Dry Eye Disease and Gut Microbiota: New Insights

Shedding fewer tears may suggest an inner peace—but for your eyes, it can signal trouble in the form of dry eye disease (DED).

DED, a complex condition affecting the ocular surface, leads to discomfort, vision problems, and even tissue damage. Though there are many causes, the modern era— with its aging populations, multiple medications, and increased screen time— has contributed to a rise in dry eye symptoms.

Emerging research now points to an unexpected player in eye health—the gut microbiome— which appears to influence tear production and the development of dry eye through immune and inflammatory pathways.

In this IPA blog, we explore the growing evidence connecting the gut microbiome to DED, along with studies investigating whether modulation strategies—such as probiotics, synbiotics, and fecal microbiota transplants—can help improve symptoms and outcomes.

Dry Eye Disease, in brief

DED is a chronic disorder of the ocular surface caused by tear film instability or an imbalance in the local microenvironment.

It is typically classified into two types: aqueous-deficient, such as in Sjögren’s syndrome (SS)—an autoimmune condition that affects the lacrimal (‘tear’) and salivary glands—and evaporative, which often results from meibomian gland dysfunction that reduces the lipid layer of the tear film. Meibomian glands are oil glands along the edge of the eyelids. The ocular surface system—including the cornea, conjunctiva, lacrimal glands, and meibomian glands—produces the tear film’s lipid, aqueous, and mucin layers, and disruption in any part of this system can initiate a cycle of inflammation and progressive damage.

Dry eye disease is influenced by a range of non-modifiable factors—including older age, female sex, East Asian ethnicity, and systemic conditions—as well as contributors like surgery, contact lens wear, and blepharitis (inflammation of the eyelids). Modifiable lifestyle risks such as low humidity, poor sleep, high screen time, diet, certain medications, and cosmetic use also play a significant role in its development.

Notably, the rise in DED during the COVID-19 pandemic highlights the impact of increased screen time and mask use, which likely reduced blink frequency and boosted tear evaporation through greater airflow over the eyes. Unsurprisingly, the ocular microbiota also influences and is influenced by DED.

Currently, treatment for DED targets the underlying cause and often includes artificial tears, anti-inflammatory medications, and light therapy for gland dysfunction. While artificial tears are generally safe, they may be limited by short retention and lack of anti-inflammatory action. Long-term corticosteroid use is restricted due to risks like increased eye pressure, redness, and infection.

Gut-eye axis

Emerging research suggests the existence of a gut-eye axis, in which gut dysbiosis may play a critical role in the onset and progression of various eye diseases. This connection is supported by growing evidence linking gut microbiota to conditions such as diabetic retinopathy, age-related macular degeneration, glaucoma, and autoimmune uveitis.

Here, we focus on what the research shows about its role in DED.

First, the gut microbiome shows significant alterations in patients with DED, particularly those with autoimmune forms. These individuals often experience damage to ocular surface tissues—such as the cornea, conjunctival goblet cells, and lacrimal glands—which has been linked to shifts in gut microbial diversity and abundance. Patients with SS, for example, consistently exhibit a lower fecal Firmicutes/Bacteroidetes ratio, a widely recognized marker of dysbiosis. This reduced microbial diversity is associated with elevated inflammatory markers and a compromised intestinal barrier, conditions that support the growth of pathogenic bacteria and fuel systemic inflammation.

However, a study found that while overall microbial diversity was similar, patients with autoimmune-associated dry eye had distinct ocular microbiome compositions and functions, suggesting differing disease mechanisms from non-autoimmune dry eye.

Specific bacterial genera may play key roles in DED; for instance, research has linked Prevotella to tear secretion, with its abundance in gut microbiota positively correlating with dry eye disease severity.

Gut dysbiosis may contribute to dry eye disease through several mechanisms, including disruption of immune balance, reduced anti-inflammatory metabolites, and activation of inflammatory pathways that impair tear production and ocular surface integrity.

For example, in CD25 knockout mice, the absence of commensal bacteria worsens Sjögren-like dry eye by increasing immune dysfunction, including more pathogenic CD4+ T cells and greater inflammation. Fecal transplants from healthy mice to germ-free mice reduced eye disease severity and restored immune balance. An additional study in mice reported that dysbiosis can increase an inflammatory response of the cornea and conjunctiva to endotoxins such as lipopolysaccharide (LPS).

Gut microbiota modulation strategies

Given the health benefits of biotics, researchers have tested their impact on DED in animals and in patients. The results are promising.

Animals

• In a mouse model of autoimmune dry eye, treatment with a mixture of five probiotics improved symptoms by altering gut microbiota and reducing antigen-presenting activity in immune cells, suggesting a microbiome-driven immunomodulatory effect.
• In addition, in a mouse model of environmental dry eye , the same probiotic treatment significantly increased tear secretion and altered gut microbiota composition and diversity.
• Strains of Lactiplantibacillus plantarum and Bifidobacterium bifidum improved tear secretion and reduced inflammation in a mouse model of dry eye by shifting gut microbiota composition, improving the anti-inflammatory and pro-inflammatory cytokines ratio.
• Streptococcus thermophilus strains mitigated induced dry eye in mice by reducing oxidative stress and inflammation, thereby improving tear production, tear film stability, and ocular surface health.
• Limosilactobacillus fermentum strains alleviated induced dry eye in mice by improving tear production and ocular surface integrity, while reducing oxidative stress, inflammation, and apoptosis.

Humans

• Supplementation with specific strains of Bifidobacterium lactis and Bifidobacterium bifidum alongside tear substitutes significantly improved tear film measures and reduced bacterial overgrowth in patients with dry eye syndrome.
• Likewise, suggesting a synergistic role for probiotics in managing DED, supplementation with strains of Saccharomyces boulardii and Enterococcus faecium alongside tear substitutes significantly improved tear film parameters and reduced ocular surface bacterial overgrowth in patients compared to those who received only eye drops.
• A double-blind clinical trial showed that oral intake of the probiotic Streptococcus thermophilus significantly improved dry eye symptoms, tear function, and reduced inflammation markers compared to placebo.
• In a randomized controlled trial, oral probiotics (Lactobacillus, Bifidobacterium, and Streptococcus) and prebiotics significantly improved dry eye symptoms in patients compared to placebo, suggesting their potential to manage dry eye disease by modulating gut-related inflammation.

Fecal microbiota transplant (FMT)

Bolstered by its efficacy in various other conditions, FMT is being explored for its usefulness in DED. A small clinical trial found that FMT was safe in individuals with immune-mediated dry eye and shifted some gut bacteria toward the donor profile, with half reporting symptom improvement three months post-treatment.

Takeaway

Emerging research reveals that gut dysbiosis may play a significant role in dry eye disease by disrupting immune balance and fueling inflammation. Animal and human studies suggest that targeting the gut microbiome with probiotics, synbiotics, or even fecal transplants may help improve symptoms and restore ocular surface health. As our understanding of the gut-eye axis grows, microbiome-based therapies could become a promising complement to traditional dry eye treatments.

Image by Pexels from Pixabay

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