Comparison of intestinal microbes and metabolites in active VKH versus acute anterior uveitis associated with ankylosing spondylitis.

Background: It has been reported that the gut microbiome is involved in the pathogenesis of uveitis, but the specific pathogenic microbes and metabolites in different types of uveitis are still unclear.

Methods: Microbiome and metabolites were detected using 16S ribosomal DNA and LC‒MS/MS (liquid chromatography tandem mass spectrometry) in 45 individuals, including 16 patients with Vogt Koyanagi Harada (VKH), 11 patients with acute anterior uveitis (AAU) and 18 healthy controls.

Result: The diversity of intestinal microbes among the VKH, AAU and control groups was not significantly different. Thirteen specific microbes and 38 metabolites were detected in the VKH group, and 7 metabolites (vanillin, erythro-isoleucine, pyrimidine, 1-aminocyclopropanecarboxylic acid, beta-tocopherol, (-)-gallocatechin and N1-methyl-4-pyridone-3-carboxamide) significantly changed only in patients with VKH, which mainly acted on nicotinamide and nicotinamide metabolism and biotin metabolism (p<0.05). Compared with the VKH group, the AAU group had milder intestinal changes. Only 11 specific microbes and 29 metabolites changed in the AAU group, while these metabolites were not specific (p<0.05). These metabolites mainly acted on arachidonic acid metabolism. In addition, three microbes and two metabolites had the same changes in the VKH and AAU groups (p<0.05). Multiple correlations were found between gut microbes and metabolites in the VKH and AAU groups. Six microbes (Pediococcus, Pseudomonas, Rhodococcus, Photobacterium, Gardnerella and Lawsonia) and two metabolites (pyrimidine and gallocatechin) as biomarkers could effectively distinguish patients with VKH from patients with AAU and healthy individuals, with AUC (area under the curve) values greater than 82%. Four microbes (Lentilactobacillus, Lachnospiraceae_UCG-010, Cetobacterium, Liquorilactobacillus) could distinguish patients with AAU from patients with VKH and healthy controls with AUC>76%.

Conclusion: Significant differences in intestinal microbes and metabolites suggest their different roles in the pathogenesis of uveitis entities. Changes in the metabolism of certain B vitamins may be involved in the pathogenesis of VKH.