The Gut-Microglia Connection: Implications for Central Nervous System Diseases

Yiliang Wang,Xiaowei Song,Zhaoyang Wang,Yifei Wang,Fujun Jin,Feng Li,Yun Wang,Shurong Qin,Rongze Wang,Jiaoyan Jia,Kaio Kitazato

doi:10.3389/fimmu.2018.02325

Abstract

The importance of the gut microbiome in central nervous system (CNS) diseases has long been recognized; however, research into this connection is limited, in part, owing to a lack of convincing mechanisms because the brain is a distant target of the gut. Previous studies on the brain revealed that most of the CNS diseases affected by the gut microbiome are closely associated with microglial dysfunction. Microglia, the major CNS-resident macrophages, are crucial for the immune response of the CNS against infection and injury, as well as for brain development and function. However, the current understanding of the mechanisms controlling the maturation and function of microglia is obscure, especially regarding the extrinsic factors affecting microglial function during the developmental process. The gut microflora has been shown to significantly influence microglia from before birth until adulthood, and the metabolites generated by the microbiota regulate the inflammation response mediated by microglia in the CNS; this inspired our hypothesis that microglia act as a critical mediator between the gut microbiome and CNS diseases. Herein, we highlight and discuss current findings that show the influence of host microbiome, as a crucial extrinsic factor, on microglia within the CNS. In addition, we summarize the CNS diseases associated with both the host microbiome and microglia and explore the potential pathways by which the gut bacteria influence the pathogenesis of CNS diseases. Our work is thus a comprehensive theoretical foundation for studies on the gut-microglia connection in the development of CNS diseases; and provides great potential for researchers to target pathways associated with the gut-microglia connection and overcome CNS diseases.

Highlights

Microglia—the major brain-resident macrophages—are involved in a myriad of processes as the first line of defense against injury and infections, including brain development, brain function, and immune response, in the central nervous system (CNS) [1]
Gut microbiome is closely associated with CNS diseases such as Alzheimer’s disease (AD), depression, Parkinson’s disease (PD), and even autism spectrum disorder (ASD) [11]
Microglia may be the crucial mediators linking gut microbiome and CNS diseases, given that microglia are crucial immune cells in the CNS, and their dysfunction has been shown to be related to most CNS-associated diseases

Summary

Introduction

Microglia—the major brain-resident macrophages—are involved in a myriad of processes as the first line of defense against injury and infections, including brain development, brain function, and immune response, in the central nervous system (CNS) [1]. The GF mice lacked gut microbiota since birth; it is possible that the host microbiome influences prenatal microglia formation, contributing to the emergence of defective microglia in adult mice, which has already been confirmed in a later study [12]. SCFAs may control the activity of microglia through other peripheral myeloid cells that express FFAR2, recognize signals from SCFAs, and migrate to the brain or secrete specific factors that can cross the BBB to regulate microglia within the CNS (Figure 1).

Results

Conclusion