Current IBD Research Projects

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Lyophilised Orally Administered Faecal Microbiota Transplantation in the Management of Ulcerative Colitis (LOTUS) Study – a Double-Blind Randomised Controlled Trial

Principal Investigator – Professor Rupert Leong 

The University of Sydney, Concord Clinical School

Inflammatory bowel disease (IBD) is a chronic disabling gastrointestinal condition thought to be caused by disturbances in the interaction between our immune system and the microorganisms in our gastrointestinal tract. Current therapies for IBD are expensive and rely on suppressing the immune system which is associated with significant side effects, increased risk of infections and certain cancers. Even if initially effective, subsequent loss of response to these therapies is common.

Faecal microbial transplantation (FMT) is the infusion of faecal material (and associated microorganisms) derived from a healthy individual (donor) to a diseased individual. It aims to correct the imbalance in the recipient’s gut microbiome by replacing it with microbiota from healthy donors. FMT is a promising non-immunosuppressive, non-pharmacological treatment for ulcerative colitis (UC) with studies showing that FMT delivered by colonoscopy followed by regular enema therapy will lead to improvement in active UC. Ongoing therapy with FMT may have the ability to maintain remission in UC, however FMT delivered through colonoscopy or regular enema therapy is not practical in the long term.

FMT in an oral capsule form is the ideal form of therapy and may revolutionise the treatment of UC. We have commenced a controlled trial assessing orally administered FMT given by capsules to treat ulcerative colitis both as an induction therapy as well a maintenance treatment. We believe findings from this trial will advance the field of microbial based treatments in IBD.

“A spectral and in vitro study of intestinal fibrogenesis and biomarkers in Crohn’s disease to inform 3D-human tissue-based models of intestinal fibrosis and identify therapeutic targets”

C.Keung Lay

Intestinal fibrosis is an over-accumulation of scar tissue within the wall of the bowel which impairs bowel function. This occurs in over 70% of patients with inflammatory bowel disease (IBD) leading to intestinal narrowing (strictures), blockages, and fistulas (abnormal connections between the bowel and other structures). While there are many treatments targeting inflammation in IBD, there are none for fibrosis. Yet complications from fibrosis are the main reason that IBD patients require hospitalisation and surgery.

In order to find treatments for intestinal fibrosis, we need to improve our understanding of the disease as well as realistic models to test new therapies. To accomplish this in our research, we are using a powerful microscopy technique called biospectroscopy, which uses infra-red laser energies to excite chemical bonds present in intestinal tissue, producing a unique chemical signature. From this we can accurately identify the components of a Crohn’s stricture and identify an energy “fingerprint” of fibrosis. Then we can predict which patients are at risk for intestinal fibrosis, as well as potential targets for drug treatments. Excitingly, these microscopes can rapidly produce results in minutes at the time of colonoscopy.

Using this information, we will create a human model of intestinal fibrosis in Crohn’s disease by growing “mini-guts” (organoids) from intestinal biopsies taken during colonoscopy. These “mini-guts” represent the patients Crohn’s disease state as they are grown from their own intestinal stem cells. The environment of these “mini-guts” will be altered to simulate fibrosis so we can then use this model to test drug and stem cell therapies that may improve fibrosis.

This research is highly important to the field of IBD with benefits of earlier detection of fibrosis in Crohn’s disease, improved clinical outcomes and reduction in health care costs. Furthermore, results of our research may discover new targets for fibrosis and new drug therapies which can progress directly to human trials without the need for animal studies.

Targeting the Clec12A pathway for the regulation of gastrointestinal inflammation.

Associate Professor Mireille Hanna Lahoud and Dr Jakob Begun

2nd year of Gutsy Group funding of proposed 3 year project ($100,000 funded to date).

The immune system’s role is to protect the body from harmful infections. Specialised cells within the body, called antigen presenting cells, monitor for signs of infection, and activate the immune system accordingly. This enables the immune system to induce a tightly regulated immune response to eliminate infected cells, but also minimise harm to the body. However, in some circumstances, the immune system can respond inappropriately to non-threatening factors (e.g. normal self-cells or commensal bacteria that are naturally present within the body) resulting in auto-inflammatory diseases. IBD, including Crohn’s disease, are chronic auto-inflammatory diseases affecting the gut. Patients require life-long therapies, with many requiring surgery. The researchers have identified a protein receptor that is expressed on the surface of antigen presenting cells and can regulate autoinflammatory responses to protect against IBD. The research aims to understand how this modulator controls inflammation and to develop strategies to target this protein and dampen gastrointestinal inflammation in IBD patients. CURRENT RESEARCH PROJECTS Pregnancy In Crohn’s and Colitis: Observations, Levels and Outcomes: The PICCOLO Study. Dr Emma Flanagan and Associate Professor Sally Bell 1st year of proposed 3 year project funded by direct donor ($50,000), Jim Carroll, The Trustee of The Donald Ratcliffe and Phyllis Macleod Trust. IBD commonly affects women when they are in their childbearing years. Most IBD medications are safe in pregnancy, and the greatest driver of poor pregnancy outcomes in patients with IBD is active disease, which can increase rates of miscarriage and preterm birth. However, women with IBD can have poor knowledge about the adverse impact of active IBD on pregnancy, and conversely, on the safety of maintenance IBD medication during pregnancy. The PICCOLO study is the first study designed to evaluate the effect of a single, individualized patient education consultation as an intervention for improving pregnancy-related knowledge and outcomes in women with IBD. The study is for female patients with IBD aged 18-45 who are pregnant or have an active pregnancy wish. In participants who are pregnant during the study period, serial assessments of disease activity will be conducted as well as monitoring of drug levels during pregnancy and after delivery (ie: for mothers and babies). Disease activity during pregnancy will be safely assessed to ensure inflammation is controlled and that both women and babies are given the best opportunities for a successful pregnancy and delivery.

Pregnancy In Crohn’s and Colitis: Observations, Levels and Outcomes: The PICCOLO Study.

Dr Emma Flanagan and Associate Professor Sally Bell

1st year of proposed 3 year project funded by direct donor ($50,000), Jim Carroll, The Trustee of The Donald Ratcliffe and Phyllis Macleod Trust.

IBD commonly affects women when they are in their childbearing years. Most IBD medications are safe in pregnancy, and the greatest driver of poor pregnancy outcomes in patients with IBD is active disease, which can increase rates of miscarriage and preterm birth. However, women with IBD can have poor knowledge about the adverse impact of active IBD on pregnancy, and conversely, on the safety of maintenance IBD medication during pregnancy. The PICCOLO study is the first study designed to evaluate the effect of a single, individualized patient education consultation as an intervention for improving pregnancy-related knowledge and outcomes in women with IBD. The study is for female patients with IBD aged 18-45 who are pregnant or have an active pregnancy wish. In participants who are pregnant during the study period, serial assessments of disease activity will be conducted as well as monitoring of drug levels during pregnancy and after delivery (ie: for mothers and babies). Disease activity during pregnancy will be safely assessed to ensure inflammation is controlled and that both women and babies are given the best opportunities for a successful pregnancy and delivery.