Women are more prone to experiencing pain from irritable bowel syndrome (IBS) due to their hormones, a recent study has found. Prior research has indicated that the chronic condition, which triggers abdominal pain, bloating, and digestive discomfort, is more prevalent in women than men.
American researchers have now uncovered that the female sexual and reproductive hormone, oestrogen, activates previously unidentified pathways in the colon that can induce pain and heighten the female gut’s sensitivity to certain foods. When male mice were administered oestrogen to replicate the levels found in females, their gut pain sensitivity rose to match that of the females.
The research team at the University of California, San Francisco (UCSF), believe their findings, published in the Journal Science, could pave the way for improved IBS treatments. Study co-senior author Professor Holly Ingraham stated: “Instead of just saying young women suffer from IBS, we wanted rigorous science explaining why. We’ve answered that question, and in the process identified new potential drug targets.”
The study also provides insight into why low-FODMAP diets, which exclude certain fermentable foods such as onions, garlic, honey, wheat, and beans, benefit some IBS patients. It also explains why women’s gut symptoms often vary with their menstrual cycles , reports the Mirror.
Study co-senior author Professor David Julius, who received a Nobel Prize in 2021 for his research into pain sensation, explained: “We knew the gut has a sophisticated pain-sensing system, but this study reveals how hormones can dial that sensitivity up by tapping into this system through an interesting and potent cellular connection.”
Earlier studies had suggested that oestrogen was responsible for the elevated incidence of IBS in women, though the mechanism remained unclear. To determine how oestrogen might be implicated, UCSF scientists first had to identify precisely where the hormone was acting within the gut.
Study co-first author Dr Archana Venkataraman explained: “At the time I started this project, we didn’t know where and how oestrogen signalling is set up in the female intestine. So, our initial step was to visualise the oestrogen receptor along the length of the female gut.”
The researchers anticipated finding oestrogen receptors in enterochromaffin (EC) cells, which were already recognised for transmitting pain signals from the gut to the spinal cord. However, they were astonished to discover that oestrogen receptors were concentrated in the lower colon and in a distinct cell type called L-cells.
The researchers uncovered a complex chain reaction triggered when oestrogen attaches to the L-cells, involving a hormone known as PYY. For years, scientists had believed PYY chiefly reduced appetite.
Pharmaceutical companies had even tried to develop it as a weight-loss treatment. However, the clinical trials were unsuccessful due to a concerning side effect that remained unexplained: participants suffered severe gut distress.
The latest findings support this observation and point towards an entirely new function for PYY.
Co-first author Dr Eric Figueroa stated: “PYY had never been directly described as a pain signal in the past. Establishing this new role for PYY in gut pain reframes our thinking about this hormone and its local effects in the colon.”
Elevated PYY wasn’t the sole way L-cells reacted to oestrogen, the research revealed. Levels of another molecule, known as Olfr78, also increased in response to the hormone.
Olfr78 identifies short-chain fatty acids – metabolites generated when gut bacteria break down certain foods. With additional Olfr78 receptors, L-cells become “hypersensitive” to those fatty acids and are more readily triggered into action, releasing greater amounts of PYY.
Dr Venkataraman explained: “It means that oestrogen is really leading to this double hit. First, it’s increasing the baseline sensitivity of the gut by increasing PYY, and then it’s also making L-cells more sensitive to these metabolites that are floating around in the colon.”
The UCSF researchers suggest the discovery may explain why low-FODMAP diets benefit some IBS sufferers. By consuming fewer FODMAPs, patients may prevent the activation of Olfr78 and, consequently, stop L-cells from producing additional pain-signalling PYY.
While men possess the same cellular pathway, their lower oestrogen levels typically keep it subdued, according to the researchers. However, this pathway could become active in men who are on androgen-blocking medications.
These drugs inhibit the effects of testosterone and can sometimes increase oestrogen levels, potentially leading to digestive side-effects.
The research team believes their findings could pave the way for new treatments for IBS in both men and women. Professor Ingraham stated: “Even for patients who see success with a low-FODMAP diet, it’s nearly impossible to stick to long-term.
“But the pathways we’ve identified here might be leveraged as new drug targets.”
The team is now exploring how these potential drugs might function, and whether other hormones, including progesterone, could also influence gut sensitivity.
This story originally appeared on Express.co.uk
