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