A Randomised Controlled Trial Studying the Impact of Diet on Inflammation In The Colon

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.

Understanding the regulation and function of OTUD3, a novel ulcerative colitis gene

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.