Microbial control of mucosal wound immunity in colorectal anastomotic healing: from barrier repair to matrix failure
- 1Department of General Surgery, Binhai County People’s Hospital
Abstract
Colorectal anastomotic leakage is commonly framed as a technical complication or a consequence of intestinal dysbiosis. Neither view fully explains how a contaminated mucosal wound restores epithelial continuity while preserving a load-bearing submucosal matrix. We define anastomotic healing as a spatially organized mucosal immune process: luminal microbes and metabolites, the epithelial wound edge, recruited immune cells, fibroblasts, collagen, and vascular support occupy distinct but interacting compartments. The most compelling available anastomosis-specific evidence supports a destructive pathway in which expressed microbial virulence, host plasminogen activation, epithelial inflammatory signaling, sustained neutrophil recruitment, and MMP9 converge on collagen loss. A complementary repair pathway is supported by human-to-mouse microbiota-transfer and metabolite-rescue experiments, but this evidence is less direct and more heterogeneous. It links commensal function and AhR-dependent IL-22 signaling to epithelial restitution, myeloid resolution, and matrix repair. NLRP3, NLRP6, and NLRC4 remain candidate threshold regulators rather than demonstrated mediators of colorectal anastomotic healing. Human macrophage atlases refine cell-state definitions, but prospective evidence linking anastomotic macrophage states or efferocytosis to leakage remains limited. We propose an evidence-weighted framework that separates human association, direct microbial-function measurements, experimental causation, and human intervention evidence. Translation will require paired spatial sampling and functional microbial assays, together with immune, matrix, mechanical, target-engagement, and ecological-safety endpoints. This framework extends beyond taxonomic dysbiosis toward testable wound-immune endotypes and mechanism-matched prevention.
Related
- A novel cystic fibrosis-mimetic Pseudomonas auxotrophic vaccine is protective in vivo and is associated with IL-17/IgA mucosal Immunity
- Integrative transcriptomic analysis reveals tumor-adjacent mucosal remodeling in colorectal cancer.
- Gut microbiota, microbial metabolites, and mucosal barrier dysfunction in benign anorectal disorders and ulcerative colitis: shared mechanisms, clinical links, and precision interventions
- Gut microbiome features associated with PIK3CA-mutated colorectal cancer: A nationwide pan-cancer genomic and microbial profiling study (MONSTAR-SCREEN)
- The Gut Microbiota-Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation.
BibTeX
@article{xu2026microbial,
title = {{Microbial control of mucosal wound immunity in colorectal anastomotic healing: from barrier repair to matrix failure}},
author = {Zhixuan Xu and Weipeng Chen and Feng Lu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1928237},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928237/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microbial control of mucosal wound immunity in colorectal anastomotic healing: from barrier repair to matrix failure
AU - Zhixuan Xu
AU - Weipeng Chen
AU - Feng Lu
PY - 2026
DA - 2026/10/21
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1928237
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928237/full
AB - Colorectal anastomotic leakage is commonly framed as a technical complication or a consequence of intestinal dysbiosis. Neither view fully explains how a contaminated mucosal wound restores epithelial continuity while preserving a load-bearing submucosal matrix. We define anastomotic healing as a spatially organized mucosal immune process: luminal microbes and metabolites, the epithelial wound edge, recruited immune cells, fibroblasts, collagen, and vascular support occupy distinct but interacting compartments. The most compelling available anastomosis-specific evidence supports a destructive pathway in which expressed microbial virulence, host plasminogen activation, epithelial inflammatory signaling, sustained neutrophil recruitment, and MMP9 converge on collagen loss. A complementary repair pathway is supported by human-to-mouse microbiota-transfer and metabolite-rescue experiments, but this evidence is less direct and more heterogeneous. It links commensal function and AhR-dependent IL-22 signaling to epithelial restitution, myeloid resolution, and matrix repair. NLRP3, NLRP6, and NLRC4 remain candidate threshold regulators rather than demonstrated mediators of colorectal anastomotic healing. Human macrophage atlases refine cell-state definitions, but prospective evidence linking anastomotic macrophage states or efferocytosis to leakage remains limited. We propose an evidence-weighted framework that separates human association, direct microbial-function measurements, experimental causation, and human intervention evidence. Translation will require paired spatial sampling and functional microbial assays, together with immune, matrix, mechanical, target-engagement, and ecological-safety endpoints. This framework extends beyond taxonomic dysbiosis toward testable wound-immune endotypes and mechanism-matched prevention.
SN - 1664-3224
ER -