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Published on: July 14, 2016
Association between gut microbiota dysbiosis and age-related macular degeneration progression: A bioinformatics
1Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China.
Abstract:
Gut microbiota dysbiosis has been linked to the progression of age-related macular degeneration, though the underlying molecular mechanisms remain unclear. This study is the first to systematically link gutMGene-derived genes to AMD pathogenesis using a multi-algorithm machine learning approach. Using the gutMGene database, we identified gut microbiota-related genes and analyzed the GSE29801 dataset for differential expression. Our enrichment analysis revealed unique insights into the involvement of gut microbiota-related genes in inflammatory, immune response, and metabolic pathways in age-related macular degeneration. Machine learning algorithms (LASSO, Random Forest, XGBoost) identified five consistent biomarker genes: CXCL10, FADS3, GHRL, APOE, and VEGFA. A nomogram was developed to predict AMD risk, showing moderate-to-high predictive accuracy with area under the curve of 0.719 (GSE29801) and 0.933 (GSE99248). Gene set variation analysis indicated upregulation of inflammatory and immune pathways and downregulation of lipid metabolism pathways in age-related macular degeneration. Single-gene set enrichment analysis further underscored the roles of diagnostic genes in immune response and metabolic regulation. This study contributes novel evidence that gut microbiota dysbiosis influences AMD progression through systemic inflammatory and metabolic pathways, and highlights potential therapeutic targets.
Insights
Gut dysbiosis, an imbalance in gut microbes, is linked to age-related macular degeneration (AMD). This study identifies key gut genes and biomarkers, revealing inflammatory and metabolic pathway involvement in AMD progression.
Area of Science:
- Microbiology
- Ophthalmology
- Genetics
Background:
- Gut microbiota dysbiosis is implicated in age-related macular degeneration (AMD) pathogenesis.
- The precise molecular mechanisms linking gut microbes to AMD remain largely unknown.
Purpose of the Study:
- To systematically identify gut microbiota-related genes associated with AMD.
- To elucidate the molecular pathways involved in AMD pathogenesis influenced by gut dysbiosis.
- To develop a predictive model for AMD risk based on identified biomarkers.
Main Methods:
- Utilized the gutMGene database to identify relevant genes.
- Analyzed differential gene expression in the GSE29801 dataset.
- Employed machine learning algorithms (LASSO, Random Forest, XGBoost) for biomarker identification.
- Performed enrichment analyses (Gene Set Variation Analysis, Single-Gene Set Enrichment Analysis) and developed a predictive nomogram.
Main Results:
- Identified five consistent biomarker genes: CXCL10, FADS3, GHRL, APOE, and VEGFA.
- Developed a nomogram with predictive accuracy (AUC 0.719 for GSE29801, 0.933 for GSE99248).
- Revealed significant roles of gut microbiota genes in inflammatory, immune response, and metabolic pathways (including lipid metabolism) in AMD.
Conclusions:
- Gut microbiota dysbiosis influences AMD progression via systemic inflammatory and metabolic alterations.
- The identified biomarkers and pathways offer potential therapeutic targets for AMD.
- This study provides novel insights into the gut-eye axis in AMD pathogenesis.
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