A Developmental Perspective on the Intestinal Microbiota in Crohn's Disease

Crohn's disease (CD) is a chronic inflammatory disorder arising from the convergence of genetic susceptibility, immune dysregulation, environmental exposures, and perturbations of the gut microbiome. This review advances a developmental and compartment-aware framework for interpreting dysbiosis in CD, integrating spatial heterogeneity, transmural pathology, and mesenteric interactions. By synthesizing evidence on microbial composition, functional metabolism, and host-immune crosstalk, we describe a dysbiotic profile shaped by disease location, inflammatory activity, and therapeutic exposure, while also considering the emerging roles of non-bacterial members. We propose that microbiome alterations in CD reflect inflammation-driven ecosystem instability rather than a static taxonomic imbalance. Moving beyond descriptive compositional profiling toward a dynamic ecological model that incorporates disease trajectory and anatomical compartmentalization is essential to refine disease stratification and guide future microbiome-informed precision therapies.