Principal Investigator – Dr Alice Day
The Queen Elizabeth Hospital & Basil Hetzel Institute, South Australia
In this study, participants with mild to moderately active ulcerative colitis are randomised to follow one of two diets for 8 weeks. One diet is the therapeutic sulphide reducing diet and the other a placebo diet. Participants are required to shop, prepare and cook simple meals following the dietary advice and they will complete a series of assessments at three time points during the study which will measure inflammation in the colon, adherence to the diet and fermentation biomarkers to monitor how food is digested and metabolized by bacteria in the colon. This includes a new, state-of-the-art gas capsule to measure production of gastrointestinal gases in real time.
The project’s hypothesis is that the intervention diet can reduce colonic inflammation by normalizing gastrointestinal transit time and altering fermentation of dietary substrate and associated production of potentially harmful gases by bacteria in the colon. Undertaking this research will:
• Advance our understanding of the role of diet in the pathogenesis and treatment of ulcerative colitis by providing mechanistic insight into whether dietary substrate and microbial fermentation may be drivers of inflammation;
• May inform a new diet therapy to use as treatment for ulcerative colitis; and
• Will provide people living with this condition practical guidance on how best to eat to control inflammation and improve their food-related quality of life.
Rabina Giri, A/Prof Jakob Begun
Mater Research Institute – The University of Queensland
Inflammatory bowel disease (IBD) can be a debilitating disease with significant morbidity and impact on quality of life. It is a complex, highly individual disease with many distinct phenotypes, which may explain the relatively low rates of clinical response (40-60%) and remission (25-40%) in the majority of clinical trials. Up to 10% of patients with ulcerative colitis (UC) may ultimately require colectomy for refractory disease, representing thousands of patients across Australia. Thus, a large unmet need exists, and a better understanding of the pathogenesis of IBD is required to enable next generation therapies targeting the underlying disorders, rather than downstream pathways targeted by currently available drugs.
We identified a novel IBD gene, OTUD3, as the causative mutation in a multigenerational family with severe UC. Amazingly, disruption of this gene in mice resulted in a spontaneous colitis caused by disrupted barrier function, similar to UC. Furthermore, we observed a significantly lower level of OTUD3expression at the RNA and protein level in UC patients. We now propose to expand our knowledge of this novel gene’s mechanisms of regulation and downstream action, including its direct targets. This will elucidate OTUD3’s mechanism of action and reveal a potential cornucopia of future therapeutic targets for our group and others in the IBD research community to explore.
Linda Yang
St Vincent’s Hospital and the University of Melbourne
Artificial Intelligence in IBD-related Dysplasia (AID) study is a multicenter prospective study that aims to develop a computer-aided image detection system to detect dysplasia in IBD patients.
Patients with inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer and precursor dysplastic lesions. Surveillance colonoscopy is recommended for patients with disease duration greater than 8-10 years. However, colonoscopic detection of dysplasia is challenging. IBD-associated dysplasia is often invisible on endoscopy and can be difficult to distinguish from inflammation. Even when an abnormality is visible, differentiating polyps from inflammatory pseudopolyps associated with IBD can be challenging. The optimal approach for endoscopic surveillance is not well established and there is a high variability in detection of dysplasia even among expert endoscopists. Guidelines vary with regards to imaging techniques and biopsy protocols.
Artificial intelligence refers to machine learning to replicate or simulate human intelligence and is rapidly coming into use in clinical medicine including in the field of endoscopy. AI in IBD is in its early development with several pilot studies. However, the use of AI in detection of dysplasia in IBD has not been published.
The AID study aims to develop an AI system to assist in endoscopic detection of visible and invisible dysplasia and other mucosal lesions in IBD colonoscopy. This is the first study assessing the feasibility and impact of a computer-aided system in endoscopic detection of IBD-related dysplasia. The results of this study may lead to future studies such as real-time validation of the AI software in patients. Improvement in the detection of IBD-related dysplasia with the use of an AI system can facilitate timely treatment of dysplasia and reduce morbidity and mortality associated with IBD-related colorectal neoplasia.
Dr Adam Peterson
Monash Medical Centre
Despite rapid advances in the management of inflammatory bowel disease (IBD), patients fail to improve their symptoms with current therapies and there is a dire need for new treatments.
Human mesenchymal stem cells (MSC) obtained from adult fatty tissues are now an established treatment for complex perianal fistulising Crohn’s disease and preliminary studies have shown the potential for these cells to also be useful in IBD within the bowel. Human amnion epithelial cells (hAEC) are isolated from the placenta and have similar therapeutic properties as MSC but can be obtained in far greater numbers from the placenta than MSC can be from adipose tissue or bone marrow.
Ulcerative proctitis is a commonly encountered type of ulcerative colitis, where the disease is confined to the rectum. It can cause debilitating symptoms and lead to a reduction in quality a life. Furthermore, it frequently fails to respond to usual treatments. Unfortunately, patients with isolated proctitis are often excluded from clinical drug trials, leaving a great unmet need. This research will expand the use of hAEC treatment to ulcerative proctitis through a clinical trial where they will be delivered via colonoscopy and injection into the bowel.
The outcomes of this research will provide a basis for their evaluation in further clinical studies and guide the development of hAEC towards a clinical therapy for IBD patients.
Dr Damjana Bogatic
The Royal Adelaide Hospital and The Queen Elizabeth Hospital, Adelaide
FMT Therapy for PSC
Primarysclerosing cholangitis (PSC) is a serious liver disease that can affect peoplewith inflammatory bowel disease (IBD), occurring in up to 3.8% of those withIBD. PSC causes damage to the bile ducts, which can lead to liver failure overtime. It is also linked to a higher risk of cancers in the gallbladder, bileducts, liver, and bowels. While new treatments for IBD have been developed in recentyears, there are no medicines that have been proven to slow the progression ofPSC, and liver transplantation is still the only treatment that can cure it.
Recentresearch suggests that the gut microbiome (the bacteria and microbes in ourgut) may play a role in both IBD and PSC. Studies have shown that people withPSC often have an unhealthy gut microbiome, and 80% of PSC patients also haveIBD, hinting at a possible connection. Faecal microbiota transplantation (FMT)is a treatment where stool from a healthy person is transferred to a patient,in order to restore the gut microbiome and help treat the disease. This studyis looking at whether FMT, given through freeze-dried capsules, is safe forpeople with PSC. The study will also examine whether this treatment can helpslow down the progression of PSC, improve symptoms, quality of life, andIBD-related outcomes. It will also explore whether substances from the gutmicrobiome, carried through the bloodstream to the liver, might be causingdamage to the bile ducts and liver in PSC patients.
