Tag Archives: Arthritis

Study expands the knowledge about gut viral diversity in healthy infants

Viruses are usually associated with illness. But our bodies are full of both bacteria and viruses that constantly proliferate and interact with each other in our gastrointestinal tract. While we have known for decades that gut bacteria in young children are vital to protect them from chronic diseases later on in life, our knowledge about the many viruses found there is minimal.

A few years back, this gave University of Copenhagen professor Dennis Sandris Nielsen the idea to delve more deeply into this question. As a result, a team of researchers from COPSAC (Copenhagen Prospective Studies on Asthma in Childhood) and the Department of Food Science at UCPH, among others, spent five years studying and mapping the diaper contents of 647 healthy Danish one-year-olds.

“We found an exceptional number of unknown viruses in the feces of these babies. Not just thousands of new virus species – but to our surprise, the viruses represented more than 200 families of yet to be described viruses. This means that, from early on in life, healthy children are tumbling about with an extreme diversity of gut viruses, which probably have a major impact on whether they develop various diseases later on in life,” says Professor Dennis Sandris Nielsen of the Department of Food Science, senior author of the research paper about the study, now published in Nature Microbiology.

The researchers found and mapped a total of 10,000 viral species in the children’s feces – a number ten times larger than the number of bacterial species in the same children. These viral species are distributed across 248 different viral families, of which only 16 were previously known. The researchers named the remaining 232 unknown viral families after the children whose diapers made the study possible. As a result, new viral families include names like Sylvesterviridae, Rigmorviridae and Tristanviridae.

Bacterial viruses are our allies

This is the first time that such a systematic an overview of gut viral diversity has been compiled. It provides an entirely new basis for discovering the importance of viruses for our microbiome and immune system development. Our hypothesis is that, because the immune system has not yet learned to separate the wheat from the chaff at the age of one, an extraordinarily high species richness of gut viruses emerges, and is likely needed to protect against chronic diseases like asthma and diabetes later on in life.”

Shiraz Shah, first author and senior researcher at COPSAC

Ninety percent of the viruses found by the researchers are bacterial viruses – known as bacteriophages. These viruses have bacteria as their hosts and do not attack the children’s own cells, meaning that they do not cause disease. The hypothesis is that bacteriophages primarily serve as allies:

“We work from the assumption that bacteriophages are largely responsible for shaping bacterial communities and their function in our intestinal system. Some bacteriophages can provide their host bacterium with properties that make it more competitive by integrating its own genome into the genome of the bacterium. When this occurs, a bacteriophage can then increase a bacterium’s ability to absorb e.g. various carbohydrates, thereby allowing the bacterium to metabolize more things,” explains Dennis Sandris Nielsen, who continues:

“It also seems like bacteriophages help keep the gut microbiome balanced by keeping individual bacterial populations in check, which ensures that there are not too many of a single bacterial species in the ecosystem. It’s a bit like lion and gazelle populations on the savannah.”

if (g_displayableSlots.mobileMiddleMrec) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
}

Shiraz Shah adds:

“Previously, the research community mostly focused on the role of bacteria in relation to health and disease. But viruses are the third leg of the stool and we need to learn more about them. Viruses, bacteria and the immune system most likely interact and affect each other in some type of balance. Any imbalance in this relationship most likely increases the risk of chronic disease.”

The remaining ten percent of viruses found in the children are eukaryotic – that is, they use human cells as hosts. These can be both friends and foes for us:

“It is thought-provoking that all children run around with 10-20 of these virus types that infect human cells. So, there is a constant viral infection taking place, which apparently doesn’t make them sick. We just know very little about what’s really at play. My guess is that they’re important for training our immune system to recognise infections later. But it may also be that they are a risk factor for diseases that we have yet to discover,” says Dennis Sandris Nielsen.

Could play an important role in inflammatory diseases

The researchers have yet to discover where the many viruses in the one-year-olds come from. Their best answer thus far is the environment:

“Our gut is sterile until we are born. During birth, we are exposed to bacteria from the mother and environment. It is likely that some of the first viruses come along with these initial bacteria, while many others are introduced later via dirty fingers, pets, dirt that kids put in their mouths and other things in the environment,” says Dennis Sandris Nielsen.

As Shiraz Shah points out, the entire field of research speaks to a huge global health problem:

“A lot of research suggests that the majority of chronic diseases that we’re familiar with – from arthritis to depression – have an inflammatory component. That is, the immune system is not working as it ought to – which might be because it wasn’t trained properly. So, if we learn more about the role that bacteria and viruses play in a well-trained immune system, it can hopefully lead us to being able to avoid many of the chronic diseases that afflict so many people today.”

The research groups have begun investigating the role of gut viruses in relation to a number of different diseases that occur in childhood, such as asthma and ADHD.

Source:
Journal reference:

Shah, S. A., et al. (2023). Expanding known viral diversity in the healthy infant gut. Nature Microbiology. doi.org/10.1038/s41564-023-01345-7.

Lupus, Sepsis, and More: Scientists Uncover Promising New Therapeutic Target for Inflammatory Diseases

What goes wrong in our bodies during the progression of an inflammatory disease? Scientists at the School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute at Trinity College Dublin have made a significant advancement in comprehending the underlying mechanisms of the progression of inflammatory diseases. The discovery has uncovered a promising new target for therapeutic intervention.

The researchers have discovered that the repression of an enzyme called Fumarate Hydratase occurs in macrophages, which are a type of inflammatory cell that play a role in various diseases such as Lupus, Arthritis, Sepsis, and COVID-19.

Professor Luke O’Neill, Professor of Biochemistry at Trinity is the lead author of the research article that has just been published in the leading international journal, Nature.

He said: “No one has made a link from Fumarate Hydratase to inflammatory macrophages before and we feel that this process might be targetable to treat debilitating diseases like Lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys, and joints.”

Joint first-author Christian Peace added: “We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases. We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”

Fumarate Hydratase was shown to be repressed in a model of sepsis, an often-fatal systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased.

“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7, therefore, presents an exciting prospect for badly needed new anti-inflammatory therapies,” said Prof O’Neill.

Excitingly, this newly published work is accompanied by another publication by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr. Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who have made similar findings in the context of kidney cancer.

“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” added Prof O’Neill.

Reference: “Macrophage fumarate hydratase restrains mtRNA-mediated interferon production” by Alexander Hooftman, Christian G. Peace, Dylan G. Ryan, Emily A. Day, Ming Yang, Anne F. McGettrick, Maureen Yin, Erica N. Montano, Lihong Huo, Juliana E. Toller-Kawahisa, Vincent Zecchini, Tristram A. J. Ryan, Alfonso Bolado-Carrancio, Alva M. Casey, Hiran A. Prag, Ana S. H. Costa, Gabriela De Los Santos, Mariko Ishimori, Daniel J. Wallace, Swamy Venuturupalli, Efterpi Nikitopoulou, Norma Frizzell, Cecilia Johansson, Alexander Von Kriegsheim, Michael P. Murphy, Caroline Jefferies, Christian Frezza and Luke A. J. O’Neill, 8 March 2023, Nature.
DOI: 10.1038/s41586-023-05720-6

The Trinity study is a collaboration between eight universities including the MRC MBU, University of Cambridge where Dr. Dylan Ryan is co-first author along with Dr. Alex Hooftman, who is now based at the Swiss Federal Institute of Technology Lausanne. Cedars Sinai Medical Centre in Los Angeles is another key collaborator helping with the study of Lupus patients.

The study was funded by the European Research Council, Medical Research Council, and Science Foundation Ireland. Work in the Frezza lab is also supported by the ERC, further illustrating the importance of ERC funding for EU science.

Decreased viral infection severity in females may be due to extra copy of X chromosome-linked gene

It has long been known that viral infections can be more severe in males than females, but the question as to why has remained a mystery – until possibly now. The key may lie in an epigenetic regulator that boosts the activity of specialized anti-viral immune cells known as natural killer (NK) cells.

In a study published March 16 in the peer-reviewed journal Nature Immunology, a collaborative team of UCLA researchers have found that female mouse and human NK cells have an extra copy of an X chromosome-linked gene called UTX. UTX acts as an epigenetic regulator to boost NK cell anti-viral function, while repressing NK cell numbers.

While it is well-known that males have more NK cells compared to females, we did not understand why the increased number of NK cells was not more protective during viral infections. It turns out that females have more UTX in their NK cells than do males, which allows them to fight viral infections more efficiently.”

Dr. Maureen Su, co-senior author, professor of microbiology immunology and molecular genetics, and of pediatrics, at the David Geffen School of Medicine at UCLA

The researchers noted that this held true whether or not the mice had gonads (ovaries in females; testes in males), indicating that the observed trait was not linked to hormones. Furthermore, female mice with lower UTX expression had more NK cells which were not as capable of controlling viral infection.

“This implicates UTX as a critical molecular determinant of sex differences in NK cells,” said the study’s lead author Mandy Cheng, graduate student in molecular biology at UCLA.

The findings suggest that therapies involving immune responses need to move beyond a “one-size-fits-all” approach and toward a precision medicine model, also known as personalized medicine, that tailors treatments that take into account people’s individual differences, such as genetics, environment and other factors that influence health and disease risk, the researchers write.

“Given the recent excitement with using NK cells in the clinic, we will need to incorporate sex as a biological factor in treatment decisions and immunotherapy design,” said co-senior author Tim O’Sullivan, assistant professor of microbiology, immunology and molecular genetics at the Geffen School.

Source:
Journal reference:

Cheng, M.I., et al. (2023) The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences. Nature Immunology. doi.org/10.1038/s41590-023-01463-8.

Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of …

Rheumatoid arthritis (RA)  is a complex, chronic inflammatory disease that is thought to affect about one percent of the world’s population. RA happens when a person’s own antibodies attack joint tissue, causing painful swelling, stiffness, and redness. Some research has suggested that there is a link between RA and gum disease.

Image credit: Pixabay

Gum disease is estimated to affect up to 47 percent of adults, and in the disorder, oral microbes can move to the blood after the gums start to bleed. An increase in disease activity has been observed in RA patients who also have gum disease. Gum disease has been shown to be more common in RA patients who carry a certain type of antibodies, called anti-citrullinated protein antibodies (ACPAs), though ACPAs are often found in the blood of individuals with RA. The presence of ACPAs can often predate the diagnosis of RA by a few years.

A new study investigated the connections between these observations. In this work, the researchers collected blood samples from a small group of ten people with RA, five with and five without gum disease. These samples were collected every week for one year, and the investigators assessed the expression of both human and bacterial genes in those samples.

Certain types of inflammatory immune cells carried gene expression signatures that were associated with the autoimmune flares of arthritis patients who also had periodontal disease, as well as the presence of certain oral bacteria in the blood.

Many of these oral bacteria were chemically altered by deimination; they were citrullinated. Citrullination can change the structure and function of proteins. Although citrullination can be a part of the normal function of tissues, high levels of citrullination have been linked to inflammation.

Citrullination can also create targets for ACPAs; when the normal, unconverted forms of the oral bacteria were incubated with ACPAs, the antibodies did not react, but when the citrullinated oral bacteria were exposed to ACPAs, there was a reaction. ACPAs appear to be bound to oral microbes in RA patients.

The findings have been reported in Science Translational Medicine.

The study noted that the immune response to oral microbes could be influencing RA flares, that oral microbes can trigger a specific antibody reaction in patients with both RA and gum disease, and that RA flares cause varying immune signatures, which could reflect different flare triggers.

It could be that gum disease repeatedly causes the immune system to respond, and as the immune system keeps reacting and repeatedly increasing inflammation, RA may eventually begin to emerge. More work will be needed, however, to fully understand whether gum disease is playing a causative role in the development of RA.

Source: Science Translational Medicine


Carmen Leitch

New Study Reveals Startling Prevalence of Rare but Deadly Mystery Illness

According to a recent study, it is estimated that approximately 13,200 men and 2,300 women over the age of 50 in the United States have VEXAS syndrome. This mysterious illness was only recently understood to have a genetic basis, which was identified in 2020 by researchers at NYU Grossman School of Medicine. The study offers the first insight into the prevalence of VEXAS syndrome within the country.

VEXAS syndrome is a rare but serious condition with a high mortality rate. Approximately half of those diagnosed, mostly men, die within five years of diagnosis. The syndrome is often associated with unexplained fevers and low blood oxygen levels in individuals who have been diagnosed with other diseases such as rheumatoid arthritis, lupus, and blood cancer. The symptoms are believed to be related to an overactive immune system, which causes inflammation and classifies VEXAS syndrome as an autoimmune disorder.

Researchers say they hope their findings will raise awareness of the disorder among physicians, particularly because high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have proven effective in controlling some symptoms.

“Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia,” says geneticist and study lead investigator David Beck, MD, Ph.D. Beck, an assistant professor in the Department of Medicine and the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, also led the federal research team that initially identified the shared UBA1 mutation among VEXAS patients.

In the new study, recently published in the Journal of the American Medical Association (JAMA), researchers analyzed the electronic health records of 163,096 mostly white men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease. Twelve were found to have the UBA1 mutation, with all experiencing VEXAS symptoms.

Statistically, this corresponded to one in 4,269 American men over age 50 and one in 26,238 women over age 50 having or are likely to develop the syndrome. This, researchers say, is a higher prevalence figure than many other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome.

“Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most to die from it,” says Beck, who is leading several clinical research efforts into VEXAS syndrome at NYU Langone’s Center for Human Genetics and Genomics.

Previous research, led by Beck, traced the origins of the syndrome to a mutation, or change in the letter code that makes up DNA, in the gene UBA1 (short for ubiquitin-like modifier activating enzyme 1.) The enzyme usually assists in protein breakdown.

VEXAS stands for many of its biological characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic.

For the study, researchers analyzed the electronic medical records of adult patients who volunteered to participate in the Geisinger MyCode Community Health Initiative. The program has been collecting data for more than 25 years from patients in Geisinger’s 10-plus hospitals in Central and Northeastern Pennsylvania. Almost all study participants who agreed to have their blood DNA tested were white; half were over the age of 60.

Beck says the team next plans to analyze patient records in more racially diverse groups, especially among those with higher rates of rheumatologic and blood disease, to gain a more precise picture of who is most at risk of VEXAS syndrome. They also plan to look for additional genetic causes, test new therapies for the syndrome, and develop a simple blood test for UBA1 to make it easier to diagnose.

Reference: “Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population” by David B. Beck, MD, Ph.D., Dale L. Bodian, Ph.D., Vandan Shah, MD, Uyenlinh L. Mirshahi, Ph.D., Jung Kim, Ph.D., Yi Ding, MD, Ph.D., Samuel J. Magaziner, MPhil, Natasha T. Strande, Ph.D., Anna Cantor, MS, Jeremy S. Haley, MS, Adam Cook, MS, Wesley Hill, Alan L. Schwartz, MD, Ph.D., Peter C. Grayson, MD, Marcela A. Ferrada, MD, Daniel L. Kastner, MD, Ph.D., David J. Carey, Ph.D. and Douglas R. Stewart, MD, 24/31 January 2023, JAMA.
DOI: 10.1001/jama.2022.24836

The study was funded by the National Institutes of Health.

Lyme disease is caused by a bacterium called Borrelia burgdorferi, which is transmitted by tick bites. The incidence …

Lyme disease is caused by a bacterium called Borrelia burgdorferi, which is transmitted by tick bites. The incidence of Lyme disease has been increasing steadily, in part because diagnosis is improving, but also because the range of ticks that spread the disease is expanding. There is still a lot we don’t know about Lyme disease, including how to treat it. But diagnosis may get easier soon, now that researchers have identified 35 genes that are more active in people with a long-term form of the disease; the genes could be useful in Lyme disease diagnostics. These genes may also aid in the development of therapeutics for Lyme. The findings have been outlined in Cell Reports Medicine.

The blacklegged ticks, Ixodes pacificus (seen here), and I. scapularis, transmit Borrelia burgdorferi, the pathogen that causes Lyme disease.  / Credit: CDC/ James Gathany; William L. Nicholson, Ph.D. / Photo Credit: James Gathany

While about 30,000 people are diagnosed with Lyme disease in the United States every year, the true number could be as high as 476,000, according to the Centers for Disease Control and Prevention. People who are diagnosed can be treated with antibiotics, but about 20 percent of patients will go on to develop long-term complications that can affect the neurological system, cause arthritis, or heart problems.

There is a major need for better tests for Lyme disease, and this work is the first to look for transcriptional changes associated with long-term cases.

“We wanted to understand whether there is a specific immune response that can be detected in the blood of patients with long-term Lyme disease to develop better diagnostics for this debilitating disease,” said senior study author Avi Ma’ayan, Ph.D., a Professor and Director of the Mount Sinai Center for Bioinformatics at Icahn Mount Sinai.

In this study, the researchers sequenced the RNA in blood samples from 152 patients with post-treatment Lyme disease symptoms, 72 patient with acute Lyme disease, and 44 uninfected individuals. That RNA can provide a snapshot of how active the patient’s genes were (in the blood) at the time the blood was drawn. The researchers were particularly interested in genes related to the immune response.

This revealed that there was a unique inflammatory pattern in the post-treatment Lyme disease patients compared to those with acute Lyme disease. Within that group of inflammatory genes, there were some that were expressed in a way that is different from other patterns caused by infections with other pathogens. Machine learning was used to create a set of mRNA biomarkers that can differentiate between healthy people, those with post-treatment Lyme disease, or acute Lyme disease. This highly expressed subset of genes has been found before, and could be used to diagnose Lyme disease, as well as which stage it is.

“A diagnostic for Lyme disease may not be a panacea but could represent meaningful progress toward a more reliable diagnosis and, as a result, potentially better management of this disease,” said Dr. Ma’ayan.

The investigators want to repeat the study with other samples, develop a diagnostic tool, and test it with patient samples. They are also interested in using machine learning to find ways to diagnose other challenging disorders.

A vaccine for Lyme disease is also being tested, as outlined in the video.

Sources: The Mount Sinai Hospital, Cell Reports Medicine


Carmen Leitch

Novel platform allowing universal off-the-shelf T and NK cell access shows potential for immunotherapies

Recent advances in immunotherapy for cancer have stimulated a plethora of studies aimed at developing T cells (white blood cells) and Natural Killer (NK) cells (immune cells with enzymes that can kill tumor cells or cells infected with a virus) in-vitro from pluripotent stem cells-;cells that are able to self-renew by dividing and developing into the three primary groups of cells that make up a human body.

Now, researchers from Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center have discovered a novel pathway based on Notch stimulation (a pathway involved in cell fate decisions, proliferation and death) very early during the in-vitro differentiation that robustly support the emergence of T and NK cells from human induced Pluripotent Stem Cells (iPSC).

A robust method of producing mature T cells from iPSCs is needed to realize their therapeutic potential.”

Gustavo Mostoslavsky, MD, PhD, corresponding author, associate professor of medicine & microbiology

NOTCH1 is known to be required for the production of hematopoietic progenitor cells (an intermediate cell type in blood cell development) with T cell potential in vivo. “We have identify a critical window when Notch activation robustly improves access to definitive intermediate cell type in blood cell development (hematopoietic progenitors) with T/NK cell lineage potential.”

According to the researchers, current practices for immunotherapy are prohibitively expensive and are accompanied by serious adverse events. “The establishment of platforms that will make this process safer, simpler and cheaper will have tremendous implications on public health and in general on the way these therapies are applied in the clinic,” adds Mostoslavsky who also is co-director of the BU/BMC Center for Regenerative Medicine (CReM).

The researchers believe a novel platform allowing universal off-the-shelf T and NK cell access has enormous potential for future immunotherapies targeting a broad range of diseases, including cancer, autoimmune diseases such as rheumatoid arthritis and lupus, as well as immunodeficiencies.

These findings appear online in the journal Stem Cell Reports.

Source:
Journal reference:

Heinze, D., et al. (2022) Notch activation during early mesoderm induction modulates emergence of the T/NK cell lineage from human iPSCs. Stem Cell Reports. doi.org/10.1016/j.stemcr.2022.10.007.

Gut bacteria have been linked to an ever-increasing number of diseases. Research is now going beyond establishing a …

Gut bacteria have been linked to an ever-increasing number of diseases. Research is now going beyond establishing a link between a disorder and the community of gut microbes, and has begun to identify specific organisms that are responsible for certain conditions. Scientists have now shown that a strain of bacteria in the Subdoligranulum genus can lead to the production of autoantibodies, which appears to cause the development of rheumatoid arthritis. The findings have been reported in Science Translational Medicine.

Image cresit: Pixabay

Rheumatoid arthritis is an autoimmune disease in which the joints are erroneously attacked by the immune system, and the inflammation and damage that occurs in affected joints causes pain, the loss of mobility, and other serious problems. Disruption of mucosal immunity, in the gut, has been proposed to be one cause of rheumatoid arthritis.

In this work, the researchers obtained blood samples from people who are at risk of developing RA, and the autoantibodies were isolated from those samples.

The scientists found that the autoantibodies were causing a response in certain bacteria in the Lachnospiraceae/Ruminococcaceae families. Further work revealed that bacteria of the genus Subdoligranulum, a member of those families that was isolated from the feces of people ate risk for RA, could bind to the autoantibodies and cause the activation of CD4+ T cells. This was occurring in individuals with RA, but not in healthy people.

The Subdoligranulum bacteria was put in an animal model, and the animals began to develop the same RA risk markers found in the blood of people who are at risk for RA. Some of the animals also developed RA.

“Through studies in humans and animal models, we were able to identify these bacteria as being associated with the risk for developing RA. They trigger an RA-like disease in the animal models, and in humans, we can show that this bacterium seems to be triggering immune responses specific to RA,” said study leader Kristine Kuhn, MD, Ph.D., an associate professor at CU School of Medicine.

This microbe could be a good therapeutic target for RA treatment, noted Kuhn. Now, the scientists want to assess large populations of people who are at risk for RA to see if the Subdoligranulum microbes are also linked to other factors like genetics, mucosal immunity, and environmental conditions that can lead to RA. It may help scientists find prevention strategies or other ways to stop the microbes from causing disease, added Kuhn.

Sources: CU Anschutz Medical Campus, Science Translational Medicine


Carmen Leitch

One Medicine: how human and veterinary medicine can benefit each other

Thought LeadersProfessor Roberto La RagioneChair of TrusteesHumanimal Trust

In this interview, News-Medical speaks to Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust, about the concept of One Medicine and how human and veterinary medicine can collaborate, share knowledge, and initiate research for the benefit of both humans and animals. 

Please can you introduce yourself, tell us about your professional background, and your role at Humanimal Trust?

I am Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust.

I graduated in 1995 and then studied for a postgraduate degree in veterinary microbiology at the Royal Veterinary College (University of London). In 1996, I moved to the government’s Veterinary Laboratories Agency (VLA) to undertake a Ph.D. on the pathogenesis of E. coli in poultry. Upon completing my Ph.D. studies, I commenced a post-doctoral position at Royal Holloway, University of London, studying E. coli virulence factors and vaccine development.

Since 2001, my work has focused largely on understanding the pathogenesis of zoonotic bacterial pathogens to develop control strategies. I have led several commercial, Defra, research councils (BBSRC, MRC, EPSRC, AHRC, Innovate) and EU projects in this area.

My current research interests focus on the pathogenesis of food-borne pathogens with a particular interest in Antimicrobial Resistance (AMR) and the development of intervention strategies, including vaccines, rapid diagnostic, pre, and probiotics. I have published over 190 papers in the area of host-microbe interaction, with a particular emphasis on E. coli, Salmonella, vaccines, probiotics, and AMR.

In 2005, I was appointed Head of Pathogenesis and Control at the AHVLA, and in 2010, I was appointed Professor of Veterinary Microbiology and Pathology at the University of Surrey. I gained the FRCPath in 2010, and in 2012, I was appointed the Associate Dean for Veterinary Strategy in the new School of Veterinary Medicine at the University of Surrey. In 2014, I was appointed to the position of Head of the Department of Pathology and Infectious Diseases and Director of the Veterinary Pathology Centre. In 2019 I was appointed Deputy Head of the School of Veterinary Medicine at the University of Surrey, and then in 2021, I was appointed Head of the School of Biosciences and Medicine.

I am the past president of the Med-Vet-Net Association and the Veterinary Research Club, the current Chair of Humanimal Trust, a member of the FSA ACMSF AMR sub-committee, a Trustee of the Houghton Trust, a member of the APHA Science Advisory Board and Chair of the Royal College of Pathologists Veterinary Pathology SAC. I am an Associate member of the European College of Veterinary Microbiology, and in 2020, I was awarded an Honorary Associateship of the Royal College of Veterinary Surgeons.

Humanimal Trust is a unique organization. Please could you tell us about the organization’s origin, purpose, and values?

Humanimal Trust is the only organization in the UK with the sole and specific purpose of progressing One Medicine.

It was founded in May 2014 by world-renowned orthopedic-neuro veterinary surgeon Professor Noel Fitzpatrick – otherwise known as the TV Supervet. As a vet, Noel Fitzpatrick experienced personally the deep divide between human and animal medicine and saw how unfair this was.

Image Credit: LightField Studios/Shutterstock.com

Image Credit: LightField Studios/Shutterstock.com

Frustrated by the lack of opportunities to share what he was learning from veterinary practice or to benefit from relevant learning from human medicine, he decided to create the platform himself. This laid the foundations for the work Humanimal Trust does today, removing barriers and seeking to close the divide between human and animal medicine.

Our five areas of work spell out I-CARE, which sums up the way we feel, our supporters feel, and we hope everybody will one day feel about One Medicine:

  • Influence – we care about bringing together everyone who cares about One Medicine to create a road map for change in public policy, education, and at the clinical coalface.
  • Collaboration – we care about creating opportunities for human and veterinary professionals and students to learn from one another (in person and virtually) by demonstrating One Medicine at work.
  • Awareness – we care that people should know and understand the benefits of One Medicine for humans and animals, about non-animal alternatives to laboratory models, and how much human and animal medicine can learn from one another’s clinical practice – saving time, money, and lives.
  • Research – we care about research – funding it, facilitating it, shouting about it – that could benefit humans and animals without using laboratory animal models.
  • Education – we care about learning – every child learning about the connections between humans and animals; veterinary and human medical students learning with and from one another; practitioners learning continuously from their peers.

Humanimal Trust advocates for One Medicine. What is One Medicine, when did this concept originate, and how has the understanding of it evolved in recent years?

The origins of One Medicine date back to the nineteenth century when Rudolf Virchow linked human and animal health. Sir William Osler, Dr. Calvin Schwabe, Lord Lawson Soulsby, and others have since continued to expand the One Medicine concept, identifying the connections, commonalities, and synergies between human and veterinary medicine.

It was whilst studying the history of medicine that Professor Fitzpatrick came upon a term used to describe human and veterinary medicine working with one another: One Medicine. The third edition of Dr. Calvin Schwabe’s seminal publication in 1984 of ‘Veterinary Medicine and Human Health’ which spoke of One Medicine, laid the foundation for what we now know as One Health, but in considering this text, Fitzpatrick identified a need to move away from a public health agenda to a common health agenda focusing on infectious and non-infectious diseases.

Moreover, when reviewing the three Rs (refinement, reduction, and replacement) in relation to animal use in research, it became clear that a fourth R was missing from the 3Rs principle – the principle of reciprocity so that not only do medical practitioners and allied researchers benefit, but also patients, regardless of their species.

By considering the contribution that animals can make to research by studying their lives and their responses to naturally occurring, spontaneous diseases rather than using experimental animal models in research, the use of animals in research can be significantly reduced.

One Medicine and the ‘Biology of the Future’ (Biology Week 2020)

Why is it currently the case that human and veterinary medicine are kept separate, and why would it be beneficial to change this?

Although the practice of bringing veterinary and human medical and research professionals together is thought to stimulate new and innovative research, historically, this has been challenging. A number of studies have investigated why this could be, and different levels of awareness and priorities may be one reason. A 2020 study, which surveyed vets and GPs in Australia, found that vets generally had more awareness and felt more confident in engaging in zoonoses management compared to GPs, and were also more likely to initiate cross-professional referrals.

The Trust believes that education is key to One Medicine. Only by learning about the similarities between humans and animals from the earliest stage to collaboration in the most advanced science and clinical practice will we promote change. Therefore, we must ensure that the best research, clinical practice and learning, benefiting both humans and animals, are accessible, funded, encouraged, and promoted.

A study published in 2017 by a group of scientists in The Netherlands noted that having a clear common goal (like One Medicine) can help to stimulate collaboration. The study also suggested that professional organizations could be important facilitators of collaboration in this area.

With this in mind, in 2020, the Trust launched the Humanimal Hub, a free online platform for all human and animal medical and veterinary professionals to meet, collaborate, share knowledge, and initiate research for the benefit of both humans and animals.

While still in its infancy, the Hub already has over 250 members. It provides a much-needed virtual space for connections to be made and conversations to be initiated, which the Trust actively seeks to nurture. For example, Anna Radford, a Consultant in Paediatric Surgery at Hull University NHS Trust and Leeds Children’s Hospital, was looking to collaborate with an individual or group in veterinary medicine with a specialty in problems with urinary tract or kidneys and/or antimicrobial resistance. Through the Hub, we were able to identify a suitable professional, and as a result, an interdisciplinary group has been set up to identify common urological conditions affecting both humans and companion animals.

Anna was also introduced to a diagnostics company working in the animal medical care field at the Trust’s inaugural global ‘One Medicine Symposium: Stronger Together’ in May 2021. Through them, Anna has set up a new collaboration to determine whether this diagnostic technology developed with companion animal medicine in mind could potentially also be useful to help diagnose urinary, joint, and cerebrospinal fluid infections in a busy NHS hospital setting.

These are just two examples of how we know that great things can happen when animal and human health professionals and scientists come together.

Which areas of medicine do you currently focus on, and what benefits does One Medicine provide to this particular area?

I believe One Medicine has transformative potential across all areas of medicine where physiological and genetic similarities exist between humans and animals. There are five main pillars of research that the Trust currently seeks to fund, namely infection control and antimicrobial resistance; cancer; bone and joint disease; brain and spinal disease; and regenerative medicine.

In line with this, the Trust began an important collaboration with the children’s charity Action Medical Research in 2020 to help support two child-focused medical research projects. The first study, led by Professor Hall-Scraggs at University College London, focuses on juvenile idiopathic arthritis (JIA). Patients with JIA have a disease that causes inflammation of their joints. This leads to pain, joint deformity, disability, and reduced quality of life. There are newer drugs now available that suppress joint inflammation, but these are expensive and can have side effects, the most serious being life-threatening infection. Magnetic resonance imaging (MRI) scans can show inflammation of joints. By measuring inflammation in patients with juvenile idiopathic arthritis, the study could help optimize their treatment by showing how much inflammation is present and whether it changes with treatment.

Image Credit: Amir Bajric/Shutterstock.com

Image Credit: Amir Bajric/Shutterstock.com

The second study, which is ongoing, is investigating infection prevention and its impact on antimicrobial resistance in critically ill children, led by Dr. Nazima Pathan, Lecturer in Paediatric Intensive Care at the University of Cambridge. The transferable data from both studies has real potential to help improve the lives of humans and animals with similar conditions.

Another example of research the Trust has funded concerns liquid biopsies for canine patients. This research was undertaken by Professor Joanna Morris and Dr. Tomoko Iwata at the University of Glasgow and is a great example of reciprocity whereby human and animal bladder cancer patients may benefit from this research.

Are there any particular examples of where either human or veterinary medicine has led to advances in the other?

Cancer research is perhaps the area for which One Medicine is most well-known. For example, dogs, long considered our best friends, don’t just share our lives but also risk factors for certain diseases. Many diseases also share genetic similarities between humans and dogs. Canine lymphoma, the second most common cancer in dogs, has relatively similar characteristics to human non-Hodgkin lymphoma. Around 1 in 8 golden retrievers will develop canine lymphoma, and CRUK estimates that 1 in 39 males and 1 in 51 females are at risk of being diagnosed with non-Hodgkin lymphoma. Both species need better, more effective ways to treat the disease, and clinical trials with canine veterinary patients have been helping to fast-track the development of new treatments in this area for several years.

Image Credit: Varvara Serebrova/Shutterstock.com

Image Credit: Varvara Serebrova/Shutterstock.com

 

The US-based DISCO initiative recognizes the value of aligning veterinary and human drug development projects and explains why it can be worthwhile to include veterinary patients at an early stage in cancer drug development trials. From shortening drug development times to encouraging cross-collaboration between the disciplines for the benefit of both human and veterinary patients, the potential advantages of this approach are clearly laid out in a landmark 2019 paper, which came about from a workshop of the World Small Animal Veterinary Association’s One Health committee.

What is the one thing you wish people knew about One Medicine?

 One Medicine is about human and animal healthcare advancing hand in hand, in an equitable and sustainable way, and not at the expense of an animal’s life.

How can people, both medical professionals and the general public, get involved with Humanimal Trust and support the One Medicine cause?

 Human and animal medical professionals, students, and researchers can join the Humanimal Hub for free and use it as an opportunity to collaborate, share knowledge, and initiate research with other like-minded individuals. The Trust also holds an annual One Medicine Day event that brings together researchers, doctors, vets, allied healthcare professionals, and students from around the world to discuss practical ways forward for One Medicine. The year’s ‘One Medicine Day Seminar: One Medicine in Action’ talks can be found here.

There are also opportunities to join our team as a volunteer Ambassador, write articles for us, present at events or act as a moderator for the Hub.

There are many ways that members of the public interested in One Medicine can get involved too, from signing The Humanimal Pledge or organizing a Paws for a Picnic fundraiser with family and friends to leaving a gift in your will or becoming a volunteer speaker in your local community.

What is next for yourself and Humanimal Trust?

We recognize the need to present One Medicine consistently through an education lens. Our absolute priority is to improve understanding at every level – from pre-school to professional training (veterinary and medical undergraduates) and development – of the relationship between human and animal health and the need for collaboration and reciprocity of benefit to humans and animals.

With this in mind, our focus for the next twelve months is on four key areas of activity:

  • Focused awareness building among key audiences
  • Developing partnerships, networks, and collaborations
  • Education
  • Research funding, engagement, and influencing activity

To help drive this, we have appointed a new CEO, Joe Bailey, who will be joining us in November from RSPCA Assured, together with a new Trustee, Anna Radford, whom I referred to earlier. I have no doubt that their understanding of and passion for our purpose will help take Humanimal Trust to the next level.

We are expanding our Science Committee, which will strengthen our ability to draw on the best available expertise to make better-informed decisions about which research activities we prioritize for funding or support. In addition, to support the strategic development of our educational program, we have created a new role – Schools Education Manager – which will enable us to initiate the long-term development of a One Medicine curriculum.

We will soon launch our new Podcast series, which I’m very excited about. This will follow the Trust’s previous series, Humanimal Connection, but with a very different feel to it, so watch this space.

Where can readers find more information?

Further details can be found on our website: www.humanimaltrust.org.uk

You can also email us at [email protected] and follow us on Facebook, Instagram, Twitter, and LinkedIn.

About Professor Roberto La Ragione, BSc (Hons) MSc Ph.D. FRSB CBiol FIBMS CSci AECVM FRCPath HonAssocRCVS

I am a Professor of Veterinary Microbiology and Pathology in the School of Veterinary Medicine and the Head of the School of Biosciences and Medicine at the University of Surrey. My role includes delivering and overseeing teaching and research in the School and running my own research group, which consists of vets, doctors, and scientists. My current research interests focus on Antimicrobial Resistance (AMR) and understanding the pathogenesis of zoonotic bacterial pathogens (those that can be transmitted from animals to humans and, in some cases, from humans to animals). I also have a particular interest in developing control and intervention strategies, including rapid diagnostics, vaccines and probiotics for controlling bacterial pathogens in companion and food-producing animals. I have published over 190 peer-reviewed papers in the area of microbiology and pathology.

https://www.news-medical.net/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js $(function() { Azom.wireUpVideoThumbnailLazyLoading(); });