title: Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.
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.
authors.affiliation: Division 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.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Frykman
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
authors.affiliation: Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States of America.
authors.forename: Akemi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Division of Pediatric Surgery, Children's Hospital Oakland, Oakland, California, United States of America.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Hui
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Granström
authors.affiliation: Division of Pediatric Surgery, Departments of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Genomics Core Laboratory, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
authors.affiliation: Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Iliyan
authors.initials: I
authors.lastname: Iliev
authors.affiliation: Genomics Core Laboratory, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Vince A
authors.initials: VA
authors.lastname: Funari
authors.affiliation: Department of Pediatric Surgery, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Wester
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification*; D041963:Bacteroidetes / Q000235:genetics / Q000302:isolation & purification; D002175:Candida / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D002648:Child; D002675:Child, Preschool; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004271:DNA, Fungal / Q000235:genetics / Q000302:isolation & purification; D004198:Disease Susceptibility; D004760:Enterocolitis / Q000150:complications* / Q000209:etiology / Q000382:microbiology*; D005260:Female; D000068536:Bacillota / Q000235:genetics / Q000302:isolation & purification; D005658:Fungi / Q000235:genetics / Q000302:isolation & purification*; D000069196:Gastrointestinal Microbiome / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006627:Hirschsprung Disease / Q000150:complications* / Q000382:microbiology*; D006801:Humans; D007223:Infant; D008297:Male; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D004271:DNA, Fungal