Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis

Abstract

Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under both physiological and pathological conditions. Although there is anatomical separation, emerging evidence has indicated the existence of bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), and brain. The cross-talk between gut microbiota and brain may have crucial impact during basic neurogenerative processes, in neurodegenerative disorders and tumors of CNS. In this review, we discuss the biological interplay between gut-brain axis, and further explore how this communication may be dysregulated in neurological diseases. Further, we highlight new insights in modification of gut microbiota composition, which may emerge as a promising therapeutic approach to treat CNS disorders.

Keywords: Central nervous system; Glioma; Gut microbiota; Gut-brain axis; Immune signaling; Neurological disorder.

Fig. 1

Microbiota and the gut-brain axis. a The majority of microorganisms reside in the gastrointestinal tract of human beings and impact wide range of physiological or pathological activities of the host. b The concept of “gut-brain axis” includes complicated direct and indirect interaction of gut microbiota and their metabolites with different cellular components in CNS through immunological signaling. Disruption of hemostasis in gut microbiota can lead to the alternations in CNS, resulting in the progression of various CNS disorders

Fig. 2

Influences of the gut microbiota on different components in the CNS. a The byproducts of bacterial metabolism in gut, SCFAs, are able to induce proliferation of Foxp3⁺ Tregs through histone-modification. Administration of specific strains of microbiota or metabolite promotes the development of Th1, Th17 cells, and other cytokines. b Gut microbiota contribute to the maturation progress of naïve microglia and the number of mature microglia decreases in the absence of microbiota while the total count of microglia remains the same. Amp-sensitive microbiota catalyze dietary tryptophan to AHR agonists which could bind to the AHR on astrocyte and induce anti-inflammatory effects. c Deletion of gut microbiota leads to neurogenesis in hippocampus in animals raised in GF conditions or treated with antibiotics. d BBB in GF mice are more permeable with decreased expression of tight junction proteins while the integrity of BBB could be restored by colonization of microbiota or supplementation of SCFAs. Vagus nerve is a critical component linking biological functions in gut and brain. Signals from gut could either directly interact with vagus nerve or indirectly through the mediation of EECs and hormonal factors