Gut-ocular axis: An emerging strategy to treat ocular diseases

Table 1 Gut microbiome alterations, mechanisms, and therapeutic targets in ocular diseases

Ocular disease	Gut microbiome alteration	Proposed mechanism	Major evidence	Potential therapy
Dry eye disease	↓ Bifidobacterium, ↓ Faecalibacterium prausnitzii; ↑ Enterobacteriaceae, ↑ Prevotella	Reduced SCFA production → systemic inflammation → lacrimal gland dysfunction → tear film instability	Cross-sectional human cohorts[20]; murine germ-free models[10]	Probiotics (Lactobacillus, Bifidobacterium); dietary fibre; pilot FMT
Uveitis	↓ Firmicutes (Faecalibacterium prausnitzii, Roseburia); ↓ Akkermansia muciniphila; ↑ Bacteroidetes	Th17 expansion → autoreactive T-cell migration to uveal tissue; molecular mimicry	EAU murine models; case-control human studies (Behçet, HLA-B27)[31]	Probiotics; SCFA supplementation; FMT (case reports)
Glaucoma	↑ Enterobacteriaceae; ↓ Lactobacillus, ↓ Bifidobacterium	Commensal-induced T-cell priming → microglial activation → retinal ganglion cell loss	Murine commensal T-cell models; preliminary human cross-sectional data[10,21]	Probiotics; anti-inflammatory dietary patterns
Diabetic Retinopathy	↓ Roseburia, ↓ Faecalibacterium prausnitzii, ↓ Akkermansia muciniphila; ↑ Escherichia, ↑ Shigella	Metabolic endotoxaemia → retinal endothelial activation → BRB breakdown → pericyte loss	Rodent DM models[28]; cross-sectional human microbiome profiling[12]	Dietary modification; prebiotics; glycaemic control with microbiome monitoring
Age-related macular degeneration	↑ Prevotella, ↑ Ruminococcus; ↓ Bacteroides, ↓ Bifidobacterium	High-fat diet → pro-inflammatory microbiota → complement activation → choroidal neovascularization	Murine high-fat diet models[25,26]; case-control human gut microbiome studies[14,22]	Mediterranean diet; omega-3 supplementation; FMT (experimental)

SCFA: Short chain fatty acid; FMT: Fecal microbiota transplantation; DM: Diabetes mellitus; HLA: Human leukocyte antigen; BRB: Blood retina barrier.

Table 2 Current level of evidence for each major ocular condition

Ocular disease	Animal studies	Human observational studies	Clinical trials/meta-analyses
Dry eye disease	Multiple murine models (germ-free, antibiotic-treated)[10]	Cross-sectional and cohort studies (Sjögren and non-Sjögren)[20]	Limited; pilot probiotic trials
Uveitis	Extensive (EAU models, gnotobiotic mice)[8,9]	Case-control studies (Behçet, HLA-B27)[31]	No published RCTs; case series with FMT
Glaucoma	Murine models (commensal T-cell priming)	Preliminary cross-sectional studies[10,21]	None published to date
Diabetic retinopathy	Rodent models of type 1 and type 2 diabetes[28]	Cross-sectional gut microbiome profiling[12]	No dedicated ocular endpoint trials
Age-related macular degeneration	High-fat diet murine models[25,26]	Case-control gut microbiome studies[14,22]	No published RCTs

HLA: Human leukocyte antigen; RCT: Randomized controlled trial; FMT: Fecal microbiota transplantation.