TL;DR
Researchers report that estrogen amplifies signalling between two specialised gut cell types, increasing serotonin release and sensitising pain pathways in females. The mechanism also raises responsiveness to short-chain fatty acids from gut bacteria, offering a biological explanation for sex differences in visceral pain and for why some dietary changes can help.
What happened
An international team led at the South Australian Health and Medical Research Institute (SAHMRI) published a peer-reviewed experimental study in Science identifying a cellular pathway that helps explain why women report more severe chronic gut pain. The group, led by Professor Stuart Brierley with collaborators including Professors Holly Ingraham and David Julius (UCSF), found that estrogen activates a colon pathway that raises release of the hormone peptide YY (PYY). PYY, in turn, stimulates nearby serotonin-producing enterochromaffin cells, increasing serotonin secretion and sensitising sensory nerves that transmit pain signals. The researchers also observed that estrogen boosts the gut’s responsiveness to short-chain fatty acids produced by bacterial fermentation of food, linking dietary metabolites to this hormone-sensitive circuit. Funders listed include the NIH and the NHMRC. The authors say interrupting points in this pathway could reduce chronic visceral pain while preserving normal digestive hormone functions.
Why it matters
- Provides a cellular explanation for longstanding sex differences in chronic visceral pain.
- Identifies specific hormone-driven interactions that could be targeted without disrupting normal digestion.
- Connects gut microbial metabolites (short-chain fatty acids) to hormonal sensitivity, clarifying dietary effects.
- Reinforces biological rationale for personalised approaches to conditions such as IBS and endometriosis.
Key facts
- Study published in the journal Science.
- Led at SAHMRI by Professor Stuart Brierley, in collaboration with Professor Holly Ingraham and Professor David Julius (UCSF).
- Estrogen activates a colon pathway that increases release of peptide YY (PYY).
- PYY stimulates serotonin-producing enterochromaffin cells, elevating serotonin output and sensitising pain-transmitting nerves.
- Estrogen enhances the gut’s responsiveness to short-chain fatty acids produced by bacterial breakdown of food.
- Findings offer an explanation for why some people respond to dietary interventions such as low FODMAP approaches.
- Research described as a peer-reviewed experimental study; source tags indicate animal models were involved.
- Funders mentioned include the National Institutes of Health (NIH) and the National Health and Medical Research Council (NHMRC).
- Authors suggest that interrupting this pathway might reduce chronic gut pain without affecting the normal digestive roles of these hormones.
What to watch next
- Development of therapies that target points in the estrogen–PYY–serotonin pathway — not confirmed in the source.
- Clinical trials testing pathway interruption or new drugs in people with IBS or endometriosis-related visceral pain — not confirmed in the source.
- Refinement of dietary recommendations based on patients’ sensitivity to short-chain fatty acids — not confirmed in the source.
Quick glossary
- Estrogen: A group of sex hormones important in reproductive development and other physiological processes; levels differ by sex and life stage.
- Peptide YY (PYY): A gut-derived hormone involved in regulating appetite and gastrointestinal function.
- Enterochromaffin cells: Specialised intestinal cells that produce and release serotonin, which can influence gut motility and sensation.
- Short-chain fatty acids (SCFAs): Metabolites produced by gut bacteria when they ferment dietary fibres; they can affect gut physiology and signalling.
- Serotonin: A neurotransmitter that, in the gut, modulates motility and sensory signalling; it is distinct from its roles in the brain.
Reader FAQ
Does this study show why women experience more gut pain than men?
The study identifies an estrogen-driven cellular pathway that increases serotonin release and nerve sensitisation, offering a biological explanation for observed sex differences.
Will this lead to new treatments right away?
Authors say interrupting the pathway might reduce chronic gut pain, but development and testing of clinical treatments are not confirmed in the source.
Do dietary changes such as a low FODMAP diet help because of this pathway?
The research links increased gut responsiveness to short-chain fatty acids with estrogen sensitivity, which helps explain why some people benefit from dietary interventions.
Was this research done in humans?
The release describes the work as a peer-reviewed experimental study and indicates animal models were involved; details on human studies are not confirmed in the source.
Why women experience more severe gut pain Publicly released: Fri 9 Jan 2026 at 0700 AEDT | Fri 9 Jan 2026 at 0900 NZDT Australia; SA Peer-reviewedExperimental studyAnimalsWhat do these…
Sources
- Why women experience more gut pain
- Estrogen found to trigger gut pain, explaining higher IBS rates in women …
- Do Hormones Explain Why Women Experience More Gut …
- What Role Does Estrogen Play in Signaling Gut Pain?
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