Colonic mucosa microbiome and host gene expression in a rat model of experimentally induced visceral hyperalgesia

Authors

• NH Fourie
• D Wang
• AL Creekmore
• S Hong
• JW Wiley
• WA Henderson

Abstract

We use a rat model of stress induced visceral hyperalgesia to examine the relationship the microbiome and host gene expression. Male Sprague–Dawley rats were exposed daily for 1 hour to water avoidance stress (WA) for 10 days (13 stressed and 12 controls). Visceral hypersensitivity was determined using colorectal distension and electromyography. Colonic mucosal DNA and RNA were isolated. Bacterial profiles were determined using 16S sequencing ( IonTorrent PGM). Host colonic mucosal gene expression was determined with Affymetrix Rat Gene 2.0 ST Arrays. WA animals showed increased bacterial richness and abundance compared to healthy controls (HC). Proteobacteria and Actinobacteria were significantly enriched in WA 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 in WA 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. Maximum parsimony analysis revealed 32 changes in gene expression associated with inflammation. Families containing butyrate producing taxa were over expressed in stress rats. Butyrate causes concentration dependent colonic hypersensitivity in rats. The expression of the pro-inflammatory gene Vtcn1 can be modulated by butyrate suggesting a functional link with microbial expression. Microbial dysbiosis in chronically stressed animals is associated with inflammation related gene expression changes in the colonic mucosa. Relationships between the identified genes and specific bacterial phylotypes remain to be further explored.

Scientific Focus Area: Microbiology and Infectious Diseases

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