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

Zi Ye, Ni Zhang, Chunyan Wu, Xinyuan Zhang, Qingfeng Wang, Xinyue Huang, Liping Du, Qingfeng Cao, Jihong Tang, Chunjiang Zhou, Shengping Hou, Yue He, Qian Xu, Xiao Xiong, Aize Kijlstra, Nan Qin, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

108 Citations (Web of Science)

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-gamma. 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.
Original languageEnglish
Article number135
Number of pages13
JournalMicrobiome
Volume6
DOIs
Publication statusPublished - 4 Aug 2018

Keywords

  • Behcet's disease
  • Gut microbiome
  • Metagenomic analysis
  • Fecal microbiota transplant
  • BUTYRATE-PRODUCING BACTERIA
  • SULFATE-REDUCING BACTERIA
  • METHANE-RICH SALINE
  • TOLL-LIKE RECEPTORS
  • REGULATORY T-CELLS
  • METABOLISM
  • PROTEIN
  • ASSOCIATION
  • SEQUENCES
  • MICE
  • Bacteria/classification
  • Humans
  • RNA, Ribosomal, 16S/genetics
  • Male
  • Phylogeny
  • DNA, Ribosomal/genetics
  • Case-Control Studies
  • Female
  • Saliva/microbiology
  • Gastrointestinal Microbiome
  • Sequence Analysis, DNA
  • Fecal Microbiota Transplantation
  • Metagenomics/methods
  • Animals
  • Feces/microbiology
  • Bacterial Capsules/genetics
  • Behcet Syndrome/microbiology
  • Mice
  • Gene Expression Regulation, Bacterial
  • DNA, Bacterial/genetics

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