Microbiota and age-related macular degeneration: where are we today?

Authors

  • Angelo Maria Minnella Università Cattolica del Sacro Cuore, Rome and UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome - Italy https://orcid.org/0000-0002-3754-7486
  • Francesca Albanesi Università Cattolica del Sacro Cuore, Rome - Italy https://orcid.org/0000-0002-1898-1367
  • Martina Maceroni Università Cattolica del Sacro Cuore, Rome and UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome - Italy https://orcid.org/0000-0001-5896-5313

DOI:

https://doi.org/10.33393/ao.2021.2241

Keywords:

Age-related macular degeneration, Gut-retina axis, Leaky gut, Microbiota, Micronutrients, Personalized medicine

Abstract

Age-related macular degeneration (AMD) is a complex degenerative multifactorial retinal disease, representing a leading cause of legal blindness among elderly individuals. It is well known that age, family history, smoking, nutrition, and inflammation contribute to the development of AMD. Recent studies support the existence of a gut-retina axis involved in the pathogenesis of several ocular diseases, including AMD. High-fat and high simple sugar diets determine a derangement of the gut microbiota, with an increase of gut permeability and systemic low-grade inflammation. Leaky gut is correlated with higher levels of circulating microbial-associated pattern molecules, which trigger the systemic release of potent proinflammatory mediators and stimulate the specific immune cells of the retina, contributing to retinal damage. All these findings suggest that microbiota is closely related to AMD and that it may be targeted in order to influence AMD pathogenesis and/or its clinical course.

References

  1. Li JQ, Welchowski T, Schmid M, Mauschitz MM, Holz FG, Finger RP. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. Br J Ophthalmol. 2020;104(8):1077-1084. https://doi.org/10.1136/bjophthalmol-2019-314422PMID:31712255
  2. Pennington KL, DeAngelis MM. Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors. Eye Vis (Lond). 2016;3(1):34. https://doi.org/10.1186/s40662-016-0063-5 PMID:28032115
  3. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e116. https://doi.org/10.1016/S2214-109X(13)70145-1 PMID:25104651
  4. Rinninella E, Mele MC, Merendino N, et al. the role of diet, micronutrients and the gut microbiota in age-related macular degeneration: new perspectives from the gut-retina axis. Nutrients. 2018;10(11):1677. https://doi.org/10.3390/nu10111677 PMID:30400586
  5. Sobrin L, Seddon JM. Nature and nurture—genes and environment—predict onset and progression of macular degeneration. Prog Retin Eye Res. 2014;40:1-15. https://doi.org/10.1016/j.preteyeres.2013.12.004 PMID:24374240
  6. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-1436. https://doi.org/10.1001/archopht.119.10.1417 PMID:11594942
  7. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015. https://doi.org/10.1001/jama.2013.4997 PMID:23644932
  8. Chew EY, Clemons TE, Sangiovanni JP, et al; Age-Related Eye Disease Study 2 (AREDS2) Research Group. Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3. JAMA Ophthalmol. 2014;132(2):142-149. https://doi.org/10.1001/jamaophthalmol.2013.7376 PMID:24310343
  9. Chiu CJ, Taylor A. Dietary hyperglycemia, glycemic index and metabolic retinal diseases. Prog Retin Eye Res. 2011;30(1):18-53. https://doi.org/10.1016/j.preteyeres.2010.09.001PMID:20868767
  10. Zhang QY, Tie LJ, Wu SS, et al. Overweight, obesity, and risk of age-related macular degeneration. Invest Ophthalmol Vis Sci. 2016;57(3):1276-1283. https://doi.org/10.1167/iovs.15-18637 PMID:26990164
  11. Peeters A, Magliano DJ, Stevens J, Duncan BB, Klein R, Wong TY. Changes in abdominal obesity and age-related macular degeneration: the Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 2008;126(11):1554-1560. https://doi.org/10.1001/archopht.126.11.1554PMID:19001224
  12. Andriessen EM, Wilson AM, Mawambo G, et al. Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization. EMBO Mol Med. 2016;8(12):1366-1379. https://doi.org/10.15252/emmm.201606531 PMID:27861126
  13. Sender R, Fuchs S, Milo R. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell. 2016;164(3):337-340. https://doi.org/10.1016/j.cell.2016.01.013 PMID:26824647
  14. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005;307(5717):1915-1920. https://doi.org/10.1126/science.1104816PMID:15790844
  15. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031. https://doi.org/10.1038/nature05414 PMID:17183312
  16. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635-1638. https://doi.org/10.1126/science.1110591 PMID:15831718
  17. Senghor B, Sokhna C, Ruimy R, Lagier JC. Gut microbiota diversity according to dietary habits and geographical provenance. Hum Microb J. 2018;7-8:1-9. https://doi.org/10.1016/j.humic.2018.01.001
  18. Semova I, Carten JD, Stombaugh J, et al. Microbiota regulate intestinal absorption and metabolism of fatty acids in the zebrafish. Cell Host Microbe. 2012;12(3):277-288. https://doi.org/10.1016/j.chom.2012.08.003 PMID:22980325
  19. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102(31):11070-11075. https://doi.org/10.1073/pnas.0504978102 PMID:16033867
  20. O’Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350(6265):1214-1215. https://doi.org/10.1126/science.aac8469 PMID:26785481
  21. Schleicher M, Weikel K, Garber C, Taylor A. Diminishing risk for age-related macular degeneration with nutrition: a current view. Nutrients. 2013;5(7):2405-2456. https://doi.org/10.3390/nu5072405 PMID:23820727
  22. Do MH, Lee E, Oh MJ, Kim Y, Park HY. High-glucose or -fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients. 2018;10(6):761. https://doi.org/10.3390/nu10060761 PMID:29899272
  23. Rowan S, Jiang S, Korem T, et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci USA. 2017;114(22):E4472-E4481. https://doi.org/10.1073/pnas.1702302114 PMID:28507131
  24. Cerf-Bensussan N, Gaboriau-Routhiau V. The immune system and the gut microbiota: friends or foes? Nat Rev Immunol. 2010;10(10):735-744. https://doi.org/10.1038/nri2850PMID:20865020
  25. Zinkernagel MS, Zysset-Burri DC, Keller I, et al. Association of the intestinal microbiome with the development of neovascular age-related macular degeneration. Sci Rep. 2017;7(1):40826. https://doi.org/10.1038/srep40826 PMID:28094305
  26. Morita Y, Jounai K, Sakamoto A, et al. Long-term intake of Lactobacillus paracasei KW3110 prevents age-related chronic inflammation and retinal cell loss in physiologically aged mice. Aging (Albany NY). 2018;10(10):2723-2740. https://doi.org/10.18632/aging.101583PMID:30341255
  27. Layana AG, Minnella AM, Garhöfer G, et al. Vitamin D and age-related macular degeneration. Nutrients. 2017;9(10):1120. https://doi.org/10.3390/nu9101120 PMID:29027953
  28. Luthold RV, Fernandes GR, Franco-de-Moraes AC, Folchetti LG, Ferreira SR. Gut microbiota interactions with the immunomodulatory role of vitamin D in normal individuals. Metabolism. 2017;69:76-86. https://doi.org/10.1016/j.metabol.2017.01.007 PMID:28285654
  29. Gubatan J, Moss AC. Vitamin D in inflammatory bowel disease: more than just a supplement. Curr Opin Gastroenterol. 2018;34(4):217-225. https://doi.org/10.1097/MOG.0000000000000449PMID:29762159
  30. Bashir M, Prietl B, Tauschmann M, et al. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. Eur J Nutr. 2016;55(4):1479-1489. https://doi.org/10.1007/s00394-015-0966-2 PMID:26130323
  31. Souied EH, Delcourt C, Querques G, et al; Nutritional AMD Treatment 2 Study Group. Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study. Ophthalmology. 2013;120(8):1619-1631. https://doi.org/10.1016/j.ophtha.2013.01.005 PMID:23395546
  32. SanGiovanni JP, Chew EY, Clemons TE, et al; Age-Related Eye Disease Study Research Group. The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS Report No. 20. Arch Ophthalmol. 2007;125(5):671-679. https://doi.org/10.1001/archopht.125.5.671 PMID:17502507
  33. Parolini C. Effects of fish n-3 PUFAs on intestinal microbiota and immune system. Mar Drugs. 2019;17(6):374. https://doi.org/10.3390/md17060374 PMID:31234533
  34. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-563. https://doi.org/10.1038/nature12820PMID:24336217
  35. Robertson RC, Kaliannan K, Strain CR, Ross RP, Stanton C, Kang JX. Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota. Microbiome. 2018;6(1):95. https://doi.org/10.1186/s40168-018-0476-6 PMID:29793531
  36. Niu J, Zhao W, Lu DQ, et al. Dual-function analysis of astaxanthin on golden pompano (Trachinotus ovatus) and its role in the regulation of gastrointestinal immunity and retinal mitochondrial dysfunction under hypoxia conditions. Front Physiol. 2020;11:568462. https://doi.org/10.3389/fphys.2020.568462 PMID:33335485
  37. Hu C, Tang L, Liu M, Lam PKS, Lam JCW, Chen L. Probiotic modulation of perfluorobutane sulfonate toxicity in zebrafish: disturbances in retinoid metabolism and visual physiology. Chemosphere. 2020;258:127409. https://doi.org/10.1016/j.chemosphere.2020.127409PMID:32569959
  38. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017;8:598. https://doi.org/10.3389/fimmu.2017.00598PMID:28588585
  39. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability—a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14(1):189. https://doi.org/10.1186/s12876-014-0189-7 PMID:25407511
  40. Berstad A, Arslan G, Folvik G; A. Berstad, G. Arslan, G. Folvik. Relationship between intestinal permeability and calprotectin concentration in gut lavage fluid. Scand J Gastroenterol. 2000;35(1):64-69. https://doi.org/10.1080/003655200750024551 PMID:10672837
  41. Iannaccone A, Giorgianni F, New DD, et al; Health ABC study. Circulating autoantibodies in age-related macular degeneration recognize human macular tissue antigens implicated in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. PLoS One. 2015;10(12):e0145323. https://doi.org/10.1371/journal.pone.0145323 PMID:26717306
  42. Daruich A, Picard E, Boatright JH, Behar-Cohen F. Review: the bile acids urso- and tauroursodeoxycholic acid as neuroprotective therapies in retinal disease. Mol Vis. 2019;25:610-624. PMID:31700226
  43. Tang J, Tang Y, Yi I, Chen DF. The role of commensal microflora-induced T cell responses in glaucoma neurodegeneration. Prog Brain Res. 2020;256(1):79-97. https://doi.org/10.1016/bs.pbr.2020.06.002 PMID:32958216
  44. Chaiwiang N, Poyomtip T. Microbial dysbiosis and microbiota-gut-retina axis: the lesson from brain neurodegenerative diseases to primary open-angle glaucoma pathogenesis of autoimmunity. Acta Microbiol Immunol Hung. 2019;66(4):541-558. https://doi.org/10.1556/030.66.2019.038PMID:31786943
  45. Zhou J, Yang J, Dai M, et al. A combination of inhibiting microglia activity and remodeling gut microenvironment suppresses the development and progression of experimental autoimmune uveitis. Biochem Pharmacol. 2020;180:114108. https://doi.org/10.1016/j.bcp.2020.114108PMID:32569628
  46. Shi C, Wang P, Airen S, et al. Nutritional and medical food therapies for diabetic retinopathy. Eye Vis (Lond). 2020;7(1):33. https://doi.org/10.1186/s40662-020-00199-y PMID:32582807