International Journal of Colorectal Disease

, Volume 34, Issue 1, pp 193–196 | Cite as

Obstructed defecation—an enteric neuropathy? An exploratory study of patient samples

  • Mia KimEmail author
  • Corinna Rosenbaum
  • Nicolas Schlegel
  • Christian Grumaz
  • Kai Sohn
  • Christoph Isbert
  • Heike Walles
  • Marco Metzger
Short Communication



Although various strategies exist for chronic constipation therapy, the pathogenesis of chronic constipation is still not completely understood. The aim of this exploratory experimental study is to elucidate alterations of the autonomous enteric nervous system at the molecular level in patients with obstructed defecation, who represent one of the most predominant groups of constipated patients.


Full-thickness rectal wall samples of patients with obstructed defecation were analyzed and compared with controls. Differential gene expression analyses by RNA-Seq transcriptome profiling were performed and gene expression profiles were assigned to gene ontology pathways by application of different biological libraries.


Analysis of the transcriptome showed that genes associated with the enteric nervous system functions were significantly downregulated in patients with obstructed defecation. These affected functions included developmental processes and synaptic transmission.


Our results therefore indicate that obstructed defecation may represent an enteric neuropathy, comparable to Hirschsprung disease and slow-transit constipation.


Chronic constipation Obstructed defecation Enteric nervous system Enteric neuropathy Transcriptome profiling, RNA-Seq 



We would like to thank Mrs. Renate Bausch, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Stuttgart, Germany, for technical assistance.


This project was funded by the Interdisciplinary Center of Clinical Studies (IZKF) Würzburg (Z-2/46).

Compliance with ethical standards

The study was approved by an institutional review board (Ethics committee, University Würzburg, Germany, approval number 23/12). All patients gave their informed, written consent.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

384_2018_3160_MOESM1_ESM.xlsx (10.7 mb)
ESM 1 (XLSX 10917 kb)


  1. 1.
    Bharucha AE, Pemberton JH, Locke GR 3rd (2013) American Gastroenterological Association technical review on constipation. Gastroenterology 144:218–238CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Andromanakos N, Skandalakis P, Troupis T, Filippou D (2006) Constipation of anorectal outlet obstruction: pathophysiology, evaluation and management. J Gastroenterol Hepatol 21:638–646CrossRefPubMedGoogle Scholar
  3. 3.
    Knowles CH, De Giorgio R, Kapur RP, Bruder E, Farrugia G, Geboes K, Lindberg G, Martin JE, Meier-Ruge WA, Milla PJ, Smith VV, Vandervinden JM, Veress B, Wedel T (2010) The London Classification of gastrointestinal neuromuscular pathology: report on behalf of the Gastro 2009 International Working Group. Gut 59:882–887CrossRefPubMedGoogle Scholar
  4. 4.
    Bassotti G, Villanacci V, Bellomi A, Fante R, Cadei M, Vicenzi L, Tonelli F, Nesi G, Asteria CR (2012) An assessment of enteric nervous system and estroprogestinic receptors in obstructed defecation associated with rectal intussusception. Neurogastroenterol Motil 24:e155–e161CrossRefPubMedGoogle Scholar
  5. 5.
    Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5:621–628CrossRefGoogle Scholar
  6. 6.
    Love MI, Huber W, Anders S (2014) Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. Genome Biol 15:550CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Parisi MA, Kapur RP (2000) Genetics of Hirschsprung disease. Curr Opin Pediatr 12(6):610–617CrossRefPubMedGoogle Scholar
  8. 8.
    Wedel T, Spiegler J, Soellner S, Roblick UJ, Schiedeck TH, Bruch HP, Krammer HJ (2002) Enteric nerves and interstitial cells of Cajal are altered in patients with slow-transit constipation and megacolon. Gastroenterology 123:1459–1467CrossRefPubMedGoogle Scholar
  9. 9.
    Geramizadeh B, Hayati K, Rahsaz M, Hosseini SV (2009) Assessing the interstitial cells of Cajal, cells of enteric nervous system and neurotransmitters in slow transit constipation, using immunohistochemistry for CD117, PGP9.5 and serotonin. Hepato-Gastroenterology 56:1670–1674PubMedGoogle Scholar
  10. 10.
    Wattchow D, Brookes S, Murphy E, Carbone S, de Fontgalland D, Costa M (2008) Regional variation in the neurochemical coding of the myenteric plexus of the human colon and changes in patients with slow transit constipation. Neurogastroenterol Motil 20:1298–1305CrossRefPubMedGoogle Scholar
  11. 11.
    Luzon-Toro B, Espino-Paisan L, Fernandez RM, Martin-Sanchez M, Antinolo G, Borrego S (2015) Next-generation-based targeted sequencing as an efficient tool for the study of the genetic background in Hirschsprung patients. BMC Med Genet 16:89CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Ravi K, Bharucha AE, Camilleri M, Rhoten D, Bakken T, Zinsmeister AR (2010) Phenotypic variation of colonic motor functions in chronic constipation. Gastroenterology 138:89–97CrossRefPubMedGoogle Scholar
  13. 13.
    Jadav AM, McMullin CM, Smith J, Chapple K, Brown SR (2013) The association between prucalopride efficacy and constipation type. Tech Coloproctol 17:555–559CrossRefPubMedGoogle Scholar
  14. 14.
    Gosselink MP, Adusumilli S, Harmston C, Wijffels NA, Jones OM, Cunningham C, Lindsey I (2013) Impact of slow transit constipation on the outcome of laparoscopic ventral rectopexy for obstructed defaecation associated with high grade internal rectal prolapse. Color Dis 15:e749–e756CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.General, Visceral, Transplantational, Vascular and Paedeatric SurgeryUniversity Hospital WürzburgWürzburgGermany
  2. 2.Department for Tissue Engineering and Regenerative MedicineUniversity Hospital WürzburgWürzburgGermany
  3. 3.Department of Molecular BiotechnologyFraunhofer Institute for Interfacial Engineering and Biotechnology (IGB)StuttgartGermany
  4. 4.Amalie Sieveking HospitalHamburgGermany
  5. 5.Translational Centre TZKMEFraunhofer-Institute Interfacial Engineering and Biotechnology IGBWürzburgGermany

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