News
Blood plasma can be analysed using infrared light to identify Crohn’s disease
A team of researchers in France have demonstrated the use of infrared spectroscopy to detect Crohn’s disease from patient’s plasma with an accuracy of 97 %. Infrared spectroscopy is a non-destructive technique that detects the characteristic absorptions of infrared light (light with longer wavelengths than what we can see) by molecules to give a “spectral fingerprint” relating to molecular composition. In plasma samples this spectral fingerprint gives information on the composition and relative abundance of biomolecules. These biomolecules are present in slightly different levels between Crohn’s disease and control patients. The researchers were able to use this spectral fingerprint with multivariate data analysis techniques to create a classification model to distinguish between Crohn’s disease and control patients. This type of technology needs to be further assessed and developed in larger studies before implementing in clinic, but it is an exciting field to follow and I hope to see it developed to a level that aids the diagnostic pathway for Crohn’s disease in the future.
How does having inflammatory bowel diseases affect your eating and physical activity habits?
A disease flare often makes it difficult to eat well or be as physically active as normal. Research from other countries suggest that people with inflammatory bowel diseases (IBD) like Crohn’s or colitis, eat differently and exercise less compared to people without IBD, but these habits are not known in New Zealand.
A recent University of Otago research known as the IBD exercise and dietary (IBDeat) study, found that around 69% of people with IBD avoided trigger foods to manage their symptoms. These were mainly gluten (from wheat, barley, rye), dairy products, or high fibre foods including fruits and vegetables. Many people also felt that fatigue, stomach cramps, bowel symptoms, and joint pain were the main challenges to being active.
It is well known that eating a balanced diet and being physically active are the few key steps to maintaining good health. A balanced diet means trying to eat a variety of grain foods, dairy products or fortified plant milks, protein foods, and a rainbow of fruits and vegetables. Although this can be fairly challenging at times for many people with IBD, some studies have shown that it is possible to achieve with proper guidance.
Based on those studies, the IBD Lifestyle Food & Exercise (IBDLiFE) study aims to find out whether providing credible resources and/or support can help people with IBD to make the desired lifestyle changes while managing their symptoms. This research will provide valuable insights to practical lifestyle advice for people with IBD.
Just over half of NZ Patients with Inflammatory Bowel Disease have ‘Good’ Medication Adherence: a look at how well patients take their medication
As former US Surgeon General, Dr C. Everett Koop, said: “Drugs don't work in patients who don't take them.” Hence, it is very important for patients to take their medications as prescribed i.e. practice medication adherence (MA). This is essential particularly for patients with Inflammatory Bowel Disease (IBD) as IBD has no cure; so, it is mainly managed using life-long medication therapy with disease monitoring, besides other interventions.
IBD is a chronic gut disease made up of Crohn’s Disease, Ulcerative Colitis and IBD-unclassified. Patients with IBD may experience periods of active disease with ‘flare-ups’ and ‘quiescent’ periods at other times. They may also have symptoms including (bloody) diarrhoea, urgency, constipation, abdominal pain, weight loss amongst others; all of which limit their quality of life and productivity.
Researchers at the University of Otago, Department of Medicine, investigated the nationwide MA levels of patients with IBD using national pharmacy dispensing claims and hospitalisation data. They found that the average MA over three years, for 4654 patients, was moderately high at 77.4%. Likewise, average MA over five years was also moderately high at 74.9% for 3148 patients. These were measured using a novel formular called daily polypharmacy possession ratio (DPPR) which calculates MA to multiple medications taken at the same time.
The picture was a bit different when they calculated how many patients had ‘good adherence’ i.e. patients whose MA was at least 80%. Only 54% and 51% of patients over three and five years, respectively, met this threshold. These findings suggest that a closer look needs to be paid into the long-term MA patterns and, importantly, the factors impacting how patients with IBD take their medications.
New radiotracer quickly detects gastrointestinal cancer biomarker and helps to identify patients for targeted therapy
Gastrointestinal (GI) cancers occur in the digestive system. It is among the most common types of cancer worldwide. Diagnosis typically involves a combination of endoscopy, imaging (like CT scans and PET scans), biopsies, and blood tests. Treatment options depend on the cancer type and stage and may include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Early detection generally leads to better outcomes, but many GI cancers are diagnosed at an advanced stage, which can complicate treatment and worsen prognosis. A new synthesized PET scan radiotracer, 68Ga-NC-BCH, helps doctors see a protein called Claudin18.2 (an important GI cancer biomarker) that is often found in high amounts in GI cancers. Uptake of 68Ga-NC-BCH is correlated with the amount of Claudin18.2. 68Ga-NC-BCH lets doctors take detailed images in one day, unlike older methods that might take longer and be more invasive. It specifically targets the Claudin18.2 protein. This means doctors can get a clear view of where the cancer is and how much of the protein is in the body. Compared to traditional methods, this new tool is non-invasive and provides quick, accurate results. It can help doctors make better treatment decisions and track how well treatments are working.
Liver transplant added to chemotherapy improves survival in advanced colorectal cancer
The incidence of colorectal cancer continues to rise worldwide. Colorectal cancers originate in the bowel but have the potential to spread or metastasize to other organs. The most common site of spread of colorectal cancer is the liver and to date the most effective treatment for this surgery is to remove the liver, usually in combination with chemotherapy. Unfortunately, only twenty percent of people with liver metastases from colorectal cancer will be able to have surgery to remove the cancer. To date there have been no other treatments that offer a potential cure for people with liver metastases that cannot be surgically removed.
In this clinical trial people with liver metastases from colorectal cancer that are unable to be removed with surgery were randomized to receive either liver transplant and chemotherapy or chemotherapy alone. Promisingly, those patients who underwent liver transplantation had better survival rates compared with those who did not. The combination of liver transplantation and chemotherapy may offer a potential cure to those people who would otherwise have a poor long-term outcome.
Source: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00187-1/fulltext
SOX17 enables immune evasion of early colorectal adenomas and cancers
Being able to treat colorectal cancer (CRC) with the right treatment and early is key to improving the health outcomes and long-term survival of patients. One of the ways cancers establish and progress is by blunting the immune defence. This study by Goto et al (2024) has shown that protein, SOX17, helps tumours escape the immune system in early tumour development. SOX17 plays a role in embryonic development and is not usually expressed in the healthy gut lining of adults. The researchers grew mini tumours with common CRC-associated mutations and transplanted them into the colons of mice. The researchers observed an increase in SOX17 expression and decreased cancer-fighting T cells and reduced activity of immune protein, interferon gamma. When the research team generated colorectal tumours that were unable to express SOX17, these tumours became susceptible to the anti-cancer immune response. These findings show that SOX17 is playing a role in the tumours ability to hide from the immune system. The research team validated that human colorectal cancers express SOX17 and, at higher levels in early CRC compared to late stage CRC, suggesting that SOX17 is important for tumour establishment and development by preventing immune surveillance.
Next steps will involve identifying other proteins in this immunosuppressive pathway mediated by SOX17, which may reveal new therapeutic targets. In the bigger picture, it may be important to consider how early CRC and pre-cancerous growths are detected and how we can utilise ‘early’ treatments when they are needed. This study evidences a new immune evasion mechanism facilitated by SOX17 in the early stages of CRC development.
Promising new immune checkpoint inhibitor for colorectal cancer
In New Zealand, colorectal cancer (CRC) is the most diagnosed cancer and the second most common cause of death due to cancer. Overall survival rates of people are highly variable even with advancements in therapy. One form of therapy, known as immune checkpoint inhibitors (ICI), aims to reinvigorate the immune response to help destroy tumour cells. However, immune checkpoint inhibitors have only been effective in people with microsatellite instable high or mismatch repair deficient CRC, which represent about 4% of CRC types. ICI therapy has been elusive for the more common form of CRC known as the microsatellite stable CRC.
In a recently concluded phase 1 clinical trial, a new ICI botensilimab (antiCTLA4) was used in conjunction with balstilimab (antiPD1) was studied for safety in patients with microsatellite stable CRC that were not responding to chemotherapy. The study involved 101 patients that were followed for 6 months after receiving therapy. Promisingly, 61% of the patients had some form of response (either tumour shrinkage or stable disease). Furthermore, the most common side effects reported by the patients in the study were diarrhoea and fatigue. The treatment modality has now entered into late-stage clinical trials.
Gut microbiome signatures modulate cardiovascular disease risk
New antibody treatment shows promise for coeliac disease
Coeliac disease affects millions of people worldwide yet the only current treatment for coeliac disease is through adherence to a strict gluten-free diet. This form of disease management is considered suboptimal as it is highly restrictive, difficult to maintain and does not always promote intestinal mucosal healing.
A recent study by the Japanese pharmaceutical company, Chugai Pharmaceuticals, has presented a successful antibody treatment, DONQ52 for coeliac disease. This treatment targets HLA-DQ2.5 gluten peptides that are present in 85% of individuals with the disease. By blocking gluten-specific T cells, DONQ52 prevents immune damage to the small intestine upon gluten ingestion in individuals with coeliac disease.
This study examined the gluten-specific immune response in blood samples from participants with coeliac disease following the consumption of wheat, rye and barley products. A significant reduction in the gluten-specific T cell response was observed. Importantly, treatment with DONQ52 did not affect the T cell responses to non-gluten antigens, making DONQ52 a promising drug candidate.
This research provides an exciting new targeted treatment for those with coeliac disease that could improve quality of life by reducing the need for a strict gluten-free diet.
Source: https://www.sciencedirect.com/science/article/pii/S1521661624003681?via%3Dihub
Faecal microbial transfer and complex carbohydrates mediate protection against COPD
Chronic obstructive pulmonary disease (COPD) is a common cause of illness in around 500 million people worldwide. It is know that those with COPD have altered microbiomes compared to those without COPD, but the direct role of microbes in the pathogenesis of the disease are unclear. A recent study using a mouse model of cigarette smoke induced COPD showed that faecal microbiota transplant (FMT) alleviated inflammation in COPR by improving the lung function and breathing, compared to mice that didn’t get a FMT. The research group then identified specific bacterial species that were associated with lung health. Next, they conducted a small human study to determine if altering the microbiome via a dietary intervention (using inulin) would improve symptoms in those with COPD. Compared to a placebo group, those given dietary inulin had an improved quality of life, which was linked to changes in microbiome composition. Overall, these results suggest that by altering the microbiome of those with COPD, disease symptoms and quality of life may improve.
Safina Gadeock awarded HRC Emerging Researcher Award
Congratulations to Dr. Safina Gadeock, who was one of the 13 researchers awarded the HRC Emerging Researcher, 2024 for her study on "Interferon-alpha targets as prognostic biomarkers for IBD patients". She aims to validate an innovative Type I Interferon (immunomodulatory molecules) biomarker panel to predict response to anti-TNFs in a cohort of NZ and US IBD patients; and elucidate the mechanism(s) driving Type I Interferon-dependent regenerative responses and epithelial barrier integrity in responsive IBD patients. This study will steer the development of an innovative biomarker panel that will help gastroenterologists tailor therapy for the approximately 50 per cent of non-responsive IBD patients.
Industrialised societies have less cellulose-digesting gut bacteria
Cellulose is a ubiquitous material in nature that makes up the cell wall of plants, and is a major component of dietary fibre. Animals such as cows and sheep have specialised digestive tracts containing ruminant bacteria that allow them to extract energy from cellulose. In 2003, it was confirmed that humans also have some gut bacteria that can process cellulose. These bacteria play an important role in supporting other bacteria in the gut to promote a healthy gut microbiome.
A recent study has shown that humans are host to many more of this variety of bacteria than previously known – some related to those found in livestock and some from our primate ancestors. It was also shown that these cellulose-digesting bacteria are being lost from industrialised societies, possibly due to our diets becoming lower in fibre. The authors suggest there may be potential for reintroduction or enrichment of cellulose-digesting bacteria in the gut through dietary changes.
Source: https://www.science.org/doi/10.1126/science.adj9223