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

Abstract

Background: Age-related macular degeneration (AMD) is a leading cause of severe vision loss in the aged population. The etiology of AMD is multifactorial and includes nutritional factors, genetic variants mainly in the complement pathway, environmental risk factors and alterations in the intestinal microbiome. However, it remains largely unexplored whether there is an interdependency of these factors leading to the development of AMD. To investigate this issue, a comprehensive shotgun metagenomics analysis of 57 AMD and 58 healthy controls as well as of 16 complement C3 deficient mice and 16 wildtypes was performed. Single nucleotide polymorphisms (SNPs) in the complement factors were assessed with pre-designed TaqMan® SNP genotyping assays. Results: The composition of the intestinal microbiome differed significantly between AMD patients and controls. Whereas the class Negativicutes was more abundant in patients, the genus Oscillibacter and Bacteroides species had a significantly higher prevalence in persons without AMD. While SNPs within the complement factor B gene were more abundant in controls, SNPs within the high temperature requirement A serine peptidase 1 and complement factor H (CFH) genes were associated with AMD. Using a classification model, Negativicutes was identified as a potential biomarker for AMD and furthermore, it positively correlated with CFH. In addition, similar taxonomic features were identified that distinguished wildtype mice from C3 deficient mice. Conclusion: The composition of the intestinal microbiome differs between AMD patients and controls as well as between C3 deficient mice and wildtype mice. Moreover, since the phylum Firmicutes has been identified as potential biomarker for AMD and positively correlates with the genetic risk factor CFH, the study suggests an association between the intestinal microbiome and the complement system in AMD.

Association of Nutrients, Specific Dietary Patterns, and Probiotics with Age-related Macular Degeneration

“…Increased numbers of Clostridia and Bacili are associated with higher risk for AMD development, whereas Bacteroidia and Eysipelotrichi are associated with lower AMD risk [88]. In a more recent human study, increased Oscillibacter genus and Bacteroides species (particularly B. cellulosilyticus and B. caccae) were observed in healthy individuals, while increased Negativicutes class belonging to the Firmicutes phylum was found to be enriched in AMD patients [89]. All these findings support the notion of a ''gut-retina axis'' that may play a significant role in the pathogenesis of AMD.…”