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UCSF Pinpoints Estrogen-Driven Gut Pain Pathway Linked to IBS Sex Gap

A Science study describes a hormone-triggered colon circuit that raises PYY, driving serotonin surges that heighten visceral sensitivity.

Overview

  • Researchers mapped estrogen acting on L-cells in the distal colon to boost PYY, which stimulates enterochromaffin cells to release serotonin and activate pain pathways.
  • Estrogen upregulated the short‑chain fatty acid receptor Olfr78 on L-cells, linking bacterial fermentation to heightened sensitivity and suggesting a rationale for low‑FODMAP relief in some patients.
  • In mice, removing ovaries or blocking estrogen, serotonin, or PYY markedly reduced visceral hypersensitivity, while giving males estrogen produced female-like sensitivity.
  • The work identifies PYY as a local pain signal in the colon, aligning with gastrointestinal distress reported in past PYY-based weight‑loss trials.
  • Authors say the pathway offers new drug targets and they will test candidates and probe other hormones, with human relevance still to be established.