Abstract
Background: Hirschsprung disease is a congenital disorder of the enteric nervous system associated with persistent gastrointestinal morbidity, particularly Hirschsprung-associated enterocolitis (HAEC). Gut microbiota dysbiosis has been increasingly implicated in HAEC and postoperative intestinal dysfunction, but findings remain heterogeneous.
Objective: This systematic review synthesized human evidence on gut microbiota alterations in Hirschsprung disease, focusing on HAEC-associated dysbiosis, postoperative microbiota changes, and microbiota-related predictive or therapeutic findings.
Methods: A qualitative systematic review was conducted in accordance with PRISMA 2020 using ScienceDirect, Wiley, SpringerLink, Taylor & Francis, and PubMed, applying full Boolean syntax with MeSH terms in PubMed and year, language, and document-type filters, supplemented by Google Scholar and citation searching. Eligible studies reported gut, fecal, mucosal, or colonic microbiota outcomes in humans with Hirschsprung disease. Certainty of evidence was rated using the GRADE approach for syntheses without meta-analysis.
Results: Twelve studies were included. The core finding was context-dependent dysbiosis rather than a single reproducible biomarker. HAEC was most consistently associated with enrichment of Proteobacteria, Enterobacteriaceae, Escherichia-Shigella, and Enterococcus, and with depletion of Bifidobacterium and Lactobacillus. Postoperative microbial recovery was partial and incomplete. Certainty was low for HAEC-associated dysbiosis and very low for predictive and microbiota-targeted findings, mainly because of small sample sizes, heterogeneous HAEC definitions, and limited adjustment for confounders.
Conclusion: Microbiota alterations are biologically relevant to Hirschsprung disease and HAEC, but current evidence does not support routine microbiota-based prediction or therapy. Standardized, prospective longitudinal studies with harmonized HAEC definitions are needed.