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.

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.

Publications

10 25 50
 
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 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 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 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 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