Evidence map›Paper›PMID 41793943›Full record

SynthesisEBioMedicine2026

Serological and faecal markers of irritable bowel syndrome: a systematic review and meta-analysis.

Grace L Burns, Freya Roberts, Jasmine A Wark, Sophie Fowler, Michael P Jones, Kerith Duncanson, Nicholas J Talley, Simon Keely

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

8 authors.

Grace L BurnsCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia.
Freya RobertsCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia.
Jasmine A WarkCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia.
Sophie FowlerCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia.
Michael P JonesNHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia; School of Psychological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, Australia.
Kerith DuncansonCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia.
Nicholas J TalleyCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia.
Simon KeelyCollege of Health, Medicine and Wellbeing, The University of Newcastle, Callaghan, Australia; Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, Australia; NHMRC Centre of Research Excellence in Transforming Gut Health, New Lambton Heights, Australia. Electronic address: simon.keely@newcastle.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe irritable bowel syndrome (IBS) has long been considered a functional disorder, but recent work has demonstrated clear biological signatures in immune, microbiome and enteric nervous systems of patients with IBS. Despite this new knowledge, there is still no clear biological marker of IBS, with patient symptom reporting and exclusion of organic disease the main criteria for diagnosis. We aimed to perform a systematic review and meta-analysis to identify consistent biomarkers for IBS in serum and stool samples.

methodsWe searched Medline, EMBASE, Cochrane Library, Web of Science and Scopus to obtain all relevant publications published between 1992 and January 2026. Original, peer-reviewed research articles including adults with IBS and healthy or outpatient controls, and/or patients with organic gastrointestinal conditions (e.g. IBD) were included. All articles had quantification of blood and faecal markers between IBS and controls. Descriptive data presented as median and range or median (interquartile range) was converted to mean ± SD. To account for methodological assay differences between studies, standardised mean difference (SMD) with 95% confidence interval was used as the primary outcome measure for the meta-analyses, with a random effects model fitted to the data.

findingsThe search strategy identified 55,444 citations across all databases. 124 studies were included encompassing 14,930 patients with IBS, 7544 healthy/asymptomatic controls and 4317 patients with organic diseases. The top serum discriminators between IBS and healthy controls were TNF-⍺ (13 studies, 1025 controls and 1244 IBS, SMD = 2.74, 95% CI = 0.70, 4.70, p = 0.006), IL-6 (13 studies, 736 controls and 1022 IBS, SMD = 1.87, 95% CI = 0.13, 3.61, p = 0.035) and IFN-ɣ (4 studies, n = 195 controls, n = 372 IBS, SMD = 2.79, 95% CI = 1.07, 4.51, p = 0.002). For faecal markers calprotectin was significantly higher in patients with IBS over controls (11 studies, 1624 controls and 1383 IBS, SMD = 0.75, 95% CI = 0.30, 1.21, p = 0.001), while faecal valerate levels were lower in IBS versus controls (4 studies, 290 controls and 488 IBS, SMD = -0.79, 95% CI = -1.48, -0.11, p = 0.02). For discriminating IBS overall from organic diseases, serum albumin (4 studies, 282 IBS and 312 organic, SMD = 2.15, 95% CI = 0.20, 4.11, p = 0.031) and faecal calprotectin (16 studies, 1591 IBS and 1685 organic, SMD = -1.13, 95% CI = -1.51, -0.75, p < 0.0001) were significantly different. In discriminating IBS subtypes from controls, only diarrhoeal IBS (IBS-D) could be distinguished by albumin (3 studies, 248 controls and 219 IBS-D, SMD = -0.39, 95% CI = -0.68, -0.11, p = 0.007) and IL-6 (4 studies, 153 IBS-D and 169 controls, SMD = 2.53, 95% CI = 0.86, 4.21, p = 0.003). Heterogeneity across the studies ranged from moderate to high, but few overly influential studies were identified between comparisons.

interpretationPatients with IBS exhibit increased peripheral cytokine levels that are consistent with reports of increased epithelial permeability and may be important in distinguishing subgroups of IBS patients. Patients with IBS also demonstrated higher faecal calprotectin levels than healthy individuals, although these levels were still significantly lower than patients with organic diseases. Similarly, patients with IBS-D have lower serum albumin levels compared to healthy controls, while patients with organic disease had lower levels compared to patients with IBS, irrespective of subtype. There are clear biological signatures at play in IBS patients that may be useful clinically in establishing IBS diagnosis and may indicate the mechanisms of disease symptoms.

fundingNational Health and Medical Research Council Centre for Research Excellence in Digestive Health (NJT, SK) G180219.

Indexed as

BiomarkersFecesIrritable Bowel SyndromeHumansBiomarkersBiomarkersBloodFaecal markersIrritable bowel syndromeSystematic review

Identifiers

PMID41793943
PMCPMC12992513

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.