A Metagenomics Study on Hirschsprung's Disease Associated Enterocolitis: Biodiversity and Gut Microbial Homeostasis Depend on Resection Length and Patient's Clinical History

Frontiers in Pediatrics

article

Alessio Pini Prato¹  Girolamo Mattioli³  Denise Larson⁴  William Pavan⁴  Carlotta De Filippo⁵  Monica Di Paola⁶  Domenico Mavilio⁷  Duccio Cavalieri⁶  Casey Bartow-McKenney⁹  Kelly Hudspeth⁷  Manuela Mosconi²  Valentina Rossi²  Stefano Avanzini²  Maria G. Faticato²  Isabella Ceccherini²  Francesca Lantieri^1,10 

[1] Division of Pediatric Surgery;Division of Pediatric Surgery, Giannina Gaslini Institute;Department of Neuroscience, Genetics and Maternal and Child Science (DINOGMI), University of Genoa;Development and Disease Section, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), United States;Institute of Agriculture Biology and Biotechnology, National Research Council;Department, University of Florence;Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center;Department of Medical Biotechnologies and Translational Medicine (BioMeTra), University of Milan;Department of Dermatology and Microbiology, University of Pennsylvania, United States;Biostatistics Section, Department of Health Science, University of Genoa

关键词: metagenomics;    enterocolitis;    Hirschsprung;    RET gene;    aganglionosis;   

DOI  :  10.3389/fped.2019.00326

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status. Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity. Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences. Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history.

【 授权许可】

CC BY