# The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?
## 2 Dry Eye Disease as an Inflammatory Disorder
### The Anti-Inflammatory Role of Probiotics, Prebiotics and Functional Foods in DED  
Modern lifestyle choices appear to be an important factor in many inflammatory diseases, particularly those with an autoimmune or metabolic component including obesity, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type I diabetes, eczema, allergy, and psoriasis [20; 49]. These illnesses comprise multifactorial aetiologies involving T-cell mediated autoimmune mechanisms leading to chronic conditions requiring ongoing disease management [49]. Regulatory and effector subsets of T cells are implicated in the pathogenesis of DED which is described as an inflammatory autoimmune disorder of the ocular surface [50] characterized by increased proinflammatory cytokines in the tears, epithelial apoptosis and leucocyte infiltration [8] and recapitulated by adoptive transfer of CD4\({}^{+}\) T [51]. DED often requires life-long management and, as such, would appear well-placed within the family of chronic disease.  
Hence, if we view DED as a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface [52] we can draw from the burgeoning body of research into other chronic autoimmune disorders that are increasingly affecting the population.  
Poor Western diets, typified by low fibre and high fat, have been shown to affect gut microbial composition and immune system functions and consequently trigger disease [53; 54; 55]. Gut dysbiosis contributes to a chronic inflammatory status and is a causative factor for various autoimmune disorders [56; 57]. Thus, diet presents a vital route for immune system modulation [21; 22; 23; 53; 54; 58].  
Perturbation of the gut microbiome illustrated by germ-free or antibiotic-treated mice has demonstrated the regulation of lymphocytic development and inflammatory responses in the gut [59; 60]. The effect of altered diet on gut microbiota in mice with systemic lupus erythematosus (SLE), an autoimmune disease mostly affecting skin and joints has been studied [56; 61]. SLE innate inflammation caused an increase in the bacterial species _Lactobacillus reuteri_ which, in turn, exacerbated systemic autoimmunity [62]. The authors reported a special starch diet decreased lupus development [62]. Such studies indicate that addressing gut dysbiosis for distal inflammatory disorders is a valid line of enquiry.  
In an effort to address aetiology of DED, our group is interested in exploring alternative treatments for dry eye that re-establish a healthy ocular microbiome both through topical and systemic means; constraining ocular and gut dysbiosis and cognate local or systemic inflammation through the use of functional foods and related bioactive substances.  
This article reviews a number of potential avenues of treatment for dry eye along the lines of functional foods and related products to work to effect healthier gut and ocular bacterial communities. Research in this arena in relation to dry eye is in its infancy but no doubt will be exploding in the next few years.  
For this narrative review, a literature search was performed between January and May 2019 using electronic databases PubMed and Google Scholar. Included studies were clinical trials and meta-analyses and reviews of such, on the oral supplementation of probiotics, prebiotics and supplements in the form of functional foods for the treatment or prevention of DED and related disorders. Exclusion criteria compromised articles for which there was no full text available, articles written in a language other than English and grey literature. For inclusion into the review, as this is yet an emerging field of research, we identified 27 articles specific to this search from the first round and additional references were identified from related studies cited within these articles.