小组发现了一种雌激素应答的旁分泌途径，其中两种肠内分泌细胞类型，表达肽YY （PYY）的L细胞和血清素能的EC细胞相互交流，以增加女性的肠道敏感性。该团队发现雌激素信号上调结肠L细胞上细菌代谢物短链脂肪酸受体Olfr78，增加PYY的释放和它们对醋酸盐的敏感性。升高的PYY通过NPY1R作用于邻近的EC细胞，从而增加血清素的释放和肠道疼痛。该研究团队认为，激素波动与内部（压力）或环境（饮食）因素相结合，放大了局部雌激素应答性结肠回路，导致肠道敏感性不适应。
据介绍，内脏疼痛紊乱，如肠易激综合征，在女性中表现出明显的患病率。肠上皮肠染色质（EC）细胞和粘膜感觉神经纤维之间的信号传导增强可能导致这种性别偏见。
附：英文原文
Title: A cellular basis for heightened gut sensitivity in females
Author: Archana Venkataraman, Eric E. Figueroa, Joel Castro, Fernanda Castro Navarro, Deepanshu Soota, Stuart M. Brierley, David Julius, Holly A. Ingraham
Issue&Volume: 2025-12-18
Abstract: Visceral pain disorders, such as irritable bowel syndrome, exhibit a marked female prevalence. Enhanced signaling between enterochromaffin (EC) cells in the gut epithelium and mucosal sensory nerve fibers likely contributes to this sex bias. We identified an estrogen-responsive paracrine pathway in which two enteroendocrine cell types, peptide YY (PYY)–expressing L cells and serotonergic EC cells, communicate to increase gut sensitivity in females. We demonstrate that estrogen signaling up-regulates the bacterial metabolite short-chain fatty acid receptor Olfr78 on colonic L cells, increasing PYY release and their sensitivity to acetate. Elevated PYY acts on neighboring EC cells by means of NPY1R, thereby enhancing serotonin release and gut pain. We propose that hormonal fluctuations, in conjunction with internal (stress) or environmental (diet) factors, amplify this local estrogen-responsive colonic circuit, resulting in maladaptive gut sensitivity.
DOI: adz1398
Source: https://www.science.org/doi/10.1126/science.adz1398