Normal flora /Microbiome of the Eye: 10 Facts

Dr. Sanchita Mitra
Published Online: October 7th, 2021 | Read Time: 10 minutes, 30 seconds

1. Definition of Microbiome

Microbiomes are communities of organisms (bacteria, fungi, viruses) that normally reside on any part of the human body (both external and internal) and are in a symbiotic relationship with the host. The members of the microbiome live in close harmony, sharing food and shelter and offering benefits to each other, e.g. some members give protection by secreting extracellular polymeric substances to form a protective covering of biofilm around the community, while some excrete metabolic by-products which are useful substrates for the others.

2. Relation of Microbiome with the host

Most of the organisms of the microbiome provide support to the good health of the host (like preventing colonization by harmful pathogens by competing for shelter and food niches, occupying the pathogen receptor sites, or secreting antibiotics and metabolic by-products like acetic and lactic acids which harm such pathogens). But some of the members can also act as opportunistic pathogens and invade the host whenever the host becomes weak as in immunocompromised states or breach in the normal protective epithelial surfaces of the body as in cuts and injuries. Microbiomes are also known to modulate our immune responses which affect our overall health and increased or reduced susceptibility to many systemic illnesses.

3. Microbiome members also need to be under host surveillance

Besides the well-known and defined gut microbiome, the skin, mouth, and ocular surfaces are also known to possess specific microbiomes. There’s also ongoing debate and research as to whether the previously known sterile closed spaces of the body like the intraocular compartments, intrauterine space, etc are also inhabited by specific microbiomes. The ocular microbiome is relatively sparsely inhabited by microbes compared to other parts of the body. This is attributed to the constant secretion of tears which keeps draining off excess surface microbes, as well as its high lysosomal and surface immunoglobulins (IgA, IgD) which make it difficult for excess microbes to survive. This, and the constant surveillance by the host's innate immunity not only prevents pathogens from colonizing ocular surfaces but also keeps in check the excessive proliferation of members of the normal microbial flora.

4. Microbiome research in the eye

Research in ocular surface microbiome affecting ocular health and disease currently spans dry eye disease and ocular microbiome, the molecular basis of endophthalmitis, ocular surface inflammation in conjunctivitis, and contact lens-related ocular surface infection and inflammation, macular degeneration, uveitis, episcleritis, scleritis. Microbiomes in other parts of the body, like gut microbiome, are also being shown to play a crucial role in ocular diseases like diabetic retinopathy, age-related macular degeneration, uveitis, and glaucoma by modulating immune responses.

5. Ocular Microbiome formation and changes

The ocular surface is supposedly sterile in the intrauterine period and first colonization by microbes occur during the passage of foetus through the maternal birth canal. Thereafter, the ocular surface microbiome keeps changing as age progresses and the human is exposed to different kinds of environments and geographic areas. This is also affected by the microbiome of the surrounding areas like the nasolacrimal duct, nasal mucosal surface, and skin of the eyelids and periorbital areas.

6. Diagnostic methods of detection of Ocular Microbiome biodiversity

To date, traditional culture-dependent methods have shown much low microbial diversity of ocular microbial flora. But the application of culture-independent next-generation sequencing methods like whole-genome sequencing to see the overall biodiversity of the microbiome of the eye, or RNA sequencing of specific genes of ocular samples have yielded increased diversity of such microbes. To this end, 16s ribosomal rRNA gene sequencing for bacteria, Internal transcribed spacer (ITS) sequencing for fungus, and dsRNA-Seq (double-stranded RNA sequencing) for viruses are performed.

7. Members of the Ocular Microbiome detected so far

Overall, the human ocular surface microbiome is dominated by bacteria of which the majority are Gram-positive cocci like aerobic Coagulase-negative Staphylococcus (like Staphylococcus epidermidis), Staphylococcus aureus, Streptococcus species, anaerobic Peptostreptococcus species; Gram-positive bacilli like the aerobic Corynebacterium species, anaerobic Propionibacterium acnes,and Bacteroides species; Gram-negative bacilli like Haemophilus species, Pseudomonas species, and Moraxella species. Among fungi, yeasts like Candida species including C. albicans, Rhodotorula species, and Malasezzia species, and molds like Aspergillus species, Penicillium species, Phialophora,and Trichoderma species were found to be part of the normal flora. For viruses, herpes simplex virus, human papillomavirus, and torque teno virus were part of the normal ocular surface flora.

8. ‘You can’t let your guards down’

Of note is that many of these microbes for normal ocular flora are also considered as ocular pathogens, which points to the fact that given a chance, by any breach in host defense mechanisms or by the unchecked proliferation of these microbes, the normal flora can turn from friend to foe.

9. Factors affecting Ocular Microbiome diversity

As microbial components of the normal microbiome may occasionally turn against the host by becoming pathogenic, so may the microbial diversity of the ocular microbiome in the same person change due to change in environment, personal habits, host immune status, and disease conditions, and random use of topical antibiotic drops or systemic antibiotics without additional probiotics or vitamins to support the good flora and harmful cosmetics. Whether topical probiotic addition to topical antibiotics protects normal ocular flora and the logistics involved is still a matter of debate and research.

10. Microbiome in ocular health and disease

Prolonged contact lens wear increases the Gram-negative bacilli population of normal ocular flora like Pseudomonas species, Methylobacterium species, Acinetobacter species while reducing the Gram-positive bacterial population. Many of the earlier so-called idiopathic ocular diseases like dry eye disease, uveitis, scleritis, episcleritis, macular degeneration, and glaucoma are now seen to have some relation with dysbiosis of both the ocular and the gut microbiome. Here, ocular surface dysbiosis probably plays a direct role in the causation of many of these diseases by replacing good microbes with pathogenic ones, while gut dysbiosis mostly leads to immunomodulation to cause these diseases at a distant site like the eye. Gut dysbiosis causes inflammation, leading to the secretion of cytokines and other inflammatory markers which enter the eye via the bloodstream to cause a local immune response. It also stimulates circulating T-cells, some of which are capable of entering the eye and causing direct damage to self tissue (autoimmune response). The recent literature supports the existing relation between HLA-B 27 positivity, ankylosing spondylitis, uveitis, and between inflammatory bowel disease like Crohn’s and uveitis and gut dysbiosis (a higher number of Klebsiella species and other harmful bacteria in stool of such patients compared to normal controls). In some of these studies, a more holistic approach of dietary modifications like low carbohydrate, gluten-free diet (i.e, excluding substances which support the growth of such harmful gut microbes), and oral probiotics (containing healthy gut microbes for replacement) as adjuvants to immunosuppressants like methotrexate, showed some positive results. The severity of Sjogren’s syndrome was also shown to be inversely proportional to the microbial diversity of the gut microbiome in another study. There’s ongoing research on the use of oral and topical probiotics for reducing the severity and incidence of such autoimmune eye diseases. It is now well known that the skin and gut microbiome affects the ocular microbiome as well, mainly by direct transfer. Infestation of eyelids by common parasites as Demodex folliculorum or D. brevis has also been shown to cause ocular surface dysbiosis as they consume the healthy bacteria and excrete toxic metabolites. Lastly, the concept of prophylactic antibiotics before any ocular surgery itself is being challenged as to whether this practice is actually predisposing our eye to infections by more robust and drug-resistant microbes post-surgery, by eliminating the less robust and helpful ones.

Dr. Sanchita Mitra
Consultant Microbiologist, LV Prasad Eye Institute, KAR Campus, Hyderabad, India.
Sanchita Mitra works as a Clinical Microbiologist at LV Prasad Eye Institute, Hyderabad, India. She completed her MBBS from NRS Medical College and Hospital, Kolkata, West Bengal, followed by post-graduate Diploma in Child Health (DCH). She worked as a paediatrician for a few years before completing her training in MD, Microbiology from SCB Medical College and Hospital, Cuttack, Odisha. Her experience in clinical medicine as a paediatrician helped her develop a broader perspective of medical microbiology and its application in human infections. With her MD thesis Clinico-microbiological profile, antibiotic sensitivity and biofilm formation in chronic dacryocystitis, she gained extensive hands-on training on ocular pathogens for which she received best free paper award at the Indian Association of Medical Microbiologists (IAMM), Odisha chapter. Currently, Dr Mitra's research work spans unusual ocular pathogens in different ocular infections (endophthalmitis, keratitis and orbital infections); antimicrobial resistance and their mechanisms in ocular pathogens (especially related to biofilms and plasmids); multidrug-resistant ocular pathogens; polymicrobial ocular infections with polymicrobial interactions and their effect on antimicrobial resistance and clinical outcome. She has published in International and Indian scientific journals on various ocular Microbiology related topics.
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