The role of nutritional risk in inflammatory bowel disease: a serial mediation model through fecal calprotectin and depression leading to impaired quality of life.

BACKGROUND: Patients with inflammatory bowel disease (IBD) frequently face high nutritional risk, persistent intestinal inflammation, and a high prevalence of comorbid depression. Dysregulation of the gut-brain axis is hypothesized to mediate the association between nutritional status and quality of life (QOL). However, the serial mediating roles of fecal calprotectin (FC) and depression in this pathway remain unclear. This study aimed to examine this serial mediation and provide evidence for developing integrated care models centered on nutritional management to modulate inflammation, manage psychological complications, and improve patient outcomes. METHODS: This cross-sectional study enrolled 327 IBD patients from four tertiary hospitals in Southwest China. Nutritional risk, depressive symptoms, and QOL were assessed using the Nutritional Risk Screening 2002 (NRS2002), the Patient Health Questionnaire-9 (PHQ-9), and the Inflammatory Bowel Disease Questionnaire (IBDQ), respectively. FC levels were measured using an enzyme-linked immunosorbent assay (ELISA). The serial mediating effects were examined using Model 6 of the SPSS PROCESS macro with 5,000 bootstrap resamples. RESULTS: Nutritional risk was positively correlated with FC (β = 1.866, p < 0.05), which in turn was positively associated with depression (β = 0.021, p < 0.05). Depression was negatively associated with QOL (β = -1.417, p < 0.001). The total indirect effect accounted for 43.86% of the total association and consisted of contributions from three pathways. Of these three pathways, the independent mediating effect of depression alone contributed 8.55%, and the serial mediating effect of FC and depression accounted for 6.36%; both were statistically significant. The remaining portion of the total indirect effect was attributable to the non-significant pathway via FC alone. CONCLUSION: Nutritional risk is associated with impaired QOL in IBD patients both directly and indirectly through a sequential pathway involving intestinal inflammation (FC) and depression. These findings suggest a shift in clinical practice toward an integrated care model anchored in proactive nutritional management, coupled with concurrent monitoring of inflammation and screening for depression. This model presents a targeted strategy for modulating inflammation, managing comorbidities, and ultimately improving symptoms and QOL in IBD.