CirculAting Bile Acids as biomarkers of metabolic health - Linking microbiotA, Diet and Health.

ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)
CirculAting Bile Acids as biomarkers of metabolic health - Linking microbiotA, Diet and Health.
Kieran Tuohy
Fondazione Edmund Mach


Partner Organization Partner Country
University Of ReadingUnited kingdom
University College CorkIreland
University of InsubriaItaly

1. Overall project description

1.1 Summary

Bile acids (BA) through G protein-coupled bile acid receptor 1 (GPBAR1 or TGR5) and nuclear receptors like Farnesoid X receptor (FXR) regulate mammalian inflammation, and lipid, glucose, energy, and xenobiotic metabolism. The gut microbiota modulates the enterohepatic circulation of BA and microbially produced secondary BA appear to be more potent receptor agonists than primary BA, providing a mechanistic link between microbiome structure/function and regulation of host physiology. Evidence mainly from animal studies shows that dietary fibers and polyphenols can bind BA driving them into the colon and modifying their absorption and/or excretion and importantly, that exercise can impact on BA metabolism. Similarly, certain bile salt hydrolysing (BSH) probiotic bacteria modulate circulating bile acid (CBA) profiles and strongly influence cholesterol uptake. However, human data confirming dietary modulation of CBA profiles and subsequent regulation of physiological homeostasis remains elusive. CABALA_DIET&HEALTH aims to establish circulating BA profiles as biomarkers of health, modulated by diet and exercise which reflect a change in metabolic health. Using samples from the RoCAV cohort and existing randomised control trials (RCT), we will correlate CBA profiles with adherence to the Mediterranean diet, intake of fiber/polyphenol rich foods and measures of metabolic health (BMI, insulin/glucose and lipid homeostasis). In a bespoke short-term RCT we will measure the ability of probiotics, prebiotics and polyphenols to modulate post-prandial BA profiles and in a long term (18 month), large-scale (n=300) existing dietary and lifestyle intervention, we will measure how polyphenol rich whole foods and exercise promote metabolic health in susceptible individuals through modulation of BA signalling (DIRECT-PLUS study). Finally, we will link BA profiles or metabotype with microbiome signatures and BA biotransformation potential using high-resolution metagenomics and establish the molecular basis of BA regulation of immune and metabolic homeostasis by measuring the relative BA-metabotype receptor activation potential. We aim to provide direct evidence in humans that diet:gut microbiota interactions, as indicated by CBA profiles, determine metabolic disease risk providing at once a validated biomarker of health and a unifying molecular basis for efficacious probiotics, prebiotics and polyphenols. Using data from existing trials, we have already correlated CBA profiles with gut microbiota, shown that in a dietary intervention with apples the observed cholesterol lowering effect may be linked to CBA regulatory processes in sex dependent manner and have developed advanced reporter systems for BA cell signalling. We have also completed measurements for the DIRECT-PLUS study and the CABALA-diet&health study in the UK. Early setbacks due to the Italian funding agency MIUR have been largely overcome and remaining analyses will be completed by project end. 

1.2 Highlights

CABALA_DIET&HEALTH aims to provide direct evidence that diet-microbiome interactions in the gut determine circulating bile acid (CBA) profiles and their physiological effects. In this second year, the project has published new analytical methodologies, analyzed data and samples from existing/ongoing studies, including the DIRECT-PLUS study in Israel, advanced in vitro models for measuring CBA cell signaling and progressed the CABALA_diet&health dietary intervention in Reading, UK.

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Duc H. Le10.1016/j.ebiom.2017.04.019Download
Rizzetto L, Fava F, Tuohy KM, Selmi C.Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex10.1016/j.jaut.2018.05.008.Download
Fava F, Rizzetto L, Tuohy KM.Gut microbiota and health: connecting actors across the metabolic system.10.1017/S0029665118002719Download
Mullish BH, McDonald JAK, Pechlivanis A, Allegretti JR, Kao D, Barker GF, Kapila D, Petrof EO, Joyce SA, Gahan CGM, Glegola-Madejska I, Williams HRT, Holmes E, Clarke TB, Thursz MR, Marchesi JR Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection 10.1136/gutjnl-2018-317842Download

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
ScientistsJulie Lovegrove, The CABALA diet & health study at University of Reading, Consortium kick-off meeting, London, 2017Presentation
Scientists, studentsCamilla Pedersen, The CABALA diet & health study, Hugh Sinclair Unit of Human Nutrition, University of Reading, 2017 Presentation
ScientistsButhaina Alathari, The CABALA diet & health study at University of Reading, JPI HDHL Conference, Brussels/Belgium, 2017Presentation
Scientists, students, general public (volunteers)Buthaina Alathari, The Effect of Probiotic, Prebiotic, and Polyphenol Intake on Platelet Function – CABALA Diet and Health, Hugh Sinclair PhD symposium, University of Reading, 2018Presentation
ScientistsKieran Tuohy, Samantha Riccadona, Lisa Rizzetto, Francesca Fava, Introducing CABALA diet & health and related existing studies, Consortium kick-off meeting, London, 2017Presentation
ScientistsKieran Tuohy, Lisa Rizzetto, EUREGIO-EFA project (including descritption of CABALA_diet&health and possibilities for collaboration), 2nd EUREGIO-EFA scientific working group meeting. Hall, Austria, 2018Presentation, workshop
ScientistsMarynka Ulaszewska. “FEM contribution WP 5.4, FOODBALL” Annual FoodBall Project Meeting in Varna (Bulgaria), 31 August-1 September 2017Presentation, workshop
General publicKieran Tuohy, “Of men and microbes” – measuring how diet:microbe interactions in the gut can reduce chronic disease risk”; International Economic Festival, Trento, Italy, 2017Presentation
General publicIris Shai “What is the actual effects of MED diet on mobilization of human fat storage pools & cardio- metabolic health? Evidence from long-term clinical trials”. International Economic Festival, Trento, Italy, 2017Presentation
Undergraduate students (nutrition)Kieran Tuohy, “A role for polyphenols in shaping the structure and function of the gut microbiome.” University of Ulster, Coleraine, UK. 2017Lecture Presentation
Scientists, Medical doctorsKieran Tuohy “Gut microbiota composition, bile acid signalling and human health: CABALA_Diet&Health”. 9th Probiotics, Prebiotics, New Foods conference, Rome, Italy, 2017Presentation
Medical doctorsKieran Tuohy, “Microbiota-diet interactions in neurodegeneration, and in Parkinson’s disease”. The selection and management of advanced therapies in the Parkinson's disease in specialist centers (National Medical Conference on Parkinsons), Rovereto, Italy, 2018Presentation
Scientists, IndustryKieran Tuohy “Probiotic reverse engineering – choose your mechanism first then your strain”. 4th Microbiome R&D and Business Collaboration Forum: Europe and Probiotics Congress: Europe. Amsterdam, 2017.Presentation
Scientists, Industry,Kieran Tuohy, “Microbiome Modulation for Improved Metabolic Health.” ILSI-Taiwan Annual meeting & Scientific Symposium, Taipei, 2018Presentation
Scientists, IndustryKieran Tuohy “ILSI Europe activities related to ‘Human Microbiome & Health”. ILSI-Europe annual Meeting, Brussels, 2017Presentation
Scientists, Medical doctorsKieran Tuohy, “The gut microbiota and human health - a molecular cross-talk”. European Medical Association Annual Conference, London 2017Presentation
General public, Medical doctorsKieran Tuohy, “The gut microbiota and human health - a molecular cross-talk”. European Medical Association Annual Conference, London 2017 Video
Medical doctors, ScientistsKieran Tuohy “Microbiota and fat tissue distribution”. Diabesità. Pisa, Italy, 2017Presentation
ScientistsKieran Tuohy “Gut microbiota functions: metabolism of nutrients and other food components.” POSITIVe Cost action meeting, Thessaloniki, 2017Presentation
General PublicAndrea Manchini, Francesca Fava, Kieran Tuohy, Siamo Europa Festival, 2018. Open-showcase of regional scientific projects funded by the EU, 3 day event, face-to-face meet the public.Meet the public face to face
Scientists, IndustryKieran Tuohy ILSI Europe Functional Foods Task force meeting, May 2018. ‘Microbiome Modulation for Improved Metabolic Health’. Brussels, 2018Presentation
General publicAlimentary Adventures- Western Gateway building UCC Spring Open Day- 17th May 2017 Meet the public face to face
Scientists /studentsOrganiser APC-ICL Postgraduate Symposium October 2017 (SLL)Presentation
Students teachersAll Ireland Schools of Pharmacy Conference (April 2017), Cork, Ireland: Impact of gut microbiota-mediated bile acid metabolism on the solubilization capacity of bile salt micelles and drug biopharmaceutical properties.Presentation
General publicScience for All Public forum and competition -finalist (April 2017), Cork, Ireland: Gut bacteria and medicines: “bugging” you to keep your health “afloat”.Presentation
General publicOctober 2017 An evening of Food at the Cornstore restaurant, Cork spoke to general public on the dietary components they were consuming and the microbes associated with fermented foodsPresentation
Students TeachersJune 2017 School representative at open days for entry students, CorkMeeting face to face
Academics & stakeholders & general publicTuohy, K. FOOD2030, PLOVDIV, Side event 6: Food in Regions – one health, from regionality to functionality. Date 13th June 2018, Venue: Sankt Petersburg Hotel, Plovdiv (BG)Presentation
Students, academics & stakeholdersKieran Tuohy, “Host:microbe cross talk in metabolic disease and healthy ageing - potential for dietary manipulation”, METAORGANISMS, MICROBIAL BIOREFINERIES AND HUMAN HEALTH, Fondazione Golinelli – Bologna, 18-19 June 2018.PresentationDownload
Academic & stakeholdersKieran Tuohy, “Microbiome and ageing – dietary microbiome modulation for improved mental and physical quality of life in old age”, at ‘Nutrition for the Ageing Brain: Moving Towards Clinical Applications’ Madrid, Spain 30– 31/08/2018Presentation
Academics, students, stakeholders & dieticiansKieran Tuohy, “The Prebiotic Effects of Whole-Grain Oats”, European Federation of the Associations of Dietitians Conference in Rotterdam, The Netherlands 28th-29thSeptember, 2018. Quaker SymposiumPresentation
Academics, students & stakeholders Kieran Tuohy, “Diet:Microbe interactions in the gut for improved health – talking molecules”, Microbiome R&D and Business Collaboration Forum: Europe, 20th to 22nd May, 2019Presentation
General publicUCC, November 2017 A series of back to back talks on Diet, microbes and health at Cork City GaolPresentation
General publicUCC, International Womens day interview for twitter and Facebook -6th March 2018Twitter/facebook
General publicUoR BBC4 Interview with Adrian Washbourne BBC Radio Science Unit 10th January 2018 broadcast as part of a four part documentary series in April 2018.Radio interview
Students & academicsDoctoral Research Conference 2019 University of Reading Film Contest - Vlog of the CABALA diet and health study by Shouq Alzoufairi (PhD student) submitted 29th April 2019Engagement focused website, blog or social media channel
Students & academicsPresentation in the UoR Food and Nutrition Science (FNS) weekly seminar, University of Reading, 22nd May 2019 - The effect of probiotic, prebiotic and polyphenol interventions on biomarkers of cardiometabolic health. Shouq Alzoufairi (PhD student)Presentation
Students & academicsJPI HDHL Science Vlog Contest - Vlog of the CABALA diet and health study by Dr Rose-Anna Pushpass and Shouq Alzoufairi (PhD student) February 20th 2019Engagement focused website, blog or social media channel
Students & academicsPresentation in the FNS Research Symposium, University of Reading, 21st February 2019 - The effect of probiotic, prebiotic and polyphenol interventions on biomarkers of cardiometabolic health. Shouq Alzoufairi (PhD student)Presentation
Students & academicsPresentation at research group meeting of UoR Nutrition Research Group: Update on the CABALA study presented by Dr Rose-Anna PushpassPresentation
Medicinal and specialist foods industryKieran Tuohy, Dr Schar ( ), presentation including CABALA_diet&health, July 19th 2018, Trieste.Presentation
Food/confectionary industry & Ferraro MSc students in nutritionKieran Tuohy, “The Gut Microbiota in health and disease - role of diet”, Ferraro and Ferraro MSc in Food and Human Nutrition, University of Turin, January 18th 2019.Presentation

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

WU Logo
This project has received funding from the European Union’s
H2020 Research and Innovation Programme under grant agreement n.696300

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