A new study by the NIHR Biomedical Research Centre’s Prof Sian Robinson suggests those who have healthier diets in adult life are fitter in older age. New research by Prof Robinson has shown that cutting out processed foods and eating more fruit and vegetables as an adult may help improve physical function in later life. Lifestyle and healthier ageing As we age, our bodies gradually lose muscle and become weaker, but our lifestyle can influence how quickly this natural aging process occurs. This study looked at the role of having a healthy diet in adult life on physical function in older age. Better performance The study examined the diet records of a group of 969 British men and women who were born in 1946. Using information collected at different points from ages 36 to 64, the study looked at links between diet quality and performance in three different tests of physical function, including chair rise, timed up-and-go speeds and a standing balance test, assessed when the participants were in their sixties. Higher diet quality at each age was consistently linked to better physical performance in later life, with a better diet across adulthood associated with beneficial effects on performance in the physical tests.

New genes potentially involved in the bone disease osteoporosis have been discovered by Southampton researchers, as part of an international study, providing potential targets for drug development. Osteoporosis affects over three million people in the UK. Most common in older age, the condition gradually weakens a person’s bones, making them fragile and more likely to break. Now large-scale genetic analysis of data from over 140,000 people has linked 153 variants to osteoporosis and shown a new gene, GPC6, may be involved in the development of the condition. This discovery, published in Nature Genetics, improves our understanding of how osteoporosis develops and could be used to identify and treat those patients most at risk of fractures. Finding the gene One of the main ways to diagnose osteoporosis is to measure bone mineral density (BMD), as a low BMD can indicate the characteristic fragile bone structure associated with the disease. To identify possible genes associated with low BMD, researchers from the University of Southampton, the University of Queensland in Australia and McGill University in Canada analysed genetic data from the UK Biobank for over 140,000 individuals, and found 153 potential targets. They went on to investigate these genes in more detail, using a wide range of computational and laboratory methods, to determine if they played a role in the development of osteoporosis. Preventing bone fractures They showed for the first time that modifying the gene GPC6 affects BMD in mice, suggesting that people who inherit a faulty copy of this gene might be more likely to develop osteoporosis. New drugs aimed at improving the function of GPC6 could therefore be developed to treat or prevent this common condition, helping keep bones strong and protect against fractures in later life.

New research has found women who have more of the amino acid tryptophan in their blood are more likely to sleep better during pregnancy. Professor Keith Godfrey and colleagues in Singapore have published in the Journal of Affective Disorders their discovery that women who had higher levels of tryptophan in their blood during pregnancy tended to sleep better. Meat, fish, dairy foods, nuts and seeds are rich sources of tryptophan, raising the possibility that a mother’s diet and nutrition may influence their sleep during pregnancy. Their results suggest that having enough tryptophan during pregnancy may be particularly important for women showing signs of anxiety, as the benefits were most apparent in this group. This is the latest finding from the long-term Growing Up in Singapore Towards healthy Outcomes (GUSTO) study, looking at the health of pregnant women and their young children. Eating to improve sleep What we eat can have a strong affect on our mood, and a poor diet can affect our mental wellbeing and contribute to anxiety and depression. While this study did not measure how much tryptophan the pregnant women ate, a diet rich in tryptophan can increase blood tryptophan levels. Tryptophan is an amino acid the body uses to help make serotonin, which is known to modulate mood, emotion, sleep and appetite. However, this is the first study to investigate how the amount of tryptophan a woman has in her blood affects sleep in pregnancy. Tryptophan in pregnancy The researchers gave 572 pregnant women three questionnaires to complete, for the first time when they were 26-28 weeks pregnant, and again three months after they gave birth; the Pittsburgh Sleep Quality Index, the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory. To measure the women’s tryptophan levels, they also took blood samples at 26-28 weeks. They found that women with more tryptophan in their blood reported a 12% lower prevalence of poor sleep quality during pregnancy. Women with anxiety symptoms tended to have less tryptophan in their blood, suggesting they could potentially benefit most from increasing the amount of tryptophan in their diet.

Omega-3 supplements have been shown to improve liver function in some patients with non-alcoholic fatty liver disease. Research led by Professor Christopher Byrne has shown that taking omega-3 supplements could be beneficial for some patients with non-alcoholic fatty liver disease (NAFLD). The results, published in the European Journal of Clinical Nutrition, showed that NAFLD patients with increased levels of omega-3 fatty acids in their blood after taking supplements had improved liver function. Fighting liver disease NAFLD, which usually affects patients who are overweight or have type 2 diabetes, is caused by a build-up of fat in the liver. If left untreated, it can lead to scarring of the liver (fibrosis), inflammation and can ultimately lead to cirrhosis and liver failure. It has recently been predicted that in the next decade NAFLD will be the most important reason for liver transplants in the developed world. High levels of fat in the liver are also associated with increases in the risk of diabetes, heart attacks and strokes. Reducing the amount of fat in the liver through changes in diet could help to restore liver function and improve the health of those with NAFLD. Omega-3 benefits Omega-3 fatty acids, particularly those found in oily fish like salmon, sardines and mackerel, help prevent cardiovascular disease and are thought to have a wide range of other health benefits. The research was conducted as a sub-study of the WELCOME trial, which previously established that patients taking a highly purified omega-3 supplement (Omacor) who had high levels of the omega-3 fatty acid docosahexanoic acid (DHA) in their blood saw the greatest reductions in their liver fat content. The trial also informed the recommendation by the National Institute for Health and Care Excellence (NICE) that omega-3 fatty acid treatments should not be given to all patients with NAFLD. This study now offers a potential explanation as to why some patients benefit from omega-3 fatty acid treatment and others do not. Patients with NAFLD who took Omacor each day for 15-18 months and achieved high levels of DHA in their blood had better liver insulin sensitivity and liver fat metabolism at the end of the study, indicating that their liver was functioning better. However, not all participants who took the supplements had sufficiently raised DHA levels in their blood. These results show the importance of personalising omega-3 fatty acid treatment to individual NAFLD patients to target the effectiveness of this treatment to those who will benefit most.

Southampton research has shown that nitric oxide can greatly improve the effects of antibiotics in tackling the chronic lung infections endured by cystic fibrosis patients. Cystic fibrosis (CF) is a genetic disease that affects around one in every 2500 children born in the UK, causing early death due to excessive build-up of sticky mucus in the lungs and problems associated with this. CF patients often suffer from lung infections by the bacteria Pseudomonas aeruginosa, causing exacerbations – a sudden worsening of the patient’s health and symptoms. Tackling these infections with antibiotics is challenging, because these bacteria produce a protective biofilm slime that shields them from the antibiotics. New research from the NIHR Southampton Biomedical Research Centre has shown that low doses of nitrogen oxide (NO) gas can greatly improve the action of antibiotics in CF infections, by breaking up the biofilm layer covering the bacteria. Enhancing treatment After tests in the lab using mucus samples from CF patients, the researchers conducted a pilot study involving 12 CF patients. They found those receiving low doses of NO gas for 5-7 days alongside a course of antibiotics had less biofilm in their mucus samples than those who only had antibiotics. Based on these initial results, published in the journal Molecular Therapy, the researchers suggest that NO treatment alongside antibiotics could help more CF patients survive severe P. aeruginosa infections. Before such a treatment is made widely available, however, the researchers seek to find the best way of delivering the NO to the patients’ lungs – inhaled as a gas, for example, or by developing new antibiotics that release NO when they come into contact with bacteria in the lungs. Fighting antibiotic resistance The research provides a much-needed new front in tackling antibiotic resistant bacteria, which can emerge due to chronic use of antibiotics enabling them to evolve ways of dealing with the drug. These bacteria, often named ‘superbugs’, cannot be killed with commonly used antibiotics and threaten to turn the clock back to a time when infections associated with surgery, disease or births were untreatable and deadly. By allowing shorter courses and lower doses of antibiotics to be used, NO treatment could help fight the rise of antibiotic resistant bacteria by targeting superbugs that produce biofilms.

Two million people in the UK are estimated to have undiagnosed COPD, a debilitating lung disease. New research has pinpointed the barriers to getting more people diagnosed and treated earlier. Southampton research led by Professor Tom Wilkinson, has investigated the views of GPs and nurses from across the South of England on offering screening to patients who may have the debilitating lung condition chronic obstructive pulmonary disease (COPD). Catching patients early COPD is a chronic lung condition, caused by smoking or exposure to dust and fumes. It sees the airways of the lung get ever narrower, making it harder to breathe and causing excess phlegm, wheezing and a persistent cough. Diagnosing the condition at an earlier stage would give patients the opportunity to make changes to their lifestyle, such as quitting smoking, that could add years to their shortened life expectancy. However, due to the gradual progression of COPD, many patients remain undiagnosed for years. Practical considerations The study team conducted interviews over the phone with GPs, nurses, and practice managers from 37 different practices across the South of England, asking their views on early COPD diagnosis and the value of introducing a screening programme to identify more patients. While generally supportive of the approach, the 36 health professionals interviewed had concerns about accommodating such a scheme within their services, particularly around the extra staffing and resources needed to carry out the screening programme. The researchers therefore suggest that additional administrators and clinicians need to be provided to support targeted searches and perform the diagnostic tests. Only then can millions more COPD patients get a diagnosis and treatment earlier.

Women who are overweight and conceive by in vitro fertilisation (IVF) are twice as likely to develop gestational diabetes – making losing weight beforehand a key target for these mothers to be. New research involving Southampton’s Professor Keith Godfrey suggests that women who lose weight before IVF could cut their risk of developing gestational diabetes during the pregnancy. The results, published in the journal Human Reproduction, showed that pregnant women who conceived by IVF were almost twice as likely to develop gestational diabetes as women who conceived naturally. The increased risk of gestational diabetes in IVF pregnancies was independent of recognised risk factors for gestational diabetes, but was only present if the mother was overweight or obese. Those conceiving by IVF who had a healthy body mass index (BMI) did not have an increased risk of developing the condition. Diabetes in pregnancy Gestational diabetes affects pregnant women and results in high blood sugar levels. This can cause pregnancy complications, including the baby growing particularly large, too much amniotic fluid being produced, pre-eclampsia, jaundice, or premature birth, and increases the risk of the baby becoming overweight in later childhood. Gestational diabetes occurs because of hormonal changes that can affect how insulin - the hormone that helps the body use sugar – works, or because the body is unable to make enough insulin to meet the extra demands of pregnancy. The importance of bodyweight The researchers assessed gestational diabetes in 1089 pregnant women (1013 natural conceptions, 76 IVF) participating in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) project, and found that women who conceived through IVF were twice as likely to develop the condition. Yet when they looked more closely at the data, they discovered that this only applied to women who were overweight or obese. Women who lose weight before undergoing IVF may be able to reduce their risk of developing gestational diabetes during their pregnancy, helping to look after their health during pregnancy and giving their child a better start in life.

Patients with lung conditions are prone to infections that can be hard to treat with antibiotics. Now researchers have found a drug that breaks down the bacteria’s protective biofilm so antibiotics can get in. A new study jointly led by Dr Raymond Allan from the NIHR Southampton Clinical Research Facility and NIHR Biomedical Research Centre has found a way to improve the effectiveness of an antibiotic used to treat lung infections in patients with chronic lung conditions. Their results, published in the journal Microbiology, show a compound called D-methionine can break down the protective slime known as a biofilm that surrounds Haemophilus influenza bacteria. This allowed the antibiotic azithromycin to reach and kill the bacteria, to better treat the infection and reduce the risk of antibiotic-resistant superbugs emerging from overuse of antibiotics. These results, from tests on the bacteria in the lab, hold the promise of better treatment of lung infections for those with chronic lung conditions. Fighting lung infection The bacteria non-typeable Haemophilus influenza is a major cause of lung infections in patients with chronic lung diseases like cystic fibrosis, primary ciliary dyskinesia (PCD) and chronic obstructive pulmonary disease (COPD). These infections greatly worsen the impacts of these conditions and are usually treated with a course of antibiotics. However, the bacteria’s protective biofilm shields them from the antibiotic, making it less effective, which can lead to persistent, recurring and hard to treat infections. D-methionine works by interfering with the biofilm production process, preventing new biofilm from forming. This removes the barrier to the antibiotic, making it a more effective treatment. Better antibiotic treatment for all As well as potentially improving the speed and results of antibiotic treatment for these patients, the approach could help tackle the rise of antibiotic resistant strains of bacteria. These bacteria, often named ‘superbugs’, cannot be killed with commonly used antibiotics, are a growing threat to health worldwide. This antibiotic resistance threatens to turn the clock back to a time when infections associated with surgery, disease or births were untreatable and deadly. Reducing antibiotic use is one of the main ways to prevent antibiotic resistance. By allowing lower doses to be used, D-methionine has the potential to help fight antibiotic resistance.

The Medical Research Council (MRC) and National Institute for Health Research (NIHR) have responded to the findings of an important report, for which Southampton’s Professor Alan Jackson was deputy chair, to address a critical need to invest in the UK’s nutrition research. Southampton has been a key player in a major review of the state of nutrition research in the UK and overseas, which highlighted a growing concern that the UK is not fulfilling its potential, and recommended ways to ‘revitalise’ the field so the public and patients continue to benefit. The Review of Nutrition and Human Health Research, commissioned by the Office of Strategic Coordination for Health Research (OSCHR), made a series of recommendations for how the challenges currently facing the field could be addressed on a national and global scale. The report found that, despite the UK’s impressive track record in nutrition research, it was not fulfilling its potential. It highlighted a lack of coordination, leadership and training, and warned that the field was facing a potential crisis as fewer younger scientists entered the field and experienced researchers approached retirement. It also recommended increased collaboration with industry, and a need for a global approach to fight the rise of diseases such as heart disease, obesity, cancer and diabetes in developing countries. In their response to the report, the MRC and NIHR pledged to establish a new UK Human Nutrition Research Partnership of experts from academia, health research and industry to tackle the challenges raised in the report. The MRC will be launching new funding opportunities to tackle the global challenges highlighted by the report, and is working with key stakeholders to develop a framework for engagement between researchers and industry, enabling them to work together so that research can lead to healthier products and improved nutritional support.

New research by Professor Robert Read into the development of Salmonella food poisoning has revealed how the bacteria get inside and hijack the body’s white blood cells. While Salmonella bacteria are commonly known to cause food poisoning, the strain of Salmonella enterica known as S. Typhimurium can lead to fatal widespread infections such as typhoid fever. Now new research, published in the Journal of Infection, has determined how S. Typhimurium uses a specific type of protein to attach to a type of white blood cell, a key stage in enabling the bacteria to spread throughout the body and cause a more serious infection. Professor Robert Read, research lead for NIHR Southampton Biomedical Research Centre’s microbial science theme, worked with researchers at the University of Sheffield to make the discovery. Invading blood cells Macrophages are a type of white blood cell that is specially designed to defend the body against threats such as bacteria, by engulfing and destroying them. Yet the Salmonella-causing bacteria S. typhimurium are very much at home inside a macrophage’s acid-filled compartments, and actively seek to get inside these cells, where they can replicate undetected by the immune system and spread in the blood to other parts of the body. The researchers revealed that the bacteria use ‘sticky’ tetraspanin proteins, particularly one called CD63, to attach themselves to the macrophages, the first step in the process of invading the cells. New target for treatments New treatments could potentially target tetraspanins such as CD63 to prevent the bacteria from attaching themselves to these white blood cells, so preventing the spread of Salmonella throughout the body. While there is still a long way to go before such a treatment can be developed, this research has identified a new way to prevent serious infections from Salmonella, like typhoid, and help save lives.

Our researchers are pioneering the use of a nose drop containing a type of ‘friendly’ bacteria that could help prevent meningitis and other infections. Professor Robert Read, director of our NIHR Southampton Biomedical Research Centre, and his team have applied to a government body to trial the use of a harmless bacterium with an inserted gene in tackling meningococcal meningitis. A deadly disease Meningitis occurs in people of all age groups but infants, young children and the elderly are most at risk. Meningococcal meningitis, which is a bacterial form of the disease and is responsible for 1,500 cases a year in the UK, can cause death in as little as four hours from the onset of symptoms. Around 10% of adults carry Neisseria meningitidis – the cause of meningococcal meningitis – in the back of their nose and throat with no signs or symptoms. However, in some people, this bacterium can invade the bloodstream and cause the life-threatening symptoms including meningitis (inflammation of the brain’s outer membrane) and blood poisoning, known as septicaemia. Helping ‘friendly’ bacteria help us In a previous study, the Prof Read’s team studied the effects of introducing into adults’ noses a ‘friendly’ bacterial strain, known as Neisseria lactamica (Nlac), on the populations of its close cousin N. Meningitides (Nmen). Their results showed Nlac settling harmlessly in the nose for months and preventing N. meningitidis from occupying the nose in ~60% of participants. They now hope genetically enhancing the bacteria with a ‘sticky’ surface protein from Nmen will increase the ability of Nlac to reside in the nose and at the same time induce immunity against the meningitis bacteria. If successful, this would offer the potential to prevent the spread of infection or the ability to rapidly control an outbreak as meningococcal meningitis cannot develop in the absence of N. meningitidis. Existing therapy, first ever trial of its type Using friendly bacteria to tackle infections, known as ‘bacteriotherapy’, is already part of some care of inflammatory bowel disease and Clostridium difficile infections. However when clinical trials of the nose drop begin at the NIHR Southampton Clinical Research Facility, it will be the first time a genetically modified bacteria has been used to prevent infections that develop in the nose and throat. “We have already shown that placing Nlac in the nose of healthy adults caused no harm to the volunteers, the bacteria settled and it caused an immune response which we believe could prevent the acquisition of harmful bacteria,” said Prof Read, who is a professor of infectious diseases at the University of Southampton. “Now, following extensive work in the laboratory, we have developed a nose drop which includes Nlac that has been enhanced with a gene to help broaden its effect to, we hope, exclude N. meningitidis.” Prof Read, who is also an honorary consultant at University Hospital Southampton NHS Foundation Trust, added: “The next stage of this process is to test the drops on healthy volunteers in a clinical trial to ensure the strain of bacteria we have created is going to stay and grow in the nose. “If successful then we will have a future therapy that we can adapt to combat other diseases caused by bacteria that breed in the nasal pathway, such as pneumonia or ear disease.” Public consultation and information As a first step in the process, Prof Read and his research team have applied to the Department for Environment, Food and Rural Affairs (DEFRA) for permission to use the genetically-modified drop in volunteers. DEFRA are keen to hear from anyone with views or concerns - more details on how to do this can be found here. It is hoped the study, being run in collaboration with Public Health England and funded by the Medical Research Council, will be underway by the end of the year.

Southampton will lead a nationwide trial of a treatment approach that could improve survival from emergency bowel surgery by guiding the amount of fluid given to patients during their operations. A potentially life-saving method for monitoring and treating emergency bowel surgery patients during their operation is being tested in a five year study. The FLO-ELA (FLuid Optimisation in Emergency LAparotomy) trial will involve 7500 patients at 100 centres nationally. It is being led by Dr Mark Edwards, consultant anaesthetist and researcher in the critical care team of the NIHR Southampton Biomedical Research Centre, a partnership between the University of Southampton and University Hospital Southampton NHS Foundation Trust. The trial is funded by the National Institute for Health Research Health Technology Assessment Programme. It will compare current care with a protocol guided by a heart monitoring device during and after surgery. The monitor tracks patients’ blood flow so that exact amounts of fluid can be given when required. This approach has shown promising early results in patients undergoing planned surgery. Major surgery Around 30,000 people need emergency bowel surgery each year in the UK. The surgery is performed for many different reasons, including bowel cancer complications or infection. These are major operations, for patients who tend to be elderly and often have additional health problems. After surgery, patients are usually cared for within intensive care units, but around one in 10 do not survive the immediate effects of surgery. Maintaining patients’ blood fluid levels and flow is key to successful recovery, but current monitoring methods to guide this such as blood pressure and heart rate may not be reliable. For these patients a fluid protocol using more advanced monitoring methods could improve outcomes. Improving survival The trial will use data from emergency bowel surgery collected by the National Emergency Laparotomy Audit (NELA), as well as information from the Office for National Statistics. NELA is a major ongoing project, commissioned by the Healthcare Quality Improvement Partnership as part of the National Clinical Audit Programme and hosted by the Royal College of Anaesthetists. It has been running since 2012 with the goal of improving the quality of care for these patients. The trial will compare survival from operations that use this treatment approach during surgery and for six hours afterwards against standard care. 7500 patients over the age of 50 years will be included in the trial. The researchers hope this approach will be as successful as for planned bowel operations, where previous studies suggest there may be a 15% reduction in deaths compared to standard care. If so, they plan to get this treatment used as part of standard practice, helping to save lives. Further information can be found at the study website www.floela.org and by following @FLOELAtrial on Twitter.