Abstract
Dysregulation of gut mucosal 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 from 353 patients with IBD and controls. Analysis of transcript-bacteria interactions identified six distinct groups of inflammation-related pathways that were associated with intestinal microbiota, findings we could partially validate in an independent cohort. An increased abundance of Bifidobacterium was associated with higher expression of genes involved in fatty acid metabolism, 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.
Competing Interest Statement
RKW acted as consultant for Takeda, received unrestricted research grants from Takeda, Johnson & Johnson, Tramedico and Ferring and received speaker fees from MSD, Abbvie, and Janssen Pharmaceuticals. GD received an unrestricted research grant from Takeda and speaker fees from Pfizer and Janssen Pharmaceuticals. All other authors declare no competing interests.
