REVIEW article
Front. Pediatr.
Sec. Children and Health
Volume 13 - 2025 | doi: 10.3389/fped.2025.1579290
Deciphering the Complexity of Enteric Niches in Hirschsprung Disease: From Metaphorical Insights to Therapeutic Transformation
Provisionally accepted
- 1Xi'an Jiaotong University, Xi'an, China
- 2Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China
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Research Overview of Hirschsprung Disease (HSCR) HSCR is a congenital disorder characterized by the absence of ganglion cells in the distal bowel, with pathogenesis closely linked to complex dysregulation of the intestinal microenvironment. Key abnormalities identified in the HSCR microenvironment include: Microbiota Dysbiosis and Metabolic Imbalance: Altered levels of microbial metabolites such as short-chain fatty acids (SCFAs) may impair neural development and intestinal function.Activated Immune-Inflammatory Response: Excessive activation of macrophages and other inflammatory cells exacerbates local tissue damage.Abnormal Extracellular Matrix (ECM) Deposition: Proliferation of myofibroblasts leads to excessive ECM accumulation, potentially hindering enteric neural crest cell migration or survival. Dysregulated Neurodevelopmental Genes: Disrupted expression of critical genes (e.g., GDNF) may interfere with neuronal fate determination, contributing to defective enteric nervous system (ENS) development.Current research highlights the need to move beyond conventional surgical interventions by targeting microenvironmental components (e.g., modulating microbiota, suppressing fibrosis, or repairing ECM) in combination with cell transplantation strategies for curative approaches. Future studies should integrate multi-omics data to decipher interactions among immune cells, stromal cells, and microbiota, advancing precision medicine for HSCR.
Keywords: Hirschsprung Disease, enteric niches, Enteric Nervous System, Neurogenesis HSCR, Microbial metabolism, Immune Modulation, disease pathogenesis "enteric niches" AND ("gut microbiome" OR "host-pathogen interactions")
Received: 19 Feb 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Yu, Pan, Tian and Gao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hui Yu, Xi'an Jiaotong University, Xi'an, China
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