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A recent investigation on mice proposes a cause for the higher occurrence of IBS diagnoses in women compared to men.(Image credit: Getty Images)ShareShare by:
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According to a study performed on mice, differing responses of intestinal cells to hormones might contribute to the reason why women undergo more recurrent and acute stomach discomfort compared to men.
Irritable bowel syndrome (IBS) has an impact on approximately 10% to 15% of the global population, with the condition being diagnosed in women up to twofold more frequently than in men. IBS manifestations — which encompass pain, constipation, diarrhea, gas, and bloating — often intensify in response to elements such as stress or particular food items. Nonetheless, the factors influencing the variation between IBS incidence in women and men have persisted as unclear.
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“It has been long assumed that female hormones have a part in intestinal discomfort, but the precise mechanism has been uncertain,” stated David Julius, lead researcher of the study and a neurophysiologist from the University of California, San Francisco, during an interview with Live Science. “The conclusions we’ve made demonstrate a definite pathway for how estrogen can increase pain responses.”
The study, which was reported Dec. 18 in the journal Science, started by assessing responses to intestinal pain in both male and female mice through documenting nerve activity in reaction to stimulation of the gut and observing their reactions to slight inflation of the colon. The outcomes of the two evaluations demonstrated that female mice showed a heightened sensitivity of the gut at the starting point.
However, eliminating the mice’s ovaries to stop estrogen creation lessened this sensitivity to levels similar to those of males. Furthermore, reintroducing estrogen back to normal ranges brought back the increased pain reaction noticed in female mice.
To ascertain the locations and processes by which estrogen implements its effects, the research team scrutinized diverse types of intestinal cells. Drawing from earlier investigations, they anticipated locating estrogen receptors on enterochromaffin cells, which generate roughly 90% of the body’s serotonin, a chemical transmitter implicated in triggering pain-sensing nerves accountable for transmitting indications to the brain. Astonishingly, the team discovered that estrogen receptors were not present on enterochromaffin cells; rather, they were situated on specialized, infrequent cells within the gut’s lining.
Upon identifying estrogen, these cells, referred to as L-cells, accelerate the manufacturing of a receptor designated as OLFR78. This receptor identifies short-chain fatty acids, which emerge as byproducts during the digestion of food by intestinal bacteria. The introduction of supplemental receptors augments the responsiveness of L-cells to these byproducts, thereby escalating the liberation of a hormone responsible for conveying a feeling of fullness to the brain shortly after an individual consumes food.
For an enhanced understanding of this chain reaction, the scientists cultivated miniature reproductions of the stomach within laboratory environments. They determined that the hormone accountable for fullness, identified as PYY, additionally signals neighboring enterochromaffin cells, which then generate an elevated amount of serotonin. Subsequently, this serotonin triggers pain-sensing nerves. This sequence of reactions initiated by estrogen could possibly clarify the reason behind women encountering more intense intestinal pain in comparison to men.
Experiments carried out on genetically modified mice deprived of estrogen receptors situated on L-cells validated the participation of these cells in gut sensitivity. The modified mice exhibited weaker nerve responses and diminished serotonin release compared to mice possessing intact receptors.
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“Because estrogen concentrations change throughout the menstrual cycle, this mechanism can provide insight into the alterations in IBS severity seen in women,” stated Marissa Scavuzzo, an assistant professor at the Case Western Reserve University School of Medicine, who had no part in the study.
“It also substantiates the experiences of patients with higher estrogen levels or those who are menstruating,” she expressed, “This is relevant because variations in pain perception in women have often been ignored or invalidated in the past.”
Despite being preliminary, these conclusions could also affect upcoming remedies for gut discomfort. “PYY and OLFR78 may potentially serve as encouraging targets for managing IBS in females,” Julius indicated. Furthermore, this work could offer insights into the reason why “low-FODMAP” diets, intended to diminish the consumption of sugars utilized as nutrients by gut bacteria, can alleviate IBS manifestations in specific patients, he included.
Scavuzzo agreed that the findings might suggest encouraging treatments. “Through pinpointing PYY and L-cell signaling, this study specifies definitive molecular targets that could direct more accurate therapies for IBS,” she explained.
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In addition, the study “emphasizes the importance of taking into account the impact of hormonal changes on IBS symptoms, not only in women who are menstruating but also in post-menopausal patients and individuals undergoing hormone replacement therapy as a component of gender-affirming care.”
Exercising caution will be necessary when extrapolating these conclusions from mice to humans. The human digestive system is more intricate than that of mice, and elements such as lifestyle, genetics, and the diversity of gut microbiota can impact the interactions between hormones and the gut in individuals.
“Mouse models offer us an initial point,” Julius stated, “however, clinical trials hold the key before we can draw firm conclusions concerning gut pain in humans.”
Disclaimer
This article is intended only for informational purposes and should not be considered as medical advice.
Isha IshtiaqLive Science Contributor
Isha Ishtiaq is a self-employed writer concentrating on medicine and well-being, possessing a B.S. (Hons) in Biotechnology along with a M.S. in Biological Sciences. She specializes in producing explicit, reliable content that associates science with everyday existence. She holds the perspective that impactful well-being communication fosters confidence, promotes well-versed choices, and honors the authentic individuals shaping each inquiry.
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