarin from serum albumin and inhibition of CYP2C9 enzyme. Biomed Pharmacol 88, 574-581. Hollands WJ*, Voorspoels S*, Jacobs G, Aaby K, Meisland A, Garcia-Villalbad R, Tomas-Barberan F, Piskula MJ, Mawson D, Vovk I, Needs PW and Kroon PA (2017). Development, validation and evaluation of an analytical method for the determination of monomeric and oligomeric procyanidins in apple extracts. J Chromatogr A 1495, 46-56. Van Rymenant E, Grootaert C, Beerens K, Needs P, Kroon P, Kerimi A, Williamson G, García Villalba R, González-Sarrías A, Tomas-Barberan F, Van Camp J, Van de Voorde J. Vasorelaxant activity of twenty-one physiologically relevant (poly)phenolic metabolites on isolated mouse arteries. Mol Nutr Food Res 13, 4331-4335. Perez-Moral N, Saha S, Philo M, Hart DJ, Winterbone MS, Hollands WJ, Spurr M, Bows J, vander Velpen V, Kroon PA*, Curtis PJC (2018) Comparative bio-accessibility, bioavailability and bioequivalence of quercetin, apigenin, glucoraphanin and carotenoids from freeze-dried vegetables incorporated into a baked snack versus minimally processed vegetables: Evidence from in vitro models and a human bioavailability study. J Func Food 48, 410-419. Poor M, Boda G, Kunsagi-Mate S, Needs PW, Kroon PA, Lemli B (2018). Fluorescence spectroscopic evaluation of the interactions of quercetin, isorhamnetin, and quercetin-3 '-sulfate with different albumins. J Luminescence 194, 156-163. Wu Q, Kroon PA, Shao HJ, Needs PW, Yang XB (2018). Differential effects of quercetin and two of its derivatives, isorhamnetin and isorhamnetin-3-glucuronide, in inhibiting the proliferation of human breast cancer MCF-7 cells. J Agric Food Chem 66, 7181-7189. Wu Q, Needs PW, Lu YL, Kroon PA, Ren DY, Yang XB (2018). Different antitumor effects of quercetin, quercetin-3'-sulfate and quercetin-3-glucuronide in human breast cancer MCF-7 cells. Food Func 9, 1736-1746.
Start Year 2010
 
Description HUNGer consortium 
Organisation Campden and Chorleywood Food Research Association
Country United Kingdom 
Sector Private 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description HUNGer consortium 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description HUNGer consortium 
Organisation Queen Mary University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description HUNGer consortium 
Organisation St Johns Research Institute
Country India 
Sector Academic/University 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description HUNGer consortium 
Organisation University of Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description HUNGer consortium 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution As part of this project we carried out in vitro fermentation's of various fibres using microbiota from children with severe acute malnutrition, demonstrating the limited capability of these children to ferment certain dietary fibres, e.g. inulin. QIB has provided expertise in and access to fermentation systems and DNA sequencing
Collaborator Contribution This is a large, multi-disciplinary collaboration with partners contributing many parts, including nutritionists, metobolomics specialists, gastronenterologists and many others. Specifically, collaborators have provided access to faecal samples from children with SAM, and access to metabolomics facilities at Imperial.
Impact https://www.imperial.ac.uk/media/imperial-college/medicine/hunger-project/Hunger-Project-White-Paper-2019-01-09.pdf
Start Year 2018
 
Description 4th Annual European Microbiome Congress 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Attendance to 4th Annual European Microbiome Congress. This Conference has a high representation from the Industry: Pharmaceutical companies and Biotechnology companies and provided an excellent opportunity to make contact and discuss work relevant to the Institute Strategic Programmes. The PROMOTING WOMEN IN SCIENCE lunch session was inspiring.
Year(s) Of Engagement Activity 2018
 
Description Academia-Industry Networking CarboMet event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact I co-organised and chaired a two day workshop on 'The Role of Carbohydrates in the Gut Microbiome' June 2018 in Brussels attended by 40 delegates from academia and industry as apart of CarboMet. CarboMet (Metrology of Carbohydrates for European Bioindustries) is a four-year Coordination and Support Action (CSA) funded by Horizon 2020 FET-OPEN. It is an European Network that facilitates engagement between key players and stakeholders of the glycoscience community across Europe to identify the current state of the art and in particular future innovation and technological challenges in carbohydrate metrology. I co-wrote and edited the CarboMet positioning paper on 'The Essential Roles of Carbohydrates in Promoting Gut Microbiota Function Through All Stages of Life' which summarises discussions that took place during the workshop.
Year(s) Of Engagement Activity 2018
URL https://carbomet.eu/news/positioning-paper-on-role-of-carbohydrates-in-gut-microbiota-function/
 
Description Biochemist article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact An article for The Biochemist, the magazine of the Biochemical Society (UK), describing our research on carbohydrates and the microbiome. This has a circulation of 7000, and reaches mainly an audience of students and researchers in the UK molecular bioscience community
Year(s) Of Engagement Activity 2018
URL http://www.portlandpresspublishing.com/content/biochemist-magazine-0
 
Description Digest article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact An article entitled 'Food and our microbiome: are we what our microbiome eats?' highlighting research as part of the ISP programme in Digest, the magazine of the Primary Care Society of Gastroenterology. Primarily aimed at gasteroenterologists and patients, this magazine reaches and estimated audience of greater than 200,000 people.
Year(s) Of Engagement Activity 2018
URL http://www.pcsg.org.uk/the-digest/
 
Description Future Food Tech Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Future Food-Tech is an international innovation and investment summit held annually in London, San Francisco and New York. Harnessing technology to address the critical issues facing the world's food industry, the summit brings together global food-tech brands, investors and entrepreneurs to accelerate the adoption and commercialisation of new products and solutions. The 2018 programme focused on plant-based and cultured proteins, personalised nutrition, ingredient innovation, gene-editing for health and sustainability, and food waste reduction, featuring 60 game-changing speakers and the most exciting start-ups on the market. Several companies expressed an interest in QIB research and exchanged business cards for follow up activities.
Year(s) Of Engagement Activity 2018
URL https://futurefoodtechlondon.com/
 
Description IBCarb 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Contributed to the final IBCarb workshop Glycobiotechnology 2018. IBCarb (Glycoscience Tools for Biotechnology and Bioenergy) is a growing network of glycoscientists from academia and industry. IBCarb was one of the Networks in Industrial Biotechnology and Bioenergy funded by the BBSRC. The workshop was very successful and attracted around 150 attendees (international audience from academia and industry) . This was an opportunity to showcase the Glycosciences carried out in the UK and in partnership with industrial/business partners.
Year(s) Of Engagement Activity 2018
URL https://ibcarb.com/events/
 
Description Microbes in Norwich 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presented a talk at the Microbes in Norwich event, which is designed to showcase the microbiological research being conducted in Norwich. This event generated new collaborative opportunities across the Norwich Research Park.
Year(s) Of Engagement Activity 2019
URL http://www.microbesinnorwich.org/