# The Case for a More Holistic Approach to Dry Eye Disease: Is It Time to Move beyond Antibiotics?
## 3 Prebiotics
### Prebiotics and Human Health and Disease  
In the last decade, evidence of prebiotics effect on the host-microbial community and the benefits for health has gained traction [81; 82; 83]. Because prebiotics are utilized by specific bacterial strains, this can elevate metabolism of select bacteria and their cognate metabolites without necessarily increasing the numbers of bacteria. In this way, other members of the community, as well as the host, can themselves benefit biologically or physiologically from prebiotics [84]. Physiological benefits of prebiotics include improvement of intestinal functions [85; 86], increased mineral absorption (calcium) and improved bone density [87; 88], regulation of lipid and glucose metabolism [79; 89], and modulation of immune functions [90; 79]. Moreover, it has been indicated that prebiotics can independently promote health, without necessarily influencing metabolism of beneficial bacteria; for example, they can bind with pathogens and create an anti-adherence effector they can improve the immune system by the effect on host immune receptors [91]. Intestinal leukocytes and specialized enterocytes sense the content of the intestinal lumen and influence the intestinal immune response. Oat \(\beta\)-glucan been shown to activate both cell types [92].  
Plant oligosaccharidescharides, flavonoids and polyphenols confer numerous benefits including anti-oxidative and anti-inflammatory actions [93]. Often these agents are discussed in relation to their inflammatory or immune modulating functions without a complete understanding of the pathways involved. For example, the bioavailability of such compounds has previously been seen as a disadvantage or a conundrum [94]. But now we are beginning to see that these compounds might be functioning as a food source for probiotic and indigenous bacteria both locally and through the gut and might even act locally as prebiotics on the ocular surface.  
The impact of prebiotics on human health and different diseases has been explored in a number of studies. The efficiency of galactooligosaccharide (GOS) has been reported in irritable bowel syndrome (IBS) [95]. Also, Inulin and lactulose were examined in a study related to inflammatory bowel disease (IBD) [96]. Various studies have indicated a relationship between improvement of allergy conditions [96], skin health [96], metabolic disorders such as obesity [97].  
Omega-3 fatty acids (FA) are essential polyunsaturated fatty acids obtained through diet. Short chain (alpha-linolenic acid) fatty acids are found in walnuts, soy, flaxseed and linseed, while long chain [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) subtypes are derived from oily fish or produced in the body from desaturation/elongation of short-chain FAs [98]. There is emerging evidence of their role as prebiotics. Omega-3 PUFAs have been shown in animal models to normalize early-life stress-induced gut dysbiosis [99] and, through the modulation of _Fimicutes/Baccroidetes_ ratio, can reduce endotoxmeia associated with low grade inflammation--a distinguishing feature of chronic conditions including insulin resistance, obesity, IBD, anxiety, mood and depression, RA and cancer [80]. Extant reports suggest a reciprocal relationship between _Faecalibacterium_ and _Bacteroides_. Additionally, omega-3 PUFAs can influence butyrate-producing genera such as _Bifidobacterium_, _Lachno-spira_, _Roseburia_ and _Lactobacillus_, many of which are reported to be in dysbiosis in IBD subjects [80]. Omega-3 PUFAs are reported to effect increases in anti-inflammatory activity in the gut through increases short chain fatty acid-producing bacteria [100]. Animal studies suggest links between the Omega 3 PUFA-mediated alteration of the gut microbiome and positive immune impacts that together work to maintain gut mucosal integrity [80].