Dataset Information

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease.

ABSTRACT:

Objectives

Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by a complex pathophysiology that is thought to result from an aberrant immune response to a dysbiotic luminal microbiota in genetically susceptible individuals. New technologies support the joint assessment of host-microbiome interaction.

Methods

Using whole genome sequencing and shotgun metagenomics, we studied the clinical features, host genome, and stool microbial metagenome of 85 IBD patients, and compared the results to 146 control individuals. Genetic risk scores, computed on 159 single nucleotide variants, and human leukocyte antigen (HLA) types differentiated IBD patients from healthy controls.

Results

Genetic risk was associated with the need for use of biologics in IBD and, modestly, with the composition of the gut microbiome. As compared with healthy controls, IBD patients had hallmarks of stool microbiome dysbiosis, with loss of a diversified core microbiome, enrichment and depletion of specific bacteria, and enrichment of bacterial virulence factors.

Conclusions

We show that genetic risk may have a role in early risk stratification in the care of IBD patients and propose that expression of virulence factors in a dysbiotic microbiome may contribute to pathogenesis in IBD.

SUBMITTER: Moustafa A

PROVIDER: S-EPMC5795019 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease.

Moustafa Ahmed A Li Weizhong W Anderson Ericka L EL Wong Emily H M EHM Dulai Parambir S PS Sandborn William J WJ Biggs William W Yooseph Shibu S Jones Marcus B MB Venter J Craig JC Nelson Karen E KE Chang John T JT Telenti Amalio A Boland Brigid S BS

Clinical and translational gastroenterology 20180118 1

<h4>Objectives</h4>Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are characterized by a complex pathophysiology that is thought to result from an aberrant immune response to a dysbiotic luminal microbiota in genetically susceptible individuals. New technologies support the joint assessment of host-microbiome interaction.<h4>Methods</h4>Using whole genome sequencing and shotgun metagenomics, we studied the clinical features, host genome, and sto ...[more]

PMID: 29345635

Similar Datasets

Project description:Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that fall into two main categories: Crohn's disease (CD) and ulcerative colitis (UC). The gastrointestinal tract extends from the mouth to the anus and harbors diverse bacterial communities. Several sequencing-based studies have identified an intestinal enrichment of oral-associated bacteria and demonstrated their ability to induce intestinal inflammation in mice, suggesting that intestinal pathobionts originate from the oral cavity, particularly members of the genus Streptococcus. This study aimed to investigate the composition of the salivary and fecal microbiome of IBD patients (n = 14) compared to healthy controls (n = 12) and to determine the abundance of common bacterial taxa in both niches. Metagenomic DNA was extracted from saliva and fecal samples, and the 16S rRNA gene was targeted for sequencing. Our results revealed that the overall microbial composition of saliva was significantly altered in the IBD patients compared to the control subjects (p = 0.038). At the genus level, Veillonella and Prevotella were highly abundant in IBD (median: 25.4% and 22.2%, respectively) compared to the control group (17.9% and 13.4%, respectively). In contrast, Neisseria, Streptococcus, Haemophilus, and Fusobacterium were associated with a healthy gut state. Regarding the fecal microbiome, the IBD group had a significantly higher abundance of Clostridium sensu stricto 1 and Escherichia-Shigella (both comprising pathogenic bacteria) compared with the control group. Members of both bacterial groups have previously been shown to positively correlate with intestinal inflammation and high expression of pro-inflammatory cytokines that disrupt intestinal barrier integrity. In addition, we demonstrate that the increased abundance of Clostridium sensu stricto 1 and Escherichia-Shigella has also been associated with significant upregulation of certain metabolic pathways in the feces of the IBD group, including bacterial invasion of epithelial cells. Streptococcus was the only common genus detected in both the salivary and fecal microbiome and represented the oral-gut axis in our study. Using culture-based methods, we isolated 57 and 91 Streptococcus strains from saliva as well as 40 and 31 strains from fecal samples of the controls and IBD patients, respectively. The phylogenetic tree of streptococci based on sodA sequences revealed several patient-specific clusters comprising salivary and fecal streptococcal isolates from the same patient and belonging to the same species, suggesting that the oral cavity is an endogenous reservoir for intestinal strains.

Project description:A group of diseases have been shown to correlate with a phenomenon called microbiome dysbiosis, where the bacterial species composition of the gut becomes abnormal. The gut microbiome of an animal is influenced by many factors including diet, exposures to bacteria during post-gestational growth, lifestyle, and disease status. Studies also show that host genetics can affect microbiome composition. We sought to test whether host genetic background is associated with gut microbiome composition in the Norwegian Lundehund dog, a highly inbred breed with an effective population size of 13 individuals. The Lundehund has a high rate of a protein-losing enteropathy in the small intestine that is often reported as Lundehund syndrome, which negatively affects longevity and life-quality. An outcrossing project with the Buhund, Norrbottenspets, and Icelandic sheepdog was recently established to reintroduce genetic diversity to the Lundehund and improve its health. To assess whether there was an association between host genetic diversity and the microbiome composition, we sampled the fecal microbiomes of 75 dogs of the parental (Lundehund), F1 (Lundehund x Buhund), and F2 (F1 x Lundehund) generations. We found significant variation in microbiome composition from the parental Lundehund generation compared to the outcross progeny. The variation observed in purebred Lundehunds corresponded to dysbiosis as seen by a highly variable microbiome composition with an elevated Firmicutes to Bacteroidetes ratio and an increase in the prevalence of Streptococcus bovis/Streptococcus equinus complex, a known pathobiont that can cause several diseases. We tracked several other environmental factors including diet, the presence of a cat in the household, living in a farm and the use of probiotics, but we did not find evidence of an effect of these on microbiome composition and alpha diversity. In conclusion, we found an association between host genetics and gut microbiome composition, which in turn may be associated with the high incidence of Lundehund syndrome in the purebred parental dogs.

Dataset Information

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease.

Objectives

Methods

Results

Conclusions

Publications

Genetic risk, dysbiosis, and treatment stratification using host genome and gut microbiome in inflammatory bowel disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets