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Purpose <p>To synthesize recent (2020–2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.</p> Methods <p>PubMed and Web of Science were searched (January 2020–October 2025) using the terms “gut microbiota”, “ocular diseases”, and “immunomodulatory therapies”. Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune–metabolic mechanisms, and intervention outcomes.</p> Results <p>Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as <i>Akkermansia</i>, <i>Ruminococcaceae</i>, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including <i>Proteobacteria</i>, <i>Staphylococcus</i>, and <i>Porphyromonas gingivalis</i>. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing <i>Lactobacillus</i> or <i>Bifidobacterium</i> improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered <i>Lactobacillus</i> expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1–7) preserved retinal integrity in diabetic models.</p> Conclusions <p>Microbial dysbiosis acts as a common driver of immune–metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.</p>

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The gut-eye axis in blinding eye diseases: microbiota-driven immune dysregulation and immunomodulatory therapies

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Chuyao Wang,
  • Hongyu Li,
  • Ting Wang,
  • Xiuyun Li,
  • Jianwei Liu,
  • Aijun Deng,
  • Xinwei Jiao

摘要

Purpose

To synthesize recent (2020–2025) advances on how gut, oral, and ocular-surface microbiota contribute to major blinding eye diseases, dry eye disease (DED), non-infectious uveitis, glaucoma, optic neuropathy, age-related macular degeneration (AMD), and diabetic retinopathy (DR), and to evaluate the therapeutic potential of microbiome-based interventions.

Methods

PubMed and Web of Science were searched (January 2020–October 2025) using the terms “gut microbiota”, “ocular diseases”, and “immunomodulatory therapies”. Eligible studies included original human and animal research demonstrating microbial dysbiosis or testing microbiome-directed therapies. Data were synthesized thematically across microbial composition, immune–metabolic mechanisms, and intervention outcomes.

Results

Across all six diseases, dysbiosis was consistently characterized by depletion of anti-inflammatory taxa such as Akkermansia, Ruminococcaceae, and other short-chain fatty acid (SCFA) producers, with enrichment of pro-inflammatory bacteria including Proteobacteria, Staphylococcus, and Porphyromonas gingivalis. These changes were associated with increased intestinal permeability, systemic lipopolysaccharide (LPS) and trimethylamine N-oxide (TMAO), Th17 (T helper 17)/Treg (regulatory T cell) imbalance, and loss of SCFA-mediated neuroprotection. Probiotics containing Lactobacillus or Bifidobacterium improved tear stability and reduced inflammation in preclinical and pilot clinical studies, while high-fiber diets ameliorated lesions in age-related macular degeneration (AMD) and diabetic retinopathy (DR). Fecal microbiota transplantation confirmed microbial causality but revealed donor-dependent effects, and engineered Lactobacillus expressing angiotensin-converting enzyme 2 (ACE2) or Ang-(1–7) preserved retinal integrity in diabetic models.

Conclusions

Microbial dysbiosis acts as a common driver of immune–metabolic dysfunction in blinding eye diseases. Microbiome-targeted strategies show promising efficacy in experimental systems, but large, longitudinal human trials are needed for clinical translation.