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

Abstract

Background 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). Methods 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. ResultsThe 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. Conclusions Our study, addressing microbiome dynamics, demonstrated relevant changes after surgical manipulation. Alphadiversity 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.

Decreased Incidence of Hirschsprung-Associated Enterocolitis During COVID-19 Across United States Children's Hospitals

“…Our data provide clinical support to the theory that abnormal immune cell function, present in ganglionic and aganglionic portions of the intestinal mucosa in patients with HSCR, may play key roles in the pathophysiology of HAEC. [ 3 , [10] , [11] , [12] , [13] , 25 , 26 ] Infectious exposures may also influence intestinal motility, mucosal integrity, and microbiota, which have been investigated as contributing mechanisms in the development of HAEC as well. [ [10] , [11] , [12] , [13] ].…”

“…[ 3 , [10] , [11] , [12] , [13] , 25 , 26 ] Infectious exposures may also influence intestinal motility, mucosal integrity, and microbiota, which have been investigated as contributing mechanisms in the development of HAEC as well. [ [10] , [11] , [12] , [13] ].…”

“…[ 3 , [9] , [10] , [11] , [12] ] These chronic abnormalities of the gastrointestinal tract can persist in the ganglionic intestinal segments that remain after corrective “pull-through” operations, and they predispose patients to fecal stasis, bacterial overgrowth, and subsequent intestinal wall inflammation, distention, and ischemia. [ [9] , [10] , [11] , [12] , [13] ].…”

A unicentric cross-sectional observational study on chronic intestinal inflammation in total colonic aganglionosis: beware of an underestimated condition

“…The microbiota peculiarities observed in TCSA patients have been already reported by our group that demonstrated a composition resembling that of healthy subjects carrying an ileostomy due to different congenital or acquired issues [ 10 ]. Of note, it is known that Proteobacteria have a pro-inflammatory effect and that, conversely, Bacteroidetes may have a protective effect over inflammation [ 15 ]. As suggested by our group [ 15 ], the intestinal dysbiosis could also trigger a RET-dependent abnormal local immune response.…”

“…Of note, it is known that Proteobacteria have a pro-inflammatory effect and that, conversely, Bacteroidetes may have a protective effect over inflammation [ 15 ]. As suggested by our group [ 15 ], the intestinal dysbiosis could also trigger a RET-dependent abnormal local immune response. In fact, we previously demonstrated an increased RET expression in circulating immune cells (PBMCs) of HSCR patients compared to healthy subjects [ 47 ].…”