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Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History
Philip K Frykman1, Agneta Nordenskjöld2, Akemi Kawaguchi3
1Division of Pediatric Surgery, Departments of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Insights
Children with Hirschsprung disease (HSCR) developing enterocolitis (HAEC) show altered gut microbial communities. Fungal dysbiosis, particularly increased Candida species, may play a role in HAEC pathogenesis.
Area of Science:
- Gastroenterology
- Microbiology
- Pediatric Surgery
Background:
- Hirschsprung-associated enterocolitis (HAEC) is a severe complication following HSCR surgery.
- The role of intestinal microbiota in HAEC development is not fully understood.
Purpose of the Study:
- To compare fecal bacterial and fungal communities in HSCR patients with and without a history of HAEC.
- To investigate potential microbial factors contributing to HAEC pathogenesis.
Main Methods:
- Next-generation sequencing of 16S (bacteria) and ITS-1 (fungi) regions from fecal DNA.
- Analysis of microbial composition in 18 post-operative HSCR patients (9 with HAEC history, 9 without).
Main Results:
- HAEC group exhibited altered bacterial composition (reduced Firmicutes/Verrucomicrobia, increased Bacteroidetes/Proteobacteria).
- Fungal communities in HAEC patients showed reduced diversity, with increased Candida sp. and decreased Malassezia/Saccharomyces sp.
- Candida species composition differed significantly between high and low burden HAEC patients, with altered diversity even in low burden cases.
Conclusions:
- Gut microbial dysbiosis, including fungal overgrowth (Candida), is associated with HAEC in HSCR patients.
- Findings suggest Candida species may contribute to HAEC pathogenesis or represent an altered commensal state.
- Further research is needed to elucidate the precise role of these microbial shifts in HAEC.
Abstract:
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.
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