Interaction between Gut microbiota and Toll-like Receptor beyond Immunity

Abstract

The commensal relationship between gut microbiota and the host is well observed. These bacteria facilitate energy harvesting, as well as modulate the development of immunity in the host. A substantial change in the pattern of gut microbiota from the first to the third trimester of pregnancy has been reported, and this change is suggested to be an adaptive mechanism for supporting the nutritional needs of mothers.1 Gut-derived bacteria are detected in umbilical cord blood and the meconium of newborns, implicating that maternal bacterial transmission happens during embryonic stages.2 However, it is unclear about the purpose of such early transmission although modulation of immunity has been hypothesized. Toll-like receptors (TLRs) are the key sensors of microbes and their products in innate immunity, and also play important roles in non-infectious inflammation. Gut-derived bacterial products are believed to be a trigger of TLR activation due to the change of gut permeability in different physiological and pathophysiological conditions.3 Other than the immunity-related function, TLRs can also regulate proliferation and differentiation in various kinds of non-immune cells including endothelial progenitor cells and mesenchymal stem cells.5 TLR pathway takes part in the regulation of embryonic development in lower biological species; however, whether such function is conserved in higher animal is unknown.4 Our in vivo model showed an increase in the levels of flagellin, the TLR5 ligand, in adipose tissue and circulation in parallel with the alteration of gut microbiota during pregnancy. We also found that the production of insulin-like growth factor-1 (IGF-1) during mid to late phase of pregnancy was TLR5 dependent. IGF-1 is one of the key growth factors for maternal adaptation and fetal development. Our data suggests a possible link between TLR with embryonic development mediated by the maternal change in gut microbiota and IGF-1 production.