Role of pattern recognition receptors and the microbiota in neurological disorders.

Abstract

In recent years, the gut microbiota has been increasingly implicated in the development of many extraintestinal disorders, including neurodevelopmental and neurodegenerative disorders. Despite this growing connection, our understanding of the precise mechanisms behind these effects is currently lacking. Pattern recognition receptors (PRRs) are important innate immune proteins expressed on the surface and within the cytoplasm of a multitude of cells, both immune and otherwise, including epithelial, endothelial and neuronal. PRRs comprise four major subfamilies: the Toll-like receptors (TLRs), the nucleotide-binding oligomerization domain leucine rich repeats-containing receptors (NLRs), the retinoic acid inducible gene 1-like receptors and the C-type lectin receptors. Recognition of commensal bacteria by PRRs is critical for maintaining host-microbe interactions and homeostasis, including behaviour. The expression of PRRs on multiple cell types makes them a highly interesting and novel target for regulation of host-microbe signalling, which may lead to gut-brain signalling. Emerging evidence indicates that two of the four known families of PRRs (the NLRs and the TLRs) are involved in the pathogenesis of neurodevelopmental and neurodegenerative disorders via the gut-brain axis. Taken together, increasing evidence supports a role for these PRRs in the development of neurological disorders, including Alzheimer's disease, Parkinson's disease and multiple sclerosis, via the microbiota-gut-brain axis.