Tag: gastrointestinal

IBD and Depression is a Two-way Street

Photo by Andrea Piacquadio on Pexels

While irritable bowel disease (IBD) and depression are known to occur together, scientists report a clinical overlap of these conditions in the Journal of Gastroenterology and Hepatology, implying the existence of a two-way relationship. Patients diagnosed with IBD were nine times as likely to develop depression than the general population. Their siblings who did not suffer from IBD were almost two times as likely to develop depression.

Conversely, patients with depression were two times as likely to develop IBD, and their siblings without depression were more than one and a half times as likely to develop IBD.

“This research reveals a clinical overlap between both conditions, and is the first study to investigate the two-way association between IBD and depression in siblings,” said Bing Zhang, MD, a gastroenterologist with Keck Medicine and co-lead author of the study.

The researchers drew on the data of more than 20 million people from Taiwan’s National Health Insurance Research Database. For 11 years, they tracked patients with either IBD or depression and their siblings without either condition, comparing onset of depression or IBD with a control group of people without either condition, but with similar age, sex and socioeconomic status.

Zhang hypothesises that many factors may contribute to the bidirectional nature of the disorders, including environmental stressors, the gut microbiome and genetics.

“The finding that people with IBD are more prone to depression makes sense because IBD causes constant gastrointestinal symptoms that can be very disruptive to a patient’s life,” he said. “And the elevated depression risk among siblings of IBD patients may reflect caregiver fatigue if the siblings have a role in caring for the patient.”

What surprised researchers was that patients with depression were prone to IBD. Zhang speculates that this discovery may have to do with what is known as the gut-brain axis, a scientifically established connection between the gastrointestinal system and the central nervous system, which consists of the spinal cord and the brain.

For example, he said, inflammation of the brain, which plays a role in depression, may be linked to the inflammation of the gastrointestinal tract, a hallmark of IBD.

The researchers are not sure why siblings of patients with depression are more likely to be diagnosed with IBD. Zhang surmises that there may be a shared genetic susceptibility for either disease that presents differently in family members.

Zhang hopes that the study findings will encourage health care professionals to take both family history and the relationship between gastrointestinal and mood disorders into consideration when evaluating or treating patients with either IBD or depression.

Through more research and better understanding of the gut-brain axis, he envisions leveraging the newfound connection between the conditions to improve the prevention, diagnosis and treatment of IBD and mental disorders.

Source: University of Southern California – Health Sciences

Using Ablation Therapy to Treat Stomach Disorders

Photo by Andrea Piacquadio on Pexels

Researchers have shown that ablation therapy, often used to correct an abnormally beating heart, could be used to correct disorders of the stomach such as ‘stomach dysrhythmias’. They outline the results of their work in AJP Gastrointestinal and Liver Physiology.

In normal circumstances the stomach is coordinated by underlying bioelectrical ‘slow wave’ activity, which coordinates the contraction of the muscles that mix and move contents into and through the gastrointestinal (GI) tract.  When these electrical slow waves don’t work as they should, described as ‘stomach dysrhythmias’, it can lead to severe GI disorders and symptoms of nausea, vomiting, pain and bloating, and is often untreatable.

When dysrhythmic activity occurs in the heart it results in atrial fibrillation, which is often treated with ablation therapy in which tissues are precisely ‘burnt’ to control the naturally occurring electricity in the heart. Dr Tim Angeli-Gordon and PhD student Zahra Aghababaie of the ABI have shown that the technique could also be applied to control the naturally occurring bioelectrical “slow wave” activity in the stomach.

With last year’s publication of the team’s initial research using ablation in the stomach, they demonstrated that it was possible to use the technique to block the electrical activation of the stomach in localised regions. “The more recent paper builds on that foundational work and is an important advance because we have now shown that we can eliminate abnormal electrical activation with ablation, and also that the normal electrical activation of the stomach can be restored after ablation,” said Dr Angeli-Gordon. “Although these studies were done in our pre-clinical lab, they demonstrate the powerful potential of ablation in the stomach which may now be able to be translated as a therapy for patients suffering from gastrointestinal disorders.”

Source: EurekAlert!

GI Issues and Anxiety Linked in Children with Autism

Male doctor with young girl patient
Photo by National Cancer Institute on Unsplash

A new study has found a bi-directional relationship between gastrointestinal (GI) issues and internalised symptoms such as anxiety in children and adolescents with autism, which means the symptoms seem to be affecting each other. The findings could inform future precision medicine research aimed at developing personalised treatments for people with autism experiencing gastrointestinal issues. The study appears in the Journal of Autism and Developmental Disorders.

Autism is known to be often associated with GI issues, and is often overlooked in children despite being a source of pain and anxiety. Food preferences are often for carbohydrates and processed foods. The most common cause of GI issues in children with autism are abdominal pain, constipation, chronic diarrhea and gastroesophageal reflux disease (GERD).

“Research has shown gastrointestinal issues are associated with an increased stress response as well as aggression and irritability in some children with autism,” said Brad Ferguson, an assistant research professor. “This likely happens because some kids with autism are unable to verbally communicate their gastrointestinal discomfort as well as how they feel in general, which can be extremely frustrating. The goal of our research is to find out what factors are associated with gastrointestinal problems in individuals with autism so we can design treatments to help these individuals feel better.”

In the study, Ferguson and his team analysed health data from more than 620 under-18 patients with autism who experience gastrointestinal issues. Then, the researchers examined the relationship between the GI issues and internalised symptoms. Ferguson explained the findings provide more evidence on the importance of the ‘gut–brain axis’ in GI disorders in individuals with autism.

“Stress signals from the brain can alter the release of neurotransmitters like serotonin and norepinephrine in the gut which control gastrointestinal motility, or the movement of stool through the intestines. Stress also impacts the balance of bacteria living in the gut, called the microbiota, which can alter gastrointestinal functioning,” Ferguson said. “The gut then sends signals back to the brain, and that can, in turn, lead to feelings of anxiety, depression and social withdrawal. The cycle then repeats, so novel treatments addressing signals from both the brain and the gut may provide the most benefit for some kids with gastrointestinal disorders and autism.”

Ferguson is collaborating with David Beversdorf, a neurologist who also studies gastrointestinal problems in individuals with autism. Beversdorf had recently helped identify specific RNA biomarkers linked with gastrointestinal issues in children with autism.

“Interestingly, the study from Beversdorf and colleagues found relationships between microRNA that are related to anxiety behaviour following prolonged stress as well as depression and gastrointestinal disturbance, providing some converging evidence with our behavioural findings,” Ferguson said.

Ferguson and Beversdorf are now together investigating the effects of a stress-reducing medication on GI issues in a clinical trial. Ferguson cautioned that treatment could be effective for certain people with autism but not others.

“Our team uses a biomarker-based approach to find what markers in the body are common in those who respond favourably to certain treatments,” Ferguson said. “Our goal is to eventually develop a quick test that tells us which treatment is likely to work for which subgroups of patients based on their unique biomarker signature, including markers of stress, composition of gut bacteria, genetics, co-occurring psychological disorders, or a combination thereof. This way, we can provide the right treatments to the right patients at the right time.”

Source: University of Missouri-Columbia

A Touch-sensing Protein Helps the Gut to ‘Feel’

Anatomy of the gut
Source: Pixabay CC0

New research published in the journal Gastroenterology has discovered that a touch-sensing protein is present in the gut, with its presence likely playing a key role in constipation. The protein, called Piezo2, was found using both human gut samples and mice is not just in our fingers, but also in our gut.

“Many people suffer from digestive issues on a daily basis, such as chronic constipation, however we still don’t understand the cause which underlies most of them,” said Lauren Jones, lead author and final year PhD student.

“Our research identified Piezo2 in cells that line the human digestive tract, allowing them to sense physical stimuli, such as touch or pressure, that would occur when food is present. The cells then respond by releasing serotonin to stimulate gut contractions and push the food along.”

Last year, international researchers Ardem Patapoutian and David Julius were awarded the Nobel Prize in Physiology or Medicine for their research on receptors responsible for the perception of touch and temperature, including the discovery of Piezo2, now known to be responsible for sensing light touch on our skin.

Of potential clinical importance, the Flinders research team also discovered that the levels of Piezo2 decrease in the gut with age, and found that if the protein was removed only from gut serotonin cells, gut motility slowed down in mice, causing constipation.

The authors say this could be a potential contributing factor to age-related constipation and provide a possible path to treatment.

Researchers discover a nuclear import mechanism essential for organ growth and development

“Age-related constipation affects 1 in 2 adults over the age of 80, whilst constipation generally affects almost everyone at some point throughout their life,” says Ms Jones.

“It’s therefore extremely important we increase our understanding of the underlying mechanisms, so that we can find targeted solutions to improve the quality of life of the many people who suffer daily from various gut disorders, including constipation.

“This research provides the building blocks for both further research and the development of highly specific treatments to reduce the impacts of constipation.”

The authors say that, though more studies are needed to firmly link Piezo2 to constipation, the research overall is an important advancement into our understanding of gut physiology, opening up new targets for the treatment of digestive issues.

The insights allow for reduced side effects, explained Ms Jones: “More specifically, we now have the potential to create treatments that are taken orally and only directly impact these cells that line the gut, therefore significantly reducing side effects typically seen with many of the current medications.”

Source: News-Medical.Net

A New Understanding of the Fundamental Order of the Abdomen

Source: Pixabay

In a research paper published in Communications Biology, researchers from the University of Limerick have detailed the development and structure of the mesentery. In doing this, they uncovered a new order by which all contents of the abdomen are organised or arranged – or the “fundamental order of the abdomen”, where organs are in one of two compartments.

Professor Calvin Coffey, Foundation Chair of Surgery at UL’s School of Medicine in Ireland, whose major discovery led to the reclassification of the mesentery as a new organ in 2016, has published new research on the makeup and structure of the abdomen.

The importance of these findings on the mesentery and the impact these have on our understanding of the abdomen have been further explained in a review article just published in the Lancet Gastroenterology and Hepatology.

Prof Coffey explained that his team have been looking at the development and structure of the mesentery since 2016.

“We showed how the mesentery is a single and continuous organ in and on which all abdominal digestive organs develop and then remain connected to throughout life,” he explained.

“These findings revealed a simplicity in the abdomen that was not apparent in conventional descriptions of anatomy.”

The international team of researchers used cutting edge techniques to clarify how the mesentery develops and the shape it has in adults.

Their work revealed that the organisation of the abdomen has a remarkably simple design.

“The abdomen is not the dauntingly complex collection of separate organs it was previously thought to be,” said Prof Coffey.

“Instead, all digestive organs are neatly packaged and arranged by the mesentery into a single digestive engine. That simplicity lay hidden until clarification of the nature of the mesentery.”

The model itself was described by the team in the most recent edition of Gray’s Anatomy. The supportive evidence was published in Communications Biology and the clinical importance was explained in the review in The Lancet Gastroenterology and Hepatology.

“The most important finding here was the discovery of the fundamental order of the abdomen. At the foundation level, all contents of the abdomen are simply organised into one of two compartments,” explained Prof Coffey.

“The fundamental order of any structure is of considerable importance, in particular when it comes to diagnosing patients with illness and treating their disease. The fundamental order is the foundation from which all science launches and clinical practice is based.

“The organisational simplicity of the abdomen now immediately explains the behaviours of viral and bacterial infections, cancer, inflammatory bowel disease, obesity, diabetes and many others,” he added.

Improvements in surgery have been made to surgery by a better understanding of the mesentery and its functions, and the new research builds on those advances. There are also exciting areas for future investigation, according to Prof Coffey.

“Patients are already benefiting from what we now call mesenteric-based approaches to the diagnosis and treatment of most abdominal conditions. The Mesenteric Model of Abdominal Anatomy – or the description of the order of the abdomen – is being incorporated into numerous reference curricula at this moment,” he said.

“Regarding the future, it is being argued that we are seeing a paradigmatic shift from old to new order. Already, intriguing questions are emerging that we can call ‘legitimate or admissible’ in the strictest scientific sense. Science can approach numerous questions in a new light.  Clinicians can design diagnostic and treatment approaches based on a new foundation,” Prof Coffey concluded.

Source: EurekAlert!

A Link Between Intestinal Changes, Diet and Disease

A new study published in Nature Metabolism has found a link between diet, intestinal cell changes and disease.

The intestine has to react quickly to changes in nutrition and nutrient balance. One of the ways it does so is with intestinal cells that are specialised in the absorption of food components or the secretion of hormones. In adult humans, the intestinal cells regenerate every five to seven days. The ability to constantly renew and develop all types of intestinal cells from intestinal stem cells is crucial for the natural adaptability of the digestive system. However, a long-term diet high in sugar and fat disrupts this adaptation and can contribute to the development of obesity, type 2 diabetes, and gastrointestinal cancer.

The molecular mechanisms behind this maladaptation are the research area of this study. Intestinal stem cells are thought to play a special role in maladaptation, and to investigate this, the researchers used a mouse model to compare the impacts of a high-sugar and high-fat diet and with a control group.

“The first thing we noticed was that the small intestine increases greatly in size on the high-calorie diet,” said study leader Anika Böttcher. “Together with Fabian Theis’ team of computational biologists at Helmholtz Munich, we then profiled 27 000 intestinal cells from control diet and high fat/high sugar diet-fed mice. Using new machine learning techniques, we thus found that intestinal stem cells divide and differentiate significantly faster in the mice on an unhealthy diet.” The researchers hypothesize that this is due to an upregulation of the relevant signaling pathways, which is associated with an acceleration of tumor growth in many cancers. “This could be an important link: Diet influences metabolic signaling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer,” says Böttcher.

Using this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, such as hormone-secreting cells. Among their findings, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can result in intestinal inertia (typical of diabetes mellitus) or increased appetite. Furthermore, the absorbing cells were shown to adapt to the high-fat diet, increasing functionality and thus directly contributing to weight gain.

The study findings enable a new understanding of disease mechanisms associated with a high-calorie diet. “What we have found out is of crucial importance for developing alternative non-invasive therapies,” said study leader Heiko Lickert. 

Presently, there is no pharmacological approach to prevent, stop or reverse obesity and diabetes. Only bariatric surgery causes permanent weight loss and can even lead to remission of diabetes. However, these surgeries are invasive, non-reversible and costly to the healthcare system. Novel non-invasive therapies could happen, for example, at the hormonal level through targeted regulation of serotonin levels. This will be an avenue of future research for the group.

Source: EurekAlert!

1 in 10 Suffer Abdominal Pain After Meals

Photo by Vanessa Loring from Pexels

Around 11% of the global population frequently experience abdominal pain when they eat meals, according to a large online survey.

The research, presented at UEG Week Virtual 2021, found that was pain associated with eating is most common in those aged 18 to 28, with 15% of that age group affected. A gender split was seen, with 13% of women and 9% of men reporting eating-linked pain.

People experiencing frequent abdominal meal-related pain were also more likely to experience bloating, feeling full too soon, constipation and diarrhoea. The same group also had more severe psychological distress and non-gastrointestinal somatic symptoms.

A total of 36% of the people with frequent (>50% of the time) meal-related pain reported suffered from anxiety compared with 25% in the occasional (10-40% of the time) symptoms group and 18 % in those who never experienced meal-related pain. Those with frequent attacks also reported higher rates of depression (35%) compared to 24% in the occasional  symptom group and 17% in the group that never had meal-related pain.
The findings came from an online survey of 54 127 people across 26 countries.
Esther Colomier, study author and a joint PhD researcher at KU Leuven, Belgium, and the University of Gothenburg, Sweden, explained, “The take home message from this study is that people who experience meal-related abdominal pain more frequently experience other gastrointestinal symptoms and more regularly fulfil criteria for disorders of the gut brain interactions (DGBIs, formerly known as functional gut disorders), including common conditions such as irritable bowel syndrome (IBS), bloating and abdominal distension.”

“They also have a higher burden of psychological and somatic symptoms, such as back pain or shortness of breath, which are associated with major distress and functioning problems. These symptoms cause distress and disruption in daily life”, she added.

Lower gastrointestinal symptoms such as constipation and diarrhoea were experienced in 30% of those who reported frequent meal-related pain, versus 20% in the group who reported occasional symptoms and 10 % in the no symptoms at all group. The same applied for bloating and abdominal distension symptoms, which were reported as often as once a week in the group who experienced frequent meal pain, compared to two or three days a month in the group with occasional pain and one day a month in the group who experienced no symptoms.

Esther Colomier concluded, “Considering meal-related symptoms in future diagnostic criteria for DGBIs should be encouraged. In clinical practice, assessing meal association in all patients with DGBIs could be of major importance for improving and individualising treatment. Here, patients could benefit from a multidisciplinary care approach, including dietary and lifestyle advice, psychological support and pharmacological therapy.

Source: EurekAlert!

Eight Factors Predict Gastrointestinal Bleeding Risk after Heart Attack

Using machine learning, researchers at Karolinska Institutet have identified eight primary factors that increase the risk of a common bleeding complication after heart attack.

Some of these factors had been known already, however, the researchers have found additional predictors, such as smoking, blood pressure and blood glucose. The study was published in the European Heart Journal – Cardiovascular Pharmacotherapy.

“If we can identify patients at high risk of upper gastrointestinal bleeding following heart attack, doctors will be able to take prophylactic measures to mitigate this risk,” said the study’s corresponding author Moa Simonsson, deputy consultant at Karolinska University Hospital and doctoral student. “There are, for instance, drugs that combat bleeding complications, gut bacteria tests that can be used on risk groups and other possibilities for personalised treatment for heart attack patients at high risk of bleeding complications.”

Upper gastrointestinal (GI) tract bleeding is one of the most common bleeding complications following acute myocardial infarction. The condition requires a lot of resources to treat, causes considerable suffering and increases mortality risk. Bleeding complications also limit antithrombotic use, which in turn can worsen the cardiovascular prognosis.

Over the past 20 years, a close focus on bleeding has resulted in several strategies for reducing the risk of upper gastrointestinal tract bleeding. However, few studies on this complication include a diverse population of heart attack patients.

For the current study, the researchers sourced data from the national SWEDEHEART registry on almost 150 000 patients with acute myocardial infarction between 2007 and 2016. Approximately 1.5 percent of these patients suffered GI bleeding within a year of their heart attack, and they also had an increased risk of death and stroke.
Several known factors that increase the risk of upper GI tract bleeding were confirmed by the analysis, including low levels of haemoglobin, previous upper GI tract bleeding, age and intensive antithrombotic treatment.

Using an algorithm, the researchers also identified additional risk factors, including smoking, blood pressure, blood glucose and previous treatment for stomach disorders, such as ulcers and acid reflux.

“If you combine traditional statistical models with machine learning methods, you can create unique opportunities to find key risk factors for previously unknown cardiovascular events,” explained co-author Philip Sarajlic, doctoral student at Karolinska Institutet. “This makes it possible for us to make effective use of valuable data from the medical quality registry by taking account of complex relationships between risk factors and outcomes in order to further optimise the current recommendations for patient care.”

The researchers will soon begin a major clinical study to explore the significance of diagnosis and treatment of a common infection in the upper GI tract.

“A pilot study last year showed a two-fold increase in the presence of Helicobacter Pylori in heart attack patients,” said last author Robin Hofmann, researcher and consultant at Karolinska Institutet. “We will now proceed with a large randomized study to ascertain whether a systematic screening of heart attack patients for Hp infection and, where relevant, its treatment, can reduce bleeding complications and improve prognosis after heart attack.”

Source: Karolinska Institute

A Leak-proof, Biocompatible Intestinal Patch

Researchers at Empa have developed a patch that stably seals two sutured pieces of intestine and thus prevents dangerous leaks.

A burst appendix or a life-threatening intestinal volvulus are emergencies that need to be treated by surgeons immediately. However, operations carry risks: highly acidic digestive juices and intestinal bacteria can leak out, causing peritonitis and sepsis.

Sealing sutured tissue with a plaster has already been tried, but the first were not well tolerated or were even toxic. Currently, these plasters are made of biodegradable proteins, which have variable clinical results. These is because they are mainly intended to support the healing process, and dissolve too quickly when in contact with digestive juices and don’t always hold tight. “Leaks after abdominal surgery are still one of the most feared complications today,” explained Empa researcher Inge Herrmann, who is also professor for nanoparticulate systems at ETH Zurich.

Searching for a material that could reliably seal intestinal injuries and surgical wounds, Hermann’s team found a synthetic composite material made up of four acrylic substances that, together, form a chemically stable hydrogel. Additionally, the patch actively cross-links with the intestinal tissue until it is fluid-tight. The quadriga of acrylic acid, methyl acylate, acrylamide and bis-acrylamide works in perfect synergy, as each component conveys a specific feature to the final product: a stable bond to the mucosa, the formation of networks, resistance to digestive juices and hydrophobicity. This new technology is detailed in Advanced Functional Materials.

In lab experiments, the researchers found the polymer system met their expectations. “Adhesion is up to ten times higher than with conventional adhesive materials,” said researcher Alexandre Anthis from Empa’s Particles-Biology Interactions lab in St. Gallen. “Further analysis also showed that our hydrogel can withstand five times the maximum pressure load in the intestine.” The material’s design uses its tailored effect: The rubbery composite selectively reacts with digestive juices that might leak through intestinal wounds, expands and closes all the more tightly. The inexpensive, biocompatible super glue, could thus shorten hospital stays and save healthcare costs, and Anthis is making plans to bring it to market.

Source: Empa

Common Gut Bacteria Could Inhibit SARS-CoV-2

Bifidobacterium eriksonii, stained with fluorescent antibodies. Source: Public Health Image Library

South Korean researchers have found that certain common gut bacteria produce compounds that inhibit SARS-CoV-2. 

The research was presented on June 20 at World Microbe Forum, an online meeting of the American Society for Microbiology (ASM), the Federation of European Microbiological Societies (FEMS), and several other societies that taking place online June 20-24.

Previous clinical findings had shown that some patients with moderate to severe COVID experience gastrointestinal symptoms, while others show signs of infection in the lungs only.

“We wondered whether gut resident bacteria could protect the intestine from invasion of the virus,” said Mohammed Ali, a PhD student in Medicine at Yonsei University in South Korea.

To investigate this hypothesis, the researchers screened dominant bacteria inhabiting the gut for activity against SARS-CoV-2. Their efforts revealed that Bifidobacteria, already shown to suppress other bacteria such as H. pylori and have proven active against irritable bowel syndrome, had such activity, said Ali. Bifidobacteria are common in the guts of breast fed infants, which is partly driven by the bifidogenic activities of specific mother milk-derived oligosaccharides

The researchers also searched for potential illness-fighting compounds in databases containing microbially produced molecules, and discovered some that might also be useful against SARS-CoV-2. “To train our model we leveraged previous coronavirus datasets in which several compounds were tested against targets from coronaviruses,” explained Ali. “This approach seems to be significant as those targets share features in common with SARS-CoV-2.”

Ali emphasised the ecological nature of his approach to this work, pointing out that numerous existing antibiotics and cancer therapies are themselves compounds that bacteria use to compete with each other within the gastrointestinal tract, and that these were initially purified from microbial secretions.

“Finding microbes that secrete anti-coronavirus molecules will be a promising method to develop natural or engineered probiotics to expand our therapeutics prevention techniques, to provide a more sustainable way to combat the viral infection,” said Ali.

Source: American Society for Microbiology