Diet-induced Arrangement of the gut Microbiome for improvement of Cardiometabolic health

Lead Research Organisation: King's College London
Department Name: Genetics and Molecular Medicine

Abstract

The gut microbiota, that is, the communities of microorganisms in the human intestine, was recently recognized as an important factor influencing health throughout all stages of life. Obesity and type-2 diabetes have globally reached pandemic-like prevalence and are major risk factors for the development of cardiovascular diseases, in particular coronary artery disease and stroke. These pathologies are referred to as cardiometabolic diseases (CMD), and to effectively tackle them it is crucial to understand interplays between dietary and microbial factors that promote or inhibit transition from early metabolic symptoms to cardiovascular complications. CMD are associated with dysbiotic microbial ecosystems in the gut, or alterations in the composition and function of the microbiota. Diet is a prime influencing factor of both the intestinal milieu and risks for developing CMD, but knowledge about the reciprocal interaction between dietary components and microbial populations is scant. Moreover, although certain gut microbial metabolites have been implicated in the onset of CMD, molecular mechanisms are poorly characterized and causal relationships have yet to be determined. The DINAMIC consortium will bridge the gap by investigating interactions between diet and the gut microbiota, and the potential of modulating these interactions for prevention of metabolic dysfunction and cardiovascular complications in humans. This would enable novel nutritional strategies for prevention of CMD. The work programme is based on a combination of analysis of prospective and genetically well-characterized human cohorts to study associations between diet, the gut microbiome and cardiometabolic health parameters, with a series of targeted nutritional and microbiota intervention studies. The complementary use of large scale and targeted strategies, and explorative and interventional approaches, will deliver insights into nutritional strategies to develop practices for modulation of the intestinal microbiome to promote cardiometabolic health.

Technical Summary

To effectively tackle cardiometabolic diseases (CMD) it is crucial to understand interplays between dietary and microbial factors that promote or inhibit transition from early metabolic symptoms to cardiovascular complications. CMD are associated with dysbiotic microbial ecosystems in the gut, that is, alterations in the composition and function of the microbiota. Diet is a prime influencing factor of both the intestinal milieu and risks for developing CMD, but knowledge about the reciprocal interaction between dietary components and microbial populations is scant. The proposal will investigate interactions between diet and the gut microbiota, and the potential of modulating these interactions for prevention of metabolic dysfunction and cardiovascular complications in humans. This would enable novel nutritional strategies for prevention of CMD. The work programme is based on: (i) state-of-the-art prospective and genetically well-characterized human cohorts to gain detailed insight into associations between dietary habits, the gut microbiome and cardiometabolic health parameters; and (ii) targeted nutritional and microbiota interventions to study causal relationships between specific diet-responsive microbial taxa and related metabolites and the development of metabolic syndrome as risk factor for cardiovascular diseases. The work is underpinned by established pipelines for assessment of 16S rRNA gene diversity and composition, as well as state-of-the-art shotgun metagenomics, metabolomics and data integration platforms. Hence, the complementary use of large scale and targeted strategies, explorative and interventional approaches, as well as standardization innovative assessment of the gut microbiota within the DINAMIC consortium will deliver penetrating insights into nutritional strategies to develop and validate practices for modulation of the intestinal microbiome to promote metabolic and cardiovascular health.

Planned Impact

The DINAMIC project will bridge the gap between observational studies linking on the one hand altered microbiota composition and function to health, and on the other, mechanistic insights and practical intervention possibilities. The proposal is a unique opportunity to combine transnational experts in epidemiology, clinical intervention, nutrition, microbial ecology, microbiome research, metabolomics and bioinformatics for the sake of diet-driven improvement of health. It joins the cohorts, expertise and facilities necessary to carry out the ambitious project. The Exploitation Strategy will be developed under the guidance of the IP case manager who will manage how results will be used in the future (e.g. further research, or commercial exploitation). The potential beneficiaries from the knowledge and materials produced include the public, industry and SMEs, and policy and decision makers. Communication (both internal & external), dissemination and exploitation of the project's activities, outcomes and products will be addressed at all stages of the project to maximize impact. The ultimate deliverables from the project will be evidence-based microbiota-based nutritional strategies to prevent cardiometabolic diseases. There will be an important teaching and training component to the research program as partners of the consortium will exchange and promote significant and outstanding transfer of knowledge and mutualisation of technological expertise and tools as well as training our future scientists. Importantly, DINAMIC will form the basis for future collaborative research that will exploit the expected novel discoveries on diet-microbiome parameters that influence cardio-metabolic disease.
 
Description Assessing the Role of Long and Short-Term Food Choices on Gut Microbiome-induced Visceral Fat Mass Accumulation
Amount £142,923 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 01/2019 
End 06/2022
 
Description Gut metabolomics 
Organisation Metabolon Inc
Country United States 
Sector Private 
PI Contribution Providing stool samples and clinical and microbiome data; data analysis; results interpretation; manuscript writing
Collaborator Contribution Providing metabolomics of gut stool samples
Impact Novel data linking gut microbe metabolites to health. Publication and on-going manuscripts, including: Zierer et al. 2018. Nature genetics
Start Year 2016
 
Description Obesity-microbiome animal model work 
Organisation Catholic University of Louvain
Country Belgium 
Sector Academic/University 
PI Contribution A collaboration started between our team and the lab of Prof Patrice Cani (Université Catholique de Louvain, Belgium). This collaboration will allow us to translate results of interest that have arisen from analysis of the TwinsUK cohort to animal models. We plan to ship gut microbiome samples from selected twins to the Belgian team for follow-on experiments.
Collaborator Contribution The Belgian team will aim to translate results of interest that have arisen from analysis of the TwinsUK cohort to animal models of obesity.
Impact No outputs have yet been generated as the material transfer agreement is still underway.
Start Year 2018
 
Company Name Zoe Global LTD 
Description Personalized nutrition company 
Year Established 2017 
Impact None yet
Website https://project-sapiens.com/
 
Description 7th Beneficial Microbes Conference - speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on research into the gut microbiome and how it impacts our general health
Year(s) Of Engagement Activity 2018
 
Description Annual European Microbiome Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Talk at the conference into research into the causative role of the microbiome in a broad spectrum of human diseases and disorders, Modelling systems.
Year(s) Of Engagement Activity 2017
URL https://10times.com/microbiome-congress
 
Description BBC Radio 4 Food Programme - That Gut Feeling 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact BBC Radio 4 Broadcast on the Food Programme entitled 'That Gut Feeling'
Year(s) Of Engagement Activity 2016
 
Description BBC Radio 4: The Second Genome 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Discussion on how the array of microbes that live on and in our bodies, is driving our metabolism and health.
Year(s) Of Engagement Activity 2018
URL https://www.bbc.co.uk/programmes/b09zgykv
 
Description BBC Radio World Service - How microbes control our weight 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Discussion on the relationship between our gut microbes and weight and how they can be the key to solve the current obesity problem
Year(s) Of Engagement Activity 2018
URL https://www.bbc.co.uk/programmes/p06pljzk
 
Description BBC online- Body fat link to bacteria in faeces 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact BBC online article featuring our research findings that link body fat to gut microbiome composition.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/news/health-37452630
 
Description BMJ Opinion on breakfast and impact on health 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Opinion article for the BMJ on how the latest scientific research has changed our views on whether skipping breakfast can contribute to weight gain
Year(s) Of Engagement Activity 2019
URL https://blogs.bmj.com/bmj/2019/01/30/tim-spector-breakfast-the-most-important-meal-of-the-day/
 
Description Blog for the Conversation UK 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article for the Conversation UK on how skipping breakfast may not have an harmful effect on our health
Year(s) Of Engagement Activity 2019
URL https://theconversation.com/skipping-breakfast-may-help-you-lose-weight-what-hunter-gatherers-can-te...
 
Description Bristol Loves Bugs 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Keynote speaker at the Bristol Loves Bugs event on 'The human microbiome in health and disease'
Year(s) Of Engagement Activity 2016
 
Description Exploring Human Host-Microbiome Interactions in Health and Disease (ClR) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact C.I. Le Roy, J.E. Castillo-Fernandez, Ruth Bowyer, T.D. Spector, C.J. Steves, S.K. Forslund, J.T. Bell. Heritability of antibiotic resistance potential in the gut microbiome. Exploring Human Host-Microbiome Interactions in Health and Disease, Cambridge UK. 2017
Year(s) Of Engagement Activity 2007
 
Description Financial Times - Diets, fads, and feeding your gut 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An interview with the Financial Times online on the subject of 'Diet, fads and feeding your gut'
Year(s) Of Engagement Activity 2016
URL https://www.ft.com/content/c52f62a1-0940-4bbf-9836-ca5db7626967
 
Description French Wix School Visit (CLR 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact CLR attended a public engagement event - the Native Scientist event the French Wix School in London, UK 2018.
Year(s) Of Engagement Activity 2018
 
Description ITV This Morning: Get Your Gut Health Right 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interview on ITV This Morning (TV) to discuss the role of gut microbes and diet in our health
Year(s) Of Engagement Activity 2018
URL https://www.itv.com/thismorning/health/get-your-gut-health-right
 
Description Intelligence squared - The bittersweet truth about what we eat 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact A talk at an event organised by Intelligence Squared entitled 'BITTERSWEET TRUTH ABOUT WHAT WE EAT: Nutrition, health, and the science of the gut'
Year(s) Of Engagement Activity 2017
 
Description JPI 'A Healthy Diet for a Healthy Life' research meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A research overview talk at the JPI 'A Healthy Diet for a Healthy Life' research meeting on 'TwinsUK gut microbiome research overview'
Year(s) Of Engagement Activity 2016
 
Description Latitude Festival of Literature - YOUR FOOD YOUR MOOD 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Talk at the Latitude Festival of Literature on the subject of 'YOUR FOOD - YOUR MOOD: Real Food and Gut Health'
Year(s) Of Engagement Activity 2016
 
Description Microbe lecture: Old Street Takeover -London 
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 Talking to the public as part of a number of talks at Old Street (London)
Year(s) Of Engagement Activity 2018
 
Description New Scientists the Gut's trick for controlling the bacteria that lives in it 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Article for the Nw Scientist
Year(s) Of Engagement Activity 2016
URL https://www.newscientist.com/article/dn28766-your-guts-trick-for-controlling-the-bacteria-that-live-...
 
Description Participation at the JPI HDHL Conference (Dec 2017) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Participation at the JPI HDHL Conference (Dec 2017) held in Brussels to engage discussion between academic, industrial and policy makers on diet and health related questions.
Year(s) Of Engagement Activity 2017
 
Description Radio 4 The Food Programme: The Big Carbs Debate 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Providing input on discussion on the role of carbohydrates in our health
Year(s) Of Engagement Activity 2018
 
Description TWINS 2017: The Joint 4th World Congress on Twin Pregnancy and 16th Congress of the International Society of Twin Studies (ISTS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk at a conference that aims to further research and public education in all fields related to twins and twin studies, for the mutual benefit of twins and their families and the scientific community.
Year(s) Of Engagement Activity 2017
URL https://www.mcascientificevents.eu/wp-content/uploads/2017/05/Scientific-Programme-29.05.pdf
 
Description Talk a the 4th Annual European Microbiome Congress, London, UK (JTB 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited talk (by JTB) on the topic of "The Human Gut Microbiome And Metabolic Health" at the 4th Annual European Microbiome Congress, London, UK, November 2018.
Year(s) Of Engagement Activity 2018
 
Description Talk at the European Association for the Study of Diabetes (EASD) 54th annual meeting, Berlin, Germany (JTB 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Symposium Talk (by JTB) at the European Association for the Study of Diabetes (EASD) 54th annual meeting, Berlin, Germany, October 2018; on the topic of "The role of the gut microbiota in human type 2 diabetes: insights from multi-omic studies".
Year(s) Of Engagement Activity 2018
 
Description Talk at the JPI HDHL DINAMIC meeting in London, UK (CLR 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk (by CLR) at the JPI HDHL DINAMIC meeting in London, UK in 2018 - discussing progress on the project; extensions and future collaborations.
Year(s) Of Engagement Activity 2018
 
Description Talk at the JPI HDHL DINAMIC meeting in Napoli, Italy (CLR 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk (by CLR) on 'Diet-gut microbiome interactions impact on cardiometabolic diseases in TwinsUK' at the JPI HDHL DINAMIC project meeting in Napoli, Italy 2018.
Year(s) Of Engagement Activity 2018
 
Description Talk at the KCL School of Life Course Sciences research meeting (CLR 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk (by CLR) at the King's College London School of Life Course Sciences postdoctoral association research meeting, London, UK (2018), on the topic of "Exploring host-gut microbiota metabolic crosstalk in prospective cases of T2D".
Year(s) Of Engagement Activity 2018
 
Description The BMJ Views and Reviews the butter versus margarine discussion 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Review on how the discourse butter versus margarine became so polarized and how we should encourage scientists to challenge current dogmas to further science
Year(s) Of Engagement Activity 2019
URL https://www.bmj.com/content/364/bmj.l70
 
Description The Conversation Blog: Postbiotics 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact How postbiotics produced by gut bacteria can help our body and health.
Year(s) Of Engagement Activity 2018
URL https://theconversation.com/postbiotics-and-smart-toilets-new-era-of-harnessing-our-microbial-chemic...
 
Description The Conversation UK Blog: Stop Measuring Obesity With A Ruler: 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Quality not quantity affects our obesity rates
Year(s) Of Engagement Activity 2018
URL https://theconversation.com/stop-measuring-obesity-with-a-ruler-weve-discovered-a-far-better-predict...
 
Description The Guardian - Is your gut making you sick? 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Article in the Guardian entitled 'Is your gut making you sick?'
Year(s) Of Engagement Activity 2016
URL https://www.theguardian.com/lifeandstyle/2016/aug/01/is-your-gut-making-you-sick
 
Description The Guardian article: Human Microbiom e 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article explaining the role gut microbes play in our health
Year(s) Of Engagement Activity 2018
URL https://www.theguardian.com/news/2018/mar/26/the-human-microbiome-why-our-microbes-could-be-key-to-o...
 
Description The Independent - Forget counting calories, fat and sugar 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact An interview in the Independent entitled 'Forget counting calories, fat and sugar - taking care of your gut is what matters'
Year(s) Of Engagement Activity 2016
URL http://www.independent.co.uk/life-style/health-and-families/health-news/forget-counting-calories-fat...
 
Description The Sugar Reduction Summit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact the debate looks at the viability and efficacy of newly proposed regulations including sugar tax, advertising and EU level changes to labelling, to explore the effectiveness and impact of voluntary measures and to look at the latest research on the role of sweeteners in sugar reduction.
Year(s) Of Engagement Activity 2017
URL http://www.thesugarreductionsummit.co.uk/
 
Description The magical microbe: how to feed your Gut (The Guardian) 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Article looking at the links between the microbiome and nutrition
Year(s) Of Engagement Activity 2018
URL https://www.theguardian.com/lifeandstyle/2018/jan/29/magical-microbes-how-to-feed-your-gut
 
Description UBS European Conference 2018- food as microbial medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on the latest research on the microbiome
Year(s) Of Engagement Activity 2018
 
Description World Precision Medicine Congress 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Talk at World Precision Medicine Congress 2017 which brings together academia, industry and healthcare to discuss and debate key challenges and opportunities within: Diagnostics | Big Data | Genomics | Infrastructure | Investment| Rare Diseases | Oncology |Neuroscience |Diabetes|
Year(s) Of Engagement Activity 2017
URL http://www.globaleventslist.elsevier.com/events/2017/05/world-precision-medicine-congress-2017/