Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA.
Clin Transl Gastroenterol. 2021 Apr 12;12(4):e00329. doi: 10.14309/ctg.0000000000000329.
Previous studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions.
We measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2(-Δ, ΔCT) formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values (P < 0.05) are reported.
In ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport).
These data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.
先前在肠易激综合征（IBS）患者中的研究表明，十二指肠、空肠或结肠黏膜存在免疫激活、分泌和屏障功能障碍。本研究旨在测量回肠黏膜中与黏膜功能相关的基因和蛋白的表达。
我们通过逆转录聚合酶链反应（RT-PCR）测量了 11 例腹泻型肠易激综合征（IBS-D）患者、17 例便秘型肠易激综合征（IBS-C）患者和 14 例健康对照者的回肠黏膜中 78 个基因（反映紧密连接蛋白、趋化因子、固有免疫、离子通道和递质）和 5 个蛋白（屏障、胆汁酸受体和离子交换体）的信使 RNA（mRNA）表达。使用 2(-ΔΔCT)公式计算 mRNA 的 fold change。使用方差分析测量组间差异。基于 Western blot 分析，计算蛋白与健康对照组的相对比值。报告名义 P 值（P<0.05）。
在回肠黏膜活检中，IBS-D 与 IBS-C 相比，mRNA 表达的显著差异为屏障蛋白（TJP1、FN1、CLDN1 和 CLDN12）、修复功能（TFF1）和细胞功能的上调。在回肠黏膜活检中，IBS-C 与健康对照组相比，GPBAR1 受体、肌球蛋白轻链激酶（MYLK，在屏障功能中）和固有免疫（TLR3）的 mRNA 表达减少，但黏附机制钙粘蛋白（CTNNB1）和转运基因 SLC9A1（Na-H 交换体[NHE1]）和 INADL（间接影响离子转运）的 mRNA 表达增加。
这些数据支持回肠黏膜功能障碍在 IBS 中的作用，包括 IBS-D 中的屏障功能障碍和 IBS-C 中的吸收/分泌机制改变。
