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Current Ophthalmology Reports

, Volume 7, Issue 3, pp 196–203 | Cite as

The Microbiome and Ocular Surface Disease

  • Arjun Watane
  • Kara M. Cavuoto
  • Santanu Banerjee
  • Anat GalorEmail author
Cornea (T Yamaguchi, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Cornea

Abstract

Purpose of Review

The human body lives in a symbiotic relationship with the bacteria, viruses, fungi, and protozoa that make up the microbiome. In this review, we discuss the compositions of the gut and ocular surface microbiomes in relationship to health and disease.

Recent Findings

The gut microbiome is dominated by Firmicutes, whereas the ocular surface is dominated by Proteobacteria. The compositions of the microbiome are similar between individuals at the phyla level, but differ at the genus level. Alterations in the microbiome have been associated with disease. For example, ocular diseases such as uveitis, dry eye, and keratitis have been associated with gut dysbiosis. In addition, ocular surface dysbiosis has been reported in diseases including dry eye, blepharitis, keratitis, and diabetic retinopathy.

Summary

Compositions of the gut and ocular surface microbiomes have been found to differ in disease states compared with controls. Further understanding of dysbiosis specific to a disease is needed to target these surfaces for therapeutic strategies.

Keywords

Gut microbiome Ocular surface disease Dysbiosis Gut-eye axis 

Notes

Funding

This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research EPID-006-15S (Dr. Galor), R01EY026174 (Dr. Galor), NIH Center Core Grant P30EY014801, and Research to Prevent Blindness Unrestricted Grant.

Compliance with Ethical Standards

Conflict of Interest

Arjun Watane, Kara M. Cavuoto, Santanu Banerjee, and Anat Galor each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baim AD, et al., The microbiome and ophthalmic disease. Exp Biol Med (Maywood). 2018;1535370218813616.Google Scholar
  2. 2.
    Qin J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59–65.CrossRefGoogle Scholar
  3. 3.
    Crow JR, Davis SL, Chaykosky DM, Smith TT, Smith JM. Probiotics and fecal microbiota transplant for primary and secondary prevention of Clostridium difficile infection. Pharmacotherapy. 2015;35(11):1016–25.CrossRefGoogle Scholar
  4. 4.
    Eckburg PB, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635–8.CrossRefGoogle Scholar
  5. 5.
    Tap J, Mondot S, Levenez F, Pelletier E, Caron C, Furet JP, et al. Towards the human intestinal microbiota phylogenetic core. Environ Microbiol. 2009;11(10):2574–84.CrossRefGoogle Scholar
  6. 6.
    Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner ACR, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010;192(19):5002–17.CrossRefGoogle Scholar
  7. 7.
    Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4):244–53.CrossRefGoogle Scholar
  8. 8.
    Ramakrishnan VR, Feazel LM, Gitomer SA, Ir D, Robertson CE, Frank DN. The microbiome of the middle meatus in healthy adults. PLoS One. 2013;8(12):e85507.CrossRefGoogle Scholar
  9. 9.
    • Huang Y, Yang B, Li W. Defining the normal core microbiome of conjunctival microbial communities. Clin Microbiol Infect. 2016;22(7):643 e7–643 e12. An important recent study characterizing the ocular surface microbiome, suggesting that phyla composition is consistent between individuals, but genera composition varies. CrossRefGoogle Scholar
  10. 10.
    Ozkan J, Willcox M, Wemheuer B, Wilcsek G, Coroneo M, Thomas T. Biogeography of the human ocular microbiota. Ocul Surf. 2019;17(1):111–8.CrossRefGoogle Scholar
  11. 11.
    • Ozkan J, et al. Identification and visualization of a distinct microbiome in ocular surface conjunctival tissue. Invest Ophthalmol Vis Sci. 2018;59(10):4268–76. An original study indicating that OSM varies by location within the eye and surrounding tissues. CrossRefGoogle Scholar
  12. 12.
    Dong Q, Brulc JM, Iovieno A, Bates B, Garoutte A, Miller D, et al. Diversity of bacteria at healthy human conjunctiva. Invest Ophthalmol Vis Sci. 2011;52(8):5408–13.CrossRefGoogle Scholar
  13. 13.
    Doan T, Akileswaran L, Andersen D, Johnson B, Ko N, Shrestha A, et al. Paucibacterial microbiome and resident DNA virome of the healthy conjunctiva. Invest Ophthalmol Vis Sci. 2016;57(13):5116–26.CrossRefGoogle Scholar
  14. 14.
    Petersen C, Round JL. Defining dysbiosis and its influence on host immunity and disease. Cell Microbiol. 2014;16(7):1024–33.CrossRefGoogle Scholar
  15. 15.
    Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012;3(4):289–306.CrossRefGoogle Scholar
  16. 16.
    LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24(2):160–8.CrossRefGoogle Scholar
  17. 17.
    Moon C, Baldridge MT, Wallace MA, Carey-Ann D, Burnham, Virgin HW, et al. Vertically transmitted faecal IgA levels determine extra-chromosomal phenotypic variation. Nature. 2015;521(7550):90–3.CrossRefGoogle Scholar
  18. 18.
    Arumugam M, Raes J, Pelletier E, le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–80.CrossRefGoogle Scholar
  19. 19.
    Palmer C, et al. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5(7):e177.CrossRefGoogle Scholar
  20. 20.
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222–7.CrossRefGoogle Scholar
  21. 21.
    Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533.CrossRefGoogle Scholar
  22. 22.
    McDermott AM. Antimicrobial compounds in tears. Exp Eye Res. 2013;117:53–61.CrossRefGoogle Scholar
  23. 23.
    Cavuoto KM, Banerjee S, Miller D, Galor A. Composition and comparison of the ocular surface microbiome in infants and older children. Transl Vis Sci Technol. 2018;7(6):16.CrossRefGoogle Scholar
  24. 24.
    • Cavuoto KM, Mendez R, Miller D, Galor A, Banerjee S. Effect of clinical parameters on the ocular surface microbiome in children and adults. Clin Ophthalmol. 2018;12:1189–97. An original study finding that the OSM composition may diversify with age. CrossRefGoogle Scholar
  25. 25.
    Wen X, Miao L, Deng Y, Bible PW, Hu X, Zou Y, et al. The influence of age and sex on ocular surface microbiota in healthy adults. Invest Ophthalmol Vis Sci. 2017;58(14):6030–7.CrossRefGoogle Scholar
  26. 26.
    Shin H, Price K, Albert L, Dodick J, Park L, Dominguez-Bello MG. Changes in the eye microbiota associated with contact lens wearing. MBio. 2016;7(2):e00198.CrossRefGoogle Scholar
  27. 27.
    Picchianti-Diamanti A, Panebianco C, Salemi S, Sorgi M, di Rosa R, Tropea A, et al. Analysis of gut microbiota in rheumatoid arthritis patients: disease-related dysbiosis and modifications induced by etanercept. Int J Mol Sci. 2018;19(10).Google Scholar
  28. 28.
    Chen J, Wright K, Davis JM, Jeraldo P, Marietta EV, Murray J, et al. An expansion of rare lineage intestinal microbes characterizes rheumatoid arthritis. Genome Med. 2016;8(1):43.CrossRefGoogle Scholar
  29. 29.
    Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202.CrossRefGoogle Scholar
  30. 30.
    Kalyana Chakravarthy S, Jayasudha R, Sai Prashanthi G, Ali MH, Sharma S, Tyagi M, et al. Dysbiosis in the gut bacterial microbiome of patients with uveitis, an inflammatory disease of the eye. Indian J Microbiol. 2018;58(4):457–69.CrossRefGoogle Scholar
  31. 31.
    Richards JL, Yap YA, McLeod KH, Mackay CR, Mariño E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunol. 2016;5(5):e82.CrossRefGoogle Scholar
  32. 32.
    Nakamura YK, Metea C, Karstens L, Asquith M, Gruner H, Moscibrocki C, et al. Gut microbial alterations associated with protection from autoimmune uveitis. Invest Ophthalmol Vis Sci. 2016;57(8):3747–58.CrossRefGoogle Scholar
  33. 33.
    de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, et al. Altered mucosal microbiome diversity and disease severity in Sjogren syndrome. Sci Rep. 2016;6:23561.CrossRefGoogle Scholar
  34. 34.
    Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, et al. Protective role of commensal bacteria in Sjogren syndrome. J Autoimmun. 2018;93:45–56.CrossRefGoogle Scholar
  35. 35.
    De Paiva CS, et al. Homeostatic control of conjunctival mucosal goblet cells by NKT-derived IL-13. Mucosal Immunol. 2011;4(4):397–408.CrossRefGoogle Scholar
  36. 36.
    • Wang C, et al. Sjogren-like lacrimal keratoconjunctivitis in germ-free mice. Int J Mol Sci. 2018;19(2) This study indicates found that desiccating stress in germ-free mice resulted in a worse dry eye phenotype compared with control mice. Google Scholar
  37. 37.
    Jayasudha R, Kalyana Chakravarthy S, Sai Prashanthi G, Sharma S, Garg P, Murthy SI, et al. Alterations in gut bacterial and fungal microbiomes are associated with bacterial keratitis, an inflammatory disease of the human eye. J Biosci. 2018;43(5):835–56.CrossRefGoogle Scholar
  38. 38.
    •• Kugadas A, et al. Impact of microbiota on resistance to ocular Pseudomonas aeruginosa-induced keratitis. PLoS Pathog. 2016;12(9):e1005855. An important study finding that when the gut of germ-free mice was re-colonized with human or mouse microbiomes, the mice became less susceptible to infection and had improved neutrophil function. CrossRefGoogle Scholar
  39. 39.
    David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63.CrossRefGoogle Scholar
  40. 40.
    Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016;529(7585):212–5.CrossRefGoogle Scholar
  41. 41.
    Dwivedi M, Kumar P, Laddha NC, Kemp EH. Induction of regulatory T cells: a role for probiotics and prebiotics to suppress autoimmunity. Autoimmun Rev. 2016;15(4):379–92.CrossRefGoogle Scholar
  42. 42.
    Andreasen AS, Larsen N, Pedersen-Skovsgaard T, Berg RMG, Møller K, Svendsen KD, et al. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects. Br J Nutr. 2010;104(12):1831–8.CrossRefGoogle Scholar
  43. 43.
    Ochoa-Reparaz J, et al. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010;3(5):487–95.CrossRefGoogle Scholar
  44. 44.
    • Morita Y, et al. Lactobacillus paracasei KW3110 prevents blue light-induced inflammation and degeneration in the retina. Nutrients. 2018;10(12). A study suggesting that eye disease may be able to be prevented with gut microbiome modulation through probiotics. Google Scholar
  45. 45.
    Kakihana K, Fujioka Y, Suda W, Najima Y, Kuwata G, Sasajima S, et al. Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut. Blood. 2016;128(16):2083–8.CrossRefGoogle Scholar
  46. 46.
    Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, et al. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha-defensins. Blood. 2012;120(1):223–31.CrossRefGoogle Scholar
  47. 47.
    Hori Y, Maeda N, Sakamoto M, Koh S, Inoue T, Tano Y. Bacteriologic profile of the conjunctiva in the patients with dry eye. Am J Ophthalmol. 2008;146(5):729–34.CrossRefGoogle Scholar
  48. 48.
    Graham JE, Moore JE, Jiru X, Moore JE, Goodall EA, Dooley JSG, et al. Ocular pathogen or commensal: a PCR-based study of surface bacterial flora in normal and dry eyes. Invest Ophthalmol Vis Sci. 2007;48(12):5616–23.CrossRefGoogle Scholar
  49. 49.
    Terzulli M, Contreras-Ruiz L, Kugadas A, Masli S, Gadjeva M. TSP-1 deficiency alters ocular microbiota: implications for Sjogren’s syndrome pathogenesis. J Ocul Pharmacol Ther. 2015;31(7):413–8.CrossRefGoogle Scholar
  50. 50.
    Duncan K, Jeng BH. Medical management of blepharitis. Curr Opin Ophthalmol. 2015;26(4):289–94.CrossRefGoogle Scholar
  51. 51.
    Zhang SD, He JN, Niu TT, Chan CY, Ren CY, Liu SS, et al. Bacteriological profile of ocular surface flora in meibomian gland dysfunction. Ocul Surf. 2017;15(2):242–7.CrossRefGoogle Scholar
  52. 52.
    Jiang X, Deng A, Yang J, Bai H, Yang Z, Wu J, et al. Pathogens in the meibomian gland and conjunctival sac: microbiome of normal subjects and patients with meibomian gland dysfunction. Infect Drug Resist. 2018;11:1729–40.CrossRefGoogle Scholar
  53. 53.
    Watters GA, Turnbull PR, Swift S, Petty A, Craig JP. Ocular surface microbiome in meibomian gland dysfunction. Clin Exp Ophthalmol. 2017;45(2):105–11.CrossRefGoogle Scholar
  54. 54.
    Lee SH, Oh DH, Jung JY, Kim JC, Jeon CO. Comparative ocular microbial communities in humans with and without blepharitis. Invest Ophthalmol Vis Sci. 2012;53(9):5585–93.CrossRefGoogle Scholar
  55. 55.
    Kulaçoğlu DN, Özbek A, Uslu H, Şahin F, Güllülü G, Koçer I, Karabela Y. Comparative lid flora in anterior blepharitis. Turk J Med Sci. 2001;31:359–63.Google Scholar
  56. 56.
    Stapleton F, Keay LJ, Sanfilippo PG, Katiyar S, Edwards KP, Naduvilath T. Relationship between climate, disease severity, and causative organism for contact lens-associated microbial keratitis in Australia. Am J Ophthalmol. 2007;144(5):690–8.CrossRefGoogle Scholar
  57. 57.
    •• St Leger AJ, et al. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal gammadelta T cells. Immunity. 2017;47(1):148–158 e5. This study shows that the depletion of C. mastitidis from the ocular surface was associated with increased susceptibility to keratitis with C. albicans and P. aeruginosa, suggesting a role of the OSM in ocular surface immunity. CrossRefGoogle Scholar
  58. 58.
    Ham B, Hwang HB, Jung SH, Chang S, Kang KD, Kwon MJ. Distribution and diversity of ocular microbial communities in diabetic patients compared with healthy subjects. Curr Eye Res. 2018;43(3):314–24.CrossRefGoogle Scholar
  59. 59.
    Adam M, Balcı M, Bayhan HA, İnkaya AÇ, Uyar M, Gürdal C. Conjunctival flora in diabetic and nondiabetic individuals. Turk J Ophthalmol. 2015;45(5):193–6.CrossRefGoogle Scholar
  60. 60.
    Yang C, Fei Y, Qin Y, Luo D, Yang S, Kou X, et al. Bacterial flora changes in conjunctiva of rats with streptozotocin-induced type I diabetes. PLoS One. 2015;10(7):e0133021.CrossRefGoogle Scholar
  61. 61.
    Krolewski AS, Warram JH, Rand LI, Christlieb AR, Busick EJ, Kahn CR. Risk of proliferative diabetic retinopathy in juvenile-onset type I diabetes: a 40-yr follow-up study. Diabetes Care. 1986;9(5):443–52.CrossRefGoogle Scholar
  62. 62.
    Iovieno A, Lambiase A, Sacchetti M, Stampachiacchiere B, Micera A, Bonini S. Preliminary evidence of the efficacy of probiotic eye-drop treatment in patients with vernal keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol. 2008;246(3):435–41.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Arjun Watane
    • 1
  • Kara M. Cavuoto
    • 1
  • Santanu Banerjee
    • 2
  • Anat Galor
    • 1
    • 3
    Email author
  1. 1.Bascom Palmer Eye InstituteUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Department of SurgeryUniversity of Miami Miller School of MedicineMiamiUSA
  3. 3.Miami Veterans Administration Medical CenterMiamiUSA

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