Unlocking the hidden causes of common gut disorders

Your gut is constantly at work.

Every meal sets off an extraordinary process as the digestive system extracts the water and nutrients needed to keep the body functioning. Most of the time, that intricate machinery works so smoothly we barely give it a second thought.

But when that finely balanced system falls out of step, the consequences can be life-changing. Chronic pain, bloating, constipation and diarrhoea are among the symptoms experienced by people with gut disorders, including the frustratingly nebulous condition known as irritable bowel syndrome (IBS). 

Gut problems can affect people's work, relationships and everyday lives. Yet despite how common these conditions are, doctors often struggle to know what’s going on.

That's the challenge Auckland Bioengineering Institute (ABI) researcher Dr Jarrah Dowrick is setting out to tackle after being awarded $820,000 over four years as part of a prestigious Mana Tūāpapa Future Leader Fellowship from Royal Society Te Apārangi.

These fellowships support some of New Zealand's most promising early-career researchers. For Dowrick, it offers the opportunity to pursue a question that has fascinated him for years: why do so many people experience chronic gut symptoms, and why are women disproportionately affected?

IBS alone affects around one in five New Zealanders. Women are diagnosed at twice the rate of men.

One problem, Dowrick says, is that many gut disorders are still defined primarily by symptoms. Two people may experience the same pain, bloating or altered bowel habits, yet the underlying causes could be completely different. Diagnosis and treatment often involve a lengthy process of trial and error, and IBS can become a catch-all diagnosis so when nothing else fits.

Earlier this year, Dowrick and colleagues at the ABI used artificial intelligence to analyse data from people diagnosed with IBS. They found evidence patients fell into a number of distinct subgroups.

"The crux of what we've found is we have these big groups of patients we treat as having the same condition, but they don't," Dowrick said when the research was published.

Imagine taking a car that won’t start to a mechanic and being told: "You have a bad car."

"It could be a dead battery, a faulty starter motor, fuel problems, an electrical fault, or any number of other causes. In the same way, irritable bowel syndrome likely encompasses multiple different conditions."

While much public discussion about gut health focuses on the microbiome, the trillions of microbes that live inside the digestive system, Dowrick is investigating how this links with another crucial piece of the puzzle: the biological processes that control how water and nutrients are absorbed by the gut.

Every day, the gut performs a complex sorting operation. As food passes through the digestive tract, water and nutrients move across the gut wall and into the bloodstream, where they can be transported throughout the body.

That process needs to be carefully regulated. If too much fluid is absorbed, stools can become hard and difficult to pass. Too little absorption can contribute to diarrhoea.

Scientists know specialised proteins help control these processes, but the role of these proteins with gut irregularities remains poorly understood.

One of Dowrick's key goals, now he has Mana Tūāpapa Future Leader Fellowship funding, is to investigate whether those mechanisms might help explain why disorders such as IBS are much more common in women than men.

Researchers know that the hormone oestrogen interacts with some of the proteins involved in regulating fluid movement across the gut wall. They know women have higher levels of oestrogen and also have higher rates of gut disorders.

Dowrick wants to find out if oestrogen is in fact a critical link.

Combining laboratory experiments with advanced computational modelling, Dowrick hopes to better understand what is happening inside the gut and identify previously hidden biological differences between patients.

Ultimately, the aim is to develop virtual tools that give clinicians greater insight into how an individual's gut is functioning. Rather than relying on symptoms, doctors could one day have a clearer picture of the biological processes driving a patient's condition, helping them select treatments that are more likely to work.

Dowrick's path to this research has crossed several disciplines, from cardiac physiology and biological data analytics to computational modelling and most recently, simulations of molecular dynamics. Those experiences, he says, have reinforced a belief that many of healthcare's biggest challenges sit at the intersection of different fields.

The fellowship will also support partnerships with clinicians, patients, Māori researchers and health practitioners, to ensure the work is both scientifically robust and grounded in the needs of the communities it aims to serve.

Dr Tim Angeli-Gordon leads the TARGET translational gut research lab in which Dowrick works. He says the fact the award provides funding for four years (at a time when funding is increasingly for one or two years) will be transformative for the field.

"Jarrah is a brilliant, persistent, deep-thinking and innovative scientist," he says. “His project is internationally unique and has legitimate potential for near-term and long-lasting impact to modern medicine."

Gastrointestinal health is an under-served area of medicine, Angeli-Gordon says.

”It's outstanding to see substantial investment into this cutting-edge research.”