## 8 Salivary Biomarkers for Monitoring Health Status in the Gut  
The exploitation of the oral-gut axis has been used to determine health status in the gut by using oral samples. Individual saliva production is between 1 and 2 L per day [132]; therefore, being an appealing biospecimen for sampling. Saliva is composed mostly of water but also contains a variety of organic and inorganic components such as proteins, enzymes electrolytes, immunoglobulins, hormones, and micronutrients [133; 134; 135; 136]. These components are essentially blood-based and permeate into the saliva due to different capillaries, acinar cells, and ductal cells [137]. As sampling saliva is noninvasive and requires minimal safety-training, saliva represents an attractive alternative to blood and serum. Advantages of using saliva as a biofluid include a fast, easy, and inexpensive collection process that is suitable outside of the laboratory without the need of medical personnel [138]. Saliva fluid is easy to store and ship, particularly in that it does not clot, and is reflective of the current physiological state of an individual. While some systemic biomarkers in health correlate well between saliva and blood in diagnosis (e.g., HIV; hepatitis; oral cancer; periodontal disease; obesity), saliva is not the best biospecimen in that it does not always accurately represent systemic concentrations such as with amylase, some proteomes, and phosphate [139]. Some diagnostic applications of saliva include oral cancer, pancreatic cancer, breast cancer, lung cancer, or gastric cancers [138]. Saliva is also a promising biofluid for use in infectious bacterial diseases, infectious viral diseases and even infectious fungal diseases [140; 141; 142; 143; 144; 145; 146]. Salivary diagnostics can also play an important role in cardiology, [147; 148] for acute myocardial infarction [149]. In addition, we have previously noted that saliva analysis enables researchers to monitor the metabolic response of individuals during physical training [139; 150]. Therefore, sampling saliva, plaque, and other surfaces in the oral cavity have the potential to conjure insight into distant, yet relative, organ systems, i.e., the gut. Controversy and uncertainty lie in the accuracy of using the oral cavity microbiota, or other parameters of biomarker testing, for specific disease states in the GI tract. As we have discussed previously, diseases such as UC and CD have shown specific oral microbiota changes parallel to gut populations. Studies evaluating salivary biomarkers and microbiota composition in connection to IBD pathology may be useful for the future development of more conservative IBD diagnostics [114]. [PERSON] et al. evaluated salivary inflammatory biomarkers and microbiota of patients with diagnosed IBD, which revealed significantly elevated inflammatory cytokine levels, IL-6, IL-8, TNF\(\alpha\), and IL-1\(\beta\) as well as elevated secretory IgA [114]. These observations in increased cytokine levels were also correlated with relative abundance of IBD-disease associated genera, _Streptococcus_, _Prevotella_, _Haemophilus_, and _Veillonella_. Recently, oral anti-TNF\(\alpha\) has been used in experimental trials for treatment of IBD, validating the oral-gut axis while providing a blueprint for non-invasive therapeutics and diagnostics alike [151]. Additionally, research in salivary exosomes as biomarkers for IBD and other inflammatory diseases has gained momentum as well [152]. Exosomes are cellular nanovesicles present in a range of biofluids including saliva and intestinal luminal fluid aspirates, and transport proteins, nucleic acids, and cellular information. Exosomes are involved in cell-cell communication and gene regulation and the information they carry has potential to act as disease biomarkers, especially in IBD [152; 153]. Newer microbiome-based technologies (the study of microbial sequences using RNA or DNA sequencing) are making it possible to unravel complex interactions between the oral and gut microbiomes.