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] |
---|
Links: |
---|
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 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM322979501 | ||
003 | DE-627 | ||
005 | 20231225183202.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.jcmgh.2021.03.004 |2 doi | |
028 | 5 | 2 | |a pubmed24n1076.xml |
035 | |a (DE-627)NLM322979501 | ||
035 | |a (NLM)33741501 | ||
035 | |a (PII)S2352-345X(21)00056-4 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Keck, Simone |e verfasserin |4 aut | |
245 | 1 | 0 | |a Lack of Mucosal Cholinergic Innervation Is Associated With Increased Risk of Enterocolitis in Hirschsprung's Disease |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 27.01.2022 | ||
500 | |a Date Revised 07.11.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a CommentIn: Cell Mol Gastroenterol Hepatol. 2021;12(2):785-786. - PMID 34087230 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Cholinergic Nerve Fibers | |
650 | 4 | |a Enterocolitis | |
650 | 4 | |a Macrophages | |
650 | 4 | |a Microbiome | |
650 | 4 | |a Neuroimmunology | |
650 | 4 | |a Th17 Cells | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a Lipopolysaccharide Receptors |2 NLM | |
650 | 7 | |a RNA, Messenger |2 NLM | |
650 | 7 | |a Acetylcholinesterase |2 NLM | |
650 | 7 | |a EC 3.1.1.7 |2 NLM | |
700 | 1 | |a Galati-Fournier, Virginie |e verfasserin |4 aut | |
700 | 1 | |a Kym, Urs |e verfasserin |4 aut | |
700 | 1 | |a Moesch, Michèle |e verfasserin |4 aut | |
700 | 1 | |a Usemann, Jakob |e verfasserin |4 aut | |
700 | 1 | |a Müller, Isabelle |e verfasserin |4 aut | |
700 | 1 | |a Subotic, Ulrike |e verfasserin |4 aut | |
700 | 1 | |a Tharakan, Sasha J |e verfasserin |4 aut | |
700 | 1 | |a Krebs, Thomas |e verfasserin |4 aut | |
700 | 1 | |a Stathopoulos, Eleuthere |e verfasserin |4 aut | |
700 | 1 | |a Schmittenbecher, Peter |e verfasserin |4 aut | |
700 | 1 | |a Cholewa, Dietmar |e verfasserin |4 aut | |
700 | 1 | |a Romero, Philipp |e verfasserin |4 aut | |
700 | 1 | |a Reingruber, Bertram |e verfasserin |4 aut | |
700 | 1 | |a Bruder, Elisabeth |e verfasserin |4 aut | |
700 | 1 | |a Group, Nig Study |e verfasserin |4 aut | |
700 | 1 | |a Holland-Cunz, Stefan |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Cellular and molecular gastroenterology and hepatology |d 2015 |g 12(2021), 2 vom: 30., Seite 507-545 |w (DE-627)NLM246683694 |x 2352-345X |7 nnns |
773 | 1 | 8 | |g volume:12 |g year:2021 |g number:2 |g day:30 |g pages:507-545 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jcmgh.2021.03.004 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 12 |j 2021 |e 2 |b 30 |h 507-545 |