OVERVIEW

Gastrointestinal Disease

Researchers at TRI are investigating various gastrointestinal disorders and diseases including irritable bowel syndrome (IBS), pancreatitis and reflux. Read more about these areas of research below.

Neurogastroenterology and research into disordered gut function (sensory, motor and intestinal permeability)

The field of Neurogastroenterology aims to identify the causes of Functional Gastrointestinal Disorders (FGIDs), which includes irritable bowel syndrome and functional dyspepsia. Symptoms of FGIDs occur in the absence of structural abnormalities that can be identified with the routine available diagnostic tests. These are chronic relapsing diseases, and FGIDs are extremely common - recent estimates indicate they affect 20-30% of the Australian population, and represent up to half of all referrals for specialist gastrointestinal consultation.

These conditions can be debilitating and significantly impair patient’s quality of life, often resulting in job absenteeism. It is well established that the manifestation of symptoms is associated with disordered gut function (e.g. abnormal motor or sensory function). In addition, there is now increasing evidence that the immune system is involved in the aetiology of FGID and that activation of the immune system may be the precipitating factor for altered gut function (i.e. sensory function). Thus research at TRI aims to elucidate underlying mechanisms that cause immune activation. This includes research into the gastrointestinal microbiome. 

Biomarker research

At the TRI the group of Prof Holtmann and at the University of Newcastle Prof NJ. Talley were awarded the United States Rome Foundation grant to develop and validate a diagnostic test for predicting functional from organic GI disease and IBS from lower organic GI diseases using the Princess Alexandra and John Hunter Hospital bio bank.

This research is being continued with the DEFINE study (Diagnostic Evaluation of Functional GI and IBS Networks) which has secured additional funding from Prometheus to determine whether serum biomarkers can distinguish functional from organic GI disease as well as IBS from other functional GI disorders in an outpatient setting. This novel study aims to develop a non-invasive diagnostic test for use in clinical practice to confidently diagnose functional gastrointestinal disorders. The study will have major implications in terms of reducing costs and complications associated with unnecessary colonoscopies in patients with functional gastrointestinal disorders and will help to prioritize patients actually requiring colonoscopy for organic disease.

Microbial Biology and Metagenomics

Professor Mark Morrison and his team of TRI-based researchers are using genomic technologies such as DNA sequencing, to produce new insights into the microbial world. The aim of this research is to improve methods for monitoring and adjusting gut microbiota in order to improve and maintain health, as well as to better diagnose and treat disease. Read more

Inflammation and GI disorders

The Neurogastroenterology group with Prof Holtmann and his research team at the Princess Alexandra Hospital along with researchers at the University of Newcastle and Imperial College have received NHMRC funding to fully characterise the immunopathology of functional dyspepsia (FD) and to test a novel therapeutic strategy.

These researchers have recently made ground-breaking observations by demonstrating that functional dyspepsia is associated with the expansion of activated eosinophils in the duodenum of a substantial proportion of patients (47% with early satiety). They have also observed evidence of aberrant immune activation in the peripheral blood of patients with functional dyspepsia.  Gut homing T-cells are increased and cultured peripheral blood immune cells produce excess inflammatory cytokines that are linked to delayed gastric emptying. From this they have developed the hypothesis that functional dyspepsia is an immune-mediated disease driven by allergic type Th2 inflammation and will test this hypothesis by assessing the roles of T cell phenotype and levels of eosinophilic cytokines and chemokines (e.g. IL-5, IL-13, eotaxins) in patients.  This study will fully define the causal roles of Th2 cells and eosinophil promoting factors in driving duodenal eosinophilia in functional dyspepsia. Focussed gene expression profiling will define novel mechanisms.  The efficacy of a therapeutic modality (budesonide), aimed at suppressing overactive immune responses in functional dyspepsia, will be assessed in a randomised, double-blind, placebo controlled trial. This study will provide novel, clinically important insights into the underlying pathophysiological mechanisms of this common and costly condition. We will translate our observations by testing a new treatment that may rapidly change clinical practice.

Chronic Pancreatitis

Prof. Holtmann at the Princess Alexandra Hospital is involved in multi-centre Australian study examining undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI patients with chronic diarrhoea, abdominal pain or IBS-diarrhoea predominant. This study is being funded by Abbott Australia and seeks to identify the clinical characteristics of patients with chronic abdominal pain and/or diarrhoea (including IBS) which can be predictive of the diagnosis of pancreatic exocrine insufficiency.  In addition, the study aims to identify the potential complications caused by undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis, including through the use of further investigations such as   endoscopic ultrasound and trans-abdominal CT scan for chronic pancreatitis.  The identification of these characteristics could allow easier recognition of pancreatic exocrine insufficiency in the community and also pinpoint a patient population which could be targeted for screening. An increase in diagnosis of pancreatic exocrine insufficiency could improve the management and prognosis of these patients.

Reflux disease and complications including Barrett’s esophagus

Heartburn and/or acid regurgitation occurring at least weekly is very common in the general population. Gastrooesophageal Reflex Disease (GORD) is defined as typical symptoms occurring two or more times weekly, or symptoms perceived as problematic to patients, or resulting in complications. While many patients with GORD respond well clinically to established therapies with acid inhibiting drugs (e.g. Proton pump inhibitors), a considerable proportion of patients do not experience sufficient control of symptoms. Moreover some patients develop complications such as Barrett’s oesophagus or even Barrett’s carcinoma as complications of GORD. Research is done in collaboration with David Whiteman from the QIMR in the field of risk factors for the manifestations of GORD complications.

Endoscopic research

Dr Hourigan is leading endoscopic research in the area of  interventional endoscopy, ERCP, endoscopic ultrasound, EMR/ESD, large colonic polypectomy, Barrett’s endotherapy and palliative stent placement. The Department also conducts research that is imbedded and supports the delivery of high quality cost efficient clinical services, particularly regarding the cost effectiveness of the FibroScan and High Resolution Oesophageal Manometry service.

 

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Gerald Holtmann
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