Gastrointestinal and Extraintestinal Symptoms Among Subjects With Celiac Disease Undergoing a Dose-Specified Gluten Challenge: A Systematic Review and Meta-Analysis.

Gluten challenges (GC) are commonly used to evaluate novel therapeutics and CeD mechanisms, but their associated symptom burden has not been well characterized.

麸质挑战（GC）常用于评估新型治疗方法和CeD机制，但其相关的症状负担尚未得到充分描述。

We aim to evaluate the proportion of subjects with gastrointestinal and extraintestinal symptoms during an experimental GC.

我们旨在评估实验性胃肠道癌（GC）期间出现胃肠道和肠外症状的受试者比例。

Methods

Pubmed, Embase, CINAHL, and Cochrane Central were searched through December 2024 for studies reporting symptoms in adult patients with CeD in remission on a gluten-free diet undergoing a GC.

通过2024年12月，我们在Pubmed、Embase、CINAHL和Cochrane Central上搜索了报告在无麸质饮食下处于缓解期的成人乳糜泻（CeD）患者症状的研究。

Studies of GC for clinical diagnosis were excluded.

排除了用于临床诊断的胃癌研究。

Eligible studies included randomized (RCT) and non-randomized trials (non-RCT) that reported symptoms.

符合条件的研究包括报告症状的随机对照试验(RCT)和非随机对照试验(non-RCT)。

Data were pooled using random-effects meta-analysis, and heterogeneity was assessed.

数据通过随机效应模型进行荟萃分析，并评估了异质性。

Results

We identified 48 eligible studies with a total of 1,409 participants of which 35 were included in the meta-analysis(6 RCTs, 29 non-RCTs).

我们确定了48项符合条件的研究，共有1,409名参与者，其中35项研究被纳入荟萃分析（6项随机对照试验，29项非随机对照试验）。

The most common symptoms were abdominal pain (RCT 0.56, 95% confidence interval[CI] 0.45-0.65; non-RCT 0.40, 95% CI 0.32-0.49), bloating (RCT 0.55, 95% CI 0.38 to 0.71; non-RCT 0.37, 95% CI 0.28-0.47), and nausea (0.41, 95% CI 0.24-0.59; non-RCT 0.34, 95% CI 0.24-0.46).

最常见的症状是腹痛（随机对照试验（RCT）0.56，95%置信区间[CI] 0.45-0.65；非随机对照试验（non-RCT）0.40，95% CI 0.32-0.49），腹胀（RCT 0.55，95% CI 0.38至0.71；non-RCT 0.37，95% CI 0.28-0.47），以及恶心（0.41，95% CI 0.24-0.59；non-RCT 0.34，95% CI 0.24-0.46）。

There was significant heterogeneity across studies, with variable GC doses and durations, no systematic reporting of all symptom categories, and missing individual data for some studies.

研究之间存在显著的异质性，胃癌（GC）剂量和持续时间各不相同，没有系统地报告所有症状类别，并且一些研究缺少个体数据。

Bloating, fatigue, flatulence, and nausea were significantly more reported in studies administering ≥6 g gluten/d.

在每天给予≥6克麸质的研究中，腹胀、疲劳、胀气和恶心的报告显著更多。

Discussion

GC commonly induces gastrointestinal symptoms in patients with CeD, with abdominal pain, bloating, and nausea being most frequent.

胃肠道症状在患有乳糜泻（CeD）的患者中很常见，其中腹痛、腹胀和恶心是最频繁的症状。

Standardized challenge protocols are needed to advance therapeutic research while minimizing symptom burden.

需要标准化的挑战协议来推进治疗研究，同时最小化症状负担。