HDHL-Biomarkers: CirculAting Bile Acids as biomarkers of metabolic health - Linking microbiotA, Diet and Health (CABALA_DIET&HEALTH)
Lead Research Organisation:
University of Reading
Department Name: Food and Nutritional Sciences
Abstract
Bile acids (BA) through TGR5 and FXR regulate mammalian inflammation, lipid, glucose, and energy metabolism, and are in turn regulated by diet:microbe interactions in the gut. CABALA_DIET&HEALTH aims to establish circulating BA profiles as biomarkers of health, modulated by diet which reflect a change in metabolic health.
Using existing data and new mechanistic studies we will provide direct evidence in humans that diet:gut microbiota interactions modulate plasma BA profiles and modulate host health. Our aim is to identify plasma BA profiles as health biomarkers and establish microbiota modulation of BA signalling as a unifying molecular basis for efficacious probiotic, prebiotic and polyphenol functional foods.
Using existing data and new mechanistic studies we will provide direct evidence in humans that diet:gut microbiota interactions modulate plasma BA profiles and modulate host health. Our aim is to identify plasma BA profiles as health biomarkers and establish microbiota modulation of BA signalling as a unifying molecular basis for efficacious probiotic, prebiotic and polyphenol functional foods.
Technical Summary
Bile acids (BA) through G protein-coupled and nuclear receptors regulate mammalian inflammation, and lipid, glucose, energy, and xenobiotic metabolism. 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 hydrolyzing 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 will establish whether dietary modulation of BA profiles indicate a change in health status. Using samples from the RoCAV cohort and existing randomised control trials (RTC), we will correlate CBA profiles with adherence to the Mediterranean diet, intake of fibre/polyphenol rich foods and measures of metabolic health. In a bespoke short-term RTC we will measure the ability of probiotics, prebiotics and polyphenols to modulate postprandial 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. 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. CABALA_DIET&HEALTH will provide direct evidence in humans that diet:gut microbiota interactions, as indicated by CBA profiles, determine metabolic disease risk providing a validated biomarker of health and a unifying molecular basis for efficacious probiotics, prebiotics and polyphenols.
Planned Impact
CABALA_DIET&HEALTH aims to improve our understanding of the fundamental link between nutrition and circulating bile acids (CBA) profiles, key signalling molecules involved in regulating host metabolic and immune homeostasis, and potential biomarkers of health status. This improved understanding we believe, will unravel a rational scientific basis for healthy eating guidelines, providing the European consumer the opportunity to make informed choices when building their diets from a variety of foods. It will provide the European food industry with key knowledge on how specific food ingredients regulate BA profiles and identify new targets to improve the foods we eat. Finally, it will also we believe, deliver health care providers a validated biomarker of the long-term trajectory from health to chronic diet/life-style associated disease. Our project will maximise the knowledge and investment from existing initiatives e.g. RoCAV cohort and create synergies with relevant initiatives in particular the JPI Biomarker projects FOODBALL and MIRDIET which members of this consortium are directly linked. This project will also provide a multidisciplinary, trans-omics and inter-sector training for early stage researchers, thereby supporting European scientific/clinical/industrial research infrastructure. This will ensure a
critical mass will be achieved to contribute to the JPI vision of improving public health through dietary strategies and a more informed society.
critical mass will be achieved to contribute to the JPI vision of improving public health through dietary strategies and a more informed society.
Organisations
Publications
Ulaszewska MM
(2020)
Two apples a day modulate human:microbiome co-metabolic processing of polyphenols, tyrosine and tryptophan.
in European journal of nutrition
Pushpass RG
(2022)
Circulating bile acids as a link between the gut microbiota and cardiovascular health: impact of prebiotics, probiotics and polyphenol-rich foods.
in Nutrition research reviews
Pushpass R
(2021)
The effect of probiotic, prebiotic and polyphenol interventions on gut hormones and markers of glycaemic control: findings from the CABALA study
in Proceedings of the Nutrition Society
Alzoufairi S
(2022)
Impact of the CYP7A1 single nucleotide polymorphism rs3808607 on postprandial lipids and gut hormones in response to functional interventions -findings from the CABALA study
in Proceedings of the Nutrition Society
Alzoufairi S
(2021)
The effect of probiotic, prebiotic, and polyphenol interventions on cardiovascular disease risk markers: findings from the CABALA study
in Proceedings of the Nutrition Society
Pushpass RG
(2023)
Chronic consumption of probiotics, oats, and apples has differential effects on postprandial bile acid profile and cardiometabolic disease risk markers compared with an isocaloric control (cornflakes): a randomized trial.
in The American journal of clinical nutrition
Koutsos A
(2020)
Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults: a randomized, controlled, crossover trial.
in The American journal of clinical nutrition
| Description | Background Dietary components which impact on the gut microbiota can have beneficial effects on cardiometabolic health, possibly mediated by altered bile acid (BA) metabolism. However, impacts of these foods on postprandial BAs, gut microbiota and cardiometabolic disease risk markers are unclear. Objective To determine acute and chronic effects of probiotics, porridge oats and apples on BAs, gut microbiota and cardiometabolic health biomarkers. Design Using an acute within chronic parallel design, 61 volunteers (mean±SD, age 52±12 y and BMI 24.8±3.4 kg/m2) were randomised to consume 40g cornflakes with 2 Lactobacillus reuteri capsules (>5 × 109 CFU), or 40g cornflakes (control), 40g whole rolled oats or 2 Renetta Canada apples, all with 2 placebo capsules daily for 8 weeks. At baseline and week 8, fasting and postprandial blood BAs and markers of cardiometabolic health were measured prior to and following a high fat test meal. Faecal samples were collected for measurement of BAs and gut microbiota composition. Results Summary measures for the postprandial unconjugated (maximum concentration (Cmax), area under the curve (AUC) and incremental AUC (iAUC)), secondary (Cmax) and hydrophobic (iAUC) BAs were significantly increased after 8 weeks probiotic intervention compared to the control (p=0.049). At week 0, the apple and oat test meals decreased postprandial serum glucose (p=0.05), insulin (AUC and iAUC) and C peptide (AUC) responses (p=0.002). Postprandial NEFA (minimum concentration, AUC and iAUC) was also higher after the apple-rich than control test meal (p=0.027). There was a trend for decreased fasting apolipoprotein B after the apples intervention than control (p=0.037). None of the interventions modulated the gut microbiota. Conclusions These results support beneficial effects of apples and oats on postprandial glycaemic control and the ability of the probiotic Lactobacillus reuteri to modulate postprandial plasma BA profiles. However, no relationships between circulating bile acids and cardiometabolic health biomarkers were evident. |
| Exploitation Route | This could be used to inform dietary policy on types of fruits to consume for health and inform future studies in this area |
| Sectors | Agriculture, Food and Drink,Healthcare |
| Title | CABALA diet and Health Study |
| Description | A randomly controlled human dietary intervention study to determine the effect of foods containing polyphenols, probiotcs and prebiotics compared with control on circulating LDL-cholesterol, bile acids and other cardiovascular risk factors. |
| Type | Preventative Intervention - Nutrition and Chemoprevention |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2017 |
| Development Status | Under active development/distribution |
| Impact | To determine whether circulating bile acids can be used as a biomarker of health status. |
| URL | https://clinicaltrials.gov/ct2/show/NCT03369548 |
| Description | 3 minute thesis presentation in the 1st Food and Nutritional Sciences 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) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | A presentation given at the Spring 2019 Food Science and Nutrition conference at University of Reading. This was in the form of a 3 minute talk summarizing the CABALA study, its aims and activities to date which led to questions from academic staff and students about the study. |
| Year(s) Of Engagement Activity | 2019 |
| Description | 4th International Conference of JPI HDHL - Introduction to CABALA study by PhD student |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | The CABALA diet & healthy study at University of Reading was presented by PhD student Buthaina AlAthari. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Doctoral Research Conference 2019 Film Contest - Vlog of the CABALA diet and health study by Shouq Alzoufairi (PhD student) June 19th 2019 |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | A VLOG was produced describing the activities of the CABALA randomized controlled clinical trial. The VLOG was shown to an audience of students and academic staff at the doctoral conference at University of Reading, showcasing our research and sparking interest in our activities to wider members of the university. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Hugh Sinclair Nutrition Research Symposium 2018-Impact of prebiotics, probiotics and polyphenols on platelet function-PhD student |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Buthaina AlAthari, PhD student, presented the protocol for the CABALA diet & health study at the annual PhD symposium. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Interview on Radio Berkshire and Talk Talk radio, 20th December 2019 - Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults/Introducing the CABALA study. Professor Julie Lovegrove. |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Professor Julie Lovegrove gave 2 regional radio interviews about the journal article "Two apples a day lower serum cholesterol and improve cardiometabolic biomarkers in mildly hypercholesterolemic adults" which was published in AJCN in 2019. This results from this study led to the CABALA study which will further explore the effects of apples and other gut friendly foods on cardiometabolic health, which Professor Lovegrove discussed in her interviews, showcasing the research to the general public and a wider audience. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited presentation at International conference. 13th Federation European Nutrition Societies (FENS) meeting. "Dietary bioactives and cardiovascular Health" Dublin, Ireland. Julie Lovegrove |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | An invited presentation at 13th Federation European Nutrition Societies (FENS) meeting. "Dietary bioactives and cardiovascular Health" Dublin, Ireland. approximately 50 scientists in the audience. Sparked questions and discussion and potential future collaborations |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited presentation at scientific workshop for the 2nd Anniversary of the Institute of Food, Nutrition and Health. Entitled "Hugh Sinclair Unit: History, Achievements and Future. Reading, UK. Professor Julie Lovegrove |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited presentation on the research performed at the Hugh Sinclair Unit of Human Nutrition . The audience was mixed and was approximately 90 scientists, those from industry, policy makers. |
| Year(s) Of Engagement Activity | 2019 |
| Description | JPI HDHL Science Vlog Contest - Vlog of the CABALA diet and health study by Dr Rose-Anna Pushpass and Shouq Alzoufairi (PhD student) |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The JPI HDHL Science Vlog Contest was part of the 5th JPI HDHL conference on February 20 2019. A 3 minute video was created to demonstrate what the CABALA project is about, the potential impact of the project and the relevance for society and health. The video was screened at the conference and will be made available on YouTube on the JPI HDHL channel. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.youtube.com/channel/UCEqSiUWuRzkhe-0R5w912DQ |
| Description | Keynote presentation at 11th Probiotics, prebiotics, new foods, nutriceuticals, botanicals & phytomedicals for nutrition and human, animal and microbiota health. by Julie Lovegrove entitled "Probiotics, prebiotics & polyphenols: bile acids & CVD risk - CABALA study" Italy |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Keynote presentation at an international conference to disseminate the finding from the CABALA study |
| Year(s) Of Engagement Activity | 2021 |
| Description | Oral presentation at the international Nutrition Society Summer Conference by Rose-Anne Pushpass entitled "The effect of probiotic, prebiotic and polyphenol interventions on gut hormones and markers of glycaemic control: findings from the CABALA study.". |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | An oral presentation to disseminate research findings and associated with a published abstract in the Proceedings of the Nutrition Society |
| Year(s) Of Engagement Activity | 2021 |
| Description | Poster presentation at Nutrition Society Summer Conference 2021 by Shouq Alzoufairi entitled "The effect of probiotic, prebiotic, and polyphenol interventions on cardiometabolic disease risk markers: findings from the CABALA study." |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | A poser presentation to disseminate research findings at an international conference to researcher. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation at CABALA consortium kick-off meeting in London-Overview of Human intervention study at University of Reading-Professor Julie Lovegrove |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Other audiences |
| Results and Impact | The presentation was given to members of the CABALA project research group with members present from projects partners from Ireland, Italy and the UK. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Presentation at STEM for Britain awards ceremony by Julie Lovegrove entitled "Importance of nutritional science today" in Parliament, London, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited presentation at STEM for Britain award ceremony in Parliament, London UK for scientist, public and Parliamentarians |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation at STEM for Britain awards ceremony by Julie Lovegrove entitled "Nutritional science and our future" in Parliament, London, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited presentation at STEM for Britain award ceremony in Parliament, London UK for scientist, public and Parliamentarians |
| Year(s) Of Engagement Activity | 2022 |
| Description | Presentation at an MRC NRP Best Practice in Human Nutrition workshop by Julie Lovegrove entitled "Design, Conduct and Reporting of Clinical Trial in Nutrition" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | A presentation given at a workshop for debate and discussion and for further collaboration |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation at research group meeting Introduction to the CABALA study presented by Dr Camilla Pedersen |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | An overview of the CABALA study protocol was presented to other members of the research group. |
| Year(s) Of Engagement Activity | 2017 |
| Description | Presentation at research group meeting Update on the CABALA study presented by Dr Rose-Anna Pushpass |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | An overview of the CABALA study progress was presented to other members of the research group. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation at the ERA-HDHL - BioNH Final Symposium, 26th October 2020 - CABALA_diet&health: CirculAting Bile Acids as biomarkers of metabolic health - Linking microbiotA, Diet and Health. Professor Kieran Tuohy. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | A presentation at the Science Foundation Ireland, ERA-HDHL - BioNH Final Symposium on the outcomes from the study's consortium partners from the UK, Ireland, Italy and Israel. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Presentation for the University of Nevarra MSc viva, 11th September 2019 - Circulating Bile Acids As Biomarkers of Metabolic Health - Analysis of the Impact of Different Diets on Body Composition, Food Intake, Blood Pressure and Gastrointestinal Symptoms. Angeles Moron Ortiz (MSc placement student) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | A presentation given describing the CABALA study and preliminary results generated during the randomized controlled trial, a visiting MSc student presented this data on return to her home institution in Spain. This sparked questions and discussion with her supervisory team. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation for the consortium meeting, 29th January 2021 - The effect of probiotic, prebiotic and polyphenol interventions on cardiometabolic disease risk markers: findings from the CABALA study. Rose-Anna Pushpass, Post-Doctoral Research Assistant |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Presentation for the consortium partners from Ireland and Italy, discussing the most recent findings from the CABALA study, questions and discussion afterwards and interest from study partners. |
| Year(s) Of Engagement Activity | 2021 |
| Description | Presentation in UK Parliament for STEM for Britain by Julie Lovegrove |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Presentation at STEM for Britain.entitled "Nutritional science and our future". Aitlee Suite Parliament, London, UK |
| Year(s) Of Engagement Activity | 2022 |
| Description | Presentation 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) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | This is an annual conference with more than 80 participants including academic staff, post-doctoral research fellows, students (PhD, MSc and BSc) and external academic and industrial visitors. The aim is to showcase and communicate research projects undertaken by current PhD students and researchers in Food and Nutritional Sciences Research at the University of Reading. Shouq Alzoufairi, a PhD student working on the project, presented her work on the CABALA project. The presentation was received well and other delegates expressed interest in the research project with questions asked at the end of the talk. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Presentation in the FNS Research Symposium, University of Reading, 3rd November 2020 - The effect of probiotic, prebiotic and polyphenol interventions on cardiometabolic disease risk markers: findings from the CABALA study. Shouq Alzoufairi (PhD student) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | An annual university school conference with more than 80 participants including academic staff, post-doctoral research fellows, students (PhD, MSc and BSc) and external academic and industrial visitors. The aim is to showcase and communicate research projects undertaken by current PhD students and researchers of the Food and Nutritional Sciences Department, University of Reading. Shouq Alzoufairi, a PhD student working on the project, presented the most up to date findings from the study. The presentation was well received and led to questions afterwards and interest from attendees. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Presentation in the FNS Research Symposium, University of Reading, 5th November 2019 - The effect of probiotic, prebiotic and polyphenol interventions on biomarkers of cardiometabolic health. Shouq Alzoufairi (PhD student) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | A poster presentation given at the Autumn 2019 food science and nutrition conference at the University of Reading, sparking questions and discussion from postgraduate students, academic staff and visiting industry professionals. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Webinar for Team Satchel by Julie Lovegrove entitled "My career in Nutrition Science" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | Webinar for Team Satchel that are engaged with school nationwide to highlight opportunities for different subjects and careers. |
| Year(s) Of Engagement Activity | 2022 |