Study identifies why women are more likely to have IBS and outlines potential drug targets

A potential cure for irritable bowel syndrome could be within reach after a breakthrough trial by scientists at the University of California, San Francisco. The team has identified a mechanism that helps explain why women are up to twice as likely to develop IBS: estrogen receptors cluster in the lower colon and drive a chain that makes L-cells release the hormone PYY, which in turn activates pain-sensing nerves. In experiments with mice, researchers blocked estrogen and PYY and observed a dramatic drop in gut pain among female subjects. The work, published in Science, underscores new drug targets rather than dietary changes to treat IBS.

The researchers described how estrogen receptors boost local estrogen signaling in the colon and influence L-cells to release PYY. PYY, long known for regulating appetite, is now described as a pain signal in the gut by these scientists. In male mice, adding estrogen raised pain sensitivity to levels seen in females, while blocking estrogen and PYY in female mice reduced pain. The findings help explain the sex disparity in IBS and point to possible therapies that interrupt this signaling at its source.

The current NHS guidance for IBS emphasizes diet, notably the low-FODMAP plan that reduces certain fermentable carbohydrates. The team noted that lowering FODMAP intake might indirectly limit PYY production by reducing activity of L-cells, which could underpin why some patients respond to the diet. Still, adherence to a low-FODMAP diet is often challenging, so the researchers stressed that the newly identified pathways could be targeted by future drugs as an alternative or adjunct to dietary management.

About one in five UK adults have IBS, though experts say the figure may underestimate because many do not seek medical help. The condition most often affects younger adults, especially those aged 20 to 39, with symptoms including abdominal pain, bloating, diarrhoea and constipation. Other symptoms may include mucus in stool, fatigue, nausea, back pain and urinary issues.

While the study marks a major step forward, researchers caution that the work was conducted in mice and will require human trials to confirm applicability to patients. If validated in people, the estrogen-PYY pathway could yield targeted drugs that reduce gut pain without forcing patients to restrict their diets. The team hopes to advance the discovery into clinical testing and eventually new treatments for IBS that address the underlying biology rather than symptom filtering alone.

The UCSF-led research, published in Science, expands understanding of IBS and the role of hormones in gut pain, offering a potential path toward therapies that tackle the condition at its source rather than solely managing symptoms.