Systematic review with meta-analysis: Diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults Original paper

What was reviewed?

This systematic review and meta-analysis assessed whether faecal calprotectin to distinguish IBD from IBS can accurately differentiate inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) in adults presenting with overlapping symptoms such as abdominal pain and diarrhoea. The authors searched major databases (MEDLINE, Embase, Scopus, Cochrane) through 1 January 2023 and included diagnostic accuracy studies where IBS was defined using the Rome criteria, and IBD was confirmed using colonoscopy with histology and/or small-bowel radiology as the reference standard. Using a bivariate random-effects model, they pooled sensitivity and specificity and explored heterogeneity via subgroup and meta-regression analyses, focusing particularly on geography (Western vs Eastern regions) and calprotectin cut-offs (≤50 μg/g vs >50 μg/g).

Who was reviewed?

Across 17 included studies, 1956 participants were evaluated: 1083 patients with IBD (585 ulcerative colitis, 498 Crohn’s disease) and 873 with IBS. Most studies enrolled adults, though three included a subgroup of teenagers; studies spanned Europe (11), Asia (4), the USA (1), and Africa (1). IBS diagnosis relied on Rome II in 10 studies and Rome III in 7 studies. Faecal calprotectin was measured mainly by ELISA (13 studies) or immunochromatographic assays (4 studies), with cut-offs varying widely (≤50 μg/g in 10 studies; >50 μg/g in 6 studies; one not reported). Methodological concerns were common: all studies were rated “high” or “unclear” risk of bias in at least one QUADAS-2 domain, largely driven by case–control designs and non–non-pre-specified cut-offs.

Most important findings

Overall diagnostic performance strongly supported faecal calprotectin as a rule-out test. Pooled sensitivity for distinguishing IBD from IBS was 85.8% (95% CI 78.3–91) and specificity 91.7% (95% CI 84.5–95.7), with a positive likelihood ratio of 10.3 and negative likelihood ratio of 0.15. Predictive values depended heavily on IBD prevalence: at 1% prevalence (typical primary care), negative predictive value was 99.8% while positive predictive value was only 9%, meaning a positive test is not very confirmatory but a negative test makes IBD very unlikely. Heterogeneity was substantial, but two key drivers emerged: geography and cut-off. Sensitivity was higher in Western countries than Eastern countries (88% vs 73%) with similar specificity, and cut-offs ≤50 μg/g produced better sensitivity than >50 μg/g (87% vs 79%) without materially reducing specificity. When separated by IBD subtype, pooled accuracy was slightly higher for Crohn’s disease (sensitivity 92.4%, specificity 93.1%) than for ulcerative colitis (sensitivity 83.1%, specificity 83.3%), consistent with the idea that Crohn’s may generate higher inflammatory biomarker signals in stool in some contexts.

Key implications

Clinically, faecal calprotectin to distinguish IBD from IBS is best interpreted as a high-value triage tool that reduces unnecessary colonoscopy and imaging in adults with IBS-like symptoms, particularly when the pre-test probability of IBD is low. A negative result provides strong reassurance (very high NPV across care settings), supporting conservative management and functional bowel workup, while a positive result should be treated as a “screen positive” that warrants further evaluation rather than an IBD diagnosis. The analysis also suggests practical optimisation: using a cut-off ≤50 μg/g may minimise missed IBD at little cost to specificity, and clinicians should be aware that sensitivity may be lower in Eastern populations—though even there, rule-out performance remains strong given low disease prevalence. From a microbiome-signature database perspective, this paper is important not because it identifies taxa, but because it validates a neutrophil-derived inflammatory biomarker that correlates with gut mucosal inflammation; this can be used as a structured clinical phenotype anchor when linking microbial community patterns to inflammatory vs functional disease presentations.

Citation

Dajti E, Frazzoni L, Iascone V, Secco M, Vestito A, Fuccio L, et al. Systematic review with meta-analysis: Diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults. Aliment Pharmacol Ther. 2023;58:1120-1131. doi:10.1111/apt.17754