Tag: irritable bowel syndrome

Categories : GastrointestinalTags :

Decades-old Puzzle Solved as Scientists Uncover Cause of IBD

On By ModernMedia

Scientists have identified the missing link between a long-known genetic signal in inflammatory bowel disease and a damaging immune response that switches off the body’s natural control of inflammation – opening the door to faster diagnosis and targeted treatment.

Interleukin-10.

Researchers at the Nuffield Department of Medicine, University of Oxford, together with Newcastle University’s Translational and Clinical Research Institute and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust, have identified an important driver of inflammatory bowel disease (IBD). This discovery reshapes understanding of IBD and opens the way to targeted approaches to diagnosis and treatment in a subset of patients. The findings suggest that inflammatory bowel disease is not a single condition, but a group of biologically distinct diseases driven by different underlying mechanisms.

In a study published in the New England Journal of Medicine, researchers analysed over 4900 patients with IBD and made two major discoveries: first, that a substantial subset of patients show autoimmune responses to one of the guardians of the immune system, interleukin-10 (IL-10), which leads to uncontrolled inflammation; and second, that this damaging immune response is the mechanism for one of the strongest known genetic risk factors for IBD.

Antibodies that block interleukin-10 (IL-10), a cell-to-cell messenger that normally acts as one of the body’s key controls on inflammation, effectively remove the immune system’s natural ‘brake’ on inflammation, allowing inflammatory responses to continue unchecked.

IBD, which includes Crohn’s disease and ulcerative colitis, affects around 500 000 people in the UK and millions worldwide. It is a lifelong condition that commonly begins in adolescence or early adulthood and can require repeated hospital treatment, long-term immunosuppressive medication and, in some cases, surgery. Despite advances in treatment, many patients cycle through multiple therapies without achieving lasting disease control – impacting their lives and costing the health care system millions.

The researchers found high levels of anti-IL10 neutralising autoantibodies in the blood of around 3.5% of IBD patients, both Crohn’s disease and ulcerative colitis, but not in healthy individuals. This could equate to 15 000-20 000 people with IBD in the UK carrying these autoantibodies.

The researchers also found that the presence of these antibodies was strongly linked to carriage of a particular genetic variant known as HLA-DRB1*01:03.

The link between HLA-DRB1*01:03 and a severe form of inflammatory bowel disease was first identified by Oxford researchers 30 years ago. The new findings show that people carrying this variant are far more likely to develop antibodies that block IL-10, helping explain how the gene contributes to disease.

The Oxford IL-10 Research GroupProfessor Holm Uhlig, a Paediatric Gastroenterologist and Director of the Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, and a senior author of the study, said: ‘We’ve suspected an important role of interleukin 10 in patients with inflammatory bowel disease for decades. The study now provides clear evidence and contributes the missing link between a well-known genetic variant that had been linked to severe inflammatory bowel disease in the past and the very recently discovered autoimmunity to interleukin 10. 

‘Understanding what drives the inflammation, provides a clear explanation for disease in this group of people and opens the door to new treatments that target the autoantibodies themselves or cells that produce those autoantibodies.’

The paper, ‘IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease’, is published in the New England Journal of Medicine.

Source: University of Oxford

Categories : GastrointestinalTags :

Some Common IBS Treatments Linked to Higher Risk of Death

On By ModernMedia
Photo by Towfiqu Barbhuiya on Unsplash

A large, long-term study led by Cedars-Sinai Health Sciences University investigators suggests that some medications commonly prescribed to treat irritable bowel syndrome (IBS) – including antidepressants – may be associated with a small but measurable increase in the risk of death.

The findings, published in Communications Medicine, are based on nearly two decades of electronic health records from more than 650 000 US adults with IBS, making it the largest real-world study to examine the long-term safety of IBS treatments.

IBS is a chronic gastrointestinal condition which has no cure, but dietary modifications, behavioural therapy and medications can help manage symptoms.

“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai and senior author of the study. “However, most clinical trials of these medications last less than a year, so we know very little about their long-term safety. This study begins to address that gap.”

Researchers assessed patients taking Food and Drug Administration-approved IBS medications, as well as antidepressants, antispasmodics and opioid-based antidiarrhoeal drugs, such as loperamide and diphenoxylate – widely used and recommended in IBS care. They found that long-term antidepressant use was associated with a 35% higher risk of death, and that loperamide and diphenoxylate use were associated with roughly double the risk of death.

The study does not establish that these medications directly cause death; rather, the observed associations may reflect higher rates of adverse outcomes, such as cardiovascular events, falls and stroke, which were more frequent among exposed patients.

Although antidepressants are not FDA-approved for IBS, they are commonly prescribed for IBS patients to help reduce pain, calm symptoms and make the condition easier to manage. The study found that other recommended treatments, including FDA-approved medications and antispasmodics, were not associated with increased mortality risk.

Researchers emphasised that while the increase in risk is significant and may sound concerning, the overall risk to any individual patient is small.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Rezaie, the director of Bioinformatics at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai. “Patients should speak with their healthcare provider about the safest and most effective options for managing their symptoms.”

Rezaie said more research is needed to confirm these findings and identify which patients may be at greatest risk. He also called for future treatment guidelines to better address the long-term safety of medications commonly used to manage IBS.

In the meantime, he emphasized a more personalised approach to IBS patient care.

“Treatment for IBS patients should focus on identifying the underlying causes and using the safest, evidence-based options available rather than relying on a single class of medications for long-term management,” Rezaie said.

By Kristin Reynolds

Source: Cedars-Sinai Medical Center