Dataset Information

A metagenomic study of the gut microbiome in Behcet's disease.

ABSTRACT: 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.

SUBMITTER: Ye Z

PROVIDER: S-EPMC6091101 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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A metagenomic study of the gut microbiome in Behcet's disease.

Ye Zi Z Zhang Ni N Wu Chunyan C Zhang Xinyuan X Wang Qingfeng Q Huang Xinyue X Du Liping L Cao Qingfeng Q Tang Jihong J Zhou Chunjiang C Hou Shengping S He Yue Y Xu Qian Q Xiong Xiao X Kijlstra Aize A Qin Nan N Yang Peizeng P

Microbiome 20180804 1

<h4>Background</h4>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.<h4>Methods</h4>Fecal and saliva samples were collected from 32 active BD patie ...[more]

PMID: 30077182

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Project description:BackgroundThis 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.MethodsA 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.ResultsThe 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?<?0.001) pathways were found at a higher relative abundance level in gut microbiome of Crohn's disease.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.

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Dataset Information

A metagenomic study of the gut microbiome in Behcet's disease.

Publications

A metagenomic study of the gut microbiome in Behcet's disease.

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