Pathways and microbiome modifications related to surgery and enterocolitis in Hirschsprung disease.

Hirschsprung disease (HSCR) is a congenital anomaly of the enteric nervous system. Abnormal microbiome composition was reported in HSCR patients. In this study, we addressed and analyzed microbiome modifications with relation tosurgery and HSCR associated enterocolitis (HAEC). The faecal microbiome of 31 HSCR patients (overall 64 samples) was analyzed. HAEC was diagnosed and classified according to a combination of Pastor's and Elhalabi's criteria. Stool samples were analyzed by 16S sequencing (7 out of 9 polymorphic regions). Compositional and relative abundance profiles, as well as the functional potentials of the microbial community, were analyzed with the marker gene sequencing profiles using PICRUSt. The relative abundance of Bacteroidetes showed a severe decrease with slow recovery after surgery. Conversely, Proteobacteria transiently increased their abundance. Noteworthy, a strong linkage has been found between Proteobacteria descendants and HAEC occurrences. The inferred functional analysis indicated that virulence factors and fimbriae or pili might be associated with HAEC. Our study, addressing microbiome dynamics, demonstrated relevant changes after surgical manipulation. Alpha-diversity analyses indicated that surgery deeply affects microbiome composition. Proteobacteria and Enterobacteriaceae seem to play a pivotal role in HAEC occurrences. Several virulence factors, such as fimbriae or pili, might explain the HAEC-predisposing potential of selected microbiomes. These results suggest some innovative therapeutic approaches that deserve to be tested in appropriate clinical trials.

Biassoni R ，Di Marco E ，Squillario M ，Ugolotti E ，Mosconi M ，Faticato MG ，Mattioli G ，Avanzini S ，Pini Prato A ... -  《-》

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

Frykman PK ，Nordenskjöld A ，Kawaguchi A ，Hui TT ，Granström AL ，Cheng Z ，Tang J ，Underhill DM ，Iliev I ，Funari VA ，Wester T ，HAEC Collaborative Research Group (HCRG) ... -  《PLoS One》

Prospective study reveals a microbiome signature that predicts the occurrence of post-operative enterocolitis in Hirschsprung disease (HSCR) patients.

Tang W ，Su Y ，Yuan C ，Zhang Y ，Zhou L ，Peng L ，Wang P ，Chen G ，Li Y ，Li H ，Zhi Z ，Chang H ，Hang B ，Mao JH ，Snijders AM ，Xia Y ... -  《-》

Bacterial Microbiome Dynamics in Post Pull-Through Hirschsprung-Associated Enterocolitis (HAEC): An Experimental Study Employing the Endothelin Receptor B-Null Mouse Model.

Cheng Z ，Zhao L ，Dhall D ，Ruegger PM ，Borneman J ，Frykman PK ... -  《Frontiers in Surgery》

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

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. 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. 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. 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.

Demehri FR ，Frykman PK ，Cheng Z ，Ruan C ，Wester T ，Nordenskjöld A ，Kawaguchi A ，Hui TT ，Granström AL ，Funari V ，Teitelbaum DH ，HAEC Collaborative Research Group ... -  《-》