{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:01:24Z","timestamp":1784196084390,"version":"3.55.0"},"reference-count":122,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Retinopathy of prematurity (ROP) is a leading cause of childhood blindness characterized by disrupted physiologic vascularization followed by pathologic neovascularization, classically organized around the insulin-like growth factor-1 (IGF-1)\u2013vascular endothelial growth factor (VEGF) axis in the retina. Increasing evidence suggests that early-life gut dysbiosis may act as an upstream modifier of this biphasic process. In this review, we synthesize human cohort studies, multi-omics analyses, and experimental animal models examining associations between the neonatal gut microbiome and ROP. Preterm infants who develop severe ROP demonstrate enrichment of facultative anaerobes and reduced acquisition of obligate anaerobes, alongside altered predicted metabolic capacity. Microbiome-derived metabolites, including short-chain fatty acids, bile acid derivatives, and lipid mediators, have been shown in experimental systems to influence systemic IGF-1 production, hypoxia-inducible factor-1\u03b1 stabilization, and VEGF signaling. Rodent oxygen-induced retinopathy models offer a translation framework to assess the functional link between microbial perturbation and retinal angiogenic responses. Collectively, these findings support a conceptual microbiome\u2013IGF-1\u2013VEGF\u2013retina axis in which early intestinal dysbiosis may modulate inflammatory tone, metabolic signaling, and retinal vascular development. Although current evidence remains largely associative, integrating microbiome profiling with mechanistic and longitudinal studies may clarify potential causal pathways and identify novel biomarkers or preventive strategies for severe ROP.<\/jats:p>","DOI":"10.3390\/ijms27073317","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:40:31Z","timestamp":1775554831000},"page":"3317","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Potential Gut\u2013Retina Axis in Retinopathy of Prematurity: Emerging Perspectives on Microbiome-Mediated Modulation of the IGF-1\u2013VEGF Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Shohan","family":"Shetty","sequence":"first","affiliation":[{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7061-6491","authenticated-orcid":false,"given":"Robert","family":"Luca","sequence":"additional","affiliation":[{"name":"Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7919-0852","authenticated-orcid":false,"given":"Sarah Hilkert","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Skondra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1136\/archdischild-2016-310532","article-title":"Epidemiology of Blindness in Children","volume":"102","author":"Solebo","year":"2017","journal-title":"Arch. 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