Abstract Background Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a chronic, multifactorial condition.1 Commonly used biomarkers such as C-reactive protein and faecal calprotectin have limitations in sensitivity and specificity.1,2 MicroRNAs (miRNAs) have emerged as potential biomarkers due to their stability, differential expression and involvement in immune–inflammatory pathways.3,4 This study aimed to synthesise the evidence published between 2010 and 2024 on the potential of miRNAs as biomarkers in IBD. Methods We conducted a systematic review in accordance with PRISMA guidelines, prospectively registered in PROSPERO (CRD42024580694). Searches were performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Library. We included human studies that evaluated miRNAs in blood, mucosa or stool and reported quantitative data or diagnostic accuracy metrics. Four reviewers independently performed study screening, data extraction and quality assessment. For miR-21, we carried out a diagnostic test meta-analysis using a random-effects model, assessing heterogeneity (Q, I²) and publication bias (Egger’s test). Results Of 1,986 records identified, 139 studies were included in the qualitative synthesis and 3 in the meta-analysis. We found 167 microRNAs with differential expression in IBD. Although most microRNAs were reported in a single study (79/167), a smaller subset (18/167) had ≥8 independent reports, supporting their prioritisation as more robust biomarker candidates that converge on key inflammatory and epithelial pathways (NF-κB and JAK/STAT signalling, NOD2- and NLRP3-mediated innate immunity, epithelial barrier integrity and fibrogenesis), reinforcing their mechanistic relevance in IBD (Table 1). Given its prominence across studies, we performed a diagnostic meta-analysis of miR-21, which yielded a pooled area under the curve (AUC) of 0.862 (95% CI 0.753–0.970), albeit with significant heterogeneity (I² = 71.6%) (Figure 1). Conclusion microRNAs emerge as promising biomarkers for diagnosis, monitoring of disease activity and neoplastic risk stratification in IBD, with miR-21 standing out as a leading but not exclusive candidate. Other frequently reported microRNAs, which converge on key inflammatory and epithelial pathways, may add complementary diagnostic and prognostic information, particularly when combined in multiplex panels. The functional involvement of these microRNAs, including miR-21, also suggests potential value as therapeutic targets. Multicentre validation, analytical standardisation and prospective evaluation of combined microRNA panels are required to support their clinical implementation. References: 1. Guan Q. A comprehensive review and update on the pathogenesis of inflammatory bowel disease. J Immunol Res. 2019;2019:1-18. 2. Nakase H, Uchino M, Shinzaki S, et al. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J Gastroenterol. 2021;56(6):489-526. 3. Liu D, Saikam V, Skrada KA, Merlin D, Iyer SS. Inflammatory bowel disease biomarkers. Med Res Rev. 2022;42(4):1856-1887. 4. Síbia CF, Quaglio AEV, Oliveira ECS, Pereira JN, Ariede JR, Lapa RML, et al. microRNA–mRNA networks linked to inflammation and immune system regulation in inflammatory bowel disease. Biomedicines. 2024;12(2). Conflict of interest: Chacón Zambrano, Laura Andrea: Patiño Rueda, Jhon Sebastián: No conflict of interest Ospina Burbano, Edwin Mauricio: No conflict of interest Niño Muñoz, Paola Andrea: No conflict of interest Triana Acosta, Natalia Paola: No conflict of interest Rincón García, Diego Fernando: No conflict of interest Rey Rubiano, Margarita: No conflict of interest Garcia Duperly, Rafael: No conflict of interest Mendoza, Belen: No conflict of interest López Panqueva, Rocío del Pilar: No conflict of interest
Zambrano et al. (Thu,) studied this question.