肠道屏障功能的非侵入性生物标志物可识别腹泻型肠易激综合征患者的两种亚型：一项病例对照研究。
Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study.
作者信息
Linsalata Michele, Riezzo Giuseppe, D'Attoma Benedetta, Clemente Caterina, Orlando Antonella, Russo Francesco
机构信息
Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology, "S. de Bellis" Research Hospital, Via Turi 27, I-70013 Castellana Grotte, Bari, Italy.
出版信息
BMC Gastroenterol. 2018 Nov 6;18(1):167. doi: 10.1186/s12876-018-0888-6.
BACKGROUND
Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(-)] increased s-IP according to normal or altered La/Ma ratio.
METHODS
The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann-Whitney or the Kruskal-Wallis with Dunn's post-test was used to assess differences among the groups.
RESULTS
As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(-) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(-) ones.
CONCLUSIONS
The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population.
TRIAL REGISTRATION
NCT01574209 . Registered March 2012. First recruitment started in April 2012.
背景
小肠通透性（s-IP）的改变可能在腹泻型肠易激综合征（D-IBS）和乳糜泻（CD）患者中起重要作用。我们的目的是分析D-IBS患者的症状特征以及尿中蔗糖（Su）、乳果糖（La）、甘露醇（Ma）水平和胃肠道（GI）屏障功能的循环生物标志物（zonulin、肠脂肪酸结合蛋白-I-FABP和二胺氧化酶-DAO）。还研究了促炎白细胞介素6和8（IL-6和IL-8）、血浆脂多糖（LPS）值和Toll样受体4（TLR-4）。此外，将这些生物标志物与CD患者和健康对照（HC）的生物标志物进行比较。最后，根据正常或改变的La/Ma比值，对s-IP增加的D-IBS患者[D-IBS(+)]和未增加s-IP的D-IBS患者[D-IBS(-)]进行比较。
方法
该研究纳入了39例D-IBS患者、32例CD患者和20例HC。通过高效液相色谱法测定尿液中的Su和La/Ma比值来检测胃肠道通透性。ELISA试剂盒检测zonulin、I-FABP、DAO、IL-6、IL-8、LPS和TLR-4的循环浓度。采用Mann-Whitney检验或Kruskal-Wallis检验及Dunn事后检验来评估组间差异。
结果
就La/Ma比值、%Su和I-FABP水平而言，D-IBS患者与CD患者有显著差异，但与HC无显著差异。CD患者的IL-6水平显著高于HC，而D-IBS患者和CD患者的IL-8水平均显著高于HC。相反，LPS和TLR-4浓度在各组间无显著差异。当根据正常或改变的s-IP对D-IBS患者进行分类时，D-IBS(+)患者的%La、%Su、I-FABP和DAO水平显著高于D-IBS(-)患者。D-IBS(+)患者的炎症参数和细菌易位标志物（即IL-6和LPS）显著高于D-IBS(-)患者。
结论
本研究表明可以识别出两种不同的D-IBS亚型。研究可能的s-IP改变（即考虑La/Ma比值）可能有助于更好地评估和分类这一异质性D-IBS人群。
试验注册
NCT01574209。2012年3月注册。2012年4月开始首次招募。
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