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Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had completed definitive surgery were enrolled: 9 had a history of HAEC and 9 did not. Fecal DNA was isolated and 16S and ITS-1 regions sequenced using Next Generation Sequencing and data analysis for species identification. The HAEC group bacterial composition showed a modest reduction in  Firmicutes  and  Verrucomicrobia  with increased  Bacteroidetes  and  Proteobacteria  compared with the HSCR group. In contrast, the fecal fungi composition of the HAEC group showed marked reduction in diversity with increased  Candida sp ., and reduced  Malassezia and Saccharomyces sp . compared with the HSCR group. The most striking finding within the HAEC group is that the  Candida  genus segregated into “high burden” patients with 97.8%  C .  albicans  and 2.2%  C .  tropicalis  compared with “low burden” patients 26.8%  C .  albicans  and 73%  C .  tropicalis . Interestingly even the low burden HAEC group had altered  Candida  community structure with just two species compared to more diverse  Candida  populations in the HSCR patients. This is the first study to identify  Candida sp . as potentially playing a role in HAEC either as expanded commensal species as a consequence of enterocolitis (or treatment), or possibly as pathobioants contributing to the pathogenesis of HAEC. These findings suggest a dysbiosis in the gut microbial ecosystem of HAEC patients, such that there may be dominance of fungi and bacteria predisposing patients to development of HAEC.

plos one

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study