A research project conducted at the University of Bern, led by Dr. Martin S. Zinkernagel, Dr. Denise C. Zysset-Burri and Prof. Dr. Dr. Sebastian Wolf, has demonstrated that the composition of the intestinal microbiome in patients with AMD, compared to controls, indicates an enrichment of certain microbial genera. The finding may open a significant field of research and therapeutic development if the observations lead to opportunities for beneficial modification of the microbiome to alter the course of the retinal pathology. AMD is the leading cause of vision loss in those 50 years and older and represents a significantly active area of research for many clinical and pharmaceutical research teams worldwide. The full paper, entitled: “Association of the Intestinal Microbiome with the Development of Neovascular Age-Related Macular Degeneration”, is published in the Nature open access online journal, Scientific Reports, 7:40826, DOI: 10.1038/srep40826.
The current research performs a relatively straight-forward comparative analysis between two groups of patients, with and without clinical diagnoses of AMD, and asks the question to what degree, if any, do intestinal microbial organisms within each group differ. As it is well established that the intestinal gut flora plays a significant role in digestion, and by extension the metabolism of the host, it thus stands to reason that different gut flora may modify human metabolism, including the metabolism associated with several pathologies. To test this hypothesis the Swiss research team isolated the intestinal microbial flora from the two sets of patients and identified the “metagenome” – the genetic sequence of the full set of genes from each microbial sample – to determine if those with and without AMD differed in terms of their microbial “signature”. While the patient numbers were relatively small, the data demonstrated that patients with AMD had an enrichment of Oscillibacter, Anaerotruncus, Eubacterium ventriosum and Ruminococcus, while patients without AMD showed an enrichment for Bacteroides eggerthii. Caution will need to be exercised to avoid an interpretation of “guilt by association”, and thus further research to capture larger numbers and greater statistical power is now underway.
Initial analysis of the microbial genera and species, associated with and without AMD, have high-lighted some interesting observations in respect of long chain fatty acid metabolism, glutamate degradation and arginine biosynthesis, all potentially relevant to the pathology of AMD. In addition, the AREDS formulation and the bioavailability of its components are likely to be affected by the microbial composition providing at least one mechanistic pathway in which an intervention to the microbiome may be engineered to alter the availability of protective nutrients and anti-oxidants. While the research results represent an early pilot study approach, the initial findings provide exciting opportunities for multiple avenues of research, not least of all in the testing of relatively simple strategies in animal models to determine if modification of the gut flora might modify the course of AMD.