Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease

• Verfasst von: Keck, Simone [VerfasserIn]
• Verfasst von: Galati-Fournier, Virginie [VerfasserIn]
• Verfasst von: Kym, Urs [VerfasserIn]
• Verfasst von: Moesch, Michèle [VerfasserIn]
• Verfasst von: Usemann, Jakob [VerfasserIn]
• Verfasst von: Müller, Isabelle [VerfasserIn]
• Verfasst von: Subotic, Ulrike [VerfasserIn]
• Verfasst von: Tharakan, Sasha J. [VerfasserIn]
• Verfasst von: Krebs, Thomas [VerfasserIn]
• Verfasst von: Stathopoulos, Eleuthere [VerfasserIn]
• Verfasst von: Schmittenbecher, Peter [VerfasserIn]
• Verfasst von: Cholewa, Dietmar [VerfasserIn]
• Verfasst von: Romero, Philipp [VerfasserIn]
• Verfasst von: Reingruber, Bertram [VerfasserIn]
• Verfasst von: Bruder, Elisabeth [VerfasserIn]
• Verfasst von: Holland-Cunz, Stefan [VerfasserIn]
• Titel: Lack of mucosal cholinergic innervation is associated with increased risk of enterocolitis in Hirschsprung’s disease
• Verf.angabe: Simone Keck, Virginie Galati-Fournier, Urs Kym, Michèle Moesch, Jakob Usemann, Isabelle Müller, Ulrike Subotic, Sasha J. Tharakan, Thomas Krebs, Eleuthere Stathopoulos, Peter Schmittenbecher, Dietmar Cholewa, Philipp Romero, Bertram Reingruber, Elisabeth Bruder, NIG Study Group, and Stefan Holland-Cunz
• E-Jahr: 2021
• Jahr: 16 March 2021
• Umfang: 39 S.
• Fussnoten: Gesehen am 18.10.2021
• Titel Quelle: Enthalten in: Cellular and Molecular Gastroenterology and Hepatology
• Ort Quelle: New York, NY : Elsevier, 2015
• Jahr Quelle: 2021
• Band/Heft Quelle: 12(2021), 2, Seite 507-545
• ISSN Quelle: 2352-345X
• DOI: doi:10.1016/j.jcmgh.2021.03.004
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Cholinergic Nerve Fibers
• Sach-SW: Enterocolitis
• Sach-SW: Macrophages
• Sach-SW: Microbiome
• Sach-SW: Neuroimmunology
• Sach-SW: Th17 Cells
• K10plus-PPN: 1774333155

Abstract

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.