PURPOSE: Dysregulation of the microbiota on different mucosal surfaces is associated with both immune-mediated and malignant diseases. Nevertheless, the involvement of different microbial communities is still poorly characterized. The aim of our study was to compare oral and gut microbiota composition between patients with uveitis, vitreoretinal lymphoma (VRL), and controls. METHODS: This study was designed as a prospective observational study. The inclusion criteria were treatment-naïve patients with immune-mediated uveitis or newly diagnosed VRL. The buccal swab and faecal samples were collected and bacterial 16S ribosomal RNA gene sequencing was used to identify the oral and gut microbiota. RESULTS: We enrolled 18 patients with uveitis, median age 39 years, 16 patients with VRL, median age 67.5 years, and 16 controls, median age 63 years. In the oral microbiota, the patients suffering from uveitis showed significant enrichment of genera Pseudomonas (p < 0.0001 and p < 0.0001), and Diaphorobacter (p = 0.007 and 0.013) and reduction of Streptococcus (p < 0.0001 and p < 0.0001) when compared to patients with VRL and control subjects, respectively. In addition, these patients had also significantly higher relative abundance of the genus Enhydrobacter (p = 0.029) and lower abundance of the genera Gemella (p = 0.002), Neisseria (p = 0.008), and Prevotella (p = 0.011) when compared to patients with VRL. We found only minor changes in the gut microbiota. CONCLUSION: Our study, as the first one, highlighted significant differences in the composition of oral microbiota among patients with uveitis, VRL, and control subjects.

1 st Department of Medicine 1 st Faculty of Medicine Charles University General University Hospital Prague Czech Republic

Department of Ophthalmology 1 st Faculty of Medicine Charles University General University Hospital Prague Czech Republic

Laboratory of Cellular and Molecular Immunology Institute of Microbiology Czech Academy of Sciences Prague Czech Republic

Laboratory of Fungal Metabolism and Genetics Institute of Microbiology Czech Academy of Sciences Prague Czech Republic

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Buttó LF, Schaubeck M, Haller D (2015) Mechanisms of Microbe-Host interaction in crohn’s disease: dysbiosis vs. Pathobiont selection. Front Immunol 6. https://doi.org/10.3389/fimmu.2015.00555

Sokol H, Seksik P, Furet JP et al (2009) Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 15:1183–1189. https://doi.org/10.1002/ibd.20903 PubMed DOI

Bajer L, Kverka M, Kostovcik M et al (2017) Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol 23:4548. https://doi.org/10.3748/wjg.v23.i25.4548 PubMed DOI PMC

Bunyavanich S, Berin MC (2019) Food allergy and the microbiome: current Understandings and future directions. J Allergy Clin Immunol 144:1468–1477. https://doi.org/10.1016/j.jaci.2019.10.019 PubMed DOI PMC

Mölzer C, Heissigerova J, Wilson HM et al (2021). Immune privilege: the Microbiome and uveitis. Front Immunol 11. https://doi.org/10.3389/fimmu.2020.608377

Cullin N, Azevedo Antunes C, Straussman R et al (2021) Microbiome and cancer. Cancer Cell 39:1317–1341. https://doi.org/10.1016/j.ccell.2021.08.006 PubMed DOI

London NJS, Rathinam SR, Cunningham ET (2010) The epidemiology of uveitis in developing countries. Int Ophthalmol Clin 50:1–17. https://doi.org/10.1097/IIO.0b013e3181d2cc6b PubMed DOI

Rothova A, Buitenhuis HJ, Meenken C et al (1992) Uveitis and systemic disease. Br J Ophthalmol 76:137–141. https://doi.org/10.1136/bjo.76.3.137 PubMed DOI PMC

Prete M, Dammacco R, Fatone MC, Racanelli V (2016) Autoimmune uveitis: clinical, pathogenetic, and therapeutic features. Clin Exp Med 16:125–136. https://doi.org/10.1007/s10238-015-0345-6 PubMed DOI

Soussain C, Malaise D, Cassoux N (2021) Primary vitreoretinal lymphoma: a diagnostic and management challenge. Blood 138:1519–1534. https://doi.org/10.1182/blood.2020008235 PubMed DOI

Farrall AL, Smith JR (2020) Eye involvement in primary central nervous system lymphoma. Surv Ophthalmol 65:548–561. https://doi.org/10.1016/j.survophthal.2020.02.001 PubMed DOI

Alaggio R, Amador C, Anagnostopoulos I et al (2022) The 5th edition of the world health organization classification of haematolymphoid tumours: lymphoid neoplasms. Leukemia 36:1720–1748. https://doi.org/10.1038/s41375-022-01620-2 PubMed DOI PMC

Horai R, Zárate-Bladés CR, Dillenburg-Pilla P et al (2015) Microbiota-Dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site. Immunity 43:343–353. https://doi.org/10.1016/j.immuni.2015.07.014 PubMed DOI PMC

Heissigerova J, Seidler Stangova P, Klimova A et al (2016) The microbiota determines susceptibility to experimental autoimmune uveoretinitis. J Immunol Res 2016:1–11. https://doi.org/10.1155/2016/5065703 DOI

Seidler Štangová P, Dusek O, Klimova A et al (2019) Metronidazole attenuates the intensity of inflammation in experimental autoimmune uveitis. Folia Biol (Praha) 65:265–274. https://doi.org/10.14712/fb2019065050265 PubMed DOI

Nakamura YK, Metea C, Karstens L et al (2016) Gut microbial alterations associated with protection from autoimmune uveitis. Invest Opthalmology Visual Sci 57:3747. https://doi.org/10.1167/iovs.16-19733 DOI

Kim J, Choi S, Kim Y et al (2017) Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye. Nutrients 9:1166. https://doi.org/10.3390/nu9111166 PubMed DOI PMC

Dusek O, Fajstova A, Klimova A et al (2020) Severity of experimental autoimmune uveitis is reduced by pretreatment with live probiotic Escherichia coli Nissle 1917. Cells 10:23. https://doi.org/10.3390/cells10010023 PubMed DOI PMC

Rosenbaum JT, Asquith M (2018) The Microbiome and HLA-B27-associated acute anterior uveitis. Nat Rev Rheumatol 14:704–713. https://doi.org/10.1038/s41584-018-0097-2 PubMed DOI PMC

Parthasarathy R, Santiago F, McCluskey P et al (2023) The Microbiome in HLA-B27-associated disease: implications for acute anterior uveitis and recommendations for future studies. Trends Microbiol 31:142–158. https://doi.org/10.1016/j.tim.2022.08.008 PubMed DOI

Morandi SC, Herzog EL, Munk M et al (2024) The gut Microbiome and HLA-B27-associated anterior uveitis: a case-control study. J Neuroinflammation 21:120. https://doi.org/10.1186/s12974-024-03109-4 PubMed DOI PMC

Joubert M, André M, Barnich N, Billard E (2023) Microbiome and behçet’s disease: a systematic review. Clin Exp Rheumatol 41:2093–2104. https://doi.org/10.55563/clinexprheumatol/zbt4gx PubMed DOI

Shimizu J, Kubota T, Takada E et al (2016) Bifidobacteria Abundance-Featured gut microbiota compositional change in patients with behcet’s disease. PLoS ONE 11:e0153746. https://doi.org/10.1371/journal.pone.0153746 PubMed DOI PMC

Sternes PR, Martin TM, Paley M et al (2020) HLA-A alleles including HLA-A29 affect the composition of the gut microbiome: a potential clue to the pathogenesis of birdshot retinochoroidopathy. Sci Rep 10:17636. https://doi.org/10.1038/s41598-020-74751-0 PubMed DOI PMC

Ye Z, Zhang N, Wu C et al (2018) A metagenomic study of the gut Microbiome in behcet’s disease. Microbiome 6:135. https://doi.org/10.1186/s40168-018-0520-6 PubMed DOI PMC

Ye Z, Wu C, Zhang N et al (2020) Altered gut Microbiome composition in patients with Vogt-Koyanagi-Harada disease. Gut Microbes 11:539–555. https://doi.org/10.1080/19490976.2019.1700754 PubMed DOI PMC

Huang X, Ye Z, Cao Q et al (2018) Gut microbiota composition and fecal metabolic phenotype in patients with acute anterior uveitis. Invest Opthalmology Visual Sci 59:1523. https://doi.org/10.1167/iovs.17-22677 DOI

Kalyana Chakravarthy S, Jayasudha R, Sai Prashanthi G et al (2018) Dysbiosis in the gut bacterial Microbiome of patients with uveitis, an inflammatory disease of the eye. Indian J Microbiol 58:457–469. https://doi.org/10.1007/s12088-018-0746-9 PubMed DOI PMC

Yamamoto ML, Schiestl RH (2014) Intestinal Microbiome and lymphoma development. Cancer J 20:190–194. https://doi.org/10.1097/PPO.0000000000000047 PubMed DOI PMC

Yamamoto ML, Maier I, Dang AT et al (2013) Intestinal Bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity. Cancer Res 73:4222–4232. https://doi.org/10.1158/0008-5472.CAN-13-0022 PubMed DOI PMC

Diefenbach CS, Peters BA, Li H et al (2021) Microbial dysbiosis is associated with aggressive histology and adverse clinical outcome in B-cell non-Hodgkin lymphoma. Blood Adv 5:1194–1198. https://doi.org/10.1182/bloodadvances.2020003129 PubMed DOI PMC

Yuan L, Wang W, Zhang W et al (2021) Gut microbiota in untreated diffuse large B cell lymphoma patients. Front Microbiol 12. https://doi.org/10.3389/fmicb.2021.646361

Lin Z, Mao D, Jin C et al (2023) The gut microbiota correlate with the disease characteristics and immune status of patients with untreated diffuse large B-cell lymphoma. Front Immunol 14. https://doi.org/10.3389/fimmu.2023.1105293

Stein-Thoeringer CK, Saini NY, Zamir E et al (2023) A non-antibiotic-disrupted gut Microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. Nat Med 29:906–916. https://doi.org/10.1038/s41591-023-02234-6 PubMed DOI PMC

Zhang Y, Han S, Xiao X et al (2023) Integration analysis of tumor metagenome and peripheral immunity data of diffuse large-B cell lymphoma. Front Immunol 14. https://doi.org/10.3389/fimmu.2023.1146861

Yoon SE, Kang W, Choi S et al (2023) The influence of microbial dysbiosis on immunochemotherapy-related efficacy and safety in diffuse large B-cell lymphoma. Blood 141. https://doi.org/10.1182/blood.2022018831

Samalia PD, Solanki J, Kam J et al (2025) From dysbiosis to disease: the microbiome’s influence on uveitis pathogenesis. Microorganisms 13:271. https://doi.org/10.3390/microorganisms13020271 PubMed DOI PMC

Mumcu G, Direskeneli H (2019) Triggering agents and Microbiome as environmental factors on behçet’s syndrome. Intern Emerg Med 14:653–660. https://doi.org/10.1007/s11739-018-2000-1 PubMed DOI

Kirino Y, Ideguchi H, Takeno M et al (2016) Continuous evolution of clinical phenotype in 578 Japanese patients with behçet’s disease: a retrospective observational study. Arthritis Res Ther 18:217. https://doi.org/10.1186/s13075-016-1115-x PubMed DOI PMC

Chung Y-R, Lee E-S, Kim MH et al (2015) Changes in ocular manifestations of behçet disease in Korean patients over time: A Single-center experience in the 1990s and 2000s. Ocul Immunol Inflamm 23:157–161. https://doi.org/10.3109/09273948.2014.918154 PubMed DOI

Kim DY, Choi MJ, Cho S et al (2014) Changing clinical expression of < scp > b ehçet disease in < scp > k orea during three decades (1983–2012): chronological analysis of 3674 hospital-based patients. Br J Dermatol 170:458–461. https://doi.org/10.1111/bjd.12661 PubMed DOI

O’Reilly PG, Claffey NM (2000) A history of oral sepsis as a cause of disease. Periodontol 2000 23:13–18. https://doi.org/10.1034/j.1600-0757.2000.2230102.x PubMed DOI

Klimova A, Heissigerova J, Rihova E et al (2018) Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse. Br J Ophthalmol 102:1579–1585. https://doi.org/10.1136/bjophthalmol-2017-311574 PubMed DOI

Stehlikova Z, Tlaskal V, Galanova N et al (2019) Oral microbiota composition and antimicrobial antibody response in patients with recurrent aphthous stomatitis. Microorganisms 7:636. https://doi.org/10.3390/microorganisms7120636 PubMed DOI PMC

Klindworth A, Pruesse E, Schweer T et al (2013) Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res 41:e1–e1. https://doi.org/10.1093/nar/gks808 PubMed DOI

Caporaso JG, Kuczynski J, Stombaugh J et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336. https://doi.org/10.1038/nmeth.f.303 PubMed DOI PMC

Wang Q, Garrity GM, Tiedje JM, Cole JR (2007) Naïve bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73:5261–5267. https://doi.org/10.1128/AEM.00062-07 PubMed DOI PMC

DeSantis TZ, Hugenholtz P, Larsen N et al (2006) Greengenes, a Chimera-Checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72:5069–5072. https://doi.org/10.1128/AEM.03006-05 PubMed DOI PMC

Lê S, Josse J, Husson F (2008) FactoMineR: an R package for multivariate analysis. J Stat Softw 25. https://doi.org/10.18637/jss.v025.i01

Kassambara A, Mundt F (2016) Factoextra: extract and visualize the results of multivariate data analyses. Contributed Packages, CRAN

Wickham H (2009) ggplot2. Springer New York, New York, NY

Oksanen J, Simpson GL, Blanchet FG et al (2001) Vegan: community ecology package. Contributed Packages, CRAN

Essex M, Rios Rodriguez V, Rademacher J et al (2024) Shared and distinct gut microbiota in spondyloarthritis, acute anterior uveitis, and crohn’s disease. Arthritis Rheumatol 76:48–58. https://doi.org/10.1002/art.42658 PubMed DOI

Wang Q, Wu S, Ye X et al (2023) Gut microbial signatures and their functions in behcet’s uveitis and Vogt-Koyanagi-Harada disease. J Autoimmun 137:103055. https://doi.org/10.1016/j.jaut.2023.103055 PubMed DOI

Leccese P, Alpsoy E (2019) Behçet’s disease: an overview of etiopathogenesis. Front Immunol 10. https://doi.org/10.3389/fimmu.2019.01067

Ogunkolade W, Senusi AA, Desai P et al (2023) Profiling the Microbiome of oral and genital mucosal surfaces in behçet’s disease. Clin Immunol 253:109654. https://doi.org/10.1016/j.clim.2023.109654 PubMed DOI

Torres-Morales J, Mark Welch JL, Dewhirst FE, Borisy GG (2023) Site-specialization of human oral Gemella species. J Oral Microbiol 15. https://doi.org/10.1080/20002297.2023.2225261

Bik EM, Long CD, Armitage GC et al (2010) Bacterial diversity in the oral cavity of 10 healthy individuals. ISME J 4:962–974. https://doi.org/10.1038/ismej.2010.30 PubMed DOI

Huse SM, Ye Y, Zhou Y, Fodor AA (2012) A core human Microbiome as viewed through 16S rRNA sequence clusters. PLoS ONE 7:e34242. https://doi.org/10.1371/journal.pone.0034242 PubMed DOI PMC

Klimesova K, Jiraskova Zakostelska Z, Tlaskalova-Hogenova H (2018) Oral bacterial and fungal Microbiome impacts colorectal carcinogenesis. Front Microbiol 9. https://doi.org/10.3389/fmicb.2018.00774

Sukmana BI, Saleh RO, Najim MA et al (2024) Oral microbiota and oral squamous cell carcinoma: a review of their relation and carcinogenic mechanisms. Front Oncol 14. https://doi.org/10.3389/fonc.2024.1319777