Associations of the intestinal microbiome with the complement system in neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial including nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a shotgun metagenomics analysis of 57 neovascular AMD and 58 healthy controls as well as of 16 complement C3-deficient mice and 16 wildtypes was performed. Whereas the class was more abundant in patients, the genus and species had a significantly higher prevalence in persons without AMD. Similar taxonomic features were identified that distinguished wildtype mice from C3-deficient mice. Moreover, several purine signaling pathways were associated with both, neovascular AMD and C3 deficiency. While SNPs within the gene were more abundant in controls, SNPs within the and (CFH) genes were associated with neovascular AMD. Using a classification model, was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. This study suggests an association between the intestinal microbiome and the complement system in neovascular AMD.