Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

Abstract

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota-gut-brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.

Keywords: Alzheimer’s disease; cognition; gut microbiota; neurodegeneration; neurotransmitters.

Figure 1

Gut microbial-mediated neurotransmitter synthesis and its impacts on cognition. Gut microbiota can either produce neurotransmitter precursors, catalyze the synthesis of neurotransmitters through dietary metabolism, or in combination. Some bacterial taxa may signal through their metabolites to promote the synthesis and release of neurotransmitters by enteroendocrine cells (e.g., metabolites produced by spore-forming bacteria serve as signaling molecules to regulate the biosynthesis of serotonin by increasing the expression of its rate-limiting gene TPH1 in enterochromaffin cells). Neurotransmitters synthesized by bacteria and enteroendocrine cells can enter the blood circulation and be transported to other parts of the body. Some neurotransmitter precursors can cross the blood–brain barrier and participate in the synthesis cycle of neurotransmitters in the brain. In addition, neuropod cells located in the intestinal epithelium synthesize and release neurotransmitters such as glutamate, which can transmit sensory signals to the brain within milliseconds through vagus nerve. Gut microbiota-modulated changes in neurotransmitter/precursor synthesis may lead to alterations in brain function and influence cognition in neurological diseases such as Alzheimer’s disease, Parkinson’s disease, autism, and schizophrenia. Abbreviations: 5-HTP, 5-hydroxytryptophan; l-DOPA, l-3,4-dihydroxy-phenylalanine; GABA, gamma-aminobutyric acid.