Farokh R Demehri1, Philip K Frykman2, Zhi Cheng2, Chunhai Ruan3, Tomas Wester4, Agneta Nordenskjöld4, Akemi Kawaguchi5, Thomas T Hui6, Anna L Granström4, Vince Funari7, Daniel H Teitelbaum8. 1. Division of Pediatric Surgery, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA. 2. Division of Pediatric Surgery and Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 3. Michigan Comprehensive Metabolomics Research Core, University of Michigan, Ann Arbor, MI, USA. 4. 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. 5. Division of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA. 6. Division of Pediatric Surgery, Children's Hospital Oakland, Oakland, CA, USA. 7. Genomics Core Laboratory, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 8. Division of Pediatric Surgery, C. S. Mott Children's Hospital, University of Michigan, Ann Arbor, MI, USA. Electronic address: dttlbm@umich.edu.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: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 HDchildren, 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 HAECchildren showed a 4-fold decline in total SCFA concentration vs. non-HAECHDpatients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAECchildren. 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. CONCLUSION: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.
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