Distinct enteric nervous system pattern in obstructed defecation syndrome and slow-transit constipation: a controlled digital pathology study

PURPOSE: Chronic constipation comprises heterogeneous clinical entities, including slow-transit constipation (STC) and functional defecation disorders such as obstructed defecation syndrome (ODS). Although neuroenteric mechanisms are implicated, reproducible histomorphological correlates remain incompletely defined, partly due to methodological heterogeneity and lack of standardized quantification. The study characterizes the myenteric plexus morphology and neuroimmune cell distribution across clinically defined subgroups of functional bowel disorders using a standardized digital pathology approach. METHODS: Retrospective observational cohort study at a tertiary colorectal referral center. A total of 100 patients after bowel surgery were included: ODS (n = 17), STC (n = 24), combined ODS + STC (n = 28), and a control cohort without clinically evident bowel motility disorders (n = 31). Digital morphometric assessment of ganglionic density and morphology, neuronal content (immunohistochemistry against MAP2, HuC/D), and the distribution of CD3-positive T-lymphocytes within and around myenteric ganglia were performed. RESULTS: Ganglionic density differed significantly between groups (p = 0.002), with increased density in ODS, whereas STC values were comparable to controls. Neuronal content per ganglion was preserved across all groups as demonstrated by MAP2 and HuC/D analyses. In contrast, the presence of CD3-positive lymphocytes was reduced in all constipation groups, most pronounced in STC, affecting both the intra- and periganglionic compartments. CONCLUSION: Functional bowel motility and defecation disorders appear to show distinct neuroarchitectural and neuroimmune patterns. Increased ganglionic density in ODS contrasts with preserved neuronal content and reduced presence of T-lymphocytes, particularly in STC. These findings represent associations rather than proven disease mechanisms, derived from comparison with a surgical rather than a healthy control cohort. Standardized digital morphometry nonetheless provides a reproducible framework for phenotypic characterization of chronic constipation and may support future studies linking enteric structure to function. TRIAL REGISTRATION: Clinicaltrials.gov (NCT05016700; 09/12/2020).