Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved..

BACKGROUND & AIMS: Hirschsprung's disease (HSCR) is a congenital intestinal motility disorder defined by the absence of enteric neuronal cells (ganglia) in the distal gut. The development of HSCR-associated enterocolitis remains a life-threatening complication. Absence of enteric ganglia implicates innervation of acetylcholine-secreting (cholinergic) nerve fibers. Cholinergic signals have been reported to control excessive inflammation, but the impact on HSCR-associated enterocolitis is unknown.

METHODS: We enrolled 44 HSCR patients in a prospective multicenter study and grouped them according to their degree of colonic mucosal acetylcholinesterase-positive innervation into low-fiber and high-fiber patient groups. The fiber phenotype was correlated with the tissue cytokine profile as well as immune cell frequencies using Luminex analysis and fluorescence-activated cell sorting analysis of colonic tissue and immune cells. Using confocal immunofluorescence microscopy, macrophages were identified in close proximity to nerve fibers and characterized by RNA-seq analysis. Microbial dysbiosis was analyzed in colonic tissue using 16S-rDNA gene sequencing. Finally, the fiber phenotype was correlated with postoperative enterocolitis manifestation.

RESULTS: The presence of mucosal nerve fiber innervation correlated with reduced T-helper 17 cytokines and cell frequencies. In high-fiber tissue, macrophages co-localized with nerve fibers and expressed significantly less interleukin 23 than macrophages from low-fiber tissue. HSCR patients lacking mucosal nerve fibers showed microbial dysbiosis and had a higher incidence of postoperative enterocolitis.

CONCLUSIONS: The mucosal fiber phenotype might serve as a prognostic marker for enterocolitis development in HSCR patients and may offer an approach to personalized patient care and new therapeutic options.

Errataetall:

CommentIn: Cell Mol Gastroenterol Hepatol. 2021;12(2):785-786. - PMID 34087230

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:12

Enthalten in:

Cellular and molecular gastroenterology and hepatology - 12(2021), 2 vom: 30., Seite 507-545

Sprache:

Englisch

Beteiligte Personen:

Keck, Simone [VerfasserIn]
Galati-Fournier, Virginie [VerfasserIn]
Kym, Urs [VerfasserIn]
Moesch, Michèle [VerfasserIn]
Usemann, Jakob [VerfasserIn]
Müller, Isabelle [VerfasserIn]
Subotic, Ulrike [VerfasserIn]
Tharakan, Sasha J [VerfasserIn]
Krebs, Thomas [VerfasserIn]
Stathopoulos, Eleuthere [VerfasserIn]
Schmittenbecher, Peter [VerfasserIn]
Cholewa, Dietmar [VerfasserIn]
Romero, Philipp [VerfasserIn]
Reingruber, Bertram [VerfasserIn]
Bruder, Elisabeth [VerfasserIn]
Group, Nig Study [VerfasserIn]
Holland-Cunz, Stefan [VerfasserIn]

Links:

Volltext

Themen:

Acetylcholinesterase
Cholinergic Nerve Fibers
Cytokines
EC 3.1.1.7
Enterocolitis
Journal Article
Lipopolysaccharide Receptors
Macrophages
Microbiome
Neuroimmunology
RNA, Messenger
Research Support, Non-U.S. Gov't
Th17 Cells

Anmerkungen:

Date Completed 27.01.2022

Date Revised 07.11.2023

published: Print-Electronic

CommentIn: Cell Mol Gastroenterol Hepatol. 2021;12(2):785-786. - PMID 34087230

Citation Status MEDLINE

doi:

10.1016/j.jcmgh.2021.03.004

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322979501