Gastric juice MicroRNAs as biomarkers for functional dyspepsia: an observational case-control study

Radu-Alexandru Farcas^1*Teodora Surdea-Blaga¹Stefan Lucian Popa¹Flaviu Viorel Rusu¹Alexandra Chira¹Cristina Sabo¹Vlad Ionut Nechita²Liviuța Budișan³Oana Zanoaga³Ioana Berindan Neagoe³Stefan Strilciuc³Dan-Lucian Dumitrașcu¹

• ¹2nd Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania, Cluj-Napoca, Romania
• ²Department of Medical Education – Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania, Cluj-Napoca, Romania
• ³University of Medicine and Pharmacy Iuliu-Hatieganu, Institute of Biomedical Research MEDFUTURE, Genomics Department, Cluj-Napoca, Cluj-Napoca, Romania

Background and Aims: MicroRNAs (miRNAs, miRs) are stable RNA molecules that regulate gene expression and hold promise as biomarkers. Functional dyspepsia (FD), a complex gastrointestinal disorder, is characterized by motility dysfunction and visceral hypersensitivity. Given the limitations of current diagnostic markers, miRNAs may offer novel insights for diagnosis and risk stratification. We conducted an observational case-control study involving 28 FD patients (14 with epigastric pain syndrome [EPS], 14 with postprandial distress syndrome [PDS]) and 22 healthy controls (HC). All subjects underwent gastroscopy with gastric juice collection. Quantitative real-time PCR was used to measure levels of selected miRNAs (miR-21-5p, miR-155-5p, miR-203). Fold-change in miRNA expression was calculated. We compared miRNA levels between groups and between FD subtypes and assessed correlations with symptom severity. Results: Gastric juice miR-21-5p was significantly elevated in FD patients compared to controls (FD:19.98±91.56 fold-change vs HC: 2.63 ±3.30 fold-change p=0.00774). PDS patients showed a distinct profile: markedly higher miR-21 and miR-155 but lower miR-203 relative to EPS patients. MiR levels correlated with symptom patterns: miR-21 and miR-155 levels were inversely correlated with epigastric pain intensity (τ = -0.517 and -0.317, respectively) but positively correlated with postprandial fullness and early satiety (τ up to 0.523, p < 0.01). Conversely, miR-203 showed direct correlation with epigastric pain (τ = 0.317, p = 0.023) and inverse correlation with fullness (τ = -0.523, p < 0.01). A history of Helicobacter pylori infection was associated with a significant reduction in gastric juice miR-203 levels (p=0.03). Conclusions: FD patients might have altered gastric juice miRNA profiles and distinctive differences between PDS and EPS subtypes. The PDS subtype is characterized by a high-miR-21 and miR-155 and low-miR-203 signature, whereas the opposite pattern is observed in EPS. These miRNA alterations align with the symptomatology of FD subtypes and may reflect underlying pathophysiological differences. Gastric juice miRNAs could serve as minimally invasive biomarkers for FD, aiding in differentiating functional subgroups and potentially guiding targeted therapies. Further studies are warranted to confirm these findings and establish their diagnostic utility and role in FD pathogenesis.