Objective Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm. Design In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS. Results Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%. Conclusion Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

中文翻译：

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血清 zonulin 及其在非腹腔麸质敏感性中的诊断性能

目的 非乳糜泻麸质敏感性 (NCGS) 的特征是与摄入含麸质食物相关的肠道和肠外症状，但不存在乳糜泻 (CD) 和小麦过敏。没有生物标志物可用于诊断 NCGS，金标准双盲安慰剂对照面筋挑战在临床上是不切实际的。我们工作的目的是研究血清 zonulin 作为 NCGS 诊断生物标志物的作用并开发诊断算法。设计 在一项多中心研究中，我们招募了 86 名自我报告或双盲确诊的 NCGS 患者、59 名腹泻型 IBS (IBS-D) 患者、15 名 CD 患者和 25 名无症状对照 (AC)。评估了 Zonulin 血清水平并计算了相关的诊断能力。记录临床和症状数据。在 NCGS 患者亚组中评估了饮食对 zonulin 水平的影响。结果 与 ACs 相比，NCGS（无论诊断方式如何）和 CD 患者的 zonulin 水平显着增加，与 IBS-D 参与者相比，NCGS 和 CD 患者也是如此。与双盲确认和未确认的 NCGS 相比，自我报告的 NCGS 显示 zonulin 水平增加。仅在患有 NCGS 的 HLA-DQ2/8 阳性参与者中，六个月的小麦避免显着降低了 zonulin 水平。zonulin 水平在区分 NCGS 和 IBS-D 方面的诊断准确率为 81%。排除 CD 后，结合 zonulin 水平、症状和性别的诊断算法将准确率提高到 89%。结论 Zonulin 可被认为是 NCGS 的诊断生物标志物，结合人口统计学和临床​​数据可以高精度区分 NCGS 和 IBS-D。仅在携带 HLA 基因型的 NCGS 中，小麦戒断与 zonulin 水平降低有关。