title: Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis.
abstract: OBJECTIVE
  Children with Hirschsprung disease (HD) who have a history of enterocolitis (HAEC) have a shift in colonic microbiota, many of which are necessary for short chain fatty acid (SCFA) production. As SCFAs play a critical role in colonic mucosal preservation, we hypothesized that fecal SCFA composition is altered in children with HAEC.
  
  
  METHODS
  A multicenter study enrolled 18 HD children, abstracting for history of feeding, antibiotic/probiotic use, and enterocolitis symptoms. HAEC status was determined per Pastor et al. criteria (12). Fresh feces were collected for microbial community analysis via 16S sequencing as well as SCFA analysis by gas chromatography-mass spectrometry.
  
  
  RESULTS
  Nine patients had a history of HAEC, and nine had never had HAEC. Fecal samples from HAEC children showed a 4-fold decline in total SCFA concentration vs. non-HAEC HD patients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAEC children. Finally, we measured relative abundance of SCFA-producing fecal microbiota. Interestingly, 10 of 12 butyrate-producing genera as well as 3 of 4 acetate-producing genera demonstrated multi-fold expansion.
  
  
  CONCLUSIONS
  Children with HAEC history have reduced fecal SCFAs and altered SCFA profile. These findings suggest a complex interplay between the colonic metabolome and changes in microbiota, which may influence the pathogenesis of HAEC.
authors.affiliation: Division of Pediatric Surgery, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Farokh R
authors.initials: FR
authors.lastname: Demehri
authors.affiliation: Division of Pediatric Surgery and Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Philip K
authors.initials: PK
authors.lastname: Frykman
authors.affiliation: Division of Pediatric Surgery and Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Michigan Comprehensive Metabolomics Research Core, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Ruan
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 of Molecular Medicine-CMM, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Wester
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 of Molecular Medicine-CMM, Karolinska Institute, Stockholm, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
authors.affiliation: Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: Akemi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Division of Pediatric Surgery, Children's Hospital Oakland, Oakland, CA, USA.
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 of Molecular Medicine-CMM, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Granström
authors.affiliation: Genomics Core Laboratory, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Vince
authors.initials: V
authors.lastname: Funari
authors.affiliation: Division of Pediatric Surgery, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA. Electronic address: dttlbm@umich.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004760:Enterocolitis / Q000209:etiology / Q000378:metabolism* / Q000382:microbiology; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005243:Feces / Q000737:chemistry*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006627:Hirschsprung Disease / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000601:surgery; D006801:Humans; D007223:Infant; D008297:Male
chemical_list: D015415:Biomarkers; D005232:Fatty Acids, Volatile
keywords: Aganglionosis; Hirschsprung disease; Hirschsprung-associated enterocolitis; Microbiome; Pediatric; Short chain fatty acids