Irritable bowel syndrome (IBS) is a chronic condition that causes digestive issues, gut pain, and bloating, and women are far more likely to experience IBS than men. Researchers may have now found an explanation for that phenomenon: estrogen. It seems that estrogen can trigger newly identified processes in the gut that may cause pain and increase sensitivity to some foods and the byproducts that are created when they are digested. The study can also explain why a low-FODMAP diet can reduce symptoms in IBS patients, and why IBS symptoms can vary with menstrual cycles. The findings have been reported in Science, and though they need to be confirmed in humans, they may lead to new IBS treatments or preventives.
"Instead of just saying young women suffer from IBS, we wanted rigorous science explaining why," said co-senior study author Holly Ingraham, Ph.D., a Professor at the University of California, San Francisco. "We've answered that question, and in the process identified new potential drug targets."
The work revealed that in the gut, estrogen receptors cluster in a lower region of the colon than thought in cells called L-cells. The scientists found that in a complicated process, estrogen binds to the L-cells, causing them to release a hormone known as PYY (peptide YY). This hormone causes EC cells in the area to secrete serotonin, activating nerves that sense pain.
Exposure to estrogen also caused an increase in the levels of a molecule called Olfr78 in L-cells; this led the cells to become hypersensitive to fatty acids that are detected by Olfr78. Ultimately, more PYY was released.
"It means that estrogen is really leading to this double hit," said co-first study author Archana Venkataraman, Ph.D., a postdoctoral researcher in the Ingraham lab. "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."
This pathway is present in men, but a lack of estrogen keeps it relatively inactive. When male mice were exposed to levels of estrogen found in females, they began to experience gut sensitivity like what was already seen in females.
Low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diets have been gaining popularity in recent years, and research by Monash University has shown that they can be very beneficial to those with IBS. The diet is bit complex, but generally eliminates many foods that are fermentable.
Gut bacteria ferment FODMAPs into the fatty acids sensed by Olfr78. This study can explain why fewer FODMAPs could prevent Olfr78 activation, thus reducing PYY release by L-cells.
"Even for patients who see success with a low-FODMAP diet, it's nearly impossible to stick to long term," Ingraham said. "But the pathways we've identified here might be leveraged as new drug targets."
Sources: University of California, San Francisco (UCSD); Science