Differential intestinal microbes and metabolites between Behcet's uveitis and Fuchs syndrome

Objective: Behcet's uveitis (BU) is a type of uveitis with a high rate of blindness, characterized by anterior segment inflammation, vitreous opacity, and retinal vasculitis. Its pathogenesis is still unclear. Fuchs syndrome (Fuchs) is another common type of uveitis, which clinically presents with anterior segment inflammation and vitreous opacity, but rarely causes blindness. This study aims to compare the gut microbiota and metabolites of two different types of uveitis to clarify whether the differences in clinical manifestations are relevant to the alterations in gut microbiota. Methods: Faecal samples were collected from new-onset BU (n = 11) patients without systemic treatment and other diseases. 16S rRNA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were performed to analyze gut microbes and metabolites. Fuchs (n = 15) was used as the disease control, and healthy controls (n = 18) without autoimmune diseases and systemic medication were included. Results: Microbial composition and metabolite profiles differed significantly among the three groups. Compared to controls, Fusicatenibacter and eight metabolites were specifically altered in BU patients, and Pantoea and five metabolites in Fuchs. Pathways involving delta-tocopherol, palmitic acid, and serotonin are significantly disrupted in BU patients. Pathways involving linoleic acid are dysregulated considerably in Fuchs. Microbial markers consisting of 4 genera and 7 metabolites can respectively distinguish BU patients from controls. AUC values of metabolite markers were greater than those of microbial markers. Furthermore, serum zonulin levels were significantly elevated in both types of uveitis, with no difference between them. Correlation analysis revealed correlations between zonulin levels and multiple microbes. Conclusions: Patients with BU and Fuchs syndrome showed significant differences in gut microbiota and metabolites. Disruption of the intestinal mucosal barrier was observed in both types of uveitis. However, the mechanism of different intestinal microbiota causing different clinical manifestations needs to be studied in the future.