These authors contributed equally to this work.
Intestinal aganglionosis is associated with early and sustained disruption of the colonic microbiome
Article first published online: 24 MAY 2012
© 2012 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 24, Issue 9, pages 874–e400, September 2012
How to Cite
Ward, N. L., Pieretti, A., Dowd, S. E., Cox, S. B. and Goldstein, A. M. (2012), Intestinal aganglionosis is associated with early and sustained disruption of the colonic microbiome. Neurogastroenterology & Motility, 24: 874–e400. doi: 10.1111/j.1365-2982.2012.01937.x
- Issue published online: 22 AUG 2012
- Article first published online: 24 MAY 2012
- Received: 20 December 2011 Accepted for publication: 23 April 2012
- enteric nervous system;
- Hirschsprung’s disease;
Background Congenital aganglionosis (Hirschsprung’s disease) results in colonic dysmotility and a risk for Hirschsprung’s-associated enterocolitis (HAEC), whose cause is unknown. We hypothesized that aganglionosis leads to microbiome changes that may contribute to HAEC risk.
Methods Colon and fecal samples were collected from endothelin receptor B-null (Ednrb−/−) mice, an established model of colorectal aganglionosis, at postnatal day 7 (P7), P20, and P24. We determined microbiome composition by 16S ribosomal RNA gene pyrosequencing and fecal metabolite profile by nuclear magnetic resonance spectroscopy.
Key Results Wild-type (WT) mice exhibited increasing species diversity with age, with mutant mice possessing even greater diversity. WT and mutant microbiomes, both fecal and colonic, significantly segregated by principal coordinates analysis based on species composition at all ages examined. Importantly, mutant mice contained more Bacteroidetes and less Firmicutes than WT, with additional genus- and species-level differences observed. Notably, mutant P7 colon was dominated by coagulase-negative Staphylococcus species, which were rare in WT. Mutant fecal metabolite profiles also differed, particularly in the abundance of formate, a short-chain fatty acid product of microbial fermentation.
Conclusions & Inferences Colorectal aganglionosis is associated with early and sustained disruption of the normal colonic and fecal microbiome, supporting the enteric nervous system as a determinant of microbiome composition. Furthermore, the differences observed suggest a potential contributory role for the microbiome in the etiology of HAEC. These findings provide a basis for further studies to determine the causative role of specific bacterial communities in HAEC and the potential to restore the normal microbiome in Hirschsprung’s disease.