Research from the University of California, San Francisco, has revealed that the primary female sex hormone, , intensifies pain in the intestines by activating certain cells. This sheds light on why irritable bowel syndrome (IBS) is more prevalent in women than in men.
Approximately 15 percent of the global population suffers from IBS. Notably, are diagnosed with this condition twice as often as men. Symptoms include pain, , diarrhea, bloating, and gas, which often worsen in response to triggers such as stress or certain foods. However, the reasons behind the differing rates of IBS between women and men have remained unclear.
Now, researchers have discovered that estrogen can trigger a chain reaction in the intestines, making its nerves more sensitive to pain.
“We have long suspected that female hormones play a role in the onset of in the intestines, but the exact mechanism has remained elusive. Now we have found that estrogen can enhance pain signals,” said Professor David Julius, a Nobel Prize winner in Physiology or Medicine in 2021 and the lead author of the study, in an interview with Live Science.
What Did the Scientists Discover?
During the study, the university team first compared the responses of male and female mice to intestinal pain. The researchers recorded nerve activity in response to stimulation of the and observed reactions to mild distension of the colon. The tests showed that female mice had a higher baseline sensitivity in their intestines.
Removing the ovaries from the mice (to stop estrogen production) reduced this sensitivity to male levels. Restoring estrogen levels to normal returned the heightened pain response characteristic of females.
To determine where and how estrogen acts, the team investigated various intestinal cells. The scientists expected to find estrogen receptors on enterochromaffin cells, which produce about 90 percent of serotonin involved in activating pain nerves that send signals to the brain. Instead, they discovered estrogen receptors on specialized, rare cells in the intestinal lining known as L-cells.
By detecting estrogen, these L-cells enhance the production of a receptor called OLFR78, which recognizes short-chain fatty acids that are byproducts formed during food digestion by gut bacteria. The additional receptors make L-cells more sensitive to these byproducts and release more hormones that signal fullness immediately after eating.
To better understand this chain reaction, the researchers grew miniature models of the intestine in the lab. The team found that a satiety hormone called PYY also sends signals to nearby enterochromaffin cells, which release additional serotonin. This serotonin then activates pain in the nerves. Such a chain reaction triggered by estrogen could potentially explain why women experience stronger intestinal pain than men.
“Since estrogen levels fluctuate throughout the menstrual cycle, this mechanism helps explain the severity of irritable bowel syndrome in women,” noted Marissa Scavuzzo, an assistant professor at the Case Western Reserve University School of Medicine (USA), who was not involved in the study. She believes the findings could lay the groundwork for developing effective treatments for intestinal pain.
Additionally, the research highlighted the importance of how hormonal changes affect IBS symptoms in women not only of reproductive age but also in postmenopause.
While mice are genetically similar to humans, translating results from rodent experiments will require caution. The human intestine is more complex than that of mice, and human-specific factors such as lifestyle, genetics, and gut microbiota diversity may also influence hormonal interactions.
“Clinical studies are needed before we can draw firm conclusions about human intestinal pain,” Professor Julius remarked.
The results of the study were published in the journal Science.
Photo: pixabay.com
