New insights into chronic gut pain offer hope of irritable bowel syndrome and anxiety treatment

Researchers from SAHMRI, Flinders University and the University of California San Francisco have made a ground-breaking discovery that could lead to a breakthrough in the treatment of irritable bowel syndrome (IBS) and associated psychological conditions, including anxiety and depression.

A team of researchers led by Adelaide-based Professor Stuart Brierley, Nobel Laureate Professor David Julius, Professor Holly Ingraham and Dr James Bayrer in San Francisco, has in a recent study published in Nature, shown evidence of a specific pathway of cells and nerves linking the gut to the brain that may be responsible for the chronic gut pain commonly experienced by 11% of the global population currently living with IBS.

Using genetic and pharmacologic tools in pre-clinical models, the team manipulated signals between gut epithelial cells and associated nerve fibres to determine how this pathway stimulates chronic gut pain and anxiety.

“We’ve found that the gut microbiome produces short chain fatty acids that act on the lining of the gut and trigger a particular cell type to release neurotransmitters. The nerves connecting to those cells become active and directly send pain signals to the brain via the gut-brain axis. Activation of these nerves also increases anxiety indicators,” Prof Brierley said.

“This mechanism is chronically overactive in females, which could explain why two-thirds of those who experience IBS are women and why IBS patients report symptoms of chronic gut pain and anxiety.”

The research suggests IBS, anxiety and depression can all be driven by signaling within the intestinal tract and people with overactive communication between the gut and brain are more susceptible to experiencing pain. Prof Brierley says added stress can make the symptoms even worse by further activating these mechanisms in the gut.

“There's a variety of ways in which your susceptibility to pain can be altered on a daily basis. Stress, infections, changes in diet and disruptions to the microbiome caused by medications, such as antibiotics, can mess with the way your gut signals to your brain,” Prof Brierley said.

Researchers are striving to address the current lack of treatments for chronic gut pain and anxiety and now that the mechanisms involved in driving these conditions have been discovered, specific interventions can be developed to block communication between the cells and nerves responsible.

“Theoretically we should be able to find a way to stop gut pain at the source and simultaneously reduce feelings of anxiety,” Prof Brierley said.

“These future interventions are likely to include drug treatments, microbiome treatments and diet-based treatments.”

The study was funded by grants from the National Health and Medical Research Council (NHMRC) and the US National Institutes of Health.