Venge Per, Tejera Valeria Castro, Petersson Christer, Xu Shengyuan, Larsson Anders, Simrén Magnus, Öhman Lena, Törnblom Hans
Department of Medical Sciences, Uppsala University and Diagnostics Development, Uppsala, Sweden.
Diagnostics Development, Uppsala, Sweden.
Neurogastroenterol Motil. 2025 Apr;37(4):e14984. doi: 10.1111/nmo.14984. Epub 2024 Dec 17.
Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder characterized by discomfort with constipation and/or diarrhea with unclear pathophysiology. We aimed to determine the activities of colorectal eosinophils, neutrophils and epithelial cells by biomarkers in feces reflecting these activities.
Fecal samples were collected from 185 patients with IBS before and after 8 weeks of placebo or mesalazine treatment and from 40 healthy subjects. Calprotectin, eosinophil derived neurotoxin (EDN), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL) (pab/765) or dimer, human phospholipase BII-precursor (HPLBII-P) and myeloperoxidase (MPO) were measured by ELISA. Symptom scores were evaluated by diaries.
HPLBII-P, HNL (pab/765) and EDN, proteins secreted by intestinal epithelial cells, were elevated in IBS patients as compared to healthy subjects (p < 0.0001-p = 0.008). In contrast, the neutrophil proteins calprotectin, MPO and HNL dimer were unaltered. The eosinophilic protein ECP was lower in IBS (p = 0.001). HNL (pab/765) (p = 0.01) and EDN (p = 0.004) increased in IBS patients after mesalazine treatment. Colo-rectal mucosa showed strong staining of HPLBII-P and western blotting of fecal extracts showed the presence of mainly monomeric, epithelial-associated HNL.
The absence of signs of involvement of neutrophils and eosinophils in IBS suggests that activity of local epithelial cells rather than inflammation may be a major determinant of the disease. The measurements of EDN, HNL (pab/765), and HPLBII-P may serve as potential fecal biomarkers in the study and monitoring of IBS.
肠易激综合征（IBS）是一种常见的功能性胃肠疾病，其特征为伴有便秘和/或腹泻的不适，病理生理学尚不明确。我们旨在通过反映这些活动的粪便生物标志物来确定结肠嗜酸性粒细胞、中性粒细胞和上皮细胞的活性。
收集185例IBS患者在接受安慰剂或美沙拉嗪治疗8周前后的粪便样本，以及40名健康受试者的粪便样本。通过酶联免疫吸附测定法（ELISA）检测钙卫蛋白、嗜酸性粒细胞衍生神经毒素（EDN）、嗜酸性粒细胞阳离子蛋白（ECP）、人中性粒细胞脂质运载蛋白（HNL）（pab/765）或二聚体、人磷脂酶BII前体（HPLBII-P）和髓过氧化物酶（MPO）。通过日记评估症状评分。
与健康受试者相比，IBS患者中由肠上皮细胞分泌的蛋白质HPLBII-P、HNL（pab/765）和EDN升高（p<0.0001 - p = 0.008）。相比之下，中性粒细胞蛋白钙卫蛋白、MPO和HNL二聚体未发生改变。IBS患者中的嗜酸性粒细胞蛋白ECP较低（p = 0.001）。美沙拉嗪治疗后，IBS患者的HNL（pab/765）（p = 0.01）和EDN（p = 0.004）升高。结肠黏膜显示HPLBII-P有强烈染色，粪便提取物的蛋白质免疫印迹显示主要存在单体的、与上皮相关的HNL。
IBS中缺乏中性粒细胞和嗜酸性粒细胞参与的迹象表明，局部上皮细胞的活性而非炎症可能是该疾病的主要决定因素。EDN、HNL（pab/765）和HPLBII-P的测量可能作为IBS研究和监测中的潜在粪便生物标志物。
