Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease

Abstract

ObjectivePatients 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.DesignStool 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.ResultsStrikingly, 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).ConclusionsWe 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.

Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines

“…Herein, we performed pyrosequencing analysis to investigate whether MIMP can improve the gut dysbiosis in the colitis model. As expected, we observed that DSS treatment caused significantly the decreased diversity of gut microbiota compared with the control group, a finding that is consistent with that in previous studies on IBD patients and the DSS-induced colitis model [34, 35]. In particular, MIMP intervention remarkably increased bacterial diversity and modified the community structure in the colitis mice, as shown by our cluster analysis and PCoA analysis.…”

Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study

“…First antibiotics may be causally related to IBD, potentially by a mediating effect on the microbiome, causing a reduced diversity and an increased dysbiosis 42. The microbiome interacts with the host through production of short-chain fatty acids (including butyrate), induction of the mucosal immune system, stimulation of the local nervous system and through interaction with the lamina propria by modification of the gut barrier function 43. A dysbiosis in the gut microbiota, characterised by reduction of beneficial bacteria such as Faecalibacterium prausnitzii , and Ruminococcaceae and an increase of pathogens or pathobionts, has consistently been shown in patients with IBD, especially ileal CD 44…”

No association between urbanisation, neighbourhood deprivation and IBD: a population-based study of 4 million individuals

“…We read with interest the recently published work in Gut by Imhann et al 1. Although this paper suggests that genetics plays an important role in IBD,1 environmental factors clearly contribute to its aetiology 2.…”

“…Although this paper suggests that genetics plays an important role in IBD,1 environmental factors clearly contribute to its aetiology 2. When Ng et al 2 reviewed environmental risk factors for IBD in this journal they noted that urbanisation may be linked to both Crohn’s disease (CD) and ulcerative colitis (UC).…”