# 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
### Potential Mechanism of Action of Prebiotics, Probiotics and Functional Foods in Addressing DED  
Ocular surface pain and discomfort are prominent symptoms of chronic dry eye and as such, often provide the impetus for presentation to a specialist [7]. Conjunctival inflammation is a hallmark of all dry eye syndromes [63] with chronic inflammatory infiltration of the conjunctiva and lacrimal glands [5]. Factors associated with inflammatory pain, including pro-inflammatory cytokines and infiltrating inflammatory cells, are present in DED [7]. Interestingly, DED often co-presents in chronic inflammatory diseases such as irritable bowel syndrome and other disorders known to have a gut dysbiosis aetiology [64]. Other autoimmune disorders that share DED symptomatology include [PERSON] syndrome, systemic lupus erythematosusous, rheumatoid arthritis, thyroid disease, asthma, osteoarthritis, allergy and rosacea (though the autoimmune link with rosacea is still debated) [65; 66]. Chronic inflammation is due in part to alterations in relative abundances between different bacterial phyla such as increases in Proteobacteria that leads to increased permeability of the gut and systemic host inflammation [67]. A similar dysbiosis has been reported in [PERSON] syndrome [16].  
In 2007 [PERSON] and colleagues [68] compared the microbiome composition of the ocular surface in a group of subjects without dry eye to a group with DED and raised the question of whether resident bacteria were pathogens or commensals. They reported significant differences between the population and kind of bacterial species residing on the ocular surface of each group. Using both conventional culture and 168 rDNA they identified specific species including _Bacillus_ spp. and _Klebsiella oxytoca_, as well as an overall increased bacterial count (CFU/swab) in participants with dry eye [68]. _Staphylococcus epidermidis_ was present in 100% of samples. Later works have suggested that _S. epidermidis_, as an integral member of epithelial microflora, rather than merely providing a benign presence, might actually exert a probiotic function by preventing colonization of more pathogenic bacteria [69].  
On the ocular surface, goblet cells are responsible for mucin production and hence reduction in these cells will reduce mucin production and disturb the healthy tear film. [PERSON] et al. [68] showed increasing bacterial burden correlated with decreasing numbers of goblet cells. As a corollary, in a mouse model of irritable bowel syndrome in which mucosal inflammation was stimulated using normal colon microflora, a similar reduction in goblet cell depletion and inflammatory cell infiltration was noted [70]. It has been suggested that production of mucin on the ocular surface is analogous to production of glycoproteins in the gastrointestinal tract [71], similarly leading to the release particular glycans and polysaccharides as in the intestinal tract which boosts the growth of certain bacterial species [72].  
There is precedence in the literature for the use of probiotic lysates, vitamins and omega-3 fatty acids to treat comorbid ocular, enteral and affective symptoms that comprise a disorder called \"irritableeye syndrome\" [73]. The authors of the study suggested that, via MALT (mucosal associated lymphoid tissue that is contiguous from the gut to the respiratory system to the naso-lacrimal system), subclinical inflammation arising from dysbiosis can cause or exacerbate signs and symptoms of DED since the eye contains its own local lymphoid tissues; the conjunctiva-associated lymphoid tissue (CALT), which samples antigens and maintains tolerance to commensal microbes [7]. Outcomes from the study indicated that supplements targeting gut dysbiosis might be a new approach to treating this syndrome.