Serum FGL2 is correlated with the severity and psychological status of diarrhea-predominant irritable bowel syndrome

Background Fibrinogen-like protein 2 (FGL2) is involved in immune-mediated inflammatory responses. However, its role in diarrhea-predominant irritable bowel syndrome (IBS-D) remains to be elucidated. This study investigated serum FGL2 levels in patients with IBS-D and examined their association with inflammatory cytokines, disease severity, and psychological status. Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, were excluded to avoid diagnostic overlaps. IBS-D diagnosis was based on the Rome III criteria. Methods A total of 117 patients with IBS-D and 110 matched healthy controls were enrolled. Serum FGL2 and inflammatory cytokine levels (TNF-α, IL-1β, IL-6, and IL-17A) were quantified using ELISA. Symptom severity (IBS-SSS), depressive symptoms (PHQ-9), anxiety/depression (HADS), and disease-specific quality of life (IBS-QOL) were assessed. In parallel, publicly available intestinal transcriptome datasets (GEO) were reanalyzed. Statistical analyses included Student’s t- test and Pearson’s correlation. Results Compared with healthy controls, patients with IBS-D exhibited significantly elevated serum FGL2, WBC, neutrophil, and pro-inflammatory cytokine levels (all P 0.05). Serum FGL2 levels were markedly higher in patients with IBS-D and demonstrated a strong discriminative ability (AUC = 0.935; cutoff = 105.5 ng/mL, sensitivity 82.9%, specificity 91.8%). FGL2 levels were positively correlated with TNF-α ( r = 0.287), IL-1β ( r = 0.338), IL-6 ( r = 0.251), and IL-17A ( r = 0.213). Higher FGL2 concentrations were also associated with increased symptom severity (IBS-SSS, r = 0.241), greater depressive symptoms (PHQ-9, r = 0.279), higher HADS scores ( r = 0.222), and poorer quality of life (IBS-QOL, r = 0.198) (all P 0.05). Transcriptomic reanalysis revealed dysregulation of FGL2 expression in IBS intestinal tissues, suggesting altered local immune regulation and a potential shift in the FGL2 isoform balance. Conclusion This study provides the first evidence that serum FGL2 levels are elevated in IBS-D and are associated with inflammation, symptom severity, and psychological distress. While the correlations with immune and psychosocial measures are consistent with previous IBS research, the detection of FGL2 and the proposed isoform imbalance hypothesis represent novel findings. These results are exploratory, and causality cannot be inferred. Further validation and mechanistic studies are required.