# The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?
## 4 Probiotics
### Probiotics and Ophthalmic Related Diseases  
In relation to ocular uses of probiotics, a comprehensive systematic review and meta-analysis of allergic rhinitis conducted in 2016 considered ocular symptoms in twenty-two randomised, double-blind, placebo-controlled studies and reported an overall positive effect of probiotics in reduction of ocular symptom scores in allergic rhinitis [147]. Recently, Jhaveri Microbiology Centre of Brien Holden Eye Research Centre in India has examined the association between gut bacterial and fungal dysbiosis and bacterial keratitis. They analysed the bacterial and fungal composition of faecal samples of 21 healthy participants versus 19 patients with bacterial keratitis (BK). Anti-inflammatory bacteria including _Dialister_, _Megasphaera_, _Faecalibacterium_, _Lachospira_, _Ruminococcus_ and _Mitsuokella_ and members of _Frimicutes_, _Veillonellaceae_, _Ruminococcaceae_ and _Lachospiraceae_ were more evident in healthy individuals compared with people suffering from bacterial keratitis. They also found more pathogenic fungus in BK groups. Their result strongly suggests the imbalance of gut bacterial community in people with BK [148] and indicates that probiotics might help ameliorate BK. Immune responses to commensal bacteria and opportunistic pathogens have been suggested as triggering [PERSON] syndrome [149]. In a relatively recent clinical trial, the efficacy of Probiotic IRT-5 (consisting of _Lactobacillus casei_, _Lactobacillus acidophilus_, _Lactobacillus reuteri_, _Bifidobacterium bifidum_ and _Streptococcus thermophiles_) on management of autoimmune uveitis (EAU) and autoimmune dry eye in mice was explored. Monitoring inflammatory score of retinal tissues for uveitis and corneal staining and tear secretion for dry eye, the authors report that probiotics can be effective in decreasing clinical signs of autoimmune dry eye [150]. Such data support the hypothesis that dry eye originates from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface. Regulatory T cells on the ocular surface have been suggested to provide protection against autoimmunity, as demonstrated at other mucosal sites [151] and to protect mice exposed to desiccating stress from developing dry eye. When these cells are depleted, mice developed full blown disease [51]. It is speculated that inflammation in DED is due to a decrease in number and/or function of regulatory T cells and an increase in pro-inflammatory cells (CD4\({}^{+}\) Th1/Th17) along with cognate inflammatory mediators [51]. As such, probiotics might well be considered as a potential therapy. In 2016, a group of researchers examined the effect of a combination of probiotics plus vitamins in people with DED. Their results suggest that synbiotics, which combine probiotics and prebiotics in a form of synergism, can decrease some signs and symptoms of DED while also modulating gut function [152]. This group explored a combination of _Lactobacillus acidophilus_, _Streptococcus thermophilus_, _Lactobacillus plantarum_, _Lactobacillus rhamnus_, _Bifidobacteriumluctis_, _Zn_, Vitamins B1, B2, B6 and niacin. Another dry eye study examining the effect of a combination of fish oil, lactoferrin, zinc, vitamin C, lutein, vitamin E, \(\gamma\)-aminobutanoate acid and _Enterococcus ficeum_ WB2000 on dry eye reported significant improvement in clinical symptoms at 4 and 8 weeks [153]. A 2017 report from Korea [150] explored the use of IRT-5 probiotics (_Lactobacillus casei_, _Lactobacillus acidophilus_, _Lactobacillus reuteri_, _Bifidobacterium bifidum and Streptococcus thermophiles_) on autoimmune dry eye. IRT-5 was efficacious in reducing dry eye through attenuation of autoreactive T cells, suggesting as the authors report, relevance to treatment of [PERSON] syndrome with IRT-5.