Roles of Diet-Associated Gut Microbial Metabolites on Brain Health: Cell-to-Cell Interactions between Gut Bacteria and the Central Nervous System

Abstract

Gut microbiota have crucial effects on brain function via the gut-brain axis. Growing evidence suggests that this interaction is mediated by signaling molecules derived from dietary components metabolized by the intestinal microbiota. Although recent studies have provided a substantial understanding of the cell-specific effects of gut microbial molecules in gut microbiome-brain research, further validation is needed. This review presents recent findings on gut microbiota-derived dietary metabolites that enter the systemic circulation and influence the cell-to-cell interactions between gut microbes and cells in the central nervous system (CNS), particularly microglia, astrocytes, and neuronal cells, ultimately affecting cognitive function, mood, and behavior. Specifically, this review highlights the roles of metabolites produced by the gut microbiota via dietary component transformation, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, in promoting the function and maturation of brain cells and suppressing inflammatory signals in the CNS. We also discuss future directions for gut microbiome-brain research, focusing on diet-induced microbial metabolite-based therapies as possible novel approaches to mental health treatment.

Keywords: astrocytes; cell-to-cell interaction; dietary metabolites; gut microbiota; gut–brain axis; mental health; microglia; neurons.

FIGURE 1

Role of diet-associated metabolites as signaling molecules in cell-to-cell interactions between the gut bacteria and CNS. The gut microbiota have crucial effects on brain function through the gut–brain axis. Gut microbiota-produced dietary metabolites enter the systemic circulation and act as signaling molecules by influencing cell-to-cell interactions between gut microbes and cells in the CNS, particularly microglia, astrocytes, and neuronal cells, which ultimately affect cognitive function, mood, and behavior. Specifically, diet-derived metabolites, including SCFAs, tryptophan metabolites, and bile acid metabolites, promote the function and maturation of brain cells and suppress inflammatory signals in the CNS. To understand the complexity of cell-to-cell interactions between gut bacteria and the CNS, a multidisciplinary dialog between researchers in nutritional science, microbiology, neuroscience, and psychology is necessary. Abbreviations: CNS, central nervous system; SCFA, short-chain fatty acid.