Mo2040 Experimentally Induced Visceral Pain, Variation in the Microbiome, and Host Gene Expression in Irritable Bowel Syndrome

Autor: Bridgett Rahim-Williams, Nicolaas H. Fourie, Dan Wang, Wendy A. Henderson, Sarah K. Abey, LeeAnne B. Sherwin, Eric G. Ferguson
Rok vydání: 2015
Předmět:
Zdroj: Gastroenterology. 148:S-777
ISSN: 0016-5085
DOI: 10.1016/s0016-5085(15)32649-4
Popis: Male Wistar rats were exposed to 1 hour of water avoidance stress (WA) each day over a 10 day period (12 stressed and 12 controls). Visceral hypersensitivity was determined using colorectal distension and electromyographic recording. Animals were sacrificed at the end of the experimental protocol and colonic tissue was dissected out. The colonic epithelium was mechanically separated and DNA and RNA was isolated. Hypervariable bacterial 16S RNA regions were amplified (V3 and V4) and sequenced on an IonTorrent PGM. Host colonic epithelial mRNA (13 stressed and 12 controls) was hybridized to Affymetrix GeneChip® Rat Gene 2.0 ST Arrays for whole genome gene expression determination. Results: WA animals showed increased bacterial richness compared to healthy controls (HC). Proteobacteria and Actinobacteria were significantly enriched inWA animals. 2991 bacterial operational taxonomic units (OTUs) were significantly differentially expressed. Of these 61% were over expressed in WA animals. All differentially expressed OTUs belonging to the families Rikenellaceae and Porphyromonadaceae (20% of OTUs) were down regulated inWA animals. Almost all differentially expressed OTUs belonging to the families Weeksellaceae, S24-7, Comamonadaceae, Lachnospiraceae, Moraxellaceae and Pseudomonadaceae (39% of OTUs) were over expressed in WA animals. Using a novel analytical methodology (maximum parsimony analysis) 32 changes in gene expression which are implicated or associated with inflammation were identified. Genes that showed the most uniform change in expression included Anxa5, Csnk2a1, Ddx19a, Hnf1a, Hoxc4, Igfbp7, Kcnh2, Map6d1, RT-M6-2, Stard10 and Vtcn1. Discussion: Bacterial richness showed the opposite of what is generally observed in disease conditions. WA animals were characterized by bacterial over expression. Specifically, families which contain butyrate producing taxa are over expressed. Although butyrate is essential for colonic mucosal health it is known to cause concentration dependent colonic hypersensitivity in rats. The expression of the proinflammatory gene Vtcn1 can be modulated by butyrate suggesting a functional link with changes in microbial expression. Microbial dysbiosis in chronically stressed animals is associated with gene expression changes in the colonic mucosa which implicate inflammatory pathways. Possible relationships between the identified genes and specific bacterial groups and species remain to be further elucidated and offer a rich source of future research.
Databáze: OpenAIRE