Why is an irritable gut so complicated?

Many of us will know someone who has or believes they have irritable bowel syndrome, so it’s unsurprising that a recent study in the Lancet found that it affects 9 percent of the population. But what exactly is IBS, how is it diagnosed, and when are we going to get a cure for it, or at least a management plan likely to work?

Short answer: it’s complicated. IBS isn’t a disease but a syndrome, a functional disorder of what we now call the gut-brain axis, a two-way communication pathway between the brain and the gut. IBS is characterised by chronic pain associated with chronically altered bowel habits. There are many subtypes of IBS, each with a constellation of unpleasant symptoms. Clinicians describe the most common as ‘constipation-predominant’, ‘diarrhoea-predominant’, ‘mixed-type’, and ‘unclassified’.

The syndrome can play havoc with a person’s quality of life. Those with it may avoid leaving their houses for fear they’ll get caught out without having a bathroom nearby. The chronic pain and unpredictable nature of IBS can contribute to feelings of anxiety, depression, and a pervading sense of frustration.

As it’s a functional disorder, people can’t get a test that shows its presence, as they can with diabetes (high blood glucose) or cancer (a visible tumour in an MRI image). Instead, clinicians need to exclude all other known causes of the symptoms before assigning a diagnosis. This can mean years of invasive or uncomfortable tests, including colonoscopies, CT scans, biopsies, and blood tests.

Eventually, a label is assigned using the symptom-based Rome IV diagnostic criteria, but this is only the beginning. People with IBS then have to experiment with several lifestyle changes such as modifying their diets (for example, gluten-free diets), managing stress, regularly using laxatives, undergoing cognitive behavioural therapy, or taking antibiotics or antidepressants. The process of developing a management plan is one of trial and error, and it can be just as frustrating as seeking a diagnosis.

Worldwide, researchers are striving to improve the lives of people with IBS, but – much like the disorder itself – researching it has its challenges. The clinical definitions alone make standardised comparisons between studies difficult. Rome IV uses gastrointestinal symptoms only, so it depends on subjective measures that are highly variable, even within the same patient over time. It doesn’t help that research funding for gastrointestinal disorders is limited, with IBS a particularly neglected area – especially when considering the relative economic burden driven by its associated medical costs, work absenteeism, and reduced productivity.
 

However, thanks to new technologies and an ever-improving understanding of the gastrointestinal system, the outlook for IBS diagnosis and management is finally looking up. Improved access to sequencing technology is empowering specialised scientists who work to make sense of large biological datasets, known as bioinformaticians, to dig deeper into how the microbiome – the community of microorganisms in our body – interacts with our digestive system and explore possible underlying genetic factors.

The accumulated efforts of our gastrointestinal research teams at the Auckland Bioengineering Institute have led to the development of objective and actionable biomarkers of gut disorders, through technologies such as minimally invasive sensors to measure bioelectrical activity in the gut. Ongoing research into the development of digital twins could be used to screen treatments on a virtual replica of a given patient – avoiding the frustrations and disappointments of trialling (often without success) different management plans.

Our research aims to shift the diagnosis and treatment of IBS and other gut disorders from subjective, symptom-based diagnostics to more precise, quantitative methods using modern, sophisticated algorithms. We’re using a type of machine learning that groups patients similar to each other into categories or clusters. Ideally, this approach will reveal patient groups with unique underlying conditions. For instance, one cluster may have a distinct microbiome imbalance and be more likely to respond to faecal microbiota transplant therapy, whereas another may present with bile acid abnormalities best managed through a low-fat diet.

We’re performing this analysis using rich datasets that include gastrointestinal and psychological symptom information as well as objective measures, such as microbiome and metabolomics data. By applying clustering algorithms, we can categorise patients into distinct subgroups based on more than the sum of their symptoms.

Irritable bowel syndrome is a complex, enigmatic disorder that imposes a substantial burden on the lives of so many. Collective scientific efforts focused on developing technologies to capture novel objective biomarkers and advancing personalised medicine offer hope that the tide is turning. In time, perhaps we can transform IBS from a common complaint into a well-understood and effectively managed condition.