Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis
<b>Background/Objectives</b>: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechani...
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2025-03-01
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| author | Pinghui Wei Shan Gao Guoge Han |
| author_facet | Pinghui Wei Shan Gao Guoge Han |
| author_sort | Pinghui Wei |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechanisms mediated by blood metabolites. <b>Methods</b>: We utilized the 211 GM dataset (n = 18,340) provided by the MiBioGen consortium. AMD outcome data were sourced from the MRC Integrated Epidemiology Unit (IEU) OpenGWAS Project. We performed bidirectional MR, two mediation analyses, and two-step MR to assess the causal links between GM and different stages of AMD (early, dry, and wet). <b>Results</b>: Our findings indicate that the <i>Bacteroidales S24.7</i> group and genus <i>Dorea</i> are associated with an increased risk of early AMD, while <i>Ruminococcaceae UCG011</i> and <i>Parasutterella</i> are linked to a higher risk of dry AMD. Conversely, <i>Lachnospiraceae UCG004</i> and <i>Anaerotruncus</i> are protective against dry AMD. In the case of wet AMD, <i>Intestinimonas</i> and <i>Sellimonas</i> increase risk, whereas <i>Anaerotruncus</i> and <i>Rikenellaceae RC9</i> reduce it. Additionally, various blood metabolites were implicated: valine, arabinose, creatine, lysine, alanine, and apolipoprotein A1 were associated with early AMD; glutamine and hyodeoxycholate—with a reduced risk of dry AMD; and androsterone sulfate, epiandrosterone sulfate, and lipopolysaccharide—with a reduced risk of wet AMD. Notably, the association between family <i>Oxalobacteraceae</i> and early AMD was mediated by valine, accounting for 19.1% of the association. <b>Conclusions</b>: This study establishes causal links between specific gut microbiota and AMD, mediated by blood metabolites, thereby enhancing our understanding of the gut–retina axis in AMD pathophysiology. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2025-03-01 |
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| series | Biomedicines |
| spelling | doaj-art-712832dba5bb47c986d9701984512db32025-08-20T02:42:35ZengMDPI AGBiomedicines2227-90592025-03-0113363910.3390/biomedicines13030639Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization AnalysisPinghui Wei0Shan Gao1Guoge Han2Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin 300020, ChinaTianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin 300020, China<b>Background/Objectives</b>: Despite substantial research, the causal relationships between gut microbiota (GM) and age-related macular degeneration (AMD) remain unclear. We aimed to explore these causal associations using Mendelian randomization (MR) and elucidate the potential mechanisms mediated by blood metabolites. <b>Methods</b>: We utilized the 211 GM dataset (n = 18,340) provided by the MiBioGen consortium. AMD outcome data were sourced from the MRC Integrated Epidemiology Unit (IEU) OpenGWAS Project. We performed bidirectional MR, two mediation analyses, and two-step MR to assess the causal links between GM and different stages of AMD (early, dry, and wet). <b>Results</b>: Our findings indicate that the <i>Bacteroidales S24.7</i> group and genus <i>Dorea</i> are associated with an increased risk of early AMD, while <i>Ruminococcaceae UCG011</i> and <i>Parasutterella</i> are linked to a higher risk of dry AMD. Conversely, <i>Lachnospiraceae UCG004</i> and <i>Anaerotruncus</i> are protective against dry AMD. In the case of wet AMD, <i>Intestinimonas</i> and <i>Sellimonas</i> increase risk, whereas <i>Anaerotruncus</i> and <i>Rikenellaceae RC9</i> reduce it. Additionally, various blood metabolites were implicated: valine, arabinose, creatine, lysine, alanine, and apolipoprotein A1 were associated with early AMD; glutamine and hyodeoxycholate—with a reduced risk of dry AMD; and androsterone sulfate, epiandrosterone sulfate, and lipopolysaccharide—with a reduced risk of wet AMD. Notably, the association between family <i>Oxalobacteraceae</i> and early AMD was mediated by valine, accounting for 19.1% of the association. <b>Conclusions</b>: This study establishes causal links between specific gut microbiota and AMD, mediated by blood metabolites, thereby enhancing our understanding of the gut–retina axis in AMD pathophysiology.https://www.mdpi.com/2227-9059/13/3/639gut microbiotamediation analysisMendelian randomizationmetabolitesage-related macular degeneration |
| spellingShingle | Pinghui Wei Shan Gao Guoge Han Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis Biomedicines gut microbiota mediation analysis Mendelian randomization metabolites age-related macular degeneration |
| title | Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis |
| title_full | Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis |
| title_fullStr | Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis |
| title_full_unstemmed | Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis |
| title_short | Evidence for Genetic Causal Association Between the Gut Microbiome, Derived Metabolites, and Age-Related Macular Degeneration: A Mediation Mendelian Randomization Analysis |
| title_sort | evidence for genetic causal association between the gut microbiome derived metabolites and age related macular degeneration a mediation mendelian randomization analysis |
| topic | gut microbiota mediation analysis Mendelian randomization metabolites age-related macular degeneration |
| url | https://www.mdpi.com/2227-9059/13/3/639 |
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