Category: Gastrointestinal

Categories : Cancer GastrointestinalTags : Leave a comment

Nerves Electrify Stomach Cancer, Sparking Growth and Spread

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Image from Pixabay.

Researchers have discovered that stomach cancers in mice make electrical connections with nearby sensory nerves and use these malignant circuits to stimulate the cancer’s growth and spread.

Reported in Nature, this is the first time that electrical contacts between nerves and a cancer outside the brain have been found, raising the possibility that many other cancers progress by making similar connections.

“We know that many cancers exploit nearby neurons to fuel their growth, but outside of cancers in the brain, these interactions have been attributed to the secretion of growth factors broadly or through indirect effects,” says Timothy Wang, the Silberberg Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons, who led the study and is one of the leaders in the growing field of cancer neuroscience.

“Now that we know the communication between the two is more direct and electrical, it raises the possibility of repurposing drugs designed for neurological conditions to treat cancer.”

The wiring of neurons to cancer cells also suggests that cancer can commandeer a particularly rapid mechanism to stimulate growth.

“There are many different cells surrounding cancers, and this microenvironment can sometimes provide a rich soil for their growth,” Wang says. Researchers have been focusing on the role of the microenvironment’s immune cells, connective tissue, and blood vessels in cancer growth but have only started to examine the role of nerves in the last two decades.

“What’s emerged recently is how advantageous the nervous system can be to cancer,” Wang adds. “The nervous system works faster than any of these other cells in the tumour microenvironment, which allows tumours to more quickly communicate and remodel their surroundings to promote their growth and survival.”

Cancer-neuron connections resemble synapses

As a gastroenterologist, Wang’s research has focused on stomach and other GI cancers. About 10 years ago, he discovered that cutting the vagus nerve in mice with stomach cancer significantly slowed tumour growth and increased survival rate.

Many different types of neurons are contained in the vagus nerve, but the researchers focused here on sensory neurons, which reacted most strongly to the presence of stomach cancer in mice. Some of these sensory neurons extended themselves deep into stomach tumours in response to a protein released by cancer cells called Nerve Growth Factor (NGF), drawing the cancer cells close to the neurons. After establishing this connection, tumours signalled the sensory nerves to release the peptide Calcitonin Gene Related Peptide (CGRP), inducing electrical signals in the tumour.  

Though the cancer cells and neurons may not form classical synapses where they meet – the team’s electron micrographs are still a bit fuzzy – “there’s no doubt that the neurons create an electric circuit with the cancer cells,” Wang says. “It’s a slower response than a typical nerve-muscle synapse, but it’s still an electrical response.”

The researchers could see this electrical activity with calcium imaging, a technique that uses fluorescent tracers that light up when calcium ions surge into a cell as an electrical impulse travels through.  

“There’s a circuit that starts from the tumour, goes up toward the brain, and then turns back down toward the tumour again,” Wang says. It’s like a feed-forward loop that keeps stimulating the cancer and promoting its growth and spread.”

Migraine drugs as a potential cancer treatment

For stomach cancer, CGRP inhibitors that are currently used to treat migraines could potentially short-circuit the electrical connection between tumours and sensory neurons.

In Wang’s study, CGRP inhibitors administered to mice with stomach cancer reduced the size of the tumors, prolonged survival, and prevented the tumors from spreading.

“Based on our analysis of stomach cancer data from patients, we believe that the circuits we’ve found in mice also exist in humans and targeting them could be an additional useful therapy,” Wang says.

Sensory neurons may also use CGRP to stimulate cancer through more indirect pathways. Unpublished findings from Wang’s lab suggest that the neurons promote stomach cancer growth via contact with connective tissue cells in the tumour microenvironment. And other researchers have found that sensory nerves may, possibly through CGRP, cause T cell exhaustion and turn off immune responses directed at other types of cancers.

“But we think it all starts with the cancer cell setting up a neural circuit,” Wang says.

“Nerves are an underappreciated master regulator of normal growth and regeneration in animals. We know that when organs form during development, the nerves lead the way. From that point of view, it was not unexpected that nerves would be driving tumour growth as well.”

Source: Columbia University Irving Medical Center

Categories : Gastrointestinal NeurologyTags :

Could the Key to IBS Treatment Lie in the Brain?

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Although irritable bowel syndrome (IBS) affects about a tenth of the global population, the underlying causes and mechanisms of IBS remain unclear and thus treatments focus on symptom management. At Tokyo University of Science (TUS), Japan, Professor Akiyoshi Saitoh and his research group have spent the past decade exploring this topic. This study, published in the British Journal of Pharmacology, discovered that a class of drugs called opioid delta-receptor (DOP) agonists may help alleviate IBS symptoms by targeting the central nervous system rather than acting directly on the intestine.

One of the main motivations for this study was the growing evidence linking IBS closely to psychological stress. Saitoh’s group aimed to address this potential root cause by focusing on finding a novel animal model for this condition. In a 2022 study, they developed a mice model repeatedly exposed to psychological stress – using a method called chronic vicarious social defeat stress (cVSDS) – which developed symptoms similar to a type of IBS called IBS-D. These symptoms included overly active intestines and heightened sensitivity to abdominal pain, even though their organs showed no physical damage. The cVSDS animal model involved having the subject mouse repeatedly witness a territorial, aggressive mouse defeating a cage mate, inducing indirect chronic stress.

Using the cVSDS model, the researchers sought to determine whether DOP in the brain, which is closely linked to pain and mood regulation, could serve as promising drug targets for treating stress-induced IBS. To achieve this, they performed a series of detailed experiments to observe the effects of DOP agonists on IBS symptoms and chemical signaling in the brain. Some experiments involved measuring the speed of a charcoal meal through the intestine to assess gastrointestinal motility and evaluate the impact of stress or treatments on bowel movement speed, along with directly measuring neurotransmitter concentrations using in vivo brain microdialysis. This revealed that re-exposure to VSDS increased glutamate levels in the insular cortex, but these elevated levels were normalised with DOP agonists.

According to the results, the administration of DOP agonists helped relieve abdominal pain and regulated bowel movements in cVSDS mice. Interestingly, applying the DOP agonists directly to a specific brain region called the insular cortex had similar effects on IBS symptoms as systemic treatment. “Our findings demonstrated that DOP agonists acted directly on the central nervous system to improve diarrhoea-predominant IBS symptoms in mice, and suggest that the mechanism of action involves the regulation of glutamate neurotransmission in the insular cortex,” highlights Saitoh.

Taken together, the continued research by Saitoh’s group on this topic could pave the way for effective treatments for IBS. “DOP agonists could represent a groundbreaking new IBS treatment that not only improves IBS-like symptoms but also provides anti-stress and emotional regulation effects. In the future, we would like to conduct clinical developments with the goal of expanding the indication of DOP agonists for IBS, in addition to depression,” remarks Saitoh.

Compared to currently available IBS treatments, such as laxatives, antidiarrhoeals, analgesics, and antispasmodics, targeting the underlying stress with DOP agonists may offer a more definitive solution with minimal adverse effects. Further clarification of the roles of stress and brain chemistry in the development of IBS will be essential in achieving this much-needed medical breakthrough. With promising prospects, future studies will translate Saitoh’s group’s findings to humans, bringing great relief to those affected by IBS.

Source: Tokyo University of Science

Categories : Exercise GastrointestinalTags :

Moderate Exercise Keeps Appetite at Bay

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Photo by Ketut Subiyanto on Unsplash

A recent study involving researchers at Murdoch University’s Health Futures Institute has revealed that moderate-intensity exercise can significantly influence appetite-related hormones and perceptions in males with obesity.

The study, titled “Acute effect of exercise on appetite-related factors in males with obesity,” provides new insights into how exercise can aid appetite control and weight management. 

One of the study authors, Associate Professor Timothy Fairchild from Murdoch’s School of Allied Health, said the study confirms their previous work showing the benefits of incorporating regular exercise into daily routines for individuals looking to manage their weight and improve their overall health. 

“People understand that exercise helps ‘burn energy’. A lot of people assume that exercise also increases hunger and energy intake afterwards,” Associate Professor Timothy Fairchild said.  

“We have previously shown, using high-intensity exercise, that this is not the case. 

“This latest study shows that even moderate-intensity exercise can have immediate and beneficial effects on appetite control in males with obesity.” 

The study not only assessed food intake and appetite, but also measured changes in hormones which help to regulate appetite.  

“Despite a strong focus on weight loss drugs in society at present, this study shows that lifestyle factors still have a strong and relevant role in helping people to live their healthiest life,” Associate Professor Fairchild said. 

“In fact, the hormones which have been shown to increase after exercise, are the same hormones which the most successful weight loss drugs are mimicking.”  

“The added benefit of exercise is that you also receive the additional physical and mental health benefits of exercise”.  

The full study can be found in Physiological Reports journal.  

Source: Murdoch University

Categories : Dermatology GastrointestinalTags :

Inflammation may Explain the Prevalence of IBD in Psoriasis Sufferers

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

People with psoriasis often have invisible inflammation in the small intestine with an increased propensity for ‘leaky gut’, according to new research at Uppsala University. These changes in the gut could explain why psoriasis sufferers often have gastrointestinal problems and are more prone to developing Crohn’s disease. The study is published in Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease.

Psoriasis is a hereditary, chronic skin condition that can also result in inflammation of the joints. Chronic inflammatory bowel diseases (IBD), especially Crohn’s disease, are more common in patients with psoriasis than in the rest of the population.

“Previous research has also shown that people with psoriasis have more gastrointestinal problems than the general population. However we didn’t know much about why this is the case. With our study, we can now show that people with psoriasis often have invisible inflammation in their small intestines, with an increased risk of what’s called leaky gut,” says Maria Lampinen, researcher at Uppsala University.

Pro-inflammatory activity in the gut

The study involved 18 patients with psoriasis and 15 healthy controls as subjects. None of the participants had been diagnosed with gastrointestinal diseases. Samples were taken from both their small and large bowel. The researchers then studied different types of immune cells in the mucous membrane.

“It turned out that psoriasis sufferers had higher numbers of certain types of immune cells in their small intestine, and the cells showed signs of pro-inflammatory activity. Interestingly, we found the same type of immune cells in skin flare-ups from psoriasis patients, suggesting that the inflammation of the skin may have an impact on the gut, or vice versa.

Increased propensity for leaky gut

Normally, the intestinal mucosa act as a protective barrier that also allows nutrients and water to pass through it. In some autoimmune diseases, the intestinal barrier may function poorly. This is called having a leaky gut, and leads to bacteria and harmful substances leaking through the intestinal barrier and causing inflammation. This can also cause more widespread inflammation when these substances are spread via the bloodstream.

Half of the psoriasis patients in the study had increased intestinal barrier permeability or leaky gut. These same patients also reported more gastrointestinal symptoms such as abdominal pain and bloating than patients with a normal intestinal barrier. They also had elevated levels of inflammatory substances in their intestines.

“Given that the psoriasis patients in our study had relatively mild skin disease and showed no visible intestinal inflammation in a gastroscopy, they had surprisingly clear changes in their small intestine compared to healthy controls. These changes could explain why psoriasis sufferers often have gastrointestinal problems, and an increased risk of developing Crohn’s disease.

Source: Uppsala University

Categories : Gastrointestinal Obstetrics & GynaecologyTags :

The Massive Changes to Mothers’ Intestines in Pregnancy and Breastfeeding

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Source: Pixabay CC0

When women are pregnant and nurse their babies, their bodies change and various organs, such as the breasts or the immune system, are adapted to ensure the health of both mother and child. This happens throughout evolution in all mammals. An international research team led by Josef Penninger and Masahiro Onji, Medical University of Vienna, now reports the surprising finding that the intestine also changes completely in pregnant and nursing females, resulting in a doubling of the intestinal surface area and a striking structural reorganisation.

Reporting their findings in Nature, the researchers also provide the first genetic and mechanistic evidence of how this intestinal epithelial expansion occurs in mothers, with direct implications for the transgenerational health of the babies.

A multinational team led by Josef Penninger observed that the intestinal villi reorganise during pregnancy and breastfeeding and significantly enlarge, doubling their surface area. The studies were carried out in genetically modified mice and intestinal organoids from mice and humans – self-organised three-dimensional tissues derived from stem cells in the intestine. Mechanistically, the researchers identified the RANK receptor/RANK ligand (RANK/RANKL) system as the key to the villous enlargement of the small intestine during reproduction, which is regulated by sex and lactation hormones. When mice were engineered to lack the RANK/RANKL system in the intestine, the villous expansion during pregnancy and breastfeeding was significantly impaired.

For decades, researchers have studied the RANK/RANKL system as a key facilitator of essential, evolutionarily conserved processes. The Penninger group has already identified key functions of the RANK/RANKL system in bone turnover, in the biology of the mammary gland, in breast cancer, and in immune tolerance in pregnancy, contributing to the development of drugs against bone loss used by millions of people and clinical trials for breast cancer prevention and cancer immunotherapies are underway. The researchers now discovered that these intestinal changes, which appear to be completely reversible when nursing is stopped, are important for proper feeding and nourishment of the babies.

“Our study shows that the impairment of this intestinal expansion by the lack of the RANK/RANKL system during pregnancy changes the milk of the nursing mothers. This results in lower weights of the babies and transgenerational long-term metabolic consequences,” states lead author Masahiro Onji. “Mothers need to eat for themselves and their babies. These new studies provide for the first time a molecular and structural explanation of how and why the intestine changes to adapt to enhanced nutrient demand of mothers, which is probably the case in all pregnant and nursing mammals,” adds study leader Josef Penninger.

How mothers adapt to the demands of pregnancy and breastfeeding remains a central question of evolution and human health. During this phase, female hormones influence multiple organs to control and change their structure and functions, which is crucial for the health of the mother and the development of the offspring. It was known that pregnant women have enhanced nutrient demands. However, this fundamental aspect has not been well studied until now:

“By identifying the RANK/RANKL system as the driving force behind intestinal adaptation during pregnancy and lactation, our study contributes to a deeper understanding of biological processes that are of fundamental importance for evolution and human health”, says Josef Penninger, summarising the impact of the findings.

This massive expansion is controlled by sex and pregnancy hormones, which change the stem cells in the gut via the RANK/RANKL system and then give the intestinal cell a survival signal to grow much larger. This growth then leads to a near doubling of the intestinal surface area, which also increases the molecular machinery for the uptake of sugar, protein, and fat, and even leads to a profound architectural change in the intestinal villi, which probably slows down the flow of food, again maximising the uptake of nutrients.

Josef Penninger said: “Our team has discovered an amazing new way how mother’s bodies change to keep babies healthy. Hardly anybody knew about this, apart from a few old studies that have largely been forgotten. We have also found that this system, via stem cells, can directly affect tumours in the intestine; maybe we can learn from pregnant and nursing mothers to reversibly rewire this system to develop new treatments and a better understanding of intestinal cancer or gut regeneration.”

Source: Medical University of Vienna

Categories : Cancer GastrointestinalTags :

Scientists Find a Molecule that Promotes Gut Healing and Stifles Tumour Growth

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

Researchers at Karolinska Institutet have found a molecule that can both help the intestines to heal after damage and suppress tumour growth in colorectal cancer. The discovery could lead to new treatments for inflammatory bowel disease (IBD) and cancer. The results are published in the journal Nature.

Many patients with inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis do not respond to available treatments, highlighting the need to identify novel therapeutic strategies. In this study, researchers propose that promoting mucosal healing through tissue regeneration could be a valid alternative to immunosuppressive drugs.  

“However, it’s virtually impossible to promote tissue regeneration without the risk of inducing tumour growth, as cancer cells can hijack the body’s natural healing processes and start to grow uncontrollably,” says lead author Srustidhar Das, research specialist in Eduardo Villablanca’s research group at Karolinska Institutet. “We’ve now identified a molecule that can help the intestines to heal after damage while suppressing tumour growth in colorectal cancer.” 

New drug candidates 

In their search for new ways to treat IBD, the researchers have identified a handful of molecules with drug-candidate potential. They found that activation of a protein called the Liver X receptor (LXR) can promote regeneration and suppress tumour growth in colorectal cancer. 

“The discovery of both these functions was astonishing,” says last author Eduardo J. Villablanca, docent at Karolinska Institutet. “We now need to study how LXR controls tumour formation more closely.” 

The researchers used a collection of advanced technologies to conduct their study, which included mapping the transcriptome of intestinal cells. The researchers also cultivated what are known as 3D organoids: small, three-dimensional cell structures that mimic the function and structure of the body’s own organs, albeit in miniature format. 

They then used spatial transcriptomics to map the gene expression in the different tissues, a technique that has been developed at SciLifeLab by scientists from the Royal Institute of Technology (KTH) and Karolinska Institutet in Sweden. 

Third most common cancer 

Patients, the third most common type in Sweden, are often treated with chemotherapy and radiotherapy, but this can cause irritation and swelling of the bowel mucosa with subsequent chronic intestinal inflammation. 

“Thus, this new therapeutic molecule has the potential to treat not only IBD patients but also cancer patients to prevent chronic bowel disorders after radiotherapy and/or chemotherapy,” says Eduardo J. Villablanca. 

Source: Karolinska Institutet

Categories : Gastrointestinal Neurodegenerative DiseasesTags :

Parkinson’s Drug Found to Promote Pathogenic Gut Bacteria

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Fig. 1: Chemical imaging of active gut microbes. After brief incubation with heavy water, culture medium and a drug, various chemical bonds (here C-D and C-H) in the stool sample are shown in yellow and green, their ratio in yellow-purple (left). Selected microbes are detected in the same image section with fluorescence-labelled oligonucleotide probes in cyan. The activity of the detected microbes can be determined based on the amount of C-D bonds. C: Xiaowei Ge (Boston University)

An international team of scientists have revealed that the widely prescribed Parkinson’s disease drug entacapone significantly disrupts the human gut microbiome by inducing iron deficiency. This international study, provides new insights into the often-overlooked impact of human-targeted drugs on the microbial communities that play a critical role in human health. The findings, published in Nature Microbiology, suggest however that iron supplementation can help counteract these impacts.

While it is well established that antibiotics can significantly disrupt the human gut microbiome, emerging research shows that a wide range of human-targeted drugs – particularly those used to treat neurological conditions – can also profoundly affect the microbial communities living in our bodies. Despite their intended therapeutic effects on different organs, these drugs can inadvertently disrupt the balance of gut microbes, leading to potential health consequences. Until now, most studies investigating these interactions relied either on patient cohort analyses affected by many confounding factors or on experiments using isolated gut bacteria, which do not fully capture the complexity of the human microbiome.

Investigating drug–bug interactions

The team, which included some from the University of Vienna, used a novel experimental approach. The researchers studied the effects of two drugs – entacapone and loxapine, a medication for schizophrenia – on faecal samples from healthy human donors. They incubated the samples with therapeutic concentrations of these drugs, then analysed the impact on the microbial communities using advanced molecular and imaging techniques, including heavy water labelling combined with Stimulated Raman Spectroscopy (SRS). The team discovered that loxapine and even more so entacapone severely inhibited many microbiome members, while E. coli dramatically expanded in the presence of entacapone.

“The results were even more striking when we examined microbial activity, rather than just their abundance,” explained Fatima Pereira, lead author of the study and former Postdoctoral researcher at the University of Vienna. “The heavy water-SRS method allowed us to observe the subtle yet significant changes in the gut microbiome, which are often missed in traditional abundance-based measurements.”

Entacapone induces iron starvation, favours pathogenic microbes

The researchers hypothesised that entacapone might interfere with iron availability in the gut, a crucial resource for many microbes. Their experiments confirmed that adding iron to faecal samples containing entacapone counteracted the drug’s microbiome-altering effects. Further investigation revealed that E. coli, which thrived under these conditions, carried a highly efficient iron-uptake system (enterobactin siderophore). This system allowed the bacteria to overcome iron starvation and proliferate, even in the presence of the drug.

“By showing that entacapone induces iron deficiency, we have uncovered a new mechanism of drug-induced gut dysbiosis, in which the drug selects for E. coli and other potentially pathogenic microbes well adapted to iron limiting conditions,” said Michael Wagner, scientific director of the Excellence Cluster and vice-head of the Centre for Microbiology and Environmental Systems Science (CeMESS) at the University of Vienna.

Wider implications for drug–microbiome interactions

This discovery has broader implications for understanding how other human-targeted drugs might affect the gut microbiome. Several drugs, including entacapone, contain metal-binding catechol groups, suggesting that this mechanism could be a more common pathway for drug-induced microbiome alterations.

The findings also present an opportunity to mitigate the side effects of drugs like entacapone. By ensuring sufficient iron availability to the large intestine, it may be possible to reduce dysbiosis and the gastrointestinal issues that often accompany Parkinson’s disease treatment.

“The next step is to explore how we can modify drug treatments to better support the gut microbiome,” said Wagner. “We are looking at strategies to selectively deliver iron to the large intestine, where it can benefit the microbiome without interfering with drug absorption in the small intestine.”

Source: University of Vienna

Categories : Diet and Nutrition GastrointestinalTags :

Genetically Tailored Diets for IBS may Soon be Possible

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

An international study has found that genetic variations in human carbohydrate-active enzymes may affect how people with irritable bowel syndrome (IBS) respond to a carbohydrate-reduced diet.

The research, which is published in Clinical Gastroenterology & Hepatology, shows that IBS patients with genetic defects in carbohydrate digestion had a better response to certain dietary interventions. This could lead to tailored treatments for IBS, using genetic markers to predict which patients benefit from specific diets.

Irritable bowel syndrome (IBS) is a digestive disorder affecting up to 10% of the global population. It is characterised by abdominal pain, bloating, diarrhoea, or constipation. Despite its prevalence, treating IBS remains a challenge as symptoms and responses to dietary or pharmacological interventions vary significantly.

Patients often connect their symptoms to eating certain foods, especially carbohydrates, and dietary elimination or reduction has emerged as an effective treatment option, though not all patients experience the same benefits.

Nutrigenetics (the science investigating the combined action of our genes and nutrition on human health) has highlighted how changes in the DNA can affect the way we process food. A well-known example is lactose intolerance, where the loss of function in the lactase enzyme hinders the digestion of dairy products.

Now, this pioneering new study suggests that genetic variations in human carbohydrate-active enzymes (hCAZymes) may similarly affect how IBS patients respond to a carbohydrate-reduced (low-FODMAP) diet.

The team have now revealed that individuals with hypomorphic (defective) variants in hCAZyme genes are more likely to benefit from a carbohydrate-reduced diet.

The study, involving 250 IBS patients, compared two treatments: a diet low in fermentable carbohydrates (FODMAPs) and the antispasmodic medication otilonium bromide. Strikingly, of the 196 patients on the diet, those carrying defective hCAZyme genes showed marked improvement compared to non-carriers, and the effect was particularly pronounced in patients with diarrhoea-predominant IBS (IBS-D), who were six times more likely to respond to the diet. In contrast, this difference was not observed in patients receiving medication, underscoring the specificity of genetic predisposition in dietary treatment efficacy.

These findings suggest that genetic variations in hCAZyme enzymes, which play a key role in digesting carbohydrates, could become critical markers for designing personalised dietary treatments for IBS. The ability to predict which patients respond best to a carbohydrate-reduced diet has the potential to strongly impact IBS management, leading to better adherence and improved outcomes.

Study leader Dr D’Amato, Gastrointestinal Genetics Research group at CIC bioGUNE and the Department of Medicine and Surgery at LUM University in in Italy.

In the future, incorporating knowledge of hCAZyme genotype into clinical practice could enable clinicians to identify in advance which patients are most likely to benefit from specific dietary interventions. This would not only avoid unnecessary restrictive diets for those unlikely to benefit but also open the door to personalised medicine in IBS.

Source: University of Nottingham

Categories : GastrointestinalTags :

Gut Health Signals could Transform Arthritis Treatment

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Changes in the gut microbiome before rheumatoid arthritis is developed could provide a window of opportunity for preventative treatments, new research suggests.

Bacteria associated with inflammation is found in the gut in higher amounts roughly 10 months before patients develop clinical rheumatoid arthritis, according to a longitudinal study by researchers at the University of Leeds. 

This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis.

Dr Christopher Rooney, Leeds Institute of Medical Research

Previous research has linked rheumatoid arthritis to the gut microbiome, which is the ecosystem of microbes in your intestines. But this new study, published in the Annals of the Rheumatic Diseases, reveals a potential intervention point. 

Lead researcher Dr Christopher Rooney, NIHR Academic Clinical Lecturer at the University of Leeds and Leeds Teaching Hospitals NHS Trust, said: “Patients at risk of rheumatoid arthritis are already experiencing symptoms such as fatigue and joint pain, and they may know someone in their family who has developed the disease. As there is no known cure, at-risk patients often feel a sense of hopelessness, or even avoid getting tested.  

“This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis.” 

Major opportunity for treatment

Funded by Versus Arthritis, the longitudinal study was conducted on 19 patients at risk of rheumatoid arthritis, with samples taken five times during a 15-month period.  

Five of these patients progressed to clinical arthritis, and the research showed they had gut instability with higher amounts of bacteria including Prevotella, which is associated with rheumatoid arthritis, about ten months before progression. The remaining 14, whose disease didn’t progress, had largely stable amounts of bacteria in their gut. 

Potential treatments that the researchers want to test at the 10-month window include changes to diet like eating more fibre, taking prebiotics or probiotics, and improving dental hygiene to keep harmful bacteria from periodontal disease away from the gut. 

The exact relationship between gut inflammation and rheumatoid arthritis development remains unclear. In a small number of patients within the study, the gut changes occurred before there were any changes to the joints observed by a rheumatologist, but more research is needed to determine whether these influence each other. 

Although bacteria is associated with rheumatoid arthritis, the researchers want to make it clear that there is no evidence this is contagious. 

Lucy Donaldson, director for research and health intelligence at Versus Arthritis, said: “At Versus Arthritis, we welcome the findings of this study which could give the clinicians of the future a crucial window of opportunity to delay – or even prevent – the onset of rheumatoid arthritis. This success is testament to the dedication of UK researchers who are working to personalise treatment and prevent chronic conditions that have significant impacts on a person’s ability to work, raise families and live independently.” 

The study initially took data from 124 individuals who had high levels of CCP+, an antibody that attacks healthy cells in the blood, which indicates risk of developing rheumatoid arthritis. The researchers compared their samples to 22 healthy individuals and seven people who had a new rheumatoid arthritis diagnosis.  

The findings from this larger group showed that the gut microbiome was less diverse in the at-risk group, compared to the healthy control group. 

The longitudinal study, which took samples from 19 patients over 15 months, revealed the changes in bacteria at ten months before progression to rheumatoid arthritis. 

The Leeds research team will now carry out an analysis of treatments that have already been trialled, to inform future testing of treatments at this potential 10-month intervention point. 

Source: University of Leeds

Categories : Exercise GastrointestinalTags :

Study Suggests that High-intensity Exercise Suppresses Appetite – Especially in Women

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Photo by Ketut Subiyanto on Unsplash

A vigorous workout does more to suppress hunger levels in healthy adults than does moderate exercise, and females may be especially susceptible to this response, according to a small study published in the Journal of the Endocrine Society.

The study examines the effects of exercise intensity on ghrelin levels and appetite between men and women. Ghrelin is known as the “hunger hormone” and is associated with perceptions of hunger.

“We found that high intensity exercise suppressed ghrelin levels more than moderate intensity exercise,” said lead author Kara Anderson, PhD, of the University of Virginia. “In addition, we found that individuals felt ‘less hungry’ after high intensity exercise compared to moderate intensity exercise.”

Ghrelin circulates in acylated (AG) and deacylated (DAG) forms, which are known to affect appetite. Data on the impact of exercise intensity on AG and DAG levels, and their effects on appetite, is sparse and primarily limited to males, the study noted.

To address this shortfall, the study examined eight males and six females. Participants fasted overnight and then completed exercises of varying intensity levels, determined by measurements of blood lactate, followed by self-reported measurements of appetite.

Females had higher levels of total ghrelin at baseline compared with males, the study noted. But only females demonstrated “significantly reduced AG” following the intense exercise, according to the findings.

“We found that moderate intensity either did not change ghrelin levels or led to a net increase,” the study noted. These findings suggest that exercise above the lactate threshold “may be necessary to elicit a suppression in ghrelin.”

Researchers also acknowledged that more work is needed to determine the extent to which the effects of exercise differ by sex. Ghrelin has been shown to have wide-ranging biological effects in areas including energy balance, appetite, glucose homeostasis, immune function, sleep, and memory.

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customised based on an individual’s personal goals,” Anderson said. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

Source: The Endocrine Society