Molecular Crosstalk of the Motilin–Somatostatin–VEGF Axis in Duodenal Dysfunction Underlying IBS-C and Functional Dyspepsia

The duodenal mucosa plays a pivotal role in gastrointestinal physiology through its endocrine cells (ECs), which secrete key regulatory factors including motilin (MLN), somatostatin (SS), and vascular endothelial growth factor (VEGF). Alterations in the expression of these mediators have been implicated in the pathogenesis of irritable bowel syndrome with constipation (IBS-C) and its overlap with functional dyspepsia (FD). In this study, immunohistochemical and morphometric analyses were performed on duodenal retrobulbar part biopsies obtained from patients with IBS-C, IBS-C combined with FD, and healthy controls. The results demonstrated a significant reduction in MLN-secreting ECs, accompanied by increased SS- and VEGF-positive ECs in IBS-C with FD patients compared to other groups. These endocrine alterations were associated with more severe abdominal pain, higher body mass index, and greater anxiety and depression scores. The findings highlight the contribution of duodenal EC dysfunction to impaired motility, visceral hypersensitivity, and low-grade inflammation, supporting the concept of the duodenum as a critical neuroendocrine hub within the gut–brain axis. This study underscores the relevance of MLN, SS, and VEGF as potential biomarkers and therapeutic targets in IBS-C and FD comorbidity.