Gut microbiome: a key driver and therapeutic target of intestinal fibrosis in Crohn's disease.
TL;DR
It is suggested that targeting the microbiome-fibrosis axis, through precision modulation of the microbiome or metabolite-based interventions, represents a promising frontier for preventing and reversing fibrostenotic Crohn's disease.
Abstract
Intestinal fibrosis is a debilitating complication of Crohn's disease that often leads to stricture formation, requiring surgical intervention. Despite its clinical significance, effective anti-fibrotic therapies remain an unmet need. Emerging evidence highlights the gut microbiome as a central orchestrator of fibrogenesis, beyond its role in inflammation. This review provides a comprehensive overview of how microbial dysbiosis, which is marked by the expansion of pathobionts such as adherent-invasive Escherichia coli and Clostridium innocuum, drives intestinal fibrosis through multifaceted pathways. We delineate the direct activation of fibroblasts via pattern recognition receptors and indirect mechanisms involving macrophage polarization, T helper 17 cell responses, and the emerging role of the "creeping fat" axis. Furthermore, we discuss how microbial translocation into the mesenteric adipose tissue triggers a profibrotic environment. By synthesizing these mechanistic insights, we suggest that targeting the microbiome-fibrosis axis, through precision modulation of the microbiome or metabolite-based interventions, represents a promising frontier for preventing and reversing fibrostenotic Crohn's disease.