Current Projects

2016-ongoing

Grant awarded: £488,040

Timescale: 3 years 

 

The Urinary Microbiome and its Relation to Morbidity in Older People
 

Urinary symptoms and signs in the elderly are closely associated to frailty, delirium and distress, but our understanding of the relationship of the urinary flora and morbidity is currently very limited, leading to overtreatment with antibiotics. This study has the potential to re-write text books, which have propagated a false dogma that the urine is sterile, and create the first step to understanding the implications for the host of different urinary patterns of microbes.  First cataloguing the populations of microbes in older people is essential at this stage of the science, to generate hypotheses that would be testable experimentally.  In the shorter term, easy-to-obtain mid stream urine analysis could also be used to stratify management of older adults. 

2014-2017

Grant awarded: £315,000

Timescale: 3 years

 

The role of the gut microbiome in cognitive decline and risk for dementia.

 

The aim of this three-year project is to explore patterns of human faecal microbiome with cognitive performance and decline in older adults, utitizing up to 900 older twins studied longitudinally to control for host and family influences and explore metabolic mechanisms

2016-ongoing

Grant awarded: £9,917.14

Timescale: 3 years

 

Biotwincot – Biology of twins from conception to toddler
 

Foetal programming – the adaptive responses of the foetus to a variety of environmental cues, and consequences of mismatch between the prenatal and postnatal environments – can permanently shape the body’s structure, function, and metabolism and contribute to adult disease. The influence of the microbiome – the microorganisms living in and on a mammalian host - and how it is acquired in humans is poorly understood. 

 

This project addresses this deficiency by studying the human microbiome longitudinally during early development, from the earliest possible time during pregnancy, using nature’s controlled experiment, twins. The project aims to pilot collection of microbiome and additional biological samples from 10 mothers and twin-pairs at four time-points during the first year of life, to assess the feasibility to support a major project of this kind.

2017 – ongoing

Grant awarded: £148,422

Timescale: 4 years 6 months

 

Exploring the cardio-metabolic health-associated with the faecal metabolome.

 

The goal of this project is to increase our understanding of how molecules produced by microbes influence our health.   This study aims to identify the biochemical signature of cardio-metabolic health in the faecal metabolome and to determine its links with diet, the gut microbiome and host genetics. An understanding of these links offers a unique target for intervention to prevent and reverse chronic disease. This is a totally novel proposal and we are the first group in the world to use faecal metabolites as health indicators.

2017 – ongoing

Grant awarded: £155,234

Timescale: 3 years

 

Utilising omega 3 and fibre to improve metabolic health: a proof of concept nutritional intervention study targeting the gut microbiome.

 

The growing importance of the gut microbiota in all aspects of human health is clear.  Unlike our genomes, this is potentially highly modifiable and tightly related to metabolic and immune efficiency, energy and fatty acid metabolism, and satiety hormones. We have recently shown that serum levels of omega-3 fatty acids correlate with higher microbiome diversity, and are linked to lower inflammation of the gut. The study will measure faecal metabolites relevant to fatty acid metabolism (short chain fatty acids) and the abundance of microbial species linked to higher or lower inflammation and immune cell phenotypes, to unravel the link between inflammation, diet and metabolic syndrome. There is a real lack of good diet intervention studies in this field and if successful this trial will pave the way to funding a wide variety of other diet intervention studies. 

2017 – ongoing

Grant awarded: £87,844

Timescale: 3 years

 

A statistical framework for personalised nutrition recommendations based on genetic and anthropometric date.

 

This project will explore the genetic influences on healthy diet, impact on disease and ageing.  The intended outcome is the identification of patterns in the genome which can predict responses to diet to improve health.  The study will investigate the relationship between genetic factors, dietary habits, anthropometric traits and cardio-metabolic traits, with the aim of proposing personalised nutrition recommendations and minimising the risk of obesity.

2018 – ongoing

Grant awarded: £147,494

Timescale: 2 years 3 months

 

Gut microbiome modulation of fasting glucose homeostasis and postprandial glycaemic response in TwinsUk and PREDICT: towards personalised diet for healthy aging.

 

This highly novel study will pioneer the identification of a personalised diet specific to an individual’s microbiome and responses to diet, using a bioinformatics approach.  Insulin resistance is highly prevalent worldwide and has strong associations with many age-related conditions. There is also evidence that age and decreased diversity and increased fragility of the gut microbiome, play an important role in insulin resistance. Preventive strategies have focused on general dietary guidelines, to reduce caloric intake or focus on the glycaemic index of food. The glycaemic response to food shows high variability between individuals and the microbiome is now recognised as a crucial element explaining this personal uniqueness. This study aims to identify bacterial species and pathways involved in fasting and postprandial glucose homeostasis and how they interact with diet and age. Our results will help to design personalized dietary guidelines and interventions aimed to prevent insulin resistance based on the individual’s age and on their gut bacterial community. 

2018 – ongoing

Grant awarded: £149,999

Timescale: 4 years

 

Influence of the gut microbiome on inter-individual differences in blood pressure at fasting and in response to a combined glycaemic and lipaemic test meal challenge.

 

The object of this study is to assess the relationship between the gut microbiome, fasting and post-prandial blood pressure (BP). The study aims to identify bacterial species and pathways involved in this process using ambulatory BP measures and to assess how they interact with diet and age. The goal is to design personalised dietary guidelines and interventions aimed at treating and preventing hypertension based on the composition of the individual's gut microbiome. 

2019 – ongoing

Grant awarded: £142,923

Timescale: 3.5 years

 

Assessing the role of long and short-term food choices on gut microbiome-induced visceral fat mass accumulation. 

The object of this study is to determine the contribution of host genetic, diet and the gut microbiome on fat accumulation. Twins are ideal for dissecting the contribution of individual genetic and environmental influence on human traits. However, there is still a lack of good models which allow the separation of diet and microbiome effects to study obesity-induced cardiometabolic diseases. The study will use food frequency questionnaires (collected at three time points) and 24h diet records coupled to shotgun metagenomics profiling of the gut microbiome of 1000 volunteers from the TwinsUK cohort. This ambitious proposal will tackle this issue by applying newly developed food classification methods to permit a more comprehensive understanding of the impact of long and short term-food choices on the gut microbiome. These results will be used to improve our understanding of how the microbiome impacts visceral fat.   

2018 – ongoing

Grant awarded: £1,351,673

Timescale: 4 years

 

Creation of a research microbiome laboratory facility.

 

As the gut microbiome research is still at its infancy, there is a lack of consent for method standardisation across laboratories. The state of our facilities at the Department of Twin Research only allows us to store raw material collected from the twin’s visits. The department then relies on collaborators or companies to perform DNA extraction and sequencing. DNA extraction is a crucial step that can induce bias in the data if not performed under rigorous and uniform conditions. The large set of faecal samples collected over the years and the sparse nature of the twin’s visits has made it difficult to standardise DNA extraction. Consequently, the bias in the data has accumulated over the years. Also, the length of raw material storage can affect the outcomes of bacterial DNA sequencing. Performing DNA extraction in-house will allow controlling for these factors.  The budget includes an amount for sequencing to be outsourced as the costs are a third of that offered by our hospital sequencing department, as it would struggle to handle the workload within two years.

2019- ongoing

Grant awarded: £321,086

Timescale: 4 years

 

Targeting the gut microbiome and its metabolites to improve cardiovascular outcomes

This study aims to identify specific factors that result in improved cardiovascular outcomes. The project will combine state-of-the-art high-throughput omics data from three population-based cohorts.  The study will use extensive longitudinal CVD phenotyping and dietary data, to identify bacterial species, microbial metabolites, nutritional intakes and pathways that impact the host cardiovascular phenotypes. The goal is to advance our understanding of the mechanisms behind cardiovascular outcomes, with the potential to lead to effective prevention, intervention, and management strategies for treating cardiovascular diseases by targeting the gut microbiome and thus mitigating its health burden.

2019 – ongoing

Grant awarded: £704,689

Time scale: 3 years

 

Using the faecal metabolomics and serum glycomics to unravel the microbiome inflammatory pathways causative of cardiovascular disease.

 

This project will use data from over 4000 twins to find how the chemical substances produced by microbes in our guts positively or negatively influence heart disease. Using a method called “Mendelian Randomization”, we will investigate how a person’s genes influence the effect of the substances produced by microbes to determine which of these microbial substances are causing heart disease (as opposed to being an effect of people who are less healthy producing these substances). We will then generate a database of all these genetic/chemical substance/disease relationships and combine it with data from a recent nutrition study called PREDICT. In the PREDICT study we gave 1000 people a very high fat content meal to raise fat and cholesterol in blood and to increase levels of proteins with sugars attached to them.  These are called “glycosylated” proteins. We will see how the type of substances produced by microbes affect the increased levels of cholesterol in blood and of these glycosylated proteins. This will help us understand how to individually modulate a person’s diet to reduce risk of heart disease.

2020- ongoing

Grant awarded: £9,990

Time scale: 12 months

 

Targeted metabolomics of urine samples to understand the role of the gut microbiota in food polyphenol metabolism.

 

Polyphenols are metabolites present in a wide range commonly consumed foods such as tea, coffee and red wine. Polyphenols exert a beneficial effect on host metabolic health that is partly mediated by the gut microbiota. However, the effect of the gut microbiota composition on polyphenol-induced health benefits are still poorly understood. The twin population is ideal to dissect the contribution of individual genetic and environmental influence on human traits. In this pilot study, the urine polyphenol profile of 100 twin pairs with concomitant dietary and gut microbiota information will permit a more comprehensive understanding of the effects of the metabolism of food polyphenols by the gut microbiota on host health. These results will be used to improve our understanding of how the gut microbiota together with food impacts host metabolism and will serve as evidence to seek for larger grants. The project will be supported by experts in polyphenols, epidemiology and gut microbiome studies at King’s College London between the Department of Twin Research and Nutritional Sciences. This work is of wide interest to microbiome, nutritionist and metabolic syndrome research communities, and is perfectly in line with this call as it will help develop new analytical methods to study diet-microbiome interactions in health and disease. 

2020 – ongoing

Grant awarded: £519,996

Time scale: 12 months

 

TwinsUK Covid-19 Research Program

 

The Covid-19 pandemic is a major public health emergency and a rapid experiment in twins can make a huge difference to understanding the disease and finding ways of preventing it. TwinsUK is an internationally unique resource with ~7000 actively participating twin pairs spread around the UK.  Apart from being twins they are representative of the UK population overall. 

 

Even in Wuhan, the initial epicentre of the pandemic, only ~5% of the population developed the classical infection, suggesting that it is highly likely that susceptibility to the infection varies widely between individuals.   Whilst much of this is likely to be related to chance of exposure to virus and behavioural factors, it is also likely that other factors known to have major effects on immune function, such as genetics, microbiome and immunological parameters themselves will be involved.

 

Using the TwinsUK cohort gives the program considerable advantages over newly recruited cohort or case only studies, because a. they are twins, enabling assessment of heritability and controlling for environmental effects in genetic studies, b. they are nationally distributed and community dwelling, so will give an accurate national picture of the pandemic, c. they are extensively characterised already, so many analyses will be possible with minimal additional phenotyping costs, d. the TwinsUK and GSTT-KCL NIHR BRC are well set up to run a study of this magnitude and e. The Wellcome trust and MRC already support the core of the cohort so may expand on this study longer term with the development of a Covid-19 Bioresource.

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