Preoperative gut microbial and metabolic signatures associated with postoperative Hirschsprung-associated enterocolitis in short-segment Hirschsprung disease

Introduction Hirschsprung-associated enterocolitis (HAEC) is a major postoperative complication of Hirschsprung disease (HSCR), but whether preoperative gut microbial and metabolic alterations are associated with its subsequent development remains unclear. This prospective cohort study investigated whether preoperative gut microbial and metabolic profiles are associated with postoperative HAEC in children with short-segment Hirschsprung disease (S-HSCR). Methods Sixty-two children with S-HSCR were enrolled, and preoperative fecal samples were collected before pull-through surgery for 16S rRNA gene sequencing, targeted short-chain fatty acid (SCFA) analysis, and untargeted metabolomic profiling. Patients were followed for 3 years after surgery and classified according to the occurrence of postoperative HAEC. Results During follow-up, 27 patients developed postoperative HAEC. Compared with patients who remained HAEC-free, those who subsequently developed HAEC showed reduced microbial diversity, a lower Gut Microbiome Health Index, a higher Microbiome Dysbiosis Index, and distinct microbial community composition before surgery. Differential abundance analyses identified depletion of several anaerobic commensals and potential SCFA-producing taxa, together with enrichment of potentially pro-inflammatory taxa such as Escherichia-Shigella . Co-occurrence network analysis revealed reduced microbial interaction complexity and connectivity in the HAEC cohort. An exploratory random forest model based on preoperative microbial signatures achieved an area under the curve of 0.80 for predicting postoperative HAEC. Children who later developed HAEC also had significantly lower fecal levels of butyric acid, valeric acid, and total SCFAs. Exploratory untargeted metabolomic analysis yielded preliminary signals across several metabolic pathways, including lysine-related metabolism. Discussion Children with S-HSCR who subsequently develop postoperative HAEC already exhibit distinct preoperative microbial dysbiosis and metabolic alterations. These findings suggest that early-life disruption of the gut microbiota and host-microbe metabolic balance may contribute to HAEC susceptibility.