The microbiome and ophthalmic disease

Abstract

Progress in microbiome research has accelerated in recent years. Through the use of 16S rRNA assays and other genomic sequencing techniques, researchers have provided new insights about the communities of microorganisms that inhabit human and animal hosts. There is mounting evidence about the importance of these ‘microbiotas’ in a wide variety of disease states, suggesting potential targets for preventative and therapeutic interventions. Until recently, however, the microbiome received relatively little attention in ophthalmology. This review explores emerging research on the roles that ocular and extraocular microbiotas may play in the pathogenesis and treatment of ophthalmic diseases. These include diseases of the ocular surface as well as autoimmune uveitis, age-related macular degeneration, and primary open angle glaucoma. Many questions remain about the potential impacts of microbiome research on the diagnosis, treatment, and prevention of ophthalmic disease. In light of current findings, we suggest directions for future study as this exciting area of research continues to expand. Impact statement This review describes a growing body of research on relationships between the microbiome and eye disease. Several groups have investigated the microbiota of the ocular surface; dysregulation of this delicate ecosystem has been associated with a variety of pro-inflammatory states. Other research has explored the effects of the gastrointestinal microbiota on ophthalmic diseases. Characterizing the ways these microbiotas influence ophthalmic homeostasis and pathogenesis may lead to research on new techniques for managing ophthalmic disease.

Integrating omics for a better understanding of Inflammatory Bowel Disease: a step towards personalized medicine

“…Changes in the gut microbial compositions or microbial dysbiosis, is defined as a decrease in the intestinal microbial diversity resulting in an imbalance between commensal "protective" versus potential pathogens "harmful", thus promoting an excessive intestinal inflammation [52]. When persistent, this response can induce a chronic, unregulated intestinal inflammation that is observed in various human diseases such as IBD, irritable bowel syndrome, asthma, obesity, cardiovascular diseases, kidney diseases, to name a few, from the wide array of diseases known to present with gut dysbiosis [39,41,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72].…”

The closed eye harbors a unique microbiome in dry eye disease

“…A strength of our analysis is the rigorous log2 normalization of the cumulative sum scaling transformation performed prior to analysis. With this normalization, our data more accurately reflect true shifts in relative abundance 17 Previous research has focused on the open eye microbiome 12 , while we focused on the closed eye microbiome. Every night during sleep, inflammatory species move into the closed eye tear film 23,24 , perhaps in response to entrapped microbiota 12,25 .…”

“…Based on the power and pairwise sample-size estimator for permutational multivariate analysis of variance (PERMANOVA) application Micropower 14 , a low abundance 16S rRNA dataset similar to previous studies of the ocular micribome 12 would require a minimal sample size of 30 to generate a discriminatory power of 0.8 with a significance level of 0.05. Therefore, we aimed for at least 35 subjects per study arm.…”

“…In contrast to previous beliefs, the human eye hosts a resident microbiome [8][9][10][11] . Culture and molecular-based swabs of the ocular surface have revealed an intrinsic microbiome distinct from the surrounding skin, but information about the tear microbiome is scarce 12 . Interestingly, the ocular microbiome impacts ocular surface inflammation 13 .…”

The interplay between inflammation, immunity and commensal microflora in glaucomatous neurodegeneration

“…More research is needed to determine transcriptional activity, protein expression and metabolic by-products profiles of host microflora to identify potential biomarkers of gut dysbiosis that lead to glaucoma progression. More evidence using from gnotobiotic animal models and functional observational studies are required before an investment into large scale longitudinal clinical trials (28). Human longitudinal studies starting in the earlier disease phases would be preferential to understand the causative relation between microflora and glaucomatous neurodegeneration and to develop treatments aimed at halting the progression of optic nerve damage.…”