{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:49:13Z","timestamp":1785829753363,"version":"3.56.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"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 Dev. Biol."],"abstract":"<jats:p>Diabetic retinopathy (DR) is a leading cause of blindness in working-age adults, with a pathogenesis that extends far beyond chronic hyperglycemia. This narrative review synthesizes current evidence to construct a comprehensive model of DR that integrates metabolic memory, epigenetic regulation, and systemic factors such as the gut-retina axis. Specifically, this review focuses on the bidirectional crosstalk between gut microbiota dysbiosis and host RNA N6-methyladenosine (m6A) modification as the central mechanism linking these factors. We examine how gut microbiota dysbiosis contributes to the initiation and progression of DR by influencing the host epigenetic landscape, particularly the dynamic RNA N6-methyladenosine (m6A) modification. Hyperglycemia and microbial dysbiosis collectively drive the dysregulation of m6A \u201cwriters\u201d (e.g., METTL3\/14), \u201cerasers\u201d (e.g., FTO, ALKBH5), and \u201creaders\u201d (e.g., YTHDF family), leading to stable alterations in the expression of genes involved in inflammation, oxidative stress, angiogenesis, and neurodegeneration, thereby establishing \u201cmetabolic memory.\u201d The gut microbiota and its metabolites (including short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and tryptophan derivatives) not only modulate host m6A modification but are also themselves influenced by the host m6A machinery, forming a bidirectional \u201cmicrobiota-m6A\u201d regulatory axis. A deep understanding of this interaction network not only offers a new perspective on the complex pathological mechanisms underlying DR but also lays a theoretical foundation for developing novel microbiome- and epitranscriptome-based biomarkers and therapeutic strategies, such as probiotics, prebiotics, and small-molecule drugs targeting m6A enzymes.<\/jats:p>","DOI":"10.3389\/fcell.2026.1841882","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:30:56Z","timestamp":1785828656000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Crosstalk between gut microbiota and RNA N6-methyladenosine modification in diabetic retinopathy"],"prefix":"10.3389","volume":"14","author":[{"given":"Junyan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University","place":["Bengbu City, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Dalian Third People\u2019s Hospital Affiliated to Dalian University of Technology","place":["Dalian City, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University","place":["Bengbu City, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University","place":["Bengbu City, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengqun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University","place":["Bengbu City, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1080\/17501911.2025.2464529","article-title":"Epigenetics in evolution and adaptation to environmental challenges: pathways for disease prevention and treatment","volume":"17","author":"Abdolmaleky","year":"2025","journal-title":"Epigenomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3759","DOI":"10.3390\/nu12123759","article-title":"The gut microbiome, aging, and longevity: a systematic review","volume":"12","author":"Badal","year":"2020","journal-title":"Nutrients"},{"key":"B3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3390\/cells11020291","article-title":"Glucose regulates m(6)A methylation of RNA in pancreatic islets","volume":"11","author":"Bornaque","year":"2022","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41387-024-00328-9","article-title":"Diabetic foot exacerbates gut mycobiome dysbiosis in adult patients with type 2 diabetes mellitus: revealing diagnostic markers","volume":"14","author":"Cai","year":"2024","journal-title":"Nutr. 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