Download fulltext
HTML
1.
Hardianti Gunardi T, Paramita Susantono D, Arus Victor A, Sitompul R. Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?. JOVR [Internet]. 2021Oct.25 [cited 2024May10];16(4):631–643. Available from: https://knepublishing.com/index.php/JOVR/article/view/9754
https://doi.org/10.18502/jovr.v16i4.9754
statistics
- 1246 Abstract Views
- 652 PDF Views
- 0 HTML Views
- Cited by 2 articles
authors
-
Triana Hardianti Gunardi
Triana Hardianti Gunardi
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
-
Diannisa Paramita Susantono
Diannisa Paramita Susantono
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
-
Andi Arus Victor
Andi Arus Victor
Department of Ophthalmology, Dr. Cipto Mangunkusumo National General Hospital – Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
-
Ratna Sitompul
Ratna Sitompul
Department of Ophthalmology, Dr. Cipto Mangunkusumo National General Hospital – Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Published Date
- Oct 25, 2021
Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?
Abstract
Purpose: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis.
Methods: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef.
Results: The basis of the gut–eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut–eye axis is needed to develop practical targeted treatment.
Conclusion: Current preliminary studies are promising in establishing a causative gut–eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.
Keywords:
Atopobiosis, Autoimmune, Dysbiosis, Gut–Eye Axis, Uveitis
References
1. Cavuoto KM, Banerjee S, Galor A. Relationship between the microbiome and ocular health. The Ocular Surface 2019;17:384–392.
2. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J 2017;474:1823–1836.
3. 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;58:457–469.
4. Stern ME, Schaumburg CS, Dana R, Calonge M, Niederkorn JY, Pflugfelder SC. Autoimmunity at the ocular surface: pathogenesis and regulation. Mucosal Immunol 2010;3:425–442.
5. Moura-Coelho N, Proença RP, Palestine A, O’Keefe GD, Duta-Medeiros M. Treatment of uveitis [Internet]. American Academy of Ophthalmology (AAO); 2019. Available from: https://eyewiki.aao.org/Treatment_of_Uveitis
6. Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009;31:677–689.
7. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013;504:451–455.
8. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010;107:12204–12209.
9. Qiu X, Zhang M, Yang X, Hong N, Yu C. Faecalibacterium prausnitzii upregulates regulatory T cells and antiinflammatory cytokines in treating TNBS-induced colitis. J Crohn’s Colitis 2013;7:e558–e568.
10. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano G, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019;7:14.
11. Ottman N, Smidt H, de Vos WM, Belzer C. The function of our microbiota: who is out there and what do they do [Internet]? Front Cell Inf Microbio 2012 [cited 2020 Jul 3];2:104. Available from: http://journal.frontiersin.org/ article/10.3389/fcimb.2012.00104/abstract
12. Rausch P, Rühlemann M, Hermes BM, Doms S, Dagan T, Dierking K, et al. Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms. Microbiome 2019;7:133.
13. Forbes JD, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases [Internet]. Front Microbiol 2016 [cited 2019 Sep 8];7:1081. Available from: http://journal.frontiersin.org/Article/10. 3389/fmicb.2016.01081/abstract
14. van der Meulen T, Harmsen H, Bootsma H, Spijkervet F, Kroese F, Vissink A. The microbiome-systemic diseases connection. Oral Dis 2016;22:719–734.
15. Baim AD, Movahedan A, Farooq AV, Skondra D. The microbiome and ophthalmic disease. Exp Biol Med 2019;244:419–429.
16. Stebbings S. Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology 2002;41:1395–1401.
17. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, et al. Intestinal dysbiosis associated with systemic lupus erythematosus. mBio 2014;5:e01548-14.
18. Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 2015;39:567–591.
19. Horai R, Caspi RR. Microbiome and autoimmune uveitis. Front Immunol 2019;10:232.
20. Crane IJ, Liversidge J. Mechanisms of leukocyte migration across the blood–retina barrier. Semin Immunopathol 2008;30:165–77.
21. Deng Y, Ge X, Li Y, Zou B, Wen X, Chen W, et al. Identification of an intraocular microbiota. Cell Discov 2021;7:13.
22. Gómez LA, De Avila J, Castillo DM, Montenegro DA, Trujillo TG, Suárez LJ, et al. Porphyromonas gingivalis placental atopobiosis and inflammatory responses in women with adverse pregnancy outcomes. Front Microbiol 2020;11:591626.
23. Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, et al. Protective role of commensal bacteria in Sjögren Syndrome. J Autoimmun 2018;93:45–56.
24. Jabs DA. Immunosuppression for the Uveitides. Ophthalmology 2018;125:193–202.
25. Lin P, Bach M, Asquith M, Lee AY, Akileswaran L, Stauffer P, et al. HLA-B27 and human b2-microglobulin affect the gut microbiota of transgenic rats. PLoS One 2014;9:9.
26. Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, et al. Bifidobacteria Abundance-featured gut microbiota compositional change in patients with Behcet’s disease. PLoS One;11:e0153746.
27. Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, et al. Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 2015;14:269–276.
28. Jayasudha R, Kalyana Chakravarthy S, Sai Prashanthi G, Sharma S, Tyagi M, Shivaji S. Implicating dysbiosis of the gut fungal microbiome in uveitis, an inflammatory disease of the eye. Invest Ophthalmol Vis Sci 2019;60:1384.
29. 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;57:3747.
30. Rowan S, Jiang S, Korem T, Szymanski J, Chang ML, Szelog J, et al. Involvement of a gut–retina axis in protection against dietary glycemia-induced agerelated macular degeneration. Proc Natl Acad Sci USA 2017;114:E4472–E4481.
31. Horai R, Sen HN, Caspi RR. Commensal microbiota as a potential trigger of autoimmune uveitis. Expert Rev Clin Immunol 2017;13:291–293.
32. Horai R, Zárate-Bladés CR, Dillenburg-Pilla P, Chen J, Kielczewski JL, Silver PB, et al. Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site. Immunity 2015;43:343–353.
33. Zhou D, Pan Q, Shen F, Cao H, Ding W, Chen Y, et al. Total fecal microbiota transplantation alleviates high-fat dietinduced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep 2017;7:1529.
34. Blackwood BP, Yuan CY, Wood DR, Nicolas JD, Grothaus JS, Hunter CJ. Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. J Prob Health [Internet] 2017 [cited 2019 Sep 8];05:159. Available from: https://www.omicsonline.org/open-access/probioticlactobacillus- species-strengthen-intestinal-barrierfunction- andtight-junction-integrity-in-experimentalnecrotizing- ent-2329-8901-1000159.php?aid=85246
35. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent clostridium difficile-associated diarrhea. J Clin Gastroenterol 2010;44:354–360.
36. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407–415.
37. Hamilton-Miller J. Probiotics in the management of irritable bowel syndrome: a review of clinical trials. Microb Ecol Health Dis 2001;13:212–216.
38. Borody T, Nowak A, Torres M. Bacteriotherapy in chronic fatigue syndrome: a retrospective review. Am J Gastroenterol Suppl 2012;107:S591–S592.
39. Borody T, Campbell J, Torres M, Nowak A, Leis S. Reversal of idiopathic thrombocytopenic purpura [itP] with fecal micro-biota transplantation [FMt]. Am J Gastroenterol Suppl 2011;106:S352.
40. Borody T, Leis SM, Campbell J. Fecal microbiota trans-plantation (FMT) in multiple sclerosis (MS). Am J Gastroenterol 2011;106:S352.
41. Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, et al. A metagenomic study of the gut microbiome in Behcet’s disease. Microbiome 2018;6:135.
42. Smits LP, Bouter KEC, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology 2013;145:946–953.
43. Costello SP, Conlon MA, Vuaran MS, Roberts-Thomson IC, Andrews JM. Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data. Aliment Pharmacol Ther 2015;42:1011–1018.
44. Zeng W, Shen J, Bo T, Peng L, Xu H, Nasser MI, et al. Cutting edge: probiotics and fecal microbiota transplantation in immunomodulation. J Immunol Res 2019;2019:1–17.
45. Kim J, Choi S, Kim Y, Jeong H, Ryu J, Lee H, et al. Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye. Nutrients 2017;9:1166.
46. Liu Y, Alookaran J, Rhoads J. Probiotics in autoimmune and inflammatory disorders. Nutrients 2018;10:1537.
47. 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;246:435–441.
48. Miraglia Del Giudice M, Indolfi C, Capasso M, Maiello N, Decimo F, Ciprandi G. Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma. Ital J Pediatr 2017;43:25.
49. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori- Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 2018;174:1388–1405.e21.
50. Khoruts A. Targeting the microbiome: from probiotics to fecal microbiota transplantation. Genome Med 2018;10:80.
51. Lin P. The role of the intestinal microbiome in ocular inflammatory disease. Curr Opin Ophthalmol 2018;29:261–266.
52. de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, et al. Altered mucosal microbiome diversity and disease severity in Sjögren syndrome. Sci Rep 2016;6:23561.
53. Mendez R, Watane A, Farhangi M, Cavuoto KM, Leith T, Budree S, et al. Gut microbial dysbiosis in individuals with Sjögren’s syndrome. Microb Cell Fact 2020;19:90.
54. Beli E, Yan Y, Moldovan L, Vieira CP, Gao R, Duan Y, et al. Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db/db mice. Diabetes 2018;67:1867–1879.
55. Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia 2015;58:2206–2217.
56. Kasselman LJ, Vernice NA, DeLeon J, Reiss AB. The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. Atherosclerosis 2018;271:203–213.
57. Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, et al. Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep 2017;7:40826.
58. Kalyana Chakravarthy S, Jayasudha R, Ranjith K, Dutta A, Pinna NK, Mande SS, et al. Alterations in the gut bacterial microbiome in fungal Keratitis patients. PLoS One 2018;13:e0199640.
2. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J 2017;474:1823–1836.
3. 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;58:457–469.
4. Stern ME, Schaumburg CS, Dana R, Calonge M, Niederkorn JY, Pflugfelder SC. Autoimmunity at the ocular surface: pathogenesis and regulation. Mucosal Immunol 2010;3:425–442.
5. Moura-Coelho N, Proença RP, Palestine A, O’Keefe GD, Duta-Medeiros M. Treatment of uveitis [Internet]. American Academy of Ophthalmology (AAO); 2019. Available from: https://eyewiki.aao.org/Treatment_of_Uveitis
6. Gaboriau-Routhiau V, Rakotobe S, Lécuyer E, Mulder I, Lan A, Bridonneau C, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity 2009;31:677–689.
7. Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013;504:451–455.
8. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci USA 2010;107:12204–12209.
9. Qiu X, Zhang M, Yang X, Hong N, Yu C. Faecalibacterium prausnitzii upregulates regulatory T cells and antiinflammatory cytokines in treating TNBS-induced colitis. J Crohn’s Colitis 2013;7:e558–e568.
10. Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano G, Gasbarrini A, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019;7:14.
11. Ottman N, Smidt H, de Vos WM, Belzer C. The function of our microbiota: who is out there and what do they do [Internet]? Front Cell Inf Microbio 2012 [cited 2020 Jul 3];2:104. Available from: http://journal.frontiersin.org/ article/10.3389/fcimb.2012.00104/abstract
12. Rausch P, Rühlemann M, Hermes BM, Doms S, Dagan T, Dierking K, et al. Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms. Microbiome 2019;7:133.
13. Forbes JD, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases [Internet]. Front Microbiol 2016 [cited 2019 Sep 8];7:1081. Available from: http://journal.frontiersin.org/Article/10. 3389/fmicb.2016.01081/abstract
14. van der Meulen T, Harmsen H, Bootsma H, Spijkervet F, Kroese F, Vissink A. The microbiome-systemic diseases connection. Oral Dis 2016;22:719–734.
15. Baim AD, Movahedan A, Farooq AV, Skondra D. The microbiome and ophthalmic disease. Exp Biol Med 2019;244:419–429.
16. Stebbings S. Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology 2002;41:1395–1401.
17. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, et al. Intestinal dysbiosis associated with systemic lupus erythematosus. mBio 2014;5:e01548-14.
18. Potgieter M, Bester J, Kell DB, Pretorius E. The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol Rev 2015;39:567–591.
19. Horai R, Caspi RR. Microbiome and autoimmune uveitis. Front Immunol 2019;10:232.
20. Crane IJ, Liversidge J. Mechanisms of leukocyte migration across the blood–retina barrier. Semin Immunopathol 2008;30:165–77.
21. Deng Y, Ge X, Li Y, Zou B, Wen X, Chen W, et al. Identification of an intraocular microbiota. Cell Discov 2021;7:13.
22. Gómez LA, De Avila J, Castillo DM, Montenegro DA, Trujillo TG, Suárez LJ, et al. Porphyromonas gingivalis placental atopobiosis and inflammatory responses in women with adverse pregnancy outcomes. Front Microbiol 2020;11:591626.
23. Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, et al. Protective role of commensal bacteria in Sjögren Syndrome. J Autoimmun 2018;93:45–56.
24. Jabs DA. Immunosuppression for the Uveitides. Ophthalmology 2018;125:193–202.
25. Lin P, Bach M, Asquith M, Lee AY, Akileswaran L, Stauffer P, et al. HLA-B27 and human b2-microglobulin affect the gut microbiota of transgenic rats. PLoS One 2014;9:9.
26. Shimizu J, Kubota T, Takada E, Takai K, Fujiwara N, Arimitsu N, et al. Bifidobacteria Abundance-featured gut microbiota compositional change in patients with Behcet’s disease. PLoS One;11:e0153746.
27. Consolandi C, Turroni S, Emmi G, Severgnini M, Fiori J, Peano C, et al. Behçet’s syndrome patients exhibit specific microbiome signature. Autoimmun Rev 2015;14:269–276.
28. Jayasudha R, Kalyana Chakravarthy S, Sai Prashanthi G, Sharma S, Tyagi M, Shivaji S. Implicating dysbiosis of the gut fungal microbiome in uveitis, an inflammatory disease of the eye. Invest Ophthalmol Vis Sci 2019;60:1384.
29. 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;57:3747.
30. Rowan S, Jiang S, Korem T, Szymanski J, Chang ML, Szelog J, et al. Involvement of a gut–retina axis in protection against dietary glycemia-induced agerelated macular degeneration. Proc Natl Acad Sci USA 2017;114:E4472–E4481.
31. Horai R, Sen HN, Caspi RR. Commensal microbiota as a potential trigger of autoimmune uveitis. Expert Rev Clin Immunol 2017;13:291–293.
32. Horai R, Zárate-Bladés CR, Dillenburg-Pilla P, Chen J, Kielczewski JL, Silver PB, et al. Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site. Immunity 2015;43:343–353.
33. Zhou D, Pan Q, Shen F, Cao H, Ding W, Chen Y, et al. Total fecal microbiota transplantation alleviates high-fat dietinduced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep 2017;7:1529.
34. Blackwood BP, Yuan CY, Wood DR, Nicolas JD, Grothaus JS, Hunter CJ. Probiotic Lactobacillus species strengthen intestinal barrier function and tight junction integrity in experimental necrotizing enterocolitis. J Prob Health [Internet] 2017 [cited 2019 Sep 8];05:159. Available from: https://www.omicsonline.org/open-access/probioticlactobacillus- species-strengthen-intestinal-barrierfunction- andtight-junction-integrity-in-experimentalnecrotizing- ent-2329-8901-1000159.php?aid=85246
35. Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent clostridium difficile-associated diarrhea. J Clin Gastroenterol 2010;44:354–360.
36. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407–415.
37. Hamilton-Miller J. Probiotics in the management of irritable bowel syndrome: a review of clinical trials. Microb Ecol Health Dis 2001;13:212–216.
38. Borody T, Nowak A, Torres M. Bacteriotherapy in chronic fatigue syndrome: a retrospective review. Am J Gastroenterol Suppl 2012;107:S591–S592.
39. Borody T, Campbell J, Torres M, Nowak A, Leis S. Reversal of idiopathic thrombocytopenic purpura [itP] with fecal micro-biota transplantation [FMt]. Am J Gastroenterol Suppl 2011;106:S352.
40. Borody T, Leis SM, Campbell J. Fecal microbiota trans-plantation (FMT) in multiple sclerosis (MS). Am J Gastroenterol 2011;106:S352.
41. Ye Z, Zhang N, Wu C, Zhang X, Wang Q, Huang X, et al. A metagenomic study of the gut microbiome in Behcet’s disease. Microbiome 2018;6:135.
42. Smits LP, Bouter KEC, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology 2013;145:946–953.
43. Costello SP, Conlon MA, Vuaran MS, Roberts-Thomson IC, Andrews JM. Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data. Aliment Pharmacol Ther 2015;42:1011–1018.
44. Zeng W, Shen J, Bo T, Peng L, Xu H, Nasser MI, et al. Cutting edge: probiotics and fecal microbiota transplantation in immunomodulation. J Immunol Res 2019;2019:1–17.
45. Kim J, Choi S, Kim Y, Jeong H, Ryu J, Lee H, et al. Clinical effect of IRT-5 probiotics on immune modulation of autoimmunity or alloimmunity in the eye. Nutrients 2017;9:1166.
46. Liu Y, Alookaran J, Rhoads J. Probiotics in autoimmune and inflammatory disorders. Nutrients 2018;10:1537.
47. 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;246:435–441.
48. Miraglia Del Giudice M, Indolfi C, Capasso M, Maiello N, Decimo F, Ciprandi G. Bifidobacterium mixture (B longum BB536, B infantis M-63, B breve M-16V) treatment in children with seasonal allergic rhinitis and intermittent asthma. Ital J Pediatr 2017;43:25.
49. Zmora N, Zilberman-Schapira G, Suez J, Mor U, Dori- Bachash M, Bashiardes S, et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 2018;174:1388–1405.e21.
50. Khoruts A. Targeting the microbiome: from probiotics to fecal microbiota transplantation. Genome Med 2018;10:80.
51. Lin P. The role of the intestinal microbiome in ocular inflammatory disease. Curr Opin Ophthalmol 2018;29:261–266.
52. de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, et al. Altered mucosal microbiome diversity and disease severity in Sjögren syndrome. Sci Rep 2016;6:23561.
53. Mendez R, Watane A, Farhangi M, Cavuoto KM, Leith T, Budree S, et al. Gut microbial dysbiosis in individuals with Sjögren’s syndrome. Microb Cell Fact 2020;19:90.
54. Beli E, Yan Y, Moldovan L, Vieira CP, Gao R, Duan Y, et al. Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db/db mice. Diabetes 2018;67:1867–1879.
55. Delzenne NM, Cani PD, Everard A, Neyrinck AM, Bindels LB. Gut microorganisms as promising targets for the management of type 2 diabetes. Diabetologia 2015;58:2206–2217.
56. Kasselman LJ, Vernice NA, DeLeon J, Reiss AB. The gut microbiome and elevated cardiovascular risk in obesity and autoimmunity. Atherosclerosis 2018;271:203–213.
57. Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, et al. Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep 2017;7:40826.
58. Kalyana Chakravarthy S, Jayasudha R, Ranjith K, Dutta A, Pinna NK, Mande SS, et al. Alterations in the gut bacterial microbiome in fungal Keratitis patients. PLoS One 2018;13:e0199640.