The microbiota eyepiece consists of all the microorganisms present inside the eye or on the ocular surface.
In recent years, the human microbiota has been the focus of numerous studies that have demonstrated the fundamental role it plays in regulating host physiology, developing the immune system and defending the host from invading pathogens. The state of dysbiosisi.e. microbiota imbalance, can cause pathogenic microbial proliferation and lead to local or systemic inflammation.1
Similarly, the ocular microbiota plays a key role in protecting eye health and inflammation.
Composition of the ocular microbiota and methods of analysis
The ocular surface is the interface between the eye and the environment, and includes the cornea, conjunctiva, eyelids, eyelashes, tear film, main and accessory glands, and the Meibomian glands (https://tfosdewsreport.org/report-definition_and_classification/48_36/en/) . The bacteria isolated from these areas of the eye are Gram-positive, including coagulase-negative Staphylococci, Streptococcus, Propionibacteriumdiphtheria bacteria and Micrococcus. Other genera, abundant in the intestinal flora, such as Escherichia, Enterococcus, Lactobacillus e Bacillusare less common on the ocular surface. Gram-negative bacteria, such as Haemophilus, Neisseria, Pseudomonas and fungal isolates are even rarer. The bacteria most commonly isolated from the ocular surface are coagulase-negative Staphylococci, present in 20-80% of conjunctival swabs and in 30-100% of swabs taken on the eyelids. The bacterial load is generally lower in the tears, and higher in the conjunctiva and eyelids.1
With regard to the intraocular area, to date there is no direct documentation of the existence of a microbiota. Historically, the intraocular environment is considered sterile due to its closed anatomical structure and the protection provided by the blood-retinal barrier, unless it is invaded by pathogens due to unnatural circumstances. Contamination could occur, for example, when the outer ocular compartments are damaged during an intraocular surgical procedure or as a result of an injury caused by a penetrating foreign object.1
In the vitreous and aqueous humour, however, was isolated Propionibacterium acnes.1
The study of the microbiota is based on both cultural and non-cultural techniques, the latter being either immunological assays, which assess the peptides produced by microorganisms or their antigens, or metagenomic sequencing, which instead analyses the genetic heritage (RNA or DNA). The various methods are often combined in order to obtain more in-depth information.1
Factors influencing the ocular microbiota
The ocular surface microbiota can be influenced by1:
- environmental conditions
- age
- sex
- personal habits
- use of contact lenses
- disease states (e.g. dry eye syndrome, conjunctivitis, diabetes, autoimmune diseases)
- antibiotics
- infections
Role of the microbiota in ocular inflammation
The role of the microbiota in inflammation has been studied in various human compartments and has led to the establishment of the key role that dysbiosis plays in human health. The state of dysbiosis is, in fact, involved in various diseases associated with systemic inflammation, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and type 1 diabetes. Furthermore, gut commensal microorganisms have been shown to play a role in the pathogenesis of several non-infectious eye diseases, such as autoimmune uveitis, macular degeneration and glaucoma.1
To date, the connections between the molecular mechanisms underlying the alteration of the gut microbiota and the progression of these inflammatory diseases are not yet known. Further studies will be needed to clarify whether translocation of microbes and/or microbial products (e.g. LPS, peptidoglycan, short-chain fatty acids and microbial DNA) from the gastrointestinal tract, or other mucosal surfaces, to the eye via the blood circulation or through the ocular lymphatic vessels occurs during ocular disease progression.1
Microbiota and ocular inflammation: a target for new therapeutic approaches
Therapies acting on the commensal microbiome (i.e. the genetic make-up of the microbiota-forming microorganisms) represent new strategies to prepare the host immune system to fight various inflammatory diseases, including intestinal inflammation, transplant rejection and HIV infection. These strategies are based on the hypothetical ability of the microbiota to shape the host immune system leading to pro-inflammatory effects. A recent study showed that the combined action of remodelling the gut microbiome and inhibiting microglia significantly attenuates the progression of autoimmune uveitis after the onset of inflammation. Underlying this process has been hypothesised to be a reprogramming of naïve CD4 T-lymphocytes into regulatory T-lymphocytes by the antigens of commensal microorganisms, thus limiting the lymphocyte response. However, it remains to be determined whether clinical intervention targeting the gut microbiome is effective in improving uveitis.1
Microbiota and COVID-19
SARS-Cov-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19, primarily determines lung infection through binding to ACE2 receptors present on alveolar epithelial cells, however, SARS-CoV-2 RNA has also recently been isolated in the faeces of patients with COVID-19. First of all, it is interesting to note that intestinal epithelial cells, in particular enterocytes of the small intestine, also express ACE2 receptors. Furthermore, respiratory infections of viral origin have been shown to lead to alterations in the intestinal microbiota. To this must be added other assessments related to diet, environmental factors and genetic profile, which play an important role in shaping the gut microbiota, which, in turn, has a strong influence on the immune response. Finally, the composition of the gut microbiota varies in old age and Covid-19 has become a fatal disease mainly in elderly patients, which again seems to indicate the role that the gut microbiota may play in this disease2.
These considerations, combined with the link between eyes and COVID-19 - demonstrated by the isolation of SARS-CoV-2 in the tears of some patients and the fact that conjunctivitis represents a possible manifestation of the disease in its severe form- leave open the possibility of a possible role for the ocular microbiota in relation to the COVID-19.
Sources:
Dr. Carmelo Chines
Direttore responsabile