Advertisement

Indian Journal of Microbiology

, Volume 58, Issue 4, pp 457–469 | Cite as

Dysbiosis in the Gut Bacterial Microbiome of Patients with Uveitis, an Inflammatory Disease of the Eye

  • Sama Kalyana Chakravarthy
  • Rajagopalaboopathi Jayasudha
  • Gumpili Sai Prashanthi
  • Mohammed Hasnat Ali
  • Savitri Sharma
  • Mudit Tyagi
  • Sisinthy ShivajiEmail author
Original Research Article

Abstract

Uveitis (UVT), an inflammatory disease of the eye significantly contributes to vision impairment and blindness. Uveitis is associated with systemic infectious and autoimmune diseases, but in most cases, the aetiology remains unidentified. Dysbiosis in the gut microbiome has been implicated in autoimmune diseases, inflammatory diseases, cancers and mental disorders. In a mice model of autoimmune UVT, it was observed that manipulating the gut microbiome reduces the inflammation and disease severity. Further, alterations in the bacterial gut microbiome and their metabolites were reported in UVT patients from a Chinese cohort. Hence, it is worth comparing the bacterial gut microbiome of UVT patients with that of healthy controls (HC) to ascertain whether dysbiosis of the gut microbiome has implications in UVT. Our analyses showed reduced diversity of several anti-inflammatory organisms including Faecalibacterium, Bacteroides, Lachnospira, Ruminococcus and members of Lachnospiraceae and Ruminococcaceae families, and enrichment of Prevotella (proinflammatory) and Streptococcus (pathogenic) OTUs in UVT microbiomes compared to HC. In addition, decrease in probiotic and antibacterial organisms was observed in UVT compared to HC microbiomes. Heatmap and PCoA plots also indicated significant variations in the microbiomes of UVT versus HC. This is the first study demonstrating dysbiosis in the gut bacterial communities of UVT patients in an Indian cohort and suggests a role of the gut microbiome in the pathophysiology of UVT.

Keywords

Uveitis Gut microbiome Dysbiosis V3–V4 region of 16S rRNA gene Illumina Miseq 

Notes

Acknowledgements

The study was supported by grants received from the Hyderabad Eye Research Foundation. We would like to thank Dr. Annie Mathai for helping in recruitment of Uveitis patients.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was taken from all the study subjects prior to sample collection. The study protocols were approved by the Institutional Review Board of L. V. Prasad Eye Institute, Hyderabad (Ethics Ref. No. LEC 06-14-060) and all methods were performed in accordance with relevant guidelines and regulations.

Supplementary material

12088_2018_746_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 16 kb)
12088_2018_746_MOESM2_ESM.xlsx (893 kb)
Supplementary material 2 (XLSX 893 kb)
12088_2018_746_MOESM3_ESM.xlsx (38 kb)
Supplementary material 3 (XLSX 37 kb)
12088_2018_746_MOESM4_ESM.docx (31 kb)
Supplementary material 4 (DOCX 31 kb)

References

  1. 1.
    Abdulaal MR, Abiad BH, Hamam RN (2015) Uveitis in the aging eye: incidence, patterns, and differential diagnosis. J Ophthalmol.  https://doi.org/10.1155/2015/509456 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Sharma SM, Fu DJ, Xue K (2017) A review of the landscape of targeted immunomodulatory therapies for non-infectious uveitis. Ophthalmol Ther.  https://doi.org/10.1007/s40123-017-0115-5 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Horai R, Sen HN, Caspi RR (2017) Commensal microbiota as a potential trigger of autoimmune uveitis. Expert Rev Clin Immunol 13:291–293.  https://doi.org/10.1080/1744666x.2017.1288098 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Shivaji S (2017) We are not alone: a case for the human microbiome in extra intestinal diseases. Gut Pathog 9:13.  https://doi.org/10.1186/s13099-017-0163-3 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Tlaskalova-Hogenova H, Stepankova R, Kozakova H, Hudcovic T, Vannucci L, Tuckova L, Rossmann P, Klimesova K, Pribylova J, Bartova J, Sanchez D, Fundova P, Borovska D, Srutkova D, Zidek Z, Schwarzer M, Drastich P, Funda DP (2011) The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases. Cell Mol Immunol 8:110–120.  https://doi.org/10.1038/cmi.2010.67 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Aas J, Gessert CE, Bakken JS (2003) Recurrent Clostridium difficile colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis 36:580–585.  https://doi.org/10.1086/367657 CrossRefPubMedGoogle Scholar
  7. 7.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1131.  https://doi.org/10.1038/nature05414 CrossRefPubMedGoogle Scholar
  8. 8.
    Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF, Chen GY, Schloss PD (2013) The gut microbiome modulates colon tumorigenesis. mBio 4:e00692–00613.  https://doi.org/10.1128/mBio.00692-13 CrossRefGoogle Scholar
  9. 9.
    Malan-Muller S, Valles-Colomer M, Raes J, Lowry CA, Seedat S, Hemmings SMJ (2017) The gut microbiome and mental health: implications for anxiety- and trauma-related disorders. OMICS 22.  https://doi.org/10.1089/omi.2017.0077 CrossRefGoogle Scholar
  10. 10.
    Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011) Human nutrition, the gut microbiome, and immune system: envisioning the future. Nature 474:327–336.  https://doi.org/10.1038/nature10213 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM, de Vos WM, Cani PD (2013) Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 110:9066–9071.  https://doi.org/10.1073/pnas.1219451110 CrossRefPubMedGoogle Scholar
  12. 12.
    Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN, Gordon JI, Onderdonk AB, Glimcher LH (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8:292–300.  https://doi.org/10.1016/j.chom.2010.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, Littman DR, Benoist C, Mathis D (2010) Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity 32:815–827.  https://doi.org/10.1016/j.immuni.2010.06.001 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Nakamura YK, Metea C, Karstens L, Asquith M, Gruner H, Moscibrocki C, Lee I, Brislawn CJ, Jansson JK, Rosenbaum JT, Lin P (2016) Gut microbial alterations associated with protection from autoimmune uveitis. Invest Ophthalmol Vis Sci 57:3747–3758.  https://doi.org/10.1167/iovs.16-19733 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rowan S, Jiang S, Korem T, Szymanski J, Chang ML, Szelog J, Cassalman C, Dasuri K, McGuire C, Nagai R, Du XL, Brownlee M, Rabbani N, Thornalley PJ, Baleja JD, Deik AA, Pierce KA, Scott JM, Clish CB, Smith DE, Weinberger A, Avnit-Sagi T, Lotan-Pompan M, Segal E, Taylor A (2017) Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci USA 114:E4472–E4481.  https://doi.org/10.1073/pnas.1702302114 CrossRefPubMedGoogle Scholar
  16. 16.
    de Paiva CS, Jones DB, Stern ME, Bian F, Moore QL, Corbiere S, Streckfus CF, Hutchinson DS, Ajami NJ, Petrosino JF, Pflugfelder SC (2016) Altered mucosal microbiome diversity and disease severity in sjögren syndrome. Sci Rep 6:23561.  https://doi.org/10.1038/srep23561 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Zinkernagel MS, Zysset-Burri DC, Keller I, Berger LE, Leichtle AB, Largiadèr CR, Fiedler GM, Wolf S (2017) Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep 7:40826.  https://doi.org/10.1038/srep40826 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Huang X, Ye Z, Cao Q, Su G, Wang Q, Deng J, Zhou C, Kijlstra A, Yang P (2018) Gut microbiota composition and fecal metabolic phenotype in patients with acute anterior uveitis. Invest Ophthalmol Vis Sci 59:1523–1531.  https://doi.org/10.1167/iovs.17-22677 CrossRefPubMedGoogle Scholar
  19. 19.
    Magoc T, Salzberg SL (2011) FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics 27:2957–2963.  https://doi.org/10.1093/bioinformatics/btr507 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF (2009) Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75:7537–7541.  https://doi.org/10.1128/aem.01541-09 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504.  https://doi.org/10.1101/gr.1239303 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Faust K, Raes J (2016) CoNet app: inference of biological association networks using Cytoscape. F1000Res 5:1519.  https://doi.org/10.12688/f1000research.9050.2 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Frank DN, St. Amand AL, Feldman RA, Boedeker EC, Harpaz N, Pace NR (2007) Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci USA 104:13780–13785.  https://doi.org/10.1073/pnas.0706625104 CrossRefPubMedGoogle Scholar
  24. 24.
    Dehingia M, Thangjam Devi K, Talukdar NC, Talukdar R, Reddy N, Mande SS, Deka M, Khan MR (2015) Gut bacterial diversity of the tribes of India and comparison with the worldwide data. Sci Rep 5:18563.  https://doi.org/10.1038/srep18563 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bhute S, Pande P, Shetty SA, Shelar R, Mane S, Kumbhare SV, Gawali A, Makhani H, Navandar M, Dhotre D, Lubree H, Agarwal D, Patil R, Ozarkar S, Ghaskadbi S, Yajnik C, Juvekar S, Makharia GK, Shouche YS (2016) Molecular characterization and meta-analysis of gut microbial communities illustrate enrichment of Prevotella and Megasphaera in Indian subjects. Front Microbiol 7:660.  https://doi.org/10.3389/fmicb.2016.00660 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Fang X, Wang X, Yang S, Meng F, Wei H, Chen T (2016) Evaluation of the microbial diversity in amyotrophic lateral sclerosis using high-throughput sequencing. Front Microbiol 7:1479.  https://doi.org/10.3389/fmicb.2016.01479 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Anand S, Kaur H, Mande SS (2016) Comparative in silico analysis of butyrate production pathways in gut commensals and pathogens. Front Microbiol 7:1945.  https://doi.org/10.3389/fmicb.2016.01945 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Richards JL, Yap YA, McLeod KH, Mackay CR, Marino E (2016) Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunol 5:e82.  https://doi.org/10.1038/cti.2016.29 CrossRefGoogle Scholar
  29. 29.
    Kang S, Denman SE, Morrison M, Yu Z, Dore J, Leclerc M, McSweeney CS (2010) Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis 16:2034–2042.  https://doi.org/10.1002/ibd.21319 CrossRefPubMedGoogle Scholar
  30. 30.
    Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, Ballet V, Claes K, Van Immerseel F, Verbeke K, Ferrante M, Verhaegen J, Rutgeerts P, Vermeire S (2014) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63:1275–1283.  https://doi.org/10.1136/gutjnl-2013-304833 CrossRefPubMedGoogle Scholar
  31. 31.
    Leser T, Myling-Petersen D, Wellejus A, Brockmann E, Olsen J, Rehdin S (2016) Probiotic strains of Bifidobacterium adolescentis. In: Conference proceedings of IPC 2016, p 108Google Scholar
  32. 32.
    Kim J, Choi SH, Kim YJ, Jeong HJ, Ryu JS, Lee HJ, Kim TW, Im SH, Oh JY, Kim MK (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 CrossRefPubMedCentralGoogle Scholar
  33. 33.
    Horai R, Zarate-Blades CR, Dillenburg-Pilla P, Chen J, Kielczewski JL, Silver PB, Jittayasothorn Y, Chan CC, Yamane H, Honda K, Caspi RR (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 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, Collini S, Pieraccini G, Lionetti P (2010) Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 107:14691–14696.  https://doi.org/10.1073/pnas.1005963107 CrossRefPubMedGoogle Scholar
  35. 35.
    Sood U, Bajaj A, Kumar R, Khurana S, Kalia VC (2018) Infection and microbiome: impact of tuberculosis on human gut microbiome of Indian cohort. Indian J Microbiol 58:123–125.  https://doi.org/10.1007/s12088-018-0706-4 CrossRefPubMedGoogle Scholar
  36. 36.
    Lukiw WJ (2016) Bacteroides fragilis lipopolysaccharide and inflammatory signaling in Alzheimer’s disease. Front Microbiol 7:1544.  https://doi.org/10.3389/fmicb.2016.01544 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Yun JH, Yim DS, Kang JY, Kang BY, Shin EA, Chung MJ, Kim SD, Baek DH, Kim K, Ha NJ (2005) Identification of Lactobacillus ruminus SPM0211 isolated from healthy Koreans and its antimicrobial activity against some pathogens. Arch Pharm Res 28:660–666.  https://doi.org/10.1007/BF02969355 CrossRefPubMedGoogle Scholar
  38. 38.
    Ferrario C, Taverniti V, Milani C, Fiore W, Laureati M, De Noni I, Stuknyte M, Chouaia B, Riso P, Guglielmetti S (2014) Modulation of fecal clostridiales bacteria and butyrate by probiotic intervention with Lactobacillus paracasei DG varies among healthy adults. J Nutr 144:1787–1796.  https://doi.org/10.3945/jn.114.197723 CrossRefPubMedGoogle Scholar
  39. 39.
    Avelar KE, Pinto LJ, Antunes LC, Lobo LA, Bastos MC, Domingues RM, Ferreira MC (1999) Production of bacteriocin by Bacteriodes fragilis and partial characterization. Lett Appl Microbiol 29:264–268.  https://doi.org/10.1046/j.1365-2672.1999.00603.x CrossRefPubMedGoogle Scholar
  40. 40.
    Chatzidaki-Livanis M, Coyne MJ, Comstock LE (2014) An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol Microbiol 94:1361–1374.  https://doi.org/10.1111/mmi.12839 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Association of Microbiologists of India 2018

Authors and Affiliations

  • Sama Kalyana Chakravarthy
    • 1
  • Rajagopalaboopathi Jayasudha
    • 1
  • Gumpili Sai Prashanthi
    • 1
  • Mohammed Hasnat Ali
    • 2
  • Savitri Sharma
    • 1
  • Mudit Tyagi
    • 3
  • Sisinthy Shivaji
    • 1
    Email author
  1. 1.Jhaveri Microbiology Centre, Brien Holden Eye Research CentreL. V. Prasad Eye InstituteHyderabadIndia
  2. 2.Clinical Epidemiology and Bio-StatisticsL. V. Prasad Eye InstituteHyderabadIndia
  3. 3.Smt. Kanuri Santhamma Center for Vitreoretinal DiseasesL. V. Prasad Eye InstituteHyderabadIndia

Personalised recommendations