{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:26:19Z","timestamp":1793384779724,"version":"4.5.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>The interplay between human microbiota and various physiological systems has garnered significant attention in recent years. The gut microbiota plays a critical role in maintaining physiological homeostasis and influences various aspects of human health, particularly via the gut brain axis. Since 2017, the challenging concept of the gut-retina axis has emerged thanks to a network analysis emphasizing the potential role of the gut microbiota disruption in the development of the age-related macular degeneration and further retinal damages. Many other ocular disorders have been linked to the dysbiosis of the gut microbiota, including uveitis and glaucoma. It has been shown that age related macular degeneration can be prevented or reversed using a diet that induces changes in the gut microbiota. The potential link between the gut microbiota as well as others types of microbiota such as the ocular surface microbiota and the development\/progression of age related as well as inherited retinal degenerations and other degenerative eye diseases, has recently been broadened. Therefore, the pathogenesis of several eye diseases has recently been associated with a larger perception called the gut eye axis. This mini-review examines the potential mechanisms underlying the gut eye axis and suggests implications for the management of eye diseases. By understanding the modulation of the gut microbiota and its impact on eye disease, this mini-review provides insight into potential therapeutic interventions and avenues for future research.<\/jats:p>","DOI":"10.3389\/fncel.2024.1468187","type":"journal-article","created":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:29:56Z","timestamp":1727310596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["The gut-eye axis: the retinal\/ocular degenerative diseases and the emergent therapeutic strategies"],"prefix":"10.3389","volume":"18","author":[{"given":"Sonda","family":"Kammoun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Rekik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryj","family":"Dlensi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Aloulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walid","family":"Smaoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahla","family":"Sellami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Trigui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Gargouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Chaari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayet","family":"Sellami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhawia","family":"Elatoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed","family":"Khemakhem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Hadrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourour","family":"Neji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balkiss","family":"Abdelmoula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouha","family":"Bouayed Abdelmoula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1038\/nrneph.2015.191","article-title":"The gut microbiome, diet, and links to cardiometabolic and chronic disorders","volume":"12","author":"Aron-Wisnewsky","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.2337\/db18-0158","article-title":"Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db\/db mice","volume":"67","author":"Beli","year":"2018","journal-title":"Diabetes"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"108867","DOI":"10.1016\/j.exer.2021.108867","article-title":"The gut microbiota in retinal diseases","volume":"214","author":"Bringer","year":"2022","journal-title":"Exp. Eye Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3390\/antiox8080281","article-title":"Carnosine decreases PMA-induced oxidative stress and inflammation in murine macrophages","volume":"8","author":"Caruso","year":"2019","journal-title":"Antioxidants (Basel, Switzerland)"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5231","DOI":"10.3390\/jcm12165231","article-title":"The impact of microbiota on the gut-brain axis: examining the complex interplay and implications","volume":"12","author":"Chaudhry","year":"2023","journal-title":"J. Clin. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1038\/s41467-018-05681-9","article-title":"Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/S0140-6736(09)62124-3","article-title":"Diabetic retinopathy","volume":"376","author":"Cheung","year":"2010","journal-title":"Lancet (London, England)"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1038\/s41598-021-82538-0","article-title":"Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy","volume":"11","author":"Das","year":"2021","journal-title":"Sci. Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41421-021-00245-6","article-title":"Identification of an intraocular microbiota","volume":"7","author":"Deng","year":"2021","journal-title":"Cell Discovery"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00109-020-01995-8","article-title":"RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy","volume":"99","author":"Dong","year":"2021","journal-title":"J. Mol. Med. (Berl)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1016\/j.ajpath.2023.03.005","article-title":"Microbiome and inherited retinal degenerations","volume":"193","author":"Douglas","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s40123-020-00278-2","article-title":"The gut-eye axis: lessons learned from murine models","volume":"9","author":"Floyd","year":"2020","journal-title":"Ophthalmol Therapy"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1225859","DOI":"10.3389\/fcimb.2023.1225859","article-title":"Gut microbiota and eye diseases: a bibliometric study and visualization analysis","volume":"13","author":"Fu","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"102535","DOI":"10.1016\/j.autrev.2020.102535","article-title":"Glaucoma is an autoimmune disease","volume":"19","author":"Geyer","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"107921","DOI":"10.1016\/j.exer.2020.107921","article-title":"Gut microbiota compositional profile and serum metabolic phenotype in patients with primary open-angle glaucoma","volume":"191","author":"Gong","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1038\/s41467-019-11262-1","article-title":"A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration","volume":"10","author":"Handa","year":"2019","journal-title":"Nat. Commun."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3390\/medicina60040592","article-title":"Microbial dynamics in ophthalmic health: exploring the interplay between human microbiota and Glaucoma pathogenesis","volume":"60","author":"Hern\u00e1ndez-Zulueta","year":"2024","journal-title":"Medicina (Kaunas)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1136\/gutjnl-2015-310027","article-title":"Real friends: Faecalibacterium prausnitzii supports mucosal immune homeostasis","volume":"65","author":"Hornef","year":"2016","journal-title":"Gut"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3390\/nu14010166","article-title":"Gut microbiota and complications of Type-2 diabetes","volume":"14","author":"Iatcu","year":"2021","journal-title":"Nutrients"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3390\/biology12020195","article-title":"From dysbiosis to neurodegenerative diseases through different communication pathways: an overview","volume":"12","author":"Intili","year":"2023","journal-title":"Biology"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e0243077","DOI":"10.1371\/journal.pone.0243077","article-title":"Gut mycobiomes are altered in people with type 2 diabetes mellitus and diabetic retinopathy","volume":"15","author":"Jayasudha","year":"2020","journal-title":"PLoS One"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s12088-018-0746-9","article-title":"Dysbiosis in the gut bacterial microbiome of patients with uveitis, an inflammatory disease of the eye","volume":"58","author":"Kalyana Chakravarthy","year":"2018","journal-title":"Indian J. Microbiol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1167\/iovs.62.7.19","article-title":"Association between gut microbial abundance and sight-threatening diabetic retinopathy","volume":"62","author":"Khan","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.3389\/fmicb.2018.01835","article-title":"The human gut microbiome \u2013 a potential controller of wellness and disease","volume":"9","author":"Kho","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41421-024-00709-5","article-title":"Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis","volume":"10","author":"Li","year":"2024","journal-title":"Cell Discovery"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1097\/ICU.0000000000000465","article-title":"The role of the intestinal microbiome in ocular inflammatory disease","volume":"29","author":"Lin","year":"2018","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1111\/ceo.13493","article-title":"Importance of the intestinal microbiota in ocular inflammatory diseases: a review","volume":"47","author":"Lin","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e0229029","DOI":"10.1371\/journal.pone.0229029","article-title":"Gut dysbiosis is prevailing in Sj\u00f6gren's syndrome and is related to dry eye severity","volume":"15","author":"Moon","year":"","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e0243176","DOI":"10.1371\/journal.pone.0243176","article-title":"Effect of IRT5 probiotics on dry eye in the experimental dry eye mouse model","volume":"15","author":"Moon","year":"","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"8443","DOI":"10.3390\/ijms21228443","article-title":"Can gut microbiota affect dry eye syndrome?","volume":"21","author":"Moon","year":"","journal-title":"Int. J. Mol. Sci."},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.01.318949","article-title":"High throughput RNA sequencing of mice retina reveals metabolic pathways involved in the gut-retina axis","volume":"2020","author":"Nadeem","year":"2020","journal-title":"bioRxiv"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1080\/07853890.2021.1925150","article-title":"Influence of gut microbiota on eye diseases: an overview","volume":"53","author":"Napolitano","year":"2021","journal-title":"Ann. Med."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s40168-022-01243-w","article-title":"Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain","volume":"10","author":"Parker","year":"2022","journal-title":"Microbiome"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/ajg.2014.427","article-title":"Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?","volume":"110","author":"Rajili\u0107-Stojanovi\u0107","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.3390\/nu10111677","article-title":"The role of diet, micronutrients and the gut microbiota in age-related macular degeneration: new perspectives from the gut-retina axis","volume":"10","author":"Rinninella","year":"2018","journal-title":"Nutrients"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jaut.2018.05.008","article-title":"Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex","volume":"92","author":"Rizzetto","year":"2018","journal-title":"J. Autoimmun."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"E4472","DOI":"10.1073\/pnas.1702302114","article-title":"Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration","volume":"114","author":"Rowan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"726792","DOI":"10.3389\/fmicb.2021.726792","article-title":"Gut microbiome in retina health: the crucial role of the gut-retina Axis","volume":"12","author":"Scuderi","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00535-015-1064-1","article-title":"The microbiota in inflammatory bowel disease","volume":"50","author":"Sheehan","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1007\/s10792-020-01587-y","article-title":"Glaucoma patients have an increased level of trimethylamine, a toxic product of gut bacteria, in the aqueous humor: a pilot study","volume":"41","author":"Skrzypecki","year":"2021","journal-title":"Int. Ophthalmol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1097\/IJG.0000000000001025","article-title":"Butyrate, a gut bacterial metabolite, lowers intraocular pressure in normotensive but not in hypertensive rats","volume":"27","author":"Skrzypecki","year":"2018","journal-title":"J. Glaucoma"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"6257","DOI":"10.3390\/ijms25116257","article-title":"Exploring the ocular surface microbiome and tear proteome in glaucoma","volume":"25","author":"Sp\u00f6rri","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuelling metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1225875","DOI":"10.3389\/fnins.2023.1225875","article-title":"The gut microbiota-brain axis in neurological disorder","volume":"17","author":"Ullah","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"eaaf9655","DOI":"10.1126\/scitranslmed.aaf9655","article-title":"IgA-coated E. coli enriched in Crohn's disease spondyloarthritis promote TH17-dependent inflammation","volume":"9","author":"Viladomiu","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"103055","DOI":"10.1016\/j.jaut.2023.103055","article-title":"Gut microbial signatures and their functions in Behcet's uveitis and Vogt-Koyanagi-Harada disease","volume":"137","author":"Wang","year":"2023","journal-title":"J. Autoimmun."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e001547","DOI":"10.1136\/bmjophth-2023-001547","article-title":"Effect of the gut microbiome in glaucoma risk from the causal perspective","volume":"9","author":"Wu","year":"2024","journal-title":"BMJ Open Ophthalmol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"759333","DOI":"10.3389\/fcimb.2021.759333","article-title":"Microbiota and ocular diseases","volume":"11","author":"Xue","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"154712","DOI":"10.1016\/j.metabol.2021.154712","article-title":"Role of the gut microbiota in type 2 diabetes and related diseases","volume":"117","author":"Yang","year":"2021","journal-title":"Metab. Clin. Exp."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1080\/19490976.2019.1700754","article-title":"Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease","volume":"11","author":"Ye","year":"2020","journal-title":"Gut Microbes"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s40168-018-0520-6","article-title":"A metagenomic study of the gut microbiome in Behcet's disease","volume":"6","author":"Ye","year":"2018","journal-title":"Microbiome"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.it.2014.08.003","article-title":"Metabolic control of regulatory T cell development and function","volume":"36","author":"Zeng","year":"2015","journal-title":"Trends Immunol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/j.ajpath.2023.01.013","article-title":"Gut microbiome and retinopathy of prematurity","volume":"193","author":"Zhang","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"4631","DOI":"10.3390\/nu15214631","article-title":"Understanding the gut-brain axis and its therapeutic implications for neurodegenerative disorders","volume":"15","author":"Zheng","year":"2023","journal-title":"Nutrients"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"40826","DOI":"10.1038\/srep40826","article-title":"Association of the intestinal microbiome with the development of neovascular age-related macular degeneration","volume":"7","author":"Zinkernagel","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2024.1468187\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:29:58Z","timestamp":1727310598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2024.1468187\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,26]]},"references-count":55,"alternative-id":["10.3389\/fncel.2024.1468187"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2024.1468187","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,26]]},"article-number":"1468187"}}