184 Chapter 6 Abstract Dysregulation of gutmucosal host–microbe interactions is a central feature of inflammatory bowel disease (IBD). To study tissue-specific interactions, we performed transcriptomic (RNA-seq) and microbial (16S-rRNA-seq) profiling of 696 intestinal biopsies derived from353 patientswith IBDand controls. Analysis of transcript-bacteria interactions identified six distinct groups of inflammationrelated pathways that were associated with intestinal microbiota, findings we could partially validate in an independent cohort. An increased abundance of Bifidobacterium was associated withhigher expressionof genes involved in fatty acidmetabolism, while Bacteroides was associated with increased metallothionein signaling. In fibrostenotic Crohn’s disease, a transcriptional network dominated by immunoregulatory genes associated with Lachnoclostridium bacteria in non-stenotic tissue. In patients using TNF-α-antagonists, a transcriptional network dominated by fatty acid metabolism genes associated with Ruminococcaceae. Mucosal microbiota composition was associated with enrichment of specific intestinal cell types. Overall, we identify multiple host– microbe interactions that may guide microbiota-directed precision medicine. Keywords inflammatory bowel disease, gene expression, mucosal microbiota, microbiome, host–microbe interactions.
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