Farcas Radu A, Surdea-Blaga Teodora, Popa Ştefan, Rusu Flaviu, Chira Alexandra, Sabo Cristina, Nechita Vlad-Ionuţ, Budişan Liviuţa, Zanoaga Oana, Berindan-Neagoe Ioana, Strilciuc Ştefan, Dumitrascu Dan L
2nd Department of Internal Medicine, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Medical Education - Medical Informatics and Biostatistics, "Iuliu Haţieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Front Med (Lausanne). 2025 Aug 26;12:1636825. doi: 10.3389/fmed.2025.1636825. eCollection 2025.
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, visceral hypersensitivity, and gut microbiome alterations. 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-203a) in gastric fluid, with miR-16 and U6 as endogenous controls. Fold-change in miRNA expression was calculated. We compared miRNA levels between groups and between FD subtypes and assessed correlations with symptom severity (using the Functional Dyspepsia Symptom Diary scores). Statistical significance was determined by non-parametric tests, with < 0.05 as threshold.
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 = 0.00774). In contrast, miR-155-5p and miR-203a levels did not differ significantly overall between FD and healthy groups. However, within FD, PDS patients showed a distinct profile: markedly higher miR-21 and miR-155 but lower miR-203 relative to EPS patients. MiRNA 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, < 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, < 0.01). A history of Helicobacter pylori infection was associated with a significant reduction in gastric juice miR-203 levels ( ∼ 0.03).
FD patients might have altered gastric juice miRNA profiles, notably an upregulation of miR-21, 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 this findings and establish their diagnostic utility and role in FD pathogenesis.
微小RNA（miRNA，miR）是稳定的RNA分子，可调节基因表达，有望成为生物标志物。功能性消化不良（FD）是一种复杂的胃肠道疾病，其特征为运动功能障碍、内脏高敏感性和肠道微生物群改变。鉴于目前诊断标志物的局限性，miRNA可能为诊断和风险分层提供新的见解。
我们进行了一项观察性病例对照研究，纳入28例FD患者（14例上腹部疼痛综合征[EPS]患者，14例餐后不适综合征[PDS]患者）和22名健康对照（HC）。所有受试者均接受胃镜检查并收集胃液。采用定量实时聚合酶链反应测量胃液中选定miRNA（miR-21-5p、miR-155-5p、miR-203a）的水平，以miR-16和U6作为内参。计算miRNA表达的倍数变化。我们比较了各组之间以及FD亚型之间的miRNA水平，并评估了其与症状严重程度的相关性（使用功能性消化不良症状日记评分）。采用非参数检验确定统计学意义，以P<0.05为阈值。
与对照组相比，FD患者胃液中的miR-21-5p显著升高（FD：19.98±91.56倍变化 vs. HC：2.63±3.30倍变化，P=0.00774）。相比之下，FD组和健康组之间miR-155-5p和miR-203a的总体水平无显著差异。然而，在FD患者中，PDS患者表现出独特的特征：相对于EPS患者，miR-21和miR-155明显更高，但miR-203更低。miRNA水平与症状模式相关：miR-21和miR-155水平与上腹部疼痛强度呈负相关（τ分别为-0.517和-0.317），但与餐后饱胀感和早饱呈正相关（τ高达0.523，P<0.01）。相反，miR-203与上腹部疼痛呈正相关（τ=0.317，P=0.023），与饱胀感呈负相关（τ=-0.523，P<0.01）。幽门螺杆菌感染史与胃液中miR-203水平显著降低相关（P~0.03）。
FD患者的胃液miRNA谱可能发生改变，尤其是miR-21上调，且PDS和EPS亚型之间存在明显差异。PDS亚型的特征是miR-21和miR-155高表达，miR-203低表达，而EPS则呈现相反模式。这些miRNA改变与FD亚型的症状学一致，可能反映了潜在的病理生理差异。胃液miRNA可作为FD的微创生物标志物，有助于区分功能亚组，并可能指导靶向治疗。有必要进一步研究以证实这一发现，并确定其在FD诊断中的效用及其在FD发病机制中的作用。
