The development, maturation, and function of the mucosal immune system are extensively dependent on microbiota, underlying a potential role of the mucosal immune system in the regulation of emotion and behavior [
2]. Segmented filamentous bacteria (SFB) are potent stimuli for the full function of B and T lymphocytes in the gut [
16,
17]. As a concept of proof, germ-free (GF) mice lack a functional immune system and colonization with gut microbiota restores their immune function [
18]. Gut microbiota communicate with the host through Toll-like receptors (TLRs) [
19]. TLR1–10 are commonly expressed in human intestinal epithelial cells, macrophages, dendritic cells, mast cells, lymphocyte, neutrophils, CNS glial cells, and neurons. TLR1–10 can be activated by microbial components, therefore triggering the release of IL-1b, IL-6, IL-8, and TNF-α [
19‐
21]. TLR knockout or transgenic animal models provide strong evidence for the interaction between gut microbiota and immune response via TLR system. For example, TLR2 knockout mice demonstrated gut dysbiosis and aberrant immune responses, which were essential for
Bacteroides fragilis-mediated prevention of DSS-induced colitis [
22,
23]. A study on TLR4 knockout mice suggests that TLR4 mediated Gulf War illness model-induced neuroinflammation and gastrointestinal disturbances via gut dysbiosis and leaky. Results from transgenic villin TLR4 mice suggest that TLR4 can modulate the susceptibility of DSS-induced colitis, which can be transmissible by gut microbiota [
24,
25]. In IBD patients, non-synonymous variants in the TLR1, TLR-2, TLR-6, and TLR-9 genes were identified in correlation with impaired host-commensal interaction and distinct disease phenotype [
21]. Moreover, the microbiota can also modulate hormonal peptide signaling by synthesis of peptide-like antigenic proteins derived from gut bacteria [
2].