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Irritable bowel syndrome (IBS) is a functional gastrointestinal disease commonly associated with psychological comorbidities. Ghrelin, a gut-derived peptide hormone participated in gut-brain axis regulation, may play a role in both gastrointestinal and emotional symptoms. This study aimed to investigate the association between ghrelin levels in serum and depression severity in a Northwestern Iranian patients with IBS. In this case–control study, 140 IBS patients (diagnosed based on Rome III criteria) and 115 age- and sex-matched healthy controls were enrolled. Depression severity was assessed using the Beck Depression Inventory-II (BDI-II). Also, serum ghrelin concentrations were measured via an enzyme-linked immune-sorbent assay (ELISA). Statistical analyses included independent t-test, ANOVA, linear regression, and Pearson’s correlation analysis. Our results showed that IBS patients had significantly lower ghrelin levels compared to healthy controls ( P = 0.001). IBS patients with minimal, mild, moderate, or severe depressive symptoms (≥ 29) exhibited lower ghrelin levels than controls with mild depression (All, P = 0.00). Serum ghrelin levels were inversely correlated with IBS severity ( r = − 0.18, P = 0.001). Also, serum ghrelin remained a significant predictor of BDI-II score (standardized β = −0.442, P < 0.001). In multivariable analysis, serum ghrelin remained independently associated with depression severity after adjustment for age, sex, and BMI ( P < 0.001). Decreased ghrelin levels in IBS patients are linked to higher depression severity and this issue is the major driver of disease severity. These findings suggest a potential role of the gut–brain axis in the IBS and psychological symptoms interactions. However, further research is needed to clarify the underlying mechanisms since causal relationships cannot be inferred based on the cross-sectional study.
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Dadkhah et al. (2026) studied this question.
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