ENIGMA - Microbes and Diet

ENIGMA Study - The Gut Microbiota

Understanding the ecosystem within us may lead to disease cures

Within the gut resides a vast ecosystem of bacteria, fungi and viruses, otherwise known as the gut microbiota. This ecosystem comprises 90 percent of the cells in our body. Our normal human cells therefore constitute only a minority of the cells in our body.

We are working with scientists to unravel the exact nature of these organisms in our gut, and the role they play in causing or curing disease. New molecular techniques are identifying previously unknown bacterial species. New insights are also emerging about the effect of diet on the gut bacteria and how this might affect gut inflammation.

The presence and function of the microbiota are essential to our wellbeing - these organisms perform a range of functions critical to development, growth, metabolic function, and protection from disease. However, the gut microbiota is now also thought to play some role in the development of inflammatory bowel disease, obesity, arthritis, and allergic diseases.

Identifying particular bacteria that play a role in disease can have an enormous impact. For example, identification of the bacterium Helicobacter pylori by Australian Nobel prize-winning researchers led to the virtual eradication of stomach and bowel ulcer disease. That single observation was one of the key medical discoveries of the twentieth century.

Of a similar magnitude, discovery of the rotavirus as the commonest cause of childhood diarrhoea, by scientists at the Royal Children’s Hospital, Melbourne, together with the subsequent development of a vaccine, has had a huge impact on childhood illness and death worldwide. There are more discoveries to be made in this area.

Manipulating the gut microbiota may also be valuable. Our recent study demonstrating the success of faecal transplant for patients with ulcerative colitis demonstrates how powerful this approach can be.

AGIRF is supporting clinical projects that will harness the power of gut bacteria manipulation. Our scientific projects will identify which gut bacteria are the most important in causing and curing disease.

The ecosystem within our gut is central to our well-being, but also to the development of many gut and non-gut disorders. Its scientific exploration is leading to new therapies and cures.

The ENIGMA II Study (Eastern Inflammatory Bowel Disease Gut Microbiota) - is a major international research project that has helped us better understand Crohn’s disease by exploring how diet, gut bacteria, environment, and inflammation are connected.

Conducted across Australia, Hong Kong, and China, the study compared populations from regions with historically different rates of Crohn’s disease. While the condition is more common in Western countries, rates are rising rapidly in developing regions. This makes it especially important to understand how westernisation—including a greater intake of processed foods, food additives, and lifestyle changes—may be increasing the risk.

The ENIGMA II Study included not only people with Crohn’s disease but also their unrelated household members and close relatives. These groups often share either a similar environment or similar genes, but not both. Comparing them helps us understand whether certain risks are more likely linked to diet and lifestyle or to inherited traits.

We have found that people with Crohn’s disease tend to eat more processed foods and additives like artificial sweeteners and emulsifiers—especially during childhood. Our laboratory studies have shown that these additives can harm helpful gut bacteria and trigger inflammation.

We also studied a bacterium called Proteus, which is more common in people with Crohn’s disease. Some food additives were found to help this bacterium grow and become more aggressive.

We have developed tools to measure how much of these additives people consume and how much ends up in the body. For the first time, we linked levels of these substances in the body with Crohn’s disease activity.

We also developed a new technique to study bacteria directly from the gut lining, offering better insight than stool samples alone. In parallel, we contributed to creating a non-invasive stool test to help diagnose Crohn’s disease.

By showing how food, environment and gut bacteria interact, ENIGMA has highlighted new opportunities to possibly prevent Crohn’s disease, improve diagnosis through non-invasive tests, and develop treatments that target the gut microbiome. Understanding these links brings us closer to personalised strategies that could reduce the burden of Crohn’s disease worldwide.

The ENIGMA II Studies would not be possible without the generous support of the Leona M. and Harry B. Helmsley Charitable Foundation.

Melbourne Clinical Site Staff

PROFESSOR MICHAEL KAMM
PROFESSOR OF

GASTROENTEROLOGY
The University of Melbourne and

St Vincent’s Hospital

MS. ANNALISE STANLEY RESEARCH NURSE SPECIALIST

University of Melbourne,

St Vincent’s Hospital

DR. GINA TRAKMAN

RESEARCH DIETITIAN

University of Melbourne,

St Vincent’s Hospital

DR. AMY HAMILTON

CLINICAL SCIENTIST

University of Melbourne,

St Vincent’s Hospital

DR. AMY WILSON-O'BRIEN

CLINICAL SCIENTIST

University of Melbourne,

St Vincent’s Hospital

Queensland Scientific Staff

PROFESSOR MARK MORRISON

PROFESSOR OF MICROBIOLOGY

The Diamantina Institute,

The University of Queensland

DR. SEUNGHA KANG

RESEARCH FELLOW

The Diamantina Institute,

The University of Queensland

DR. ERWIN BERENDSEN

RESEARCH FELLOW

The Diamantina Institute,

The University of Queensland

DR. EMILY HOEDT

RESEARCH FELLOW

The Diamantina Institute,

The University of Queensland

MR JING JIE TEH

PHD CANDIDATE

The Diamantina Institute,

The University of Queensland