Multicellular organisms are composed of the macroscopic host and its symbiotic commensal microbiota. These complex communities of microbes include bacteria, fungi, viruses, other microbial & eukaryotic species.1,2 The immune system-microbiota interactions have a symbiotic relationship where microbiota plays an important role in the induction, training, and function of the host immune system and the immune system, in return, maintain these highly diverse and evolving microbes of the host.3 This symbiotic interaction between microbiota and the host helps in functioning of immune system in mammalians, plants, insects and aquatic organisms. Furthermore, the immune system and microbiota also engage “cross-talk” which involves exchange of chemical signals in many animals. This helps immune system to recognize the types of bacteria which are harmful to the host and then combating them, and it also helps in identifying the beneficial microbiota and allowing them to carry out their functions like immune reactivity and targeting.4-5

Mechanisms of microbiota in the immune system:

Cytokine induction:

Microbiota modulates immune response by acting locally and systemically. Shift in composition and density of microbiota affects systemic immunity. It promotes dermal T cell function and thereby producing IL-1α which in turn directly controls the capacity of dermal resident T cells in to producing inflammatory cytokines like IFN-γ and IL-17A. Furthermore, oral cavity also harbors a unique and complex microbiota which have role in promoting the inflammasome activity resulting in local increase of the inflammatory cytokine IL1β.6Reduction of gut microbiota via broad-spectrum antibiotic treatment have shown blunted T and B cell response against intranasal infection with influenza which helps in considering its role in promoting the inflammasome-mediated induction of IL-1β and IL-18 secretion.7-8

Induction of regulatory responses:

Tissue homeostatsis maintenance is extremely important for the host survival and it depends on a complex and coordinated set of innate and adaptive responses involving microbiota and pathogens. Foxp3 regulatory T (Treg) cells helps in maintaining both peripheral and mucosal homeostasis throughout the lifespan of the host.9-11 If disruption occurs in the homeostasis of these cells, it would cause loss of oral tolerance and development of aberrant effector responses in the gut. Induction of Treg cells is known to confer a health benefit to the host. Microbiota also helps in controlling oral antigen sampling by mucosal DCs and they also promote the induction of lamina propria resident macrophages by local expansion of Treg cells.12-13 Also, tissue specific factors like Vitamin A and MUC2 which are produced by intestinal goblet cells helps in regulation of mucosal dendritic cells.14-15Production of polysaccharide A (PSA) by a prominent human symbiont Bacteroides fragilis provided first demonstration of induction of regulatory responses by microbiota.16 B. Fragilis helped in promoting Treg cell function and induction via engaging the microbial derived PSA with TLR2 expressed by T cells.17Furthermore, SCFA and in particular butyrate also helps in regulating the size and function of the regulatory T cell network by promoting the induction of regulatory T cells in the colonic e