Evidence map›Paper›PMID 40298233›Full record

SynthesisThe American journal of gastroenterology2026

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

Marcela Banegas, David Flores-Marin, Namrata Naskar, Tulio L Correa, Chloe Rotman, Stephanie Regis, Amelia Simpson, Denis Chang, Jocelyn Silvester, Amelie Therrien

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in The American journal of gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Marcela BanegasCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0000-0003-2604-1348
David Flores-MarinCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0000-0001-5310-9649
Namrata NaskarCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0009-0005-2508-4460
Tulio L CorreaCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0000-0003-4524-6736
Chloe RotmanHarvard Catalyst Program Boston Children's Hospital, Boston, Massachusetts, USA.
Stephanie RegisDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-6756-9715
Amelia SimpsonBoston University, Boston, Massachusetts, USA.
Denis ChangDepartment of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-3843-5785
Jocelyn SilvesterCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0000-0002-3615-1666
Amelie TherrienCeliac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.ORCID 0000-0002-6911-8598

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Mechanisms and Markers of Small Intestinal Epithelial Injury and Villous AtrophyK23DK119584 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI SILVESTER, JOCELYN ANNE · 2019 to 2023
$971k
American College of Gastroenterology Junior Faculty Career Development AwardDivision of Diabetes, Endocrinology, and Metabolic Diseases K23DK119584Harvard Catalyst UL1TR002541NCATS NIH HHS UL1 TR002541NIDDK NIH HHS K23 DK119584
6 · The paper itself

Abstract

introductionCeliac disease (CeD) is an immune-mediated enteropathy driven by gluten ingestion. Gluten challenges (GC) are commonly used to evaluate novel therapeutics and CeD mechanisms, but their associated symptom burden has not been well characterized. We aim to evaluate the proportion of subjects with gastrointestinal and extraintestinal symptoms during an experimental GC.

methodsPubmed, 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. Studies of GC for clinical diagnosis were excluded. Eligible studies included randomized (RCT) and non-randomized trials (non-RCT) that reported symptoms. Data were pooled using random-effects meta-analysis, and heterogeneity was assessed.

resultsWe 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). 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). 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. Bloating, fatigue, flatulence, and nausea were significantly more reported in studies administering ≥6 g gluten/d. DISCUSSION: GC commonly induces gastrointestinal symptoms in patients with CeD, with abdominal pain, bloating, and nausea being most frequent. Standardized challenge protocols are needed to advance therapeutic research while minimizing symptom burden.

Indexed as

Celiac DiseaseGastrointestinal DiseasesGlutensAbdominal PainDiet, Gluten-FreeHumansGlutensceliac diseaseclinical trialglutengluten challengemeta-analysissymptomssystematic review

Identifiers

PMID40298233
PMCPMC12352593

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.