https://orcid.org/0000-0002-5848-4066
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
Background
Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.
Results
Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice.
Conclusion
Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.
Author contributions
Z. Y., C. W., N. Z., N.Q. and P. Y. conceived and directed the study; N.Q., C.W. and X.X. analyzed the data; P. Y. made clinical diagnoses and performed treatment; N. Z., X. H., J. T., Q. C., L. D., F. L. and C. Z. collected the samples; Z. Y., X. H., J. T., and Q. W. extracted the fecal DNA; Z. Y., X. H. and J. T. extracted the genomic DNA and contributed the SNP genotyping; Q. X. and X. X. performed the 16S rRNA and Metagenomic sequencing; Z. Y., Q. W. and X. H. performed the animal experiment; Z. Y., C. W., and N. Z. drafted the manuscript; P. Y., N. Q., and A. K. reviewed data analysis and edited the manuscript. All authors reviewed the manuscript.
Availability of data and materials
Metagenomic sequencing data for all samples have been deposited in NCBI with accession number of PRJNA356225.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Ethics approval and consent to participate
All procedures followed the tenets of the Declaration of Helsinki and were approved by the Ethics Committee of Chongqing Medical University with written informed consent.
Supplementary material
Supplemental data for this article can be accessed on the publisher’s website.
Abbreviations
| AS | = | Ankylosing spondylitis |
| AUC | = | Area under the receiver operating characteristic curve |
| BMI | = | Body mass index |
| CNS | = | Central nervous system |
| EAU | = | Experimental autoimmune uveitis |
| eggnog | = | Evolutionary genealogy of genes: Non-supervised Orthologous Groups database |
| Gb | = | Gigabases |
| GWAS | = | Genome-wide association analysis |
| IBD | = | Inflammatory bowel disease |
| KEGG | = | Kyoto Encyclopedia of Genes and Genomes database |
| KO | = | KEGG orthologues |
| LPS | = | Lipopolysaccharide |
| MGS | = | Metagenomic Species |
| MS | = | Multiple sclerosis |
| NCBI | = | National Center for Biological Information |
| OG | = | EggNOG orthologues |
| ORFs | = | Non-redundant open reading frames |
| OUT | = | Operational taxonomic unit |
| PA | = | Psoriatic arthritis |
| PCoA | = | Principal component analysis |
| RA | = | rheumatoid arthritis |
| SLE | = | systemic lupus erythematosus |
| VKH | = | Vogt-Koyanagi-Harada |
Correction Statement
This article has been republished with minor changes. These changes do not impact the academic content of the article.