News release

From: South Australian Health and Medical Research Institute (SAHMRI)

Scientists discover why women experience more severe gut pain

New research has pinpointed the cellular mechanism responsible for driving the long-observed sex differences in chronic visceral pain.

Recently published in the journal Science, the international study, led at SAHMRI by Professor Stuart Brierley, in collaboration with Professor Holly Ingraham and Professor David Julius from the University of California, San Francisco, shows that estrogen is the main culprit.

“We found that estrogen directly amplifies communication between two specialised gut cell types, triggering heightened sensitivity to pain signals in females,” Prof Brierley said.

“Estrogen activates a pathway in the colon that increases the release of the gut hormone PYY. PYY then stimulates neighbouring serotonin-producing enterochromaffin cells, boosting serotonin output and sensitising the nerves that send pain messages to the brain.”

Researchers have been tracking the pathway for years, and say their latest study brings all the pieces together, with significant implications for conditions like irritable bowel syndrome (IBS).
“If we can interrupt this pathway at the right point, we may be able to reduce chronic gut pain without affecting the normal digestive functions of these hormones,” Prof Brierley said.

“That is incredibly promising for women living with IBS and other debilitating visceral pain disorders like endometriosis.”

The study also revealed that estrogen increases the gut’s responsiveness to short-chain fatty acids, which are produced when bacteria break down food, clarifying why dietary interventions like low FODMAP diets can reduce symptoms in some people.

“We now understand that certain foods can feed into this estrogen-sensitive pathway through the metabolites they produce,” Prof Brierley said.

“This gives us a clearer biological rationale for why dietary changes may help and how they could be refined.”

The work is a major step toward developing more personalised treatments for chronic gut pain conditions.