When I was an intern rotating through the emergency department, my attending assigned me a patient who had just arrived complaining of blood in his stool. The attending pushed a blank medical intake form into one of my hands. Into the other, he placed a clear plastic cylinder. “Here. You’ll be needing this.” he told me. Puzzled, I asked him what the object was. “You’ve never used one before? Then I will teach you something valuable today. No matter what field of medicine you choose to go into, this will come in handy!” he said proudly. “It is an anoscope!”
“I’m going into ophthalmology,” I said. “Oh, OK maybe not so handy then,” he said. “But go use it anyway to see if that guy has hemorrhoids.”
I am happy to say that in the decades since, I have never once had the opportunity to perform another anoscopy. But it is just possible that I may have to resurrect that skill in the future; the connection between the gut microbiome and diseases of all kinds has become a very hot field. It has long been established that the microbes existing on and within the human body have multiple useful functions, including strengthening the immune system, providing protection from autoimmune diseases and aiding in metabolism and digestion. Recent work has focused on additional specific and far-reaching effects of the microbiome on diverse aspects of human health such as aging, neurocognition, autism, allergy, cardiovascular disease, cancer, obesity, inflammatory bowel disease, and diabetes. There are a few researchers who have additionally begun exploring stool collection and direct sampling of gut flora for studies on ocular diseases such as age-related macular degeneration and uveitis.
The National Institutes of Health established The Human Microbiome Project in 2008 with the goal of facilitating the comprehensive characterization of the human microbiome and elucidating its role in both health and disease. Thus far, over 1300 organism reference genomes have been sequenced from 5 major body sites of 300 healthy adults. As in other “omics” fields, microbiome projects offer the tantalizing promise of enormous data sets that may be mined to discover novel associations (not necessarily cause and effect) with human disease that might not otherwise have been identified. However, there are also substantial challenges that will be faced in translating these potential discoveries into therapeutics. These challenges include the successful design of treatments that can provide stable microbial colonization for specific geographic locations within the human body despite local fluctuations in diet and other environmental factors.
Thus far, there is no definitive evidence that the microbiome from the gut or any other place in the human body plays a critical role in retinal pathology. However, there have been links found between differences in gut flora and autoimmune diseases, such as systemic lupus erythematosus, which also have retinal manifestations. It is also clear that dietary considerations may play a role in age-related macular degeneration, so there is rationale to support a possible connection between the gut flora and this common retinal pathology. A mouse study published earlier this year identified a functional interaction between changes in diet, gut microbiota, and the development of features consistent with age-related macular degeneration such as photoreceptor loss, retinal pigment epithelial hypopigmentation, and accumulation of lipofuscin.
Even with these early findings, I don’t see any imminent reasons to dust off gastrointestinal exam skills in the service of my retina patients. I do, however, suspect that the microbiome field will yield a great deal of data in the years to come. The resulting challenges will be to first validate initial proposed associations between microbial differences and ocular pathology and then, once validated, to create safe and effective therapies from these discoveries. Despite the long road ahead, however, I have a gut feeling that this emerging field will provide useful insights to help us optimize outcomes for our patients in the field of retina.