Dataset Information

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.

ABSTRACT:

Background

This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn's disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison.

Methods

A case-control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Microbial DNA were extracted, libraries prepared and sequenced reads profiled. Taxonomic diversity, taxonomic association, strain typing and microbial gene pathway analyses were conducted.

Results

The study recruited 25 subjects with CD and 25 healthy controls. The oral microbe Streptococcus salivarius was found to be enriched and of concordant strains in the gut and oral microbiome of Crohn's disease subjects. This was more likely in CD subjects with higher Crohn's Disease Activity Index (184.3?±?2.9 vs 67.1?±?82.5, p?=?0.012) and active disease status (Diarrhoea/abdominal pain/blood-in-stool/fever and fatigue) (p?=?0.016). Gut species found to be significantly depleted in CD compared to control (Relative abundance: Median[Range]) include: Faecalibacterium prausnitzii (0.03[0.00-4.56] vs 13.69[5.32-18.71], p?=?0.010), Roseburia inulinivorans (0.00[0.00-0.03] vs 0.21[0.01-0.53], p?=?0.010) and Alistipes senegalensis (0.00[0.00-0.00] vs 0.00[0.00-0.02], p?=?0.029). While Clostridium nexile (0.00[0.00-0.12] vs 0.00[0.00-0.00], p?=?0.038) and Ruminococcus gnavus (0.43[0.02-0.33] vs 0.00[0.00-0.13], p?=?0.043) were found to be enriched. C. nexile enrichment was not found in CD subjects of European descent. Microbial arginine (Linear-discriminant-analysis: 3.162, p?=?0.001) and isoprene (Linear-discriminant-analysis: 3.058, p?ConclusionsThere was evidence of ectopic gut colonization by oral bacteria, especially during the active phase of CD. Previously studied gut microbial differences were detected, in addition to novel associations which could have resulted from geographical/ethnic differences to subjects of European descent. Differences in microbial pathways provide possible targets for microbiome modification.

SUBMITTER: Hu S

PROVIDER: S-EPMC7905567 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.

Hu Shijia S Png Eileen E Gowans Michelle M Ong David E H DEH de Sessions Paola Florez PF Song Jie J Nagarajan Niranjan N

Gut pathogens 20210225 1

<h4>Background</h4>This study aims to characterize, the gut and oral microbiome in Asian subjects with Crohn's disease (CD) using whole genome shotgun sequencing, thereby allowing for strain-level comparison.<h4>Methods</h4>A case-control study with age, sex and ethnicity matched healthy controls was conducted. CD subjects were limited to well-controlled patients without oral manifestations. Fecal and saliva samples were collected for characterization of gut and oral microbiome respectively. Mic ...[more]

PMID: 33632307

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Project description:BACKGROUND:Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease. METHODS:Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD. RESULTS:Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-?. CONCLUSIONS:Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

Project description:ObjectivesA number of converging strands of research suggest that the intestinal Enterobacteriaceae plays a crucial role in the development and progression of inflammatory bowel disease (IBD), however, the changes in the abundance of Enterobacteriaceae species and their related metabolic pathways in Crohn's disease (CD) and ulcerative colitis (UC) compared to healthy people are not fully explained by comprehensive comparative metagenomics analysis. In the current study, we investigated the alternations of the Enterobacterales population in the gut microbiome of patients with CD and UC compared to healthy subjects.MethodsMetagenomic datasets were selected from the Integrative Human Microbiome Project (HMP2) through the Inflammatory Bowel Disease Multi'omics Database (IBDMDB). We performed metagenome-wide association studies on fecal samples from 191 CD patients, 132 UC patients, and 125 healthy controls (HCs). We used the metagenomics dataset to study bacterial community structure, relative abundance, differentially abundant bacteria, functional analysis, and Enterobacteriaceae-related biosynthetic pathways.ResultsCompared to the gut microbiome of HCs, six Enterobacteriaceae species were significantly elevated in both CD and UC patients, including Escherichia coli, Klebsiella variicola, Klebsiella quasipneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, and Citrobacter youngae, while Klebsiella oxytoca, Morganella morganii, and Citrobacter amalonaticus were uniquely differentially abundant and enriched in the CD cohort. Four species were uniquely differentially abundant and enriched in the UC cohort, including Citrobacter portucalensis, Citrobacter pasteurii, Citrobacter werkmanii, and Proteus hauseri. Our analysis also showed a dramatically increased abundance of E. coli in their intestinal bacterial community. Biosynthetic pathways of aerobactin siderophore, LPS, enterobacterial common antigen, nitrogen metabolism, and sulfur relay systems encoded by E. coli were significantly elevated in the CD samples compared to the HCs. Menaquinol biosynthetic pathways were associated with UC that belonged to K. pneumoniae strains.ConclusionsIn conclusion, compared with healthy people, the taxonomic and functional composition of intestinal bacteria in CD and UC patients was significantly shifted to Enterobacteriaceae species, mainly E. coli and Klebsiella species.

Dataset Information

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.

Background

Methods

Results

Publications

Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.

Similar Datasets

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