The Link Between Gut Viruses and Cardiometabolic Disease 

21st February 2024 – By TwinsUK

A recent review published by researchers at TwinsUK sheds light on the potential role of viruses living in the gut, known as phages, in cardiometabolic diseases (CMDs).  

CMDs are a group of common and often preventable chronic diseases that affect the system of the heart and include type 2 diabetes mellitus, hypertension, cardiovascular disease, and non-alcoholic fatty liver disease.  They have been increasingly prevalent worldwide, with factors such as genetics, lifestyle, and diet contributing to their rise.  

More recently, the gut microbiome, a collection of microorganisms that exist in our large intestine, has also been implicated in CMDs. Interesting links have been found between bacteria and aspects of metabolic health, such as bodyweight, blood sugar and inflammation. However, the majority of existing research has focused on bacteria, overlooking other microorganisms such as phages. 

Phages are viruses that, instead of infecting human cells, infect bacteria cells, and in doing so play a crucial role in shaping bacterial communities within the gut, which in turn can affect human health. By infecting gut bacteria, phages can alter the abundance of bacteria, which may cause their levels to increase or decrease. Additionally, phages can change the way bacteria behave, for example by changing the metabolites that they release.    

Until now, studying the viruses in the gut has been challenging, which is one of the reasons why they have not been a focus of research. However, recent advancements are enabling researchers to investigate this potentially important but neglected aspect of gut health, with increasing interest being reflected in efforts such as the national Centre for Phage Research in Leicester, which aims to tackle a variety of global challenges through phages.  

Daniel Kirk, first author of the review, emphasises the importance of exploring the role of phages in CMDs: 

” As phages modulate gut bacteria communities, which in turn influence systemic health and susceptibility to cardiometabolic diseases, there is a need for a deeper understanding of how gut viruses contribute to cardiometabolic health.”   

To summarise what is currently known about phages in the gut microbiome in relation to CMDs, the authors searched for literature in this area. Across 15 studies, they found potential links between phages and obesity, type-2 diabetes mellitus, hypertension, and metabolic syndrome, amongst others. Their review highlights the potential involvement of phages in human health and provides information to inspire future research in the field, which is still at its inception and yet to be fully explored. 

The review also emphasises that harnessing the therapeutic potential of phages through phage therapy and faecal viral transplants could offer new avenues for treating CMDs. However, while the research is promising, more extensive studies and clinical trials are necessary to validate the efficacy of phage-based therapies in treating CMDs.

Lead author of the paper, Cristina Menni says:

“We highlight the broader implications of phage therapies beyond bacterial infections, extending to other diseases involving microbial imbalances in various organ systems.” 

The gut microbiome can predict treatment response in rheumatoid arthritis

Monday 19th February – by King’s College London

Professor Frances Williams’ chronic pain research group within TwinsUK at King’s College London has recently published an important article which helps understand the complex and varied response to treatment in rheumatoid arthritis. 

Rheumatoid arthritis is an autoimmune disorder affecting many bodily systems, it is often characterised by painful swelling of the joints in the hands called flares, which creates irreversible damage. When an individual is diagnosed with rheumatoid arthritis, it is important to quickly work out the most suitable medication for them to halt or subdue flares. Disease Modifying Anti Rheumatic Drugs (DMARDs) are usually prescribed when a patient is diagnosed with rheumatoid arthritis. For about a third of patients these medications work well, however for others, they do not, and some people experience very unpleasant side-effects. Knowing who will respond well to DMARD therapy such as a drug called methotrexate before medication regimes begin will save a lot of pain and joint damage for those with rheumatoid arthritis. 

This large project, funded by Versus Arthritis, recruited newly-diagnosed rheumatoid arthritis patients from 12 NHS rheumatology outpatient clinics throughout London and Southeast England. 160 patients agreed to take part before they started DMARD treatment. Participants completed health questionnaires and gave samples of stool to assess their gut microbiome. Then they started methotrexate treatment and were followed up three and six months later.

The aim of the research was to see if the gut microbiome could be used to predict who would respond well to DMARD treatment and who would require alternative medication to manage their rheumatoid arthritis. 

Lead co-author Max Freidin said:

“We currently have no tools to help us know who will do well on DMARD medication. It is difficult to establish the correct treatment without a trial-and-error approach, which sometimes takes many months, during which time significant joint damage can occur.”

The participants’ gut microbiome data predicted treatment who would respond well to methotrexate and who wouldn’t. The work sheds light on how methotrexate treats the disease – with decreased prevotella bugs seen early on in the stool in those who responded well to methotrexate. This suggests the early stool testing could lead to more rapid drug switching and improve outcomes.

Such steps forward are only made possible with the generous support of charities such as Versus Arthritis, along with the time and efforts of the clinicians, research nurses and of course rheumatoid arthritis patients attending rheumatology out-patient clinics. 

TwinsUK Twins Undergo First MRI Scan in New Study on Healthy Ageing 

19th January 2024 – By Aaruthy Suthahar

TwinsUK and the School of Biomedical Engineering & Imaging Sciences at King’s College London welcomed the first pair of twins to undergo an MRI scan for our new study on ageing, at the King’s Advanced MRI Centre at St Thomas’ Hospital. This milestone event marks the start of an exploration into early markers of disease and ageing throughout the body. 

Magnetic Resonance Imaging (MRI) is a non-invasive scanning technique that uses magnetic fields and radio waves to generate detailed images of the internal structures of the body. MRI allows us to safely see changes inside the body, often long before any clinical signs or symptoms are noticed. 

The Twins MR Imaging Study, utilising the UK’s first MAGNETOM Free.Max, signifies a leap in the field of medical imaging. This state-of-the-art scanner, installed at the King’s Advanced MRI Centre, represents a collaborative effort to push the boundaries of accessibility and innovation in healthcare. 2,500 TwinsUK members will undergo comprehensive MRI scans of the brain, spine, heart, and other vital organs at the King’s Advanced MRI Centre. 

Using the MRI data, the team will look at the size, structure, and function of organs like the heart, liver, blood vessels and brain, and body tissue composition such as muscles, fat and ligaments. The MRI data gathered will be connected with health record data and a wealth of new and historical data generously donated by TwinsUK members for up to 30 years. The outcome will be a comprehensive and powerful resource to explore and support research into health and ageing-related topics.  

Study co-lead Professor Claire Steves, Head of Department at TwinsUK said: 

“Twin studies provide an ideal way to explore how the body develops as it matures and how age-related diseases form. They help us unpick the effects of genetics and life experiences on how the body changes.” 

Professor Sebastien Ourselin FReng FMedSci, Head of the School of Biomedical Engineering & Imaging Sciences explained:

The opportunity to bring more than 20 years of twins health data into collaboration with the advanced medical imaging facilities of our school will enable us to create one of the most complete research biobanks of the UK population. From this we can look to learn more about the effects of environment and lifestyle on health and how they impact on normal human aging. This is an exciting time for cross-disciplinary research, and I look forward to the outcomes of this new study.

TwinUK members Jean and Sharon said:

“While we engage in familiar tests when we come in for visits at TwinsUK, our experience has continually been enriched by technological upgrades and our involvement in cutting-edge research studies.

Our journey with TwinsUK has not only contributed to scientific advancements but has also remarkably enhanced our well-being. We’ve noticed a significant improvement in our health since becoming members. Sharing a day together when we come in also adds an extra layer of joy to the experience.

Joining this new MRI study is especially exciting for us, drawing from a past MRI that identified a back issue, leading to successful corrective surgery. This really shows how important and effective MRI scans are, and we’re super excited to be part of this new study.”

Eligible TwinsUK members will be invited to take part in the study over the next few years.

In Search of Clues: Circulating Inflammatory Proteins and Unchanging Tinnitus

3rd January 2024 – by Kings College London

Professor Frances Williams’ Chronic Pain and Hearing Loss Research Group, part of our team at TwinsUK, has recently published another piece of the puzzle in the quest to understand and treat tinnitus. 

The large project – funded by Tinnitus UK as part of their Large Research Grants Programme – spanned Sweden and the UK, recruiting participants with tinnitus and matched controls firstly in over 1,000 participants in Sweden and then ran a replication of the study in over 1,000 twins from Twins UK. The primary objective of the research was to identify biomarkers for tinnitus.  

Co-author Max Freiden said:  

“It is difficult to establish biomarkers to detect or treat the disorder, because tinnitus is heterogeneous, indicating that various factors determine whether a person develops tinnitus.” 

Surprisingly, tinnitus shares several signs and symptoms with chronic pain. Neuroimaging suggests similar disturbances in the prefrontal cortex of the brain, leading to distorted interpretation of sensory inputs, such as sound.  A localised brain inflammatory response, detectable in the bloodstream, has been reported to occur with chronic pain. The team investigated whether inflammatory biomarkers could be found in people with tinnitus, hypothesising that chronic pain and constant tinnitus may be associated with neuroinflammation. 

Importantly, factors unrelated to hearing difficulties that affect inflammatory marker levels, such as age, sex, and body mass index, were accounted for. Tinnitus tends to be accompanied by stress, anxiety, depression, hypersensitivity to sound, face pain, and headache; however, none of these conditions were related to inflammatory marker levels. While a weak association of five inflammatory proteins was seen in the Swedish cohort, the finding was not replicated in the UK cohort, leading researchers to conclude there is a lack of association between plasma biomarkers and constant tinnitus. Other research has shown that biomarkers can be derived from electrophysiological measures, but this does not appear to be the case for blood biomarkers. 

Although the team didn’t find a tinnitus biomarker, negative results are considered progress and constitute an important aspect of directing future research and treatment. Such advancements are only possible with the generous research investments from charities like Tinnitus UK, and the important contribution of participants from TwinsUK and others who consent to research.  

Link to the article is HERE

My work experience at TwinsUK

12th December 2023 – by Emily Herbert

My work experience at TwinsUK has been wonderful. I was incredibly nervous to start, especially because some of the tasks planned for me were things I had never experienced before – namely, research ethics, shadowing clinical visits, and working alongside very experienced scientists. However, from the minute I arrived, everyone was incredibly welcoming, kind, and supportive of me being alongside them in the department.

Over the course of my five days at TwinsUK, I have learned so much about what it is like to work in a scientific role. I have discovered roles that I didn’t even know were a possibility, and it has really opened my eyes to the variety of careers available.

During my first day, I had the opportunity to shadow visits with the twins in the clinic. I saw the huge variety of work that’s carried out and the different stages of the TwinsUK research programme. This included a variety of tests, including blood tests, memory exams, and bone density scans.

Throughout my week, I had the chance to speak to members of staff across different teams, learning about how the data is organised and analysed, as well as the research ethics that underpin all the work in the department. It was also really interesting to see how the logistics of sample collection work. Each person I spoke to was enthusiastic about their role within the team, and it was extremely helpful to learn about their career path and the work they do each day as part of TwinsUK. It was also extremely inspiring to listen to the researchers talk about the work they are doing, including the lecture I attended from a PhD student.

My last day was spent in the lab, the last piece of the jigsaw puzzle that is the TwinsUK research programme. I found it fascinating to see how samples are used and interpreted. Everyone in the lab team was encouraging and answered my many questions!

Sometimes it’s hard to think ahead to what careers might be possible for a particular subject, but this experience has been invaluable in understanding the wide range of possibilities within scientific research organizations like TwinsUK, which one day I hope to be a part of.

What struck me the most about everyone in the department was how connected and encouraging they are to one another. The work being done in the department is fascinating, and the relationship built with each set of twins is really lovely. It’s also amazing that the data is not only used for the incredible work within the department but is also shared with scientists worldwide.

I highly recommend TwinsUK as an inspiring placement for work experience. I have had an extremely enjoyable week, and it’s been everything I could have hoped for.

Exciting News at TwinsUK: Meet Our New Head of Department!  

28th November 2023 – by Aaruthy Suthahar

We are delighted to let you know that whilst Tim Spector continues to be the Director of TwinsUK , Professor Claire Steves is now the Head of the Department of Twin Research as well as being the Clinical Director of TwinsUK.  

About Professor Claire Steves: 

Claire is a Professor of Ageing and Health and a Consultant Geriatrician at Guy’s and St Thomas’ NHS Foundation Trust, has a longstanding affiliation with the department, having pursued her Ph.D. from 2009 to 2014. Her enduring commitment and expertise have significantly contributed to the department’s success. In 2016, she further elevated her role, assuming the position of Deputy Clinical Director at TwinsUK, where she continues to make impactful strides in her field.

Her expertise lies in memory loss and dementia assessment and management. Claire’s career began by caring for frail older individuals, but her curiosity led her to research. She is interested in understanding how to prevent frailty and has a diverse research portfolio, utilising population studies like TwinsUK. Claire’s work explores the unique ways each one of us ages and has identified modifiable factors to build resilience in older adults. 

Leading Through Challenges: 

Claire’s leadership during the COVID-19 pandemic showcased her dedication to research. She led the science behind the Zoe COVID Symptom Study app, impacting over 4 million people. Her team’s work on the implications of COVID-19 infection, especially in older adults, earned them the Dhole-Eddlestone Memorial Prize for the most impactful paper in Ageing research in 2020. 

Innovative Initiatives: 

Claire’s commitment extends beyond ageing research. She recently initiated the King’s Centre for Ageing Resilience in a Changing Environment (CARICE). This groundbreaking initiative addresses the global challenges of climate change and ageing populations, fostering resilience through inclusive, interdisciplinary research. This centre aims to assist researchers at various points in their careers by establishing a welcoming, cross-disciplinary research setting, enabling them to channel future grants towards research that promotes resilience. 

Claire has also been awarded a prestigious Wellcome Leap award, focusing on factors influencing the ageing process and our ability to bounce back in the face of challenges. 

We can’t wait for you to get to know Claire better and embark on this exciting new chapter together.  

Webinar and 5-Minute Interview: 

To get to know Claire better, we invite you to watch her webinar HERE. Additionally, we have got a 5-minute interview with Claire HERE, offering insights into her journey and aspirations. 

TwinsUK Featured in ITV and BBC Documentaries on Ultra-Processed Foods 

21st November 2023 – by Aaruthy Suthahar

TwinsUK has recently been in the spotlight as our Director, Tim Spector, and TwinsUK members featured in two TV documentaries: “Ultra-Processed Food: What Are We Eating?” on ITV and “Ultra-Processed Food: A Recipe for Ill Health?” on BBC Panorama. The documentaries delved into the potential alarming effects of ultra-processed foods on our health, making waves in public discourse. 

The ITV documentary, “Ultra-Processed Food: What Are We Eating?” (available HERE), explored the types of foods commonly found on supermarket shelves and their effects on the human body. It featured our Department of Twin Research and Jo and Katie, TwinsUK members who helped to demonstrate the health implications of consuming ultra-processed foods. An experiment was arranged with the identical twins, where both had a breakfast meal with equivalent nutritional value, but one was made up of whole foods and the other of UPFs. They were observed throughout the programme to determine the duration and calorie intake required for each twin to reach a contented sense of fullness and better understand individuals’ responses to diets rich in ultra-processed foods.  

BBC Panorama’s “Ultra-Processed Food: A Recipe for Ill Health?” (available HERE) dug deeper into the potentially alarming health consequences of consuming these processed foods. Director Tim Spector shared his extensive knowledge and research findings, underscoring the role research, including TwinsUK, plays in unraveling the impact of genetics and lifestyle on health. In addition, TwinsUK members Aimee and Nancy took part in an experiment where Aimee had UPFs and Nancy had a matched diet made of whole foods for a couple of weeks, to demonstrate the effects of these diets. 

Both documentaries demonstrated the importance of our study in advancing our understanding of how our genes and environment interact, and how this interplay significantly impacts our health. We have been at the forefront of investigating the complex web of genetic and environmental factors that influence health, and these documentaries served as a valuable platform to disseminate this knowledge to the wider public. 

With the rising awareness of the detrimental effects of ultra-processed foods on health, TwinsUK’s involvement in these documentaries underscores the urgency of further research to understand the effects of ultra-processed foods to support individuals to make informed dietary choices. However, the food environment, spanning neighbourhoods, schools, and workplaces, also significantly influences individuals’ decisions about what to eat. It encompasses factors like the availability, affordability, and accessibility of food options. A nurturing food environment encourages the intake of wholesome, nutritious foods. On the other hand, an environment saturated with ultra-processed foods may contribute to less-than-optimal dietary habits, leading to concerning health issues. Recognising the broad-reaching effects of the food environment emphasizes the importance of adopting comprehensive strategies. 

As the world continues to deal with the consequences of dietary decisions, TwinsUK remains committed in its mission to uncover the unknown implications of genetics and lifestyle on our health and well-being. 

New Study Reveals Faecal Metabolite Signature Linked to Prediabetes and Type-2 Diabetes 

18th October 2023 – by Aaruthy Suthahar

Researchers from TwinsUK have recently identified eight biochemical compounds measured in stool (faecal metabolites) that are involved in prediabetes and type-2 diabetes risk in a large study. Impaired fasting glucose, also known as prediabetes, refers to elevated blood sugar levels that are not high enough to mean that the person has type.2 diabetes. Most importantly, prediabetes is a reversible condition: you can prevent or delay prediabetes from turning into type-2 diabetes with well-established lifestyle changes. However, over 80% of individuals with prediabetes remain unaware of their condition. Previous research found a link between type-2 diabetes, prediabetes and the bacteria living in our gut, but mechanisms remain elusive.  Faecal metabolites can provide valuable insights into their metabolic health, as they are the result of various metabolic processes occurring in the body, including the digestion and breakdown of food, as well as the activities of gut bacteria. 

The team analysed the gut microbiome and blood glucose levels collected from 1,018 TwinsUK participants, and then checked their findings in an additional cohort from Germany. The researchers discovered eight specific faecal metabolites linked to prediabetes risk. Importantly, though these metabolites were chemicals or substances that are not naturally found in the body and come from outside sources, they were still reflective of the individuals’ gut bacteria, suggesting a complex interplay between the gut microbiome and the host’s metabolic processes. Moreover, these metabolites were also predictive of type-2 diabetes in a sub-analysis, showing a potential connection with the development of type-2 diabetes. 

First author Ana Nogal stated: 

“Our findings open up new avenues for understanding the role of the gut microbiome in prediabetes and type-2 diabetes. The gut microbiome seems to influence the intestinal absorption or excretion of compounds that are not produced by the human body, and this is linked to prediabetes risk, adding another layer to the complex web of interactions between the gut microbiota and metabolic health.” 

Senior author Cristina Menni explained: 

“This research has the potential to transform our understanding of prediabetes and type-2 diabetes development, offering new insights into the role of the gut microbiome. The implications of this study are far-reaching, and it has the potential to pave the way for innovative treatments and preventive measures for these prevalent metabolic conditions.” 

The study highlights the importance of considering the gut microbiome’s impact on the absorption and excretion of compounds in understanding the onset of type-2 diabetes. Further research is needed to explore this mechanism and its potential implications for diabetes prevention and management. 

Groundbreaking Insights into Predictive Metabolites of Heart Attacks 

11th October 2023 – by Aaruthy Suthahar

In a groundbreaking collaborative effort encompassing six intercontinental cohorts including TwinsUK, the Consortium of Metabolomics Studies (COMETS) has identified 10 novel molecules measured in serum that were associated with incident myocardial infarction (MI), commonly known as a heart attack. This research, representing the largest of its kind, included 7,897 people and has far-reaching implications for identifying at-risk individuals before the onset of this life-threatening condition. 

MI is a leading global cause of death and disability, underscoring the importance of early prediction and intervention. Previous studies measuring hundreds of serum molecules to identify biomarkers of MI have been restricted by limited participant numbers and/or demographic diversity. However, COMETS’ extensive research has addressed these limitations. 

In this study, individuals averaging 66 years of age were drawn from six distinct international cohorts, with their blood metabolomes analyzed. Coupled with data on 1,373 MI cases, the researchers executed a two-stage Individual Patient Data meta-analysis. 

The results were nothing short of groundbreaking. 56 metabolites, including 21 lipids and 17 amino acids, were linked to incident MI, with 10 of them not being reported before notably, the carbohydrate mannitol/sorbitol emerged with the highest increased risk, while glutamine exhibited the most significant decrease in risk. 

Moreover, these identified metabolites were substantially enriched in pathways previously associated with cardiovascular diseases, such as aminoacyl-tRNA biosynthesis. This reinforces the potential clinical relevance of these biomarkers. 

Senior author Cristina Menni explained:  

‘The identified molecules offer a promising avenue for early detection and risk assessment before the onset of heart disease. This is a significant breakthrough in cardiovascular research, as it can potentially enable healthcare professionals to identify individuals at risk of heart attacks well in advance, allowing for proactive interventions and personalized healthcare strategies.’ 

First author Ana Nogal said: 

‘The implications of this study are profound. The identified metabolites could serve as powerful tools for identifying individuals at high risk of MI before the disease manifests clinically. As a result, this research not only advances our comprehension of the molecular changes underlying MI development but also opens new avenues for clinical prediction and a more profound understanding of causal mechanisms.’ 

In a world where heart attacks remain a major public health concern, COMETS’ collaborative effort signifies the importance of multidisciplinary research and holds the promise of uncovering universal biomarkers that can save countless lives. 

Study Reveals Higher BMI Puts Adolescents at Risk for Depression 

5th September 2023 – by King’s College London

Children between the ages of 12 and 16 with a higher body mass index (BMI) are more susceptible to developing symptoms of depression, according to a recent study conducted by researchers from TwinsUK. The findings emphasize the importance of understanding the connection between mental health and weight in adolescence and suggest that early intervention strategies could be beneficial. 

The research, published in Psychological Medicine, used data from over 10,000 twins participating in the Twins Early Development Study (TEDS) and our TwinsUK cohort. Twins born between 1994 and 1996 self-reported depressive symptoms, including low mood, loneliness, and exhaustion, at ages 12, 16, and 21. The study’s key findings indicate a significant link between higher BMI and depression among individuals aged 12 to 16, with weaker association in the 16 to 21 age group. 

The team also found that children with a higher BMI during early adolescence were at an increased risk of developing depression later in life than those who experienced depression first and then saw an increase in their BMI.  

First author, Dr. Ellen Thompson explained: 

“Understanding the relationship between mental ill-health and weight in adolescence is vital to provide timely support where needed. This study shows a stronger association between having a higher BMI at age 12 years and subsequent depression symptoms at age 16 years than the reverse.” 

The study also highlighted that environmental factors played a significant role in the connection between BMI and depression at each age. While the study did not delve into the specific reasons for this effect, prior research has suggested that factors like body dissatisfaction and weight-related stigma from external sources could contribute to the association. 

Surprisingly, the study’s results remained consistent even after adjusting for socio-economic status, dispelling the notion from previous research that poverty might be the primary risk factor in this relationship. 

This shows the importance of early adolescence as a crucial period for addressing the potential consequences of higher BMI on mental health. Preventative measures, such as support structures and positive body image messages, could be incorporated into Personal, Social, Health and Economic (PSHE) education to counteract depressive symptoms in young teens. 

Co-senior author, Professor Claire Steves said: 

“Using the TwinsUK cohort, which focuses on older adult twins, our study showed that the relationship between BMI and depression was much weaker in later life. The exact reasons for these changes over the life course need further investigation.” 

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