Wheat Proteins, The Duodenal Microbiome And Immune Activation In The Aetiopathogenesis Of Non-coeliac Gluten Sensitivity And Functional Dyspepsia
Funder
National Health and Medical Research Council
Funding Amount
$1,997,150.00
Summary
Functional dyspepsia, characterised by troublesome pain in the upper abdomen, or an inability to finish a regular sized meal, is common, affecting up to 15% of Australians. There are no effective treatments. This project will evaluate the role of diet, in particular wheat, as a driver of the subtle inflammation and disturbances in the microbiome seen in the small intestine of functional dyspepsia patients, and test whether a gluten or wheat free diet is an effective treatment option.
Pathophysiology Of Functional Dyspepsia: Integration Of Upper Gut Function, Inflammation And A Systems Biology Approach.
Funder
National Health and Medical Research Council
Funding Amount
$748,593.00
Summary
Functional dyspepsia (FD) is an extremely common and costly problem with no cure. We and others have found that inflammation and immune activation play a role in FD but to date no studies have linked these findings with well known diseases markers including disordered sensory and motor function or psychiatric comorbidity. This study will explore the interrelationships between inflammatory and immune mechanisms, disease markers as well as the microbiome. This study could unravel the cause of FD.
Functional Dyspepsia: Characterisation Of The Immunopathology And Testing A Novel Therapeutic Strategy.
Funder
National Health and Medical Research Council
Funding Amount
$739,604.00
Summary
Dyspepsia, unexplained stomach discomfort and pain, is a common and costly problem; few effective treatments exist and the causes are unknown. We have found that the numbers of a type of immune cell, the eosinophil, are increased in the top of the small bowel in patients with dyspepsia. This study will explore the mechanisms that lead to increased eosinophils and then test the effectiveness of a treatment to suppress this overactive immune response which could rapidly change clinical practice.
Mechanics Of Normal And Disordered Gastric Emptying Studied Using Simultaneous Ultrasound And High Resolution Manometry
Funder
National Health and Medical Research Council
Funding Amount
$145,626.00
Summary
Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties ....Optimal digestion and absorption relies on the stomach breaking down food and delivering it to the small intestine at an optimal rate. Abnormalities in the processes controlling the stomach's processing of food may lead to malnutrition, gastrointestinal symptoms or unpredictable drug absorption, and are commonly seen in patients with diabetes mellitus, gastrointestinal reflux disease and nonulcer dyspepsia, or following stomach surgery. Currently our understanding of the way the stomach empties food is incomplete, and there is little information as to the mechanisms by which diseases cause abnormal stomach emptying. Recent developments in recording methods mean that we can now simultaneously measure stomach contractions, the pressures these generate and flow from the stomach. This information is synchronised and displayed for analysis using computer techniques. In this project these novel methods will be used initially to examine the normal processes by which meals with a variety of compositions and consistencies empty from the stomach. This will provide information as to which aspects of the way the stomach functions are important for breaking down food into particles, and which aspects control the flow of food from the stomach into the intestine. The mechanisms by which the rate of emptying of the stomach is controlled by feedback signals caused by the presence of foodstuffs in the small intestine will be investigated by examining the effects of infusing nutrients into the intestine on the motions of the stomach wall, pressures within the stomach and the passage of stomach contents into the small intestine. The mechanism of action of drugs and diseases which slow stomach emptying will then be examined by measuring the movements, pressures and emptying of the stomach in subjects receiving the drug, or in patients with dibetes, and comparing this information with the processes observed during normal stomach emptying.Read moreRead less
Immune Activation In Functional Gastrointestinal Disorders
Funder
National Health and Medical Research Council
Funding Amount
$471,597.00
Summary
Up to 30% of Australians are estimated to suffer from Functional Gastrointestinal Diseases such as Irritable Bowel Syndrome and Functional Dyspepsia, but the cause of these chronic diseases is unknown. Alterations in the immune system are increasingly suggested, but little is known about how this leads to the debilitating symptoms of discomfort and pain. This project combines immunology studies with neuroscience to determine the key mediators involved and how they communicate with nerves.
Relationships Between Diet And Gastric Motor Function In Functional Dyspepsia
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
Functional dyspepsia (FD) is a condition characterised by abdominal symptoms without a cause that is identifiable by conventional diagnostic tests. Symptoms (eg fullness, bloating) are frequently induced by eating. 20 - 40 % of the adult population in Western countries are affected by FD, and the condition, therefore, represents a considerable financial burden to the health care system. FD affects quality of life adversely. In many people with FD, stomach contractions and the 'sensitivity' of th ....Functional dyspepsia (FD) is a condition characterised by abdominal symptoms without a cause that is identifiable by conventional diagnostic tests. Symptoms (eg fullness, bloating) are frequently induced by eating. 20 - 40 % of the adult population in Western countries are affected by FD, and the condition, therefore, represents a considerable financial burden to the health care system. FD affects quality of life adversely. In many people with FD, stomach contractions and the 'sensitivity' of the stomach are abnormal. Often, people with FD avoid fatty foods in the belief that these cause or exacerbate symptoms. There is, however, little information about the potential role of dietary habits in causing symptoms, the relationship between eating and disturbances in stomach function, and the impact of dietary changes on symptoms. Our previous studies suggest an important role for nutrients, particularly fat, in FD. We will address the hypothesis that dietary factors, particularly fat intake, have substantial implications for the pathophysiology and treatment of FD. Our studies will involve physiological (stomach emptying, appetite and food intake) and epidemiological (dietary habits, dyspeptic symptoms and quality of life-related aspects) measurements. The subjects-patients with FD will receive standardised test meals of varying nutrient composition, and we will study the effects on their stomach and on symptoms. We will also test some medications in an attempt to alleviate symptoms during and after food ingestion, particularly after fatty foods. Other studies will assess the dietary habits of patients with FD in relation to symptom occurrence and investigate the possibility that dietary intervention (reduction of fat content in the diet, exclusion of offending foods) will benefit these patients. The proposed studies will provide the most comprehensive studies to date of the relationship between symptoms in patients with FD with dietary habits and stomach function.Read moreRead less
Gastrointestinal Sensory Function In Normal And Diseased States
Funder
National Health and Medical Research Council
Funding Amount
$691,026.00
Summary
Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that ....Chronic pain and discomfort from the digestive system is a major health care issue world-wide. There is currently no effective treatment for these problems, which often have no apparent organic cause. Lack of treatment is due to a lack of understanding about how sensations are transmitted from the digestive system to the brain. Our research group has unique and powerful techniques that allow us to probe the basic mechanisms of sensory function, and make rapid progress towards finding drugs that reduce specific types of sensory signals from the gut. We shall investigate sensory mechanisms in the upper and lower regions of the gut, where symptoms are most prevalent in diseases such as non-cardiac chest pain, functional dyspepsia and irritable bowel syndrome. Six aspects of sensory nerve endings in the gut are to be investigated: 1. The grouping of endings into functional classes (similar to touch or pressure receptors in skin) 2. How endings respond to chemicals and hormones found in the gut 3. How currently available drugs may be useful in reducing sensitivity 4. The mechanisms by which inflammation affects sensitivity 5. How nerve growth factors may trigger changes in sensitivity 6. How pores or channels in nerve endings determine their functionRead moreRead less