The Interplay of Host Genetics and the Gut Microbiota Underlying the Onset and Clinical Presentation of Inflammatory Bowel Disease

By F. Imhann, A. V. Vila, M. Bonder, Jingyuan Fu, Dirk Gevers, M. Visschedijk, L. Spekhorst, R. Alberts, Lude Franke, H. V. van Dullemen and 8 more. Gut, 2016

719 citations recorded by the source corpus.

Objective Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. Design Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2. Results Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10−13). Conclusions We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/f5556807ea957d9f2f3c64cfb432253ec128a3a3

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Citations in the corpus

The gut microbiota and inflammatory bowel disease (2014, neutral): “The host provides a nutrient-rich environment and residence for the gut bacteria, and in turn, they contribute to the host by producing short-chain fatty acids and essential vitamins.”
Short-chain fatty acids: linking diet, the microbiome and immunity (2024, positive): “Recent evidence indicates that healthy individuals with a high genetic risk for IBD have decreased Roseburia spp. in the gut microbiota 109 .”