Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China.
Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China.
Dig Liver Dis. 2021 Sep;53(9):1120-1127. doi: 10.1016/j.dld.2021.04.022. Epub 2021 May 28.
To compare both the faecal bile acids (BAs) and the levels of two bile acid receptors, Takeda G protein-coupled receptor 5 (TGR5) and vitamin D receptor (VDR), in the colonic mucosa between patients with irritable bowel syndrome with predominant diarrhea (IBS-D) and healthy controls, and explore the correlations among clinical characteristics, bile acid receptors expression, and BAs.
The severity of abdominal pain and diarrhoea was assessed in IBS-D patients using validated questionnaires, faecal BAs were measured by ultraperformance liquid chromatography coupled to tandem mass spectrometry, and rectosigmoid biopsies were taken for the analyses of TGR5 and VDR expression using immunohistochemistry.
The level of TGR5 immunoreactivity in rectosigmoid mucosal biopsies was significantly higher in IBS-D patients than in controls, while the VDR immunoreactivity displayed no significant difference between patients and controls. The patients with more severe or more frequent abdominal pain had significantly higher TGR5 level. Faecal primary BAs were significantly increased in IBS-D patients and were positively correlated with the severity of diarrhoea. The level of TGR5 was positively associated with primary BAs and negatively associated with secondary BAs among all participants providing both mucosal and stool samples.
Colonic mucosal TGR5 protein expression and faecal bile acids were correlated with the symptom severity of IBS-D patients.
比较肠易激综合征腹泻型(IBS-D)患者和健康对照者的粪便胆汁酸(BAs)和两种胆汁酸受体(Takeda G 蛋白偶联受体 5(TGR5)和维生素 D 受体(VDR))在结肠黏膜中的水平,并探讨临床特征、胆汁酸受体表达与 BAs 之间的相关性。
采用经过验证的问卷评估 IBS-D 患者的腹痛和腹泻严重程度,采用超高效液相色谱-串联质谱法检测粪便 BAs,采用免疫组织化学法检测直肠乙状结肠黏膜活检组织中 TGR5 和 VDR 的表达。
IBS-D 患者直肠乙状结肠黏膜活检组织中 TGR5 免疫反应性水平明显高于对照组,而 VDR 免疫反应性在患者和对照组之间无显著差异。腹痛更严重或更频繁的患者 TGR5 水平明显升高。IBS-D 患者的初级 BAs 明显增加,且与腹泻严重程度呈正相关。在所有提供黏膜和粪便样本的参与者中,TGR5 水平与初级 BAs 呈正相关,与次级 BAs 呈负相关。
结肠黏膜 TGR5 蛋白表达和粪便胆汁酸与 IBS-D 患者的症状严重程度相关。