Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (ChroMetA), KU Leuven, 3000 Leuven, Belgium.
Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium.
Cells. 2022 Apr 4;11(7):1214. doi: 10.3390/cells11071214.
Disorders of the gut-brain interaction (DGBI), such as irritable bowel syndrome and functional dyspepsia, are more prevalent in women than in men, with a ratio of 2:1. Furthermore, stressful life events have been reported as one of the triggers for symptoms in DGBI patients.
Here, we studied the effect of an early-life stressor (maternal separation (MS)) on jejunal and colonic alterations, including colonic sensitivity and immune cells infiltration and activation in a validated spontaneous model of DGBI (BBDP-N), and investigated the involvement of β-estradiol on stress-worsened intestinal alterations.
We found that maternal separation exacerbated colonic sensitivity and mast cell and eosinophil infiltration and activation in females only. Ovariectomy partially rescued the stress phenotype by decreasing colonic sensitivity, which was restored by β-estradiol injections and did not impact immune cells infiltration and activation. Stressed males exposed to β-estradiol demonstrated similar intestinal alterations as MS females.
Estrogen plays a direct critical role in colonic hypersensitivity in a spontaneous animal model of DGBI, while for immune activation, estrogen seems to be involved in the first step of their recruitment and activation. Our data point towards a complex interaction between stress and β-estradiol in DGBI.
肠道-大脑相互作用障碍（DGBI），如肠易激综合征和功能性消化不良，在女性中比男性更为常见，比例为 2:1。此外，压力性生活事件被报道为 DGBI 患者症状的触发因素之一。
在这里，我们研究了早期生活应激源（母体分离（MS））对验证的 DGBI 自发模型（BBDP-N）中空肠和结肠改变的影响，包括结肠敏感性和免疫细胞浸润和激活，并研究了β-雌二醇对压力加重的肠道改变的参与。
我们发现，母体分离仅在雌性中加剧了结肠敏感性以及肥大细胞和嗜酸性粒细胞的浸润和激活。卵巢切除术通过降低结肠敏感性部分挽救了应激表型，这一表型可通过β-雌二醇注射恢复，并且不影响免疫细胞浸润和激活。暴露于β-雌二醇的应激雄性表现出与 MS 雌性相似的肠道改变。
雌激素在 DGBI 的自发动物模型中对结肠高敏感性起着直接的关键作用，而对于免疫激活，雌激素似乎参与了它们募集和激活的第一步。我们的数据表明，DGBI 中存在应激和β-雌二醇之间的复杂相互作用。
