# Immunomodulatory Properties of Probiotics and Their Derived Bioactive Compounds
## 3 Gut Microbiota and Immunity Crosstalk in Health and Disease  
The gut microbiota represents a group of microorganisms that are strictly compartmentalized to the intestinal lumen of the mammalian gastrointestinal (GI) tract [42]. This complex microbial community that harbors the gut involves more than 1000 bacterial species [43] which contribute to the maintenance of host health. A balanced gut microbiota combats harmful opportunistic pathogens while showing tolerance to beneficial commensal bacteria, and thus it is directly associated with the establishment of gut homeostasis [44]. Gut microbiota has a prominent participation in the execution of various gut functions, such as degradation of unmetabolized dietary components, production of essential nutrients, and secretion of bioactive compounds with anti-inflammatory and immunomodulatory properties, such as SCFAs and bacterioxins [3; 45]. Gut microbiota imbalance, known as gut dysbiosis, is often implicated in the development of acute or chronic inflammation and oxidative stress, provoking givevous health disorders [24]. Changes in the composition and diversity of the gut microbiota are associated with increased susceptibility to non-communicable gastrointestinal diseases [42], such as inflammatory bowel disease (IBD) or colorectal cancer (CRC), metabolic disorders including obesity or type 2 diabetes [46], and cardiovascular and neurodegenerative diseases [47]. Although the connection between diseases and disrupted gut microbiota composition has been documented [47; 48], it is still ambiguous whether gut dysbiosis is the cause or consequence for the development of detrimental health issues [49]. It is generally argued that resilience, defined as the ability of an ecosystem to return to its original state after perturbation caused by drug administration, invasion of pathogens, and unhealthy lifestyle habits, constitutes the preponderant factor for a healthy gut microbiota [50]. Resilient microbiota is often associated with increased complexity and diversity of gut microbial communities [51]. However, the determination of a healthy gut microbiota, which might contribute to personalized medicine approaches, has not been achieved yet. This lack of evidence is due to the microbiome diversity among individuals and age groups, as demonstrated by the Human Microbiome Project, rendering the need for further research imperative [52]. Considering the fact that approximately 70% of immune cells reside in the gut [51], the interaction of gut microbiota with the intestinal immune system is a prerequisite towards the achievement of a balance between inflammation and immune tolerance [48]. The intestinal immune system comprises four main compartments: the gut-associated lymphoid tissue (GALT), the mesenteric lymph nodes (MLN), the lamina propria (LP), and the epithelial tissue [53]. GALT utilizes multiple mechanisms in order to eliminate the presence of pathogens in the intestinal lumen of mammals [54] and consists mostly of aggregated lymphoid follicles, the Peyer's patches, which are characterized as the immune sensors of the intestine [55]. Peyer's patches contribute to the generation of IgA-producingB cells [2] and are covered by the follicle-associated epithelium (FAE), the interface between the intestinal lumen and the GALT [55]. Except for the intestinal epithelial cells (IECs), two distinct types of specialized epithelial cells are incorporated in the FAE: microfold (M) cells, which recognize various mucosal antigens and transfer them to the LP, where the underlying APCs stimulate the adaptive immune response [54; 55], and goblet cells, which are involved in the secretion of mucus [3]. The FAE serves as an effective barrier which enhances the isolation of host immune cells residing in the LP from commensal or pathogenic bacteria [3] and may be disrupted in case of gut dysbiosis [51]. Several studies in germ-free (GF) mice, a representative model system of immunodeficiency, have indicated the supreme impact of gut microbiota on the development of the immune system [44; 48].