There has been a recent push by mainstream medicine and Big Pharma to legitimize estrogenic HRT again, despite the damning findings of the WHI studies. However, the bad news for estrogen keep piling on in the scientific literature. Of course, whenever one sees estrogen rear its ugly head it is reasonable to expect that others of its ilk will also be implicated as “co-conspirators” (e.g. 5-HT, the synthesis of which is promoted by estrogen). For decades, medicine has recognized the fact that women have higher rates of GI conditions, especially the “mysterious” syndrome known as IBS. About two decades ago, the 5-HT agonist (5-HT4 receptor agonist, to be precise) drug Zelnorm was demonstrated to reliably cause all symptoms of IBS and in fact caused much more severe GI issues, which led to a few deaths in the group of people prescribed the drug, and the drug was eventually withdrawn from the market. However, there has been a recent push to re-introduce the drug into the market, as well as a push to develop other 5-HT(4) agonists as a “treatment” for IBS. Given the results of the study below, I think it would be a disaster if that is allowed to happen. Btw, the study below highlights another important dietary issue. Namely, that of soluble fiber. That type of fiber is still routinely prescribed by doctors as a way to both lower cholesterol as well as “boost” gut health by increasing the production of short-chain fatty acids by gut bacteria. While the short-chain fatty acids to have a role in health, especially considering their effects as HDAC inhibitors (which protects against cancer), the study below states that boosting the production of said fatty acids by eating more soluble fiber may be problematic in people with high estrogen, as it would further exacerbate the estrogen-driven 5-HT overload and thus worsen IBS symptoms. Just as importantly, the study states that estrogen and 5-HT increase the gut sensitivity to ALL toxic stimuli, not just soluble fiber. As such, focusing more on insoluble fiber and anti-estrogenic remedies such as aspirin, vitamin E and progesterone may be a better option, especially considering the fact that aspirin and progesterone have a direct anti-serotonin effects as well.
https://pubmed.ncbi.nlm.nih.gov/41411420/
“…A new study into why women experience more severe gut pain suggests that oestrogen, the female sexual hormone, increases the release of a gut hormone that promotes satiety, boosting serotonin production, and sensitising nerves in the gut that trigger pain response. A comparative study of male and female mouse models conducted by researchers from South Australian Health and Medical Research Institute and University of California, San Francisco, revealed an oestrogen-dependent pathway that promotes gut sensitivity to toxic stimuli, according to the findings published in the ‘Science’ journal. “Oestrogen activates a pathway in the colon that increases the release of the gut hormone PYY. PYY then stimulates neighbouring serotonin-producing enterochromaffin cells, boosting serotonin output and sensitising the nerves that send pain messages to the brain,” Stuart Brierley, director of the visceral pain research group at South Australian Health and Medical Research Institute, said. Gastrointestinal and visceral pain disorders are more common among women, but its reasons remain poorly understood, the researchers said. The study has also revealed that oestrogen increases the gut’s response to short-chain fatty acids — produced when bacteria break down food — possibly explaining why dietary interventions like low FODMAP diets can reduce symptoms of gastrointestinal distress in some people. A FODMAP diet restricts the intake of short-chain carbohydrates, common in foods such as garlic, apples, wheat and dairy. “We now understand that certain foods can feed into this oestrogen-sensitive pathway through the metabolites they produce. This gives us a clearer biological rationale for why dietary changes may help and how they could be refined,” Brierley said. The researchers said the study links hormonal activity, digestive processes and nerve response, with significant implications for conditions like irritable bowel syndrome (IBS). “If we can interrupt this (oestrogen-dependent) pathway at the right point, we may be able to reduce chronic gut pain without affecting the normal digestive functions of these hormones,” Brierley said.”
