The Gut-Eye Axis as a Formulation Target: A New Direction for Nutraceutical Development in Dry Eye

Introduction

Dry eye is one of the most common eye disorders, affecting hundreds of millions of people worldwide (1, 2). It is characterised by tear film instability and ocular surface inflammation, manifesting with symptoms such as dryness, burning sensations, and visual disturbances. Despite its prevalence, management is largely symptomatic. Artificial tears provide temporary relief, while anti-inflammatory agents alleviate local inflammation, but these approaches do not address the upstream biological contributions to tear film dysfunction.

Evidence increasingly suggests that dry eye is not merely a local eye disorder. Systemic factors, including hormonal status, autoimmune activity, and, more recently, gut microbiome composition, play a role in its pathogenesis. The gut-eye axis describes the connection between the gastrointestinal system and the ocular surface. It has emerged as a potential intervention target.

For the nutraceutical industry, this shift has practical implications. Formulations designed around surface-level mechanisms, such as omega-3 supplementation, have shown meaningful benefits for certain dry eye parameters, yet they address only one aspect of a multifactorial condition and do not address the systemic pathways associated with tear film dysfunction (3,4). This article reviews the evidence for the gut-eye axis and its relevance to dry eye pathogenesis, and considers what this suggests for next-generation nutraceutical formulation strategies.

The Gut-Eye Axis: Mechanisms and Evidence

The human microbiota, the community of bacteria, viruses and fungi living across the body, does more than support digestion. Growing evidence points to a meaningful connection between gut microbiota composition and ocular health. The same bacterial metabolites that regulate intestinal immunity are showing up as relevant factors in tear film stability (5, 6).

The gut microbiota communicates with distant organs through immune, metabolic and inflammatory pathways. Commensal bacteria produce short-chain fatty acids, particularly butyrate, by fermenting dietary fibre. These metabolites strengthen the gut barrier, regulate immune activity and reduce systemic inflammation (6). When microbial balance is disrupted, the gut barrier becomes more permeable. Inflammatory signals enter circulation and can reach the ocular surface, where they contribute to tissue damage and tear film instability (6).

Short-chain fatty acids have emerged as particularly relevant in this context. Butyrate and related compounds influence immune signalling, reduce inflammation and show promise as targets for novel therapeutic approaches in ocular disease (7).

Studies have found specific differences in the gut microbiota of dry eye patients compared to healthy individuals, including a reduction in SCFA-producing bacteria and an increase in pro-inflammatory species (6).

Implications for Nutraceutical Formulation

Research on the gut-eye axis raises a straightforward question for the nutraceutical industry: if the gut microbiome really plays a meaningful role in dry eye symptoms, why do most products still focus mainly on treating the ocular surface directly?

Most eye-health nutraceuticals are built around ingredients already linked to ocular function. Lutein, zeaxanthin, and omega-3 fatty acids are common examples (8). There is evidence behind these choices, but they tend to share the same limitation: they are usually selected from population-level findings and broad, general mechanisms, rather than from the gut-microbiome-linked mechanisms that may contribute to ocular surface homeostasis. In other words, the formulation often begins with the ingredient, not the target.

An alternative is to start with the biology. In dry eye, that means figuring out which gut microbiome pathways are altered, which metabolites are lacking, and which food-grade inputs could help restore or support their production. Here, the ingredient is a tool to reach a defined biological outcome, not the default starting point.

This target-first approach also demands more advanced biological modelling than conventional formulation methods. Genome-scale metabolic modelling of gut bacteria, paired with simulations across large, diverse microbiome datasets, can help identify the smallest set of food-grade inputs needed to support specific metabolic goals. That computational framework is used to develop condition-specific formulations, including a clinically investigated eye health formulation developed using Digital Twin and AI technology.

The difference is not only scientific. Buyers and partners in the nutraceutical industry are increasingly asking for a defined biological rationale and clinical evidence, not just an ingredient list.

A Clinical Perspective

Evidence supporting the gut-eye axis is starting to go beyond purely observational work. In a prospective pilot study, researchers looked at whether a food-grade oral formulation designed to act on this pathway could lead to meaningful clinical improvements for people with dry eye.

Participants took the formulation once a day for eight weeks, then returned for a follow-up at week sixteen. Across several clinical measures, including tear production and patient-reported symptom scores, improvements were seen. Importantly, the benefits were not limited to the eight-week mark; they continued to increase through week sixteen, even after the intervention had stopped.

Compared with the most commonly prescribed pharmaceutical treatment for dry eye, the formulation produced a larger increase in tear production (article submitted for peer review). That stands out because the two strategies work in completely different ways: one acts directly on the ocular surface, while the other works via the gut.

Because this was a single-arm pilot study, the results need to be viewed with that limitation in mind. A randomised controlled trial is already in progress. Still, these early findings suggest that gut-targeted, food-grade formulations may be a promising clinical direction for managing dry eye.

Conclusion

Dry eye has traditionally been treated as a purely local problem of the eye. The evidence reviewed here suggests that view is only part of the story. Gut microbiome composition, immune signalling, and systemic inflammation can all contribute to tear film dysfunction, and the links between the gut and the ocular surface are becoming increasingly well understood.

For the nutraceutical industry, the implications are straightforward. Products built mainly around ocular surface mechanisms may help, but they do not capture the full biology. Formulations developed around the systemic pathways associated with the condition may go further. In practice, the key difference is where the formulation strategy starts: with a chosen ingredient, or with a defined biological target.

Early clinical results indicate that gut-targeted, food-grade formulations can deliver meaningful benefits for dry eye, including improvements that compare well with established pharmaceutical options. The data are still preliminary, but the overall direction is consistent.

The gut-eye axis is still an emerging field, but it is a credible and increasingly practical area of research. For companies focused on eye health nutrition, it offers both a real scientific opportunity and a way to differentiate, based on biology, not just ingredient positioning.

References and notes

1. Perez VL, Chen W, Craig JP, Dogru M, Jones L, Stapleton F, et al. TFOS DEWS III Editorial. Am J Ophthalmol. 2025;278:166-167. https://doi.org/10.1016/j.ajo.2025.05.038
2. Xiao K, Li L, Zhang X, Ye Y, Yao Y, Liu Y, et al. Global prevalence of dry eye: a systematic review and meta-analysis. Contact Lens Anterior Eye. 2025;49(2):102627. https://doi.org/10.1016/j.clae.2026.102627
3. Wang WX, Ko ML. Efficacy of omega-3 intake in managing dry eye disease: a systematic review and meta-analysis of randomized controlled trials. J Clin Med. 2023;12(22):7026. https://pubmed.ncbi.nlm.nih.gov/38002640/
4. Bhargava R, Pandey K, Ranjan S, Mehta B, Malik A. Omega-3 fatty acids supplements for dry eye: are they effective or ineffective? Indian J Ophthalmol. 2023;71(4):1619-1625. https://pubmed.ncbi.nlm.nih.gov/37026312/
5. Campagnoli LIM, Varesi A, Barbieri A, Marchesi N, Pascale A. Targeting the gut-eye axis: an emerging strategy to face ocular diseases. Int J Mol Sci. 2023;24(17):13338. https://pubmed.ncbi.nlm.nih.gov/37686143/
6. Song J, Dong H, Wang T, Yu H, Yu J, Ma S, et al. What is the impact of microbiota on dry eye: a literature review of the gut-eye axis. BMC Ophthalmol. 2024;24(1):262. https://pubmed.ncbi.nlm.nih.gov/38898418/
7. Ciurariu E, Tirziu AT, Varga NI, Hirtie B, Alexandru A, Ivan CS, Nicolescu L. Short-chain fatty acids and the gut-retina connection: a systematic review. Int J Mol Sci. 2025;26(6):2470. https://pubmed.ncbi.nlm.nih.gov/40141114/
8. Huang SC, Lei YP, Hsiao MC, Hsieh YK, Tang QP, Chen C, Hsu MY. Multicomponent dietary supplementation: impact on tear secretion and ocular surface inflammation in dry eye syndrome patients. Antioxidants. 2025;14(1):103. https://pubmed.ncbi.nlm.nih.gov/39857437/