P688. Associations between host transcription and the intestinal microbiome
B. Kabakchiev1, A. Tyler1, J. Stempak1, M. Silverberg2, 1Mount Sinai Hospital, SLRI, Toronto, Canada, 2Mount Sinai Hospital, Gastroenterology, Toronto, Canada
Interplay between host intestinal cells and commensal bacteria is known to be necessary for the development of gastrointestinal disorders such as inflammatory bowel disease (IBD). We examined whether modulation of specific host genes associates with perturbations in the microbiome.
205 ulcerative colitis (UC) and familial adenomatous polyposis (FAP) patients who had undergone ileal pouch anal anastomosis (IPAA) and closure of ileostomy at least one year prior to recruitment was prospectively accrued. Biopsies from the pouch and pre-pouch ileum were collected. Samples designated for gene expression analysis were preserved in RNAlater; those for microbiome analysis were snap-frozen in liquid nitrogen. Transcriptomes were analyzed on Affymetrix Human Gene 1.0 ST arrays and the data were background corrected and normalized. IBD-associated genes and their interactors as well as genes know to interact with bacterial partners were selected for further analysis after k-medoid reduction to 100 representatives. Microbial 16S rRNA genes were sequenced on Illumina MiSeq at the Broad Institute. Raw sequences were filtered, clustered into operational taxonomic units (OTUs) and identified using reference-based picking with GreenGenes in QIIME. Associative analysis was performed using MaAsLin, a sparse linear model for relative abundance data, providing correlations of OTUs with gene expression while correcting for biopsy location, disease status, inflammation and antibiotic use. Raw p-values were corrected for multiple comparisons by the false discovery rate method.
In a preliminary analysis, a strong positive correlation was observed between stratifin (SFN), a versatile molecule involved in numerous cellular functions, and OTUs corresponding to Blautia (p = 0.009) and Coprococcus (p = 0.025) in the Firmicutes as well as Prevotella (p = 0.085) from the Bacteroidetes phylum. SFN expression was also negatively associated with another Firmicute genus, Clostridium (p = 0.085). Another positive correlation was detected between CXCR1 and Enterobacteriaceae (p = 0.095). Interestingly, CXCR1 was highly co-expressed with IL6, IL8, NOD2, MMP7 and MMP13 among others. In total, 16 significant associations between host gene expression and bacterial abundance were detected.
These findings indicate that altered transcription or shifts in the cell type composition of the gut are the cause or result of microbiome fluctuations; these changes could have significant impact on health and disease.