Metagenomic Profiling of Ocular Surface Microbiome Changes in Meibomian Gland Dysfunction

Abstract Background: Ocular surface microbiome changes can affect meibomian gland dysfunction (MGD) development, which in turn may increase the risk of tissue infection. To delineate what these changes are, we used shot-gun metagenomic analysis to determine if there are differences between the microbial communities in ocular sites surrounding the meibomian gland in healthy and patients afflicted with MGD. This comparison entailed comparing the microbe content in different microbiomes of the eyelid skin, conjunctiva and meibum with those from the same locations in healthy individuals (HC) and those with this disease. Results: The meibum bacterial content of these microbiomes was different in these two different types of individuals. Almost all of the most significant taxonomic changes in the meibum microbiome of these individuals with MGD were also present in their eyelid skin, but not in the conjunctiva. Such site-specific microbe pattern changes accompany increases in the gene expression levels controlling carbohydrate and lipid metabolism. Most of the microbiomes in MGD disease possess a microbe population capable of metabolizing benzoate. Interestingly, microbe preponderance seemed to be less in patients afflicted with more severe MGD. Nevertheless, pathogens known to underlie ocular infection were evident in these patients. In meibum samples from HC, Pseudomonas fluorescens was present in more than 90% of the samples. Cupriavidus metallidurans and Pseudomonas putida had a positive rate over 50%. MGD meibum contained instead an abundance of Campylobacter coli, Campylobacter jejuni, and Enterococcus faecium pathogens, which were almost absent from HC. Functional annotation indicated that in the microbiomes of MGD meibum their capability to undergo chemotaxis and display immune evasive virulence and mediate Type IV secretion was different than that in the microbiomes of meibum isolated from HC. Conclusions: MGD meibum contained distinct microbiota different from HC, and MGD meibum microbiome community population was much smaller than in the HC group. Profiling differences in the meibum microbiome makeup between HC and MGD patients may uncover unique targets for improved treatment of this disease.