The gut microbiome significantly affects digestion and — as research now shows — systemic inflammation. Recent literature has begun to explore a growing interest in how this microbiota affects organs beyond the digestive system, with researchers now believing that even several eye diseases have associations with gut dysbiosis.
Increasing evidence sheds light on the numerous potential connections between specific microbial strains and eye conditions, such as uveitis, dry eye, glaucoma, and macular degeneration.1 Microorganisms in the gut and on the ocular surface appear to produce certain by-products associated with anti-inflammatory or proinflammatory effects.2
Understanding the delicate pathways involved in these connections may provide researchers the key to unlock precision treatments for ocular disease that may start with making changes to the gut.
The Gut-Eye Axis
The human gut is home to more than 100 trillion microorganisms.2 Researchers have identified more than 50 phyla, including Bacteroidetes, which encompasses 7000 gram-negative bacteria linked to lipopolysaccharide (LPS)- and flagellin-mediated immune responses. The gram-positive bacteria Firmicutes synthesizes short-chain fatty acids, which benefit the host. In humans, the vast majority (70%) of microbes are located in the large intestine, but other organs, including the eyes, also have a microbial ecosystem.4 Growing evidence suggests that a gut-eye axis links these microorganisms to specific eye tissues and functions. In addition, the composition of microbes that are present on the ocular surface can also influence eye health and disease.
When the healthy balance of gut microbiota is disturbed, the mucosal barrier becomes compromised, leading to systemic inflammation from the translocation of pathogenic microbes that cross the epithelial barrier. A variety of factors, including age, genetics, diet, stress, disease, alcohol use, medication intake, and the environment may cause this disruption. Alterations in the population of B and T cells and the production of proinflammatory cytokines can wreak havoc on organs throughout the body.4
Uveal, Ocular Surface Inflammation
Inflammatory and infectious ocular disease can also be affected by the ocular surface and gut microbiome, and probiotic treatment may modulate some of these ocular surface disorders, explains Anat Galor, MD, of the Bascom Palmer Eye Institute. This is likely because gut microbiome composition affects the type and activity of immune cells within the lacrimal gland, ocular surface, and the eye. These are the cells that drive some forms of dry eye and uveitis, Dr Galor says.
Research indicates that, in the setting of autoimmune disease (particularly rheumatoid arthritis), connections between specific bacteria and immune responses may affect the eyes. In addition, changes in the ocular surface microbiome may increase the risk of eye infections.1,2
Most of the available data between eyes and the gut microbiome is presently relegated to animal studies. The current human evidence is mostly rooted in epidemiological studies. Nonetheless, she believes gut health is a hot topic that’s gaining traction quickly among patients and clinicians, so more robust research is likely on the horizon.
Several conditions, including dry eye syndrome, blepharitis, conjunctivitis, keratitis, trachoma, are affected by changes in the composition of ocular microbes. For example, wearing contact lenses increases the risk of bacterial keratitis, a condition associated with the gram-negative bacteria Pseudomonas aeruginosa. Trachoma is caused by Chlamydia trachomatis. Meibomian gland dysfunction (MGD), which can lead to evaporative dry eye syndrome, and has been associated with Staphylococcus, Corynebacterium, and Sphingomonas.1
Uveitis can also cause blurred vision and blindness, often related to autoimmunity. One of the most common types is acute anterior uveitis (AAU), which comprises 85% of total cases.2 Despite its idiopathic nature, AAU is connected to the leukocyte cell surface protein–human leukocyte antigen B27 (HLA-B27). Animal models have shown significant differences in the composition of intestinal bacteria in uveitis, suggesting that gut alterations may produce certain favorable conditions that could be altered with probiotics.2
AMD, Glaucoma Genetics and the Gut Microbiome
Glaucoma is increasingly being recognized as a possible immune system related disorder.3 Most glaucoma cases — more than 70% — are primary open-angle glaucoma (POAG). Currently, the only modifiable risk factor in these patients is reduction of intraocular pressure Researchers suspect that additional neurodegenerative and vascular mechanisms may be involved. Gut bacteria may influence the regulation of ocular system disorders, according to the researchers behind a 2023 study published in the European Association for Predictive, Preventive and Personalised Medicine (EPMA) journal. The research suggests that immune responses modulated by macrophages play a role in POAG development, presenting new opportunities for early detection and and personalized treatment.3
The study shows several genes are related to both glaucoma and the gut’s microbiome. These include NFKB1, IL18, TLR9, FKBP2, KITLG, and HDAC4. The genes were identified in the database of gut microbiota regulation and as hub genes in POAG patients. Specifically, these critical pathogenic genes are closely relevant to certain bacterial strains, including Bifidobacterium adolescentis and Lactobacillus paracasei JS1, suggesting that metabolites such as Equol, Butyrate, and Indole may impact the progression of POAG.
A mini-review published in the American Journal of Pathology also emphasized the relationship between gut bacteria and metabolites on glaucoma.5 POAG patients had more gram-negative bacteria with pro-inflammatory effects. Using gas chromatography and mass spectrometry, investigators detected 35 metabolites that differed significantly in those with POAG and those without. For instance, glutathione and spermidine offered protective effects. These findings were in line with other studies that consistently show the influence of microbiota and metabolites in specific immune functions in the retina and retinal diseases.
Age-related macular degeneration (AMD) has also been associated with intestinal dysbiosis. For example, Anaerotruncus and Oscillibacter and the species Ruminococcus torques and Eubacterium ventriosum are more likely present in the guts of people with advanced AMD compared with healthy controls.
People with AMD also have lower levels of Oscillospira, Blautia, and Dorea.2 There are a few different theories about the interaction between AMD and the gut. Experts believe this connection may be related to inflammatory cascades and the body’s use of protective antioxidant vitamins as mediated by intestinal microbia.1
Practical Applications of Microbial Findings
In the future, nonocular labs have the potential to predict and identify eye diseases such as glaucoma earlier, and in a more personalized manner. As part of an overall risk assessment, microbiome phenotype may serve as a new biomarker to help guide preventative approaches, such as dietary interventions and probiotics.3
While there is no established dietary protocol for a healthier gut, diets high in fat and sugar have been associated with intestinal dysbiosis in studies on mice.2 In addition, the consumption of fiber and short-chain carbohydrates serve as prebiotics that support the proliferation of beneficial microbes.1
Currently, Dr Galor says she doesn’t have a specific diet to recommend to her patients, but an anti-inflammatory diet may help. She feels it never hurts to encourage patients to eat healthy.
Fecal transplants, which may be appropriate for some infectious diseases, such as clostridium difficile, probably won’t play a role in eye care. “I don’t think fecal transplants are the best way to modulate specific components of the microbiome because you don’t know if the donor microbiome has an optimal concentration of the bacteria you want to transfer or how to deliver the material in a way that recolonizes the microbiome of the host,” according to Dr Galor. “However, newer methods are being studied that transfer a specific concentration of microbes to the host, an approach that I think is more promising.”
While diet and supplemental probiotics can influence the microbiome, Dr. Galor believes some diseases may be better modulated with probiotic eye drops. However, more research could eventually lead to personalized treatments.
“Many people already take probiotics and prebiotics,” Dr Galor said. “Ingesting them by mouth is something that is widely accepted. But the gut is not the only location that has a microbiome, and oral approaches are not the only way to manipulate the microbiome. The ocular surface microbiome may be modulated with eye drops and other approaches. The field is still in its infancy because we still don’t know what aspects of the microbiome should be targeted and how to best target them. However, these are important avenues of investigation as a better understanding of the influence of various microbiomes (e.g., gut, ocular surface, oral) on ocular health and disease will improve our treatment approaches in the future.”
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