Using temporal multi-omics, biomechanical profiling, and spatial fate mapping in colitis mouse models, this study examined whether colonic extracellular matrix (ECM) fully reverts after gut inflammation resolves, and how persistent ECM changes affect intestinal stem cell (ISC) fate and chronic inflammation — with validation in inflamed rectal biopsies from people with ulcerative colitis (UC).
Post-inflammatory colonic ECM did not revert to homeostasis; instead, it underwent lasting pathological reprogramming ('modECM'), marked by collagen XVIII (COL18A1) accumulation and immune-driven proteolysis. modECM alone suppressed Wnt signaling and redirected Lgr5+ ISCs toward a KRT14+ wound-associated epithelial state with a pro-inflammatory transcriptional program. modECM-rich zones sustained T cell infiltration in vivo, and this aberrant epithelial program was confirmed in inflamed UC rectal biopsies.
The study relies primarily on mouse colitis models (DSS and IL-10 knockout); direct causal human data are limited to correlative biopsy findings. The sample size of human UC biopsies is not specified in the abstract. Long-term functional consequences of modECM targeting in vivo were not tested therapeutically.
Post-inflammatory 'ECM memory' may sustain chronic epithelial inflammation and T cell recruitment in UC even after overt injury resolves — clinicians should consider that mucosal healing endpoints measuring epithelium alone may miss persistent pro-inflammatory ECM remodeling. Collagen XVIII-rich ECM niches represent a potential new therapeutic target in chronic IBD.
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