# Probiotic Molecules That Inhib Inflammatory Diseases
## 1 Introduction Mod  
The World Health Organization defines probiotics as \"live microorganisms that when administered in adequate amounts, confer a health benefit on the host.\" (FAO/WHO 2002). Consumption of live organisms for maintaining good health is a concept accepted by the general population, and in fact, The National Health Interview Survey showed that probiotics were the third most used non-vitamin, non-mineral dietary supplement in 2012 [1]. Despite their popular use, probiotics have yet to be approved for any medical indication by the US Food Drug Administration [2], in part because results from clinical trials on the efficacy of probiotics in the treatment or prevention of disease have been equivocal [3]. The lack of clarity emanating from the clinical trials has created a state of confusion regarding the clinical use of probiotics. Some of the confusion may arise from the use of different probiotic strains, or combinations thereof, batch preparation, and the outcomes readout. Furthermore, humans vary widely in their diets, genetic backgrounds, and gut microbiome composition, all of which likely influence the efficacy of probiotics. The probiotic bacteria most widely studied belong to the _Lactobacillus_ sp., _Bacterioides_ sp., _Bifidobacteria_ sp., and _Bacillus_ sp. These bacteria have been used to treat diarrhea, irritable bowel syndrome [4], and atopic dermatitis [5], among other diseases. Probiotic bacteria can be beneficial to human health, for example, by inhibiting growth of pathogenic bacteria in the intestine and by secreting bioactive metabolites, such as short-chain fatty acids [6]. The use of intact bacteria for clinical interventions can be challenging, however, in part because the administration of bacteria may alter the endogenous microbiome,causing dysbiosis, and also affect intestinal immunity in a manner not yet fully understood. An alternative approach to administering live bacteria is to isolate and administer the active bacterial molecule responsible for the health benefits. As discussed below, we argue that future scientific research into probiotics should focus not only on specific probiotic organisms but more importantly, on identifying the active molecules of these organisms and determining the mechanism of action by which they provide protection from disease. Such a process will lead to probiotic molecules or probiotic-treated host cells as therapeutics. Here we focus on probiotic molecules that affect the innate and/or adaptive immune system. Bioactive probiotic molecules with anti-inflammatory properties include cell envelope molecules, secreted proteins, and exopolysaccharide, many of which are shown in Table 1. Although bacterial metabolites, such as short-chain fatty acids, lactate, and bacteriocins, can also be active probiotic molecules, we do not discuss them in this review. Instead, we briefly describe cell envelope-associated probiotic molecules, as well as secreted protein and carbohydrate probiotic molecules, and discuss in-depth the anti-inflammatory probiotic exopolysaccharide (EPS) produced by _Bacillus subtilis_. This EPS designated EPS\({}^{\text{Bg}}\), ameliorates disease due to enteric or blood-borne pathogens, allergic eosinophil, and graft vs. host disease [7; 8; 9; 10; 11; 12; 13].