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

Abstract

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.

Evidence for Differentiation of Colon Tissue Microbiota in Patients with and without Postoperative Hirschsprung's Associated Enterocolitis: A Pilot Study

“…Another possible explanation for the observed differences in bacterial taxa in our study compared to others is that we specifically analyzed tissue samples from the surgically resected aganglionic bowel and we identified particular bacterial profiles as possible predictors for postoperative HAEC. In contrast, other studies analyzed fecal samples from the remaining ganglionic bowel of variable lengths at different time points after definitive corrective surgery that could lead to intestinal dysmotility and fecal matter stasis, all variables that have been shown to alter the diversity of the intestinal microbiota [ 17 ]. In addition, the discrepancies between the microbiota profiles from our study and even across other studies could be explained by the heterogenicity of the patient population, ethnicity, geographic location, disease state, antibiotic exposure and age at the time of definitive corrective surgery.…”

Predictive factors for the development of postoperative Hirschsprung-associated enterocolitis in children operated during infancy

“…The etiology of HAEC is known to be dysbiosis of the gut microbiota, mucosal barrier dysfunction, change in the gut immune system, and bacterial translocation [19]. A recent study showed that total colonic resections in HD patients, compared with sigmoid resection, changed the composition of intestinal microbiota and reduced microbial diversity [20]. It is, thus, speculated that the longer aganglionic segment impairs the gut micro-environment and induces enteric inflammation of more vulnerable intestinal regions than the shorter aganglionic segment does, even after radical surgery.…”

Hirschsprung’s disease presenting as intractable anemia: a report of two cases and review of the literature

“…Moreover, anemia in patients with HD may be associated with altered intestinal microenvironments. A recent study revealed that it lacks a part of probiotics in the intestines of children with HD, the intestinal microecology balance is broken, and the biological barrier provided by the intestinal mucosa is damaged [ 9 ]. The microbes in the colon not only affect the solubility and forms of trace minerals considerably [ 9 ] but also regulate the expression of iron transporter genes.…”

“…A recent study revealed that it lacks a part of probiotics in the intestines of children with HD, the intestinal microecology balance is broken, and the biological barrier provided by the intestinal mucosa is damaged [ 9 ]. The microbes in the colon not only affect the solubility and forms of trace minerals considerably [ 9 ] but also regulate the expression of iron transporter genes. Therefore, the composition and quantity of the intestinal microbiota affect iron absorption [ 10 ].…”