Digestion and Fermentation in the Lower GI Tract

Lead Research Organisation: Quadram Institute Bioscience
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 6 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. Long read nanopore based sequencing has been employed which has been able to identify a large number of complete bacterial genomes in sequenced material from a subset of samples, as well as identifying shifts in the relative abundance of carbohydrate active enzyme genes within the bacterial populations in response to different starches, allowing the identification of key starch degrading species for different starch substrate.
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 which relate to organoid swelling in the presence of a nutrient. We have established and validated the gut microbiota humanised mouse models (germ-free mice colonised with human faecal microbiota) and confirmed that diet is a major discriminant of gut microbiota structure and function using these models. Informed by our recent Nature Food paper (Petropoulou et al., Nature Food 1 (11)) we are currently working on the design of a bespoke dietary study with peas from high and low resistant starch genotypes of different particle sizes, with the view to resume the humanised mouse experiments (delayed to Covid-19 due to the lack of access to human gut faecal samples) in Spring 2021 or as soon as Ethical approval has been granted for the new procedures required to use CRF stool sample from donors).
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. We have also demonstrated that some structures are due to metabolism by the gut microbiota while others are a consequence of spontaneous degradation, i.e. we now have chemical markers distinct for each process. In addition, we have elucidated metabolic pathways by feeding early appearing metabolites and later appearing metabolites and developing the step-by-step metabolic pathways. 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. Shotgun metagenomic sequencing on the human faecal samples has been completed and will now be interrogated for (a) changes in microbiome structure and diversity and (b) relative abundance of genes encoding enzymes probably involved in anthocyanin transformations. Work to identify isolated bacterial strains or groups of bacteria that can thrive on anthocyanins and metabolise them is ongoing.
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. These studies have been completely halted in 2020 due to the COVID-19 pandemic, a direct consequence of has been the complete suspension of human intervention studies. As a result, all the intervention studies planned in Obj.3.4 have been severely disrupted and will be aiming to recommence in the second half of 2021.
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 Academic/University
Country United Kingdom
Start 04/2019 
End 11/2019
 
Description NRP DTP studentship
Amount £10,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2020 
End 09/2024
 
Description Novel tools for evaluating intestinal dysfunction in children and adults with malnutrition disorders
Amount £2,500,000 (GBP)
Funding ID MR/V012452/1 
Organisation Queen Mary University of London 
Sector Academic/University
Country United Kingdom
Start 06/2021 
End 07/2026
 
Description Nutrileads project
Amount £33,350 (GBP)
Organisation NutriLeads 
Sector Private
Country Netherlands
Start 03/2020 
End 08/2020
 
Description The biosynthetic control of amylose fine structure and its implications for nutrition
Amount £160,908 (GBP)
Organisation John Innes Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2020 
End 11/2022
 
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 Collaboration with Protexin for development of functional foods 
Organisation Protexin
Country United Kingdom 
Sector Private 
PI Contribution Collaboration with Protexin for development of functional foods
Collaborator Contribution Collaboration with Protexin for development of functional foods
Impact Collaboration with Protexin for development of functional foods
Start Year 2019
 
Description HUNGer consortium 
Organisation Campden BRI
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 Health ingredient company 
Organisation NutriLeads
Country Netherlands 
Sector Private 
PI Contribution Test effect of plant-derived polysaccharides on gut barrier function
Collaborator Contribution Provided compounds to be tested Funded project
Impact Report to the company
Start Year 2020
 
Description STFC Food network 2.0 
Organisation Science and Technologies Facilities Council (STFC)
Country United Kingdom 
Sector Public 
PI Contribution I am a member of the advisory board for the UKRI/STFC Food Network 2.0 grant. My role on this project is to provide oversight for the development of projects using STFC facilties for applications in Food Science
Collaborator Contribution The other partners on the award are directly involved in selecting projects to fund, organising meetings and disbersing funds.
Impact Several successful projects have been funded as a result of the STFC 2.0 network, see the attached URL for full details
Start Year 2019
 
Description STFC Food network 2.0 
Organisation University of Manchester
Country United Kingdom 
Sector Academic/University 
PI Contribution I am a member of the advisory board for the UKRI/STFC Food Network 2.0 grant. My role on this project is to provide oversight for the development of projects using STFC facilties for applications in Food Science
Collaborator Contribution The other partners on the award are directly involved in selecting projects to fund, organising meetings and disbersing funds.
Impact Several successful projects have been funded as a result of the STFC 2.0 network, see the attached URL for full details
Start Year 2019
 
Description STFC Food network 2.0 
Organisation University of Sheffield
Country United Kingdom 
Sector Academic/University 
PI Contribution I am a member of the advisory board for the UKRI/STFC Food Network 2.0 grant. My role on this project is to provide oversight for the development of projects using STFC facilties for applications in Food Science
Collaborator Contribution The other partners on the award are directly involved in selecting projects to fund, organising meetings and disbersing funds.
Impact Several successful projects have been funded as a result of the STFC 2.0 network, see the attached URL for full details
Start Year 2019
 
Description Vitamin B12 Biology 
Organisation University of Kent
Country United Kingdom 
Sector Academic/University 
PI Contribution Secured a joint PhD studentship and grant
Collaborator Contribution Input into grant applications and supervisory expertise
Impact Secured a joint PhD studentship and grant
Start Year 2019
 
Description 'Heroes of Food Research' Public Engagement activity 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The purpose of the set of activities was to engage in a dialogue with members of the public in the region where we recruit participants to partake in dietary intervention studies. The activities included two sessions in Norwich's Forum Library public space where visitors could read about the types of studies that were going on, discuss what was involved when volunteering to participate in a study, ask questions of study PIs and study managers, taste intervention foods, complete a short questionnaire, and sign up for future activities which included an evening session with audience participation and voting and a workshop to gather feedback from potential volunteers. As a result of the activities and the significant feedback from the general public and those who had previously participated in human studies, we completely revamped our institute's Human Studies internet pages, recorded feedback and subsequently changed various features of our adverts that invited people to participate in specific studies, and recruited a significant number of new people to our database of interested volunteers.
Year(s) Of Engagement Activity 2015,2016
URL https://quadram.ac.uk/volunteer/
 
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 Bioavailability 2018 International Conference, 'Understanding the bioavailability of micronutrients and bioactive compounds for improved public health', the 8th in the series of Bioavailability conferences. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Bioavailability 2018 International Conference, 'Understanding the bioavailability of micronutrients and bioactive compounds for improved public health', the 8th in the series of Bioavailability conferences.
Year(s) Of Engagement Activity 2018
 
Description Bioavailability Conference Poster 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I presented a poster on my findings on the urinary metabolites of anthocyanins post dietary intervention. This was seen by numerous different researchers from all over the world.
Year(s) Of Engagement Activity 2018
 
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 CCG representatives visit to discuss collaborative opportunities for food and health research 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact CCG representatives visit to discuss collaborative opportunities for food and health research
Year(s) Of Engagement Activity 2019
 
Description Cool Food Facts - primary school BIO outreach event in Lowestoft 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Lowestoft primary school requested the activity for the science day to the School of Biology, UEA (contact - Carl Harrington). The session ran 4 times for Yr2 to Yr6, with approximately 30 students in each session.
Year(s) Of Engagement Activity 2018
 
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 Engagement with government 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Understanding how research and policy interact and identify gaps in the diabetes research that need to be addressed. Understanding NHS long term and short programme for diabetes prevention and care Discussing funding opportunities for diabetes research
Year(s) Of Engagement Activity 2019
 
Description FDNC & FIH School Activity - Clever Food Trail session with primary school children 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visited Hethersett Primary School to speak and provide a number of activities on the clever food trail.
Year(s) Of Engagement Activity 2020
 
Description FENS conference Dublon 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Spoke to an audance of over 100 one food and the gut covering aspects from many of my awards
Year(s) Of Engagement Activity 2019
URL http://www.fens2019.org/
 
Description FoodHack 2020 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Food Hack 2020 bought together experts from across the food industry to bridge the gap between research and the market. Using Sprint & Lean Start Up methodology, multi-disciplinary teams designed an innovative food proposition which harnesses the health benefits of a natural genetic variation in peas with the ultimate aim of preventing diabetes and cardiovascular disease. The event was hosted at Imperial College in collaboration with Quadram Institute
Year(s) Of Engagement Activity 2020
URL https://www.imperialhackspace.com/whats-on/food-hack/
 
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 Imperial Lates "Food for Thought" 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact This was a science outreach week focused on food. If gaave feed back from the general public on our research
Year(s) Of Engagement Activity 2020
URL https://www.imperial.ac.uk/be-inspired/lates/food-for-thought/
 
Description International Clinical Trial Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact International Clinical Trial Day
Year(s) Of Engagement Activity 2019
 
Description London Allied Health Professionals research conference 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Spoke to about 100 allied health professional on my experiance of research in clinical practice
Year(s) Of Engagement Activity 2019
 
Description Meeting in London with collaborators from the University of Leicester and Protexin 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Meeting in London with collaborators from the University of Leicester and Protexin
Year(s) Of Engagement Activity 2018
 
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/
 
Description Norwich Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Norwich Science Festival
Year(s) Of Engagement Activity 2018
 
Description Norwich Science Festival Nutrition Workshop with School Children 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Ran a workshop on nutrition with school children aged 10 looking at what foods are health and what food groups they fall into.
Year(s) Of Engagement Activity 2018
 
Description Norwich Science Festival: Clever Food Stall 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Welcome posters, Research posters, EatWell Guide Poster, Clever Food Trail, Recipe cards, Certificates, Landyards, Stickers, Smelling jars
Year(s) Of Engagement Activity 2019
 
Description Pint of Science talk- Are Low-Carb Diets Cancelled? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact PhD student Molly Miller gave a talk at the 2019 Norwich pint of science event describing her research on Bifidobacterium breakdown on dietary starches and implications for diet and health. The event was attended by around 50 people, and raised a number of questions about beneficial carbohydrates, diet and health.
Year(s) Of Engagement Activity 2019
URL https://pintofscience.co.uk/event/the-scientific-way-to-eat-a-recipe-for-success
 
Description Reepham Food Festival - Fun Food Science Activity 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Reepham Food Festival - Fun Food Science Activity
Year(s) Of Engagement Activity 2018
 
Description Research Presentation- Knowledge Exchange (Munich) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Presented an overview of my research to students and academics at the university of Munich, this sparked questions and ideas on what I could next and other avenues to explore within my project.
Year(s) Of Engagement Activity 2019
 
Description Royal Norfolk Show 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Royal Norfolk Show
Year(s) Of Engagement Activity 2019
 
Description STFC Food Network 2.0 Steering commitee 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact I sit on the steering commitee for the STFC food network 2.0 grant, bringing together STFC facilties and expertise with food and nutrition acadmics and industry partners for innovative projects. In this role I influence the funding directions and decision making for food industry-academia collaborations covering ~700 members.
Year(s) Of Engagement Activity 2020
URL https://www.stfcfoodnetwork.org/
 
Description School Visit (Hethersett) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Myself along with other PhD students visited Hethersett primary school to run an activity with 60 year 2 pupils to educate them on the 'eat well plate', this involved the children going to different stations and discussing all the different food groups and why they're important as well as coming up with a balanced meal.
Year(s) Of Engagement Activity 2020
 
Description The interplay between plant, human and microbial sulphur metabolism in the prevention of aggressive prostate cancer 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presentation - The interplay between plant, human and microbial sulphur metabolism in the prevention of aggressive prostate cancer
Year(s) Of Engagement Activity 2018
 
Description The role of 3,4-dihydroxyphenyl-y-valerolactone, the gut microbiota metabolite of (-)-epicatechin, in reducing insulin resistance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact NuGo Conference, Bern Switzerland 16h-19th September 2019
Year(s) Of Engagement Activity 2019
 
Description The role of 3,4-dihydroxyphenyl-y-valerolactone, the gut microbiota metabolite of (-)-epicatechin, in reducing insulin resistance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact International conference on polyphenols and health
Year(s) Of Engagement Activity 2019
 
Description Training for placement student from the University of Surrey 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Training for placement student from the University of Surrey
Year(s) Of Engagement Activity 2019
 
Description Transcriptional changes in prostate of men on active surveillance following a 12-month glucoraphanin-rich broccoli intervention - results from the ESCAPE study 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact PRESENTATION - Transcriptional changes in prostate of men on active surveillance following a 12-month glucoraphanin-rich broccoli intervention - results from the ESCAPE study
Year(s) Of Engagement Activity 2018
 
Description UEA ELSA Metagenomics Workshop 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Metagenomigs workshop held across the Norwich Research Park to increase awareness and collaboration between metagenomics research. I was invited to present my work in this are to ~150 metagenomics practitioners (including post grad and undergrad students), mainly from Norwich but also with a number of external attendees
Year(s) Of Engagement Activity 2021
URL http://www.nrp.ac.uk/nrp-strategic-alliances/elsa/about-elsa/
 
Description Visit by Waitrose. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact To present the research of QIB to representatives of the Waitrose Nutrition and Technology elements.
Year(s) Of Engagement Activity 2019
 
Description Visit to Norway to talk to opinion makes about Nutrition 
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 Talk to 15 Norwegian opinion leaders about the role of Nutrition in the prevention of non communicable disease highlighting my research
Year(s) Of Engagement Activity 2019
 
Description Wageningen European Study trip 2020 A series of presentations and tours for these undergraduate/masters students of nutrition and health. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact A series of presentations and tours for these undergraduate/masters students of nutrition and health.
Year(s) Of Engagement Activity 2020
 
Description Women of the Future Conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This event for ~250 Year 10 female students aimed to inspire the students into studying and developing careers in science through meeting scientists
Year(s) Of Engagement Activity 2019
 
Description Year 10 UEA Summer School Protein Workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact This session enabled students to understand the concept of protein biochemistry and basic bioinformatics by use of online free available software.
Year(s) Of Engagement Activity 2019
 
Description speed networking event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact We attended a speed networking event for pupils in year 12 at Wymondham Sixth Form College. This involved talking about our career trajectories, what we do as scientists on a day to day basis and importantly the important work being carried out here at the Quadram Institute. Students were keen to hear more about the interaction of food and the gut microbiota and their influence to health.
Year(s) Of Engagement Activity 2019