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Deshen Mao, Borui Tao, Shuyan Sheng, Hui Jin, Wenxuan Chen, Huimin Gao, Jianyi Deng, Zhuo Li, Fan Chen, Shixin Chan, Longqi Qian; Causal Effects of Gut Microbiota on Age-Related Macular Degeneration: A Mendelian Randomization Study. Invest. Ophthalmol. Vis. Sci. 2023;64(12):32. https://doi.org/10.1167/iovs.64.12.32.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, the association between gut microbiota and age-related macular degeneration (AMD) through the gut–retina axis has attracted great interest. However, the causal relationship between them has not been elucidated. Using publicly available genome-wide association study summary statistics, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the gut microbiota and the occurrence of AMD.
The study used a variety of quality control techniques to select instrumental single nucleotide polymorphisms (SNPs) with strong exposure associations. We used a set of SNPs as instrumental variable that were below the genome-wide statistical significance threshold (5 × 10−8). Additionally, a separate group of SNPs below the locus-wide significance level (1 × 10–5) were selected as instrumental variables to ensure a comprehensive conclusion. Inverse variance-weighted (IVW) analysis was the primary technique we used to examine causality in order to confirm the validity of our findings. The MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis were used to evaluate the horizontal pleiotropy, heterogeneities, and stability of the genetic variants.
IVW results showed that genus Anaerotruncus (P = 5.00 × 10−3), genus Candidatus Soleaferrea (P = 1.83 × 10−2), and genus unknown id.2071 (P = 3.12 × 10−2) were protective factors for AMD. The Eubacterium oxidoreducens group (P = 3.17 × 10−2), genus Faecalibacterium (P = 2.67 × 10−2), and genus Ruminococcaceae UCG-011 (P = 4.04 × 10−2) were risk factors of AMD. No gut microbiota (GM) taxa were found to be causally related to AMD at the phylum, class, order, and family levels (P > 0.05). The robustness of MR results were confirmed by heterogeneity and pleiotropy analysis. (P > 0.05). We also performed a bidirectional analysis, which showed that genus Anaerotruncus, genus Candidatus Soleaferrea, genus unknown id.2071 and the Eubacterium oxidoreducens group had an interaction with AMD, whereas genus Faecalibacterium showed only a unilateral unfavorable effect on AMD.
We confirmed a causal relationship between AMD and GM taxa, including the Eubacterium oxidoreducens group, Faecalibacterium, Ruminococcaceae UCG-011, Anaerotruncus, and Candidatus Soleaferrea. These strains have the potential to serve as new biomarkers, offering valuable insights into the treatment and prevention of AMD.
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