Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung's disease (HSCR) patients

Hirschsprung's disease (HSCR) is a birth defect with an approximate incidence of 1/5,000 live births, and up to one third of HSCR patients develop Hirschsprung-associated enterocolitis (HAEC), the leading cause of HSCR-related death. Very little is known about the pathogenesis, prevention, and early diagnosis of HAEC. Here, we used a prospective study to investigate the enteric microbiome composition at the time of surgery as a predictor for developing postoperative HAEC. We identified a microbiome signature containing 21 operational taxonomic units (OTUs) that can potentially predict postoperative HAEC with ~85% accuracy. Furthermore, we identified exclusive breastfeeding as a novel protective factor for total HAEC (i.e., preoperative and postoperative HAEC combined). Mechanistically, we discovered that breast feeding lowered risk for HAEC by modulating the gut microbiome composition characterized by lower abundance of Gram-negative bacteria and lower LPS concentrations. In conclusion, modulating the gut microbiome by encouraging breast feeding or pro-biotic food might prevent HAEC progression in HSCR patients.