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Meta-Analysis
. 2023 Jul;8(7):646-659.
doi: 10.1016/S2468-1253(23)00102-4. Epub 2023 May 18.

Overlap of disorders of gut-brain interaction: a systematic review and meta-analysis

Thomas Fairlie  1 , Ayesha Shah  1 , Nicholas J Talley  2 , William D Chey  3 , Natasha Koloski  4 , Yeong Yeh Lee  5 , Kok-Ann Gwee  6 , Michael P Jones  7 , Gerald Holtmann  8
Affiliations
Meta-Analysis

Overlap of disorders of gut-brain interaction: a systematic review and meta-analysis

Thomas Fairlie et al. Lancet Gastroenterol Hepatol. 2023 Jul.

Abstract

Background: Rome criteria differentiate distinct types of disorders of gut-brain interaction (DGBI); also known as functional gastrointestinal disorders. Overlap of symptom categories frequently occurs. This systematic review and meta-analysis aimed to define the prevalence of DGBI overlap and compare overlap in population-based, primary care or tertiary care health settings. Furthermore, we aimed to compare symptom severity of psychological comorbidities in DGBI with and without overlap.

Methods: For this systematic review and meta-analysis we searched MEDLINE (PubMed) and Embase electronic databases from inception until March 1, 2022, for original articles and conference abstracts of observational cross-sectional, case-controlled, or cohort design studies that reported the prevalence of DGBI overlap in adult participants (aged ≥18 years). We included only those studies where the diagnosis of DGBI was based on clinical assessment, questionnaire data, or specific symptom-based criteria. Studies were excluded if reporting on mixed populations of DGBI and organic diseases. Aggregate patient data were extracted from eligible published studies. The prevalence of DGBI overlap in all studies was pooled using the DerSimonian and Laird random effects model, and further analysis stratified by subgroups (care setting, diagnostic criteria, geographic region, and gross domestic product per capita). We also assessed the relationship between DGBI overlap with anxiety, depression, and quality of life symptom scores. This study was registered with PROSPERO (CRD42022311101).

Findings: 46 of 1268 screened studies, reporting on 75 682 adult DGBI participants, were eligible for inclusion in this systematic review and meta-analysis. Overall, 24 424 (pooled prevalence 36·5% [95% CI 30·7 to 42·6]) participants had a DGBI overlap, with considerable between-study heterogeneity (I2=99·51, p=0·0001). In the tertiary health-care setting, overlap among participants with DGBI was more prevalent (8373 of 22 617, pooled prevalence 47·3% [95% CI 33·2 to 61·7]) compared with population-based cohorts (11 332 of 39 749, pooled prevalence 26·5% [95% CI 20·5 to 33·4]; odds ratio 2·50 [95% CI 1·28 to 4·87]; p=0·0084). Quality of life physical component scores were significantly lower in participants with DGBI overlap compared with participants without overlap (standardised mean difference -0·47 [95% CI -0·80 to -0·14]; p=0·025). Participants with DGBI overlap had both increased symptom scores for anxiety (0·39 [95% CI 0·24 to 0·54]; p=0·0001) and depression (0·41 [0·30 to 0·51]; p=0·0001).

Interpretation: Overlap of DGBI subtypes is frequent, and is more prevalent in tertiary care settings and associated with more severe symptom manifestations or psychological comorbidities. Despite the large sample size, the comparative analyses revealed substantial heterogeneity, and the results should be interpreted with caution.

Funding: National Health and Medical Research Council and Centre for Research Excellence.

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Conflict of interest statement

Declaration of interests GH has received payments or honoraria for lectures, presentations, or speakers bureaus from Bayer, and has also received travel/support for attending meetings from Bayer. He has participated on data safety monitoring boards or advisory boards from Australian Biotherapeutics, Glutagen, and Bayer. GH holds stock or stock options in Bayer. He serves on the boards of the West Moreton Hospital and Health Service (WMHHS), Queensland, UQ Healthcare, Brisbane, and is vice president of Gastro-Liga, Germany, and Chair of the WMHHS Board Quality and Safety Committee. He is on the Research Committee of the Royal Australasian College of Physicians. GH acknowledges funding from the National Health and Medical Research Council (NHMRC) for the Centre for Research Excellence in Digestive Health. GH holds a Medical Research Future Fund grant and an NHMRC ideas grant. NJT reports grants from NHMRC (Centre for Research Excellence in Digestive Health; investigator grant), HMRI, Defence department of the Australian government (Cognobiome grant), AusEE, Astra Zeneca, Allakos, and Intrinsic Medicine. He reports personal fees from Adelphi values, Allakos, Astra Zeneca, Bayer AG, Comvita Mānuka Honey, BluMaiden, twoXAR, Dr Falk Pharma/Jorveza, Glutagen, IsoThrive, Intrinsic Medicine, and Rose Pharma, and has acted as an educational speaker for GlaxoSmithKline Australia. He has non-financial support from Norgine for an IBS interest group. NJT has a patent for biomarkers of IBS licensed (#12735358·9 -1405/2710383 and #12735358·9 -1405/2710384), has licensed questionnaires (Talley Bowel Disease Questionnaire) to the Mayo Clinic, has a Nestec European Patent Application (No. 12735358·9), has a provision Australian patent application for a diagnostic marker for functional gastrointestinal disorders (2021901692), a Singapore provisional patent (NTU Ref: TD/129/17 “Microbiota Modulation Of BDNF Tissue Repair Pathway”), and copyright Nepean Dyspepsia Index (NDI) 1998. He has acted on an advisory board for Bristol Myers Squibb. NJT declares the following other financial or non-financial interests: Medical Journal of Australia (Editor in Chief), Up to Date (Section Editor), Precision and Future Medicine, Sungkyunkwan University School of Medicine, South Korea (Editorial Board Member), Med (Journal of Cell Press; Editorial Board Member), eGastroenterology (Editorial Board Member), and has received personal fees for a textbook from Elsevier. NJT has leadership or fiduciary roles (all unpaid) in the International Foundation for Functional Gastrointestinal Disorders (IFFGD; advisory board), AusEE (advisory board), OzSage, NHMRC Principal Committee (Research Committee), Asia Pacific Association of Medical Journal Editors (APAME), AAHMS, Rome V working team member (gastroduodenal committee), International Plausibility Project Co-Chair (Rome Foundation funded), COVID-19 vaccine forum member. WDC reports grants from Biomerica, Commonwealth Diagnostics International, QOL Medical, and Salix/Valeant, has received consulting fees from AbbVie, Alnylam, Biomerica, Gemelli, Ironwood, Isothrive, QOL Medical, Nestle, Redhill, Salix/Valenat, Urovant, Takeda, and Vibrant. He is on the board of trustees and an officer of the American College of Gastroenterology, board of directors of the Rome Foundation, and board of directors and is vice president of the IFFGD. TF, AS, NK, YYL, KAG, and MPG declare no competing interests.

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