The Influence of Gut Microbiota on Neurogenesis: Evidence and Hopes

Abstract

Adult neurogenesis (i.e., the life-long generation of new neurons from undifferentiated neuronal precursors in the adult brain) may contribute to brain repair after damage, and participates in plasticity-related processes including memory, cognition, mood and sensory functions. Among the many intrinsic (oxidative stress, inflammation, and ageing), and extrinsic (environmental pollution, lifestyle, and diet) factors deemed to impact neurogenesis, significant attention has been recently attracted by the myriad of saprophytic microorganismal communities inhabiting the intestinal ecosystem and collectively referred to as the gut microbiota. A growing body of evidence, mainly from animal studies, reveal the influence of microbiota and its disease-associated imbalances on neural stem cell proliferative and differentiative activities in brain neurogenic niches. On the other hand, the long-claimed pro-neurogenic activity of natural dietary compounds endowed with antioxidants and anti-inflammatory properties (such as polyphenols, polyunsaturated fatty acids, or pro/prebiotics) may be mediated, at least in part, by their action on the intestinal microflora. The purpose of this review is to summarise the available information regarding the influence of the gut microbiota on neurogenesis, analyse the possible underlying mechanisms, and discuss the potential implications of this emerging knowledge for the fight against neurodegeneration and brain ageing.

Keywords: adult neurogenesis; ageing; antioxidants; gut microbiota; gut-brain axis; neural stem cells; neurodegeneration; nutrients; polyphenols.

Figure 1

Schematic representation of the four main experimental models used to investigate the functional linkages between intestinal bacteria and adult (mainly hippocampal) neurogenesis. Biochemical and functional parameters employed in most studies for the evaluation of neurogenesis and its microbiota-induced modifications are listed in the central, brain-shaped field.

Figure 2

Anatomic-functional structure of the GBA. Dietary factors modify microbiota composition and metabolism leading to the formation of secondary compounds that signal to the brain. Microbial inputs are either relayed by the vagus nerve afferent fibers (green route) or travel through the systemic circulation and the BBB to the SNC, where they perturb the HPA (red route). Vagus nerve afferences and HPA, together with signals from the monoaminergic system and immune/inflammatory molecules modify neurogenic circuits. More details regarding the brain-gut limb of the axis are in the main text.

Figure 3

Central role of the SIRT1-NF-kB signalling pathway in neuroinflammation and its modulation by dietary, microbial and immune factors from the intestine. Cytokines, bacterial wall components and ROS activate NF-kB, while polyphenols inhibit proinflammatory signalling via SIRT-1 mediated inhibitory deacetylation of the factor. Both enteric and BBB act as microbe-modifiable checkpoints in the intestine-gut communication. See the text for details.