Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis

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.

Keywords: Aganglionosis; Hirschsprung disease; Hirschsprung-associated enterocolitis; Microbiome; Pediatric; Short chain fatty acids.

Conflict of interest statement

Conflicts of Interest: The authors declare no conflicts of interest.

Copyright © 2016. Published by Elsevier Inc.

Figures

Fig. 1

(A) Fecal SCFA concentration was significantly reduced in HAEC children versus those with HD without HAEC. (B) Individual SCFAs expressed as % of total SCFAs from HD children with a history of HAEC and those with no history of HAEC. (C) Histograms demonstrating the fecal SCFA composition of individual subjects with HD and HAEC (D). Individual subject numbers are labeled on the X axis and expressed as relative SCFA abundance per each subject. *p

Fig. 2

Genus-level identification of fecal microbiota via 16s rRNA sequencing. Percent change in mean OTUs of (A) butyrogenic bacteria and (B) acetogenic bacteria in fecal samples from children with a history of HAEC versus HD children without HAEC.