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Updated: Oct 5, 2026

Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Gut bacteria and their metabolites may influence our decisions, intelligence, cognition, and consciousness
Leon M T Dicks1,2, Alfred Botha1, Carolina Pohl2
1Department of Microbiology, Stellenbosch University, Stellenbosch, South Africa.
Abstract:
The human gut hosts approximately 38 trillion bacteria, representing 400 to 500 species. Gut bacteria are in constant communication with the central nervous system (CNS) via the enteric nervous system (ENS), the peripheral nervous system (PNS), the autonomic nervous system (ANS), the immune system, the enteroendocrine system (EES), and the vagus nerve (VN). Short-chain fatty acids (SCFAs), especially butyrate, strengthen the blood-brain barrier (BBB) and modulate inflammatory signaling, thereby affecting brain function and cognitive performance. Acetate enhances the synthesis of lipid-rich myelin that protects neurons. Signaling molecules that cross the gut wall may optimize synaptic signaling in the frontal cortex. Bacterial metabolites that stimulate inflammatory responses activate the hypothalamic-pituitary-adrenal (HPA) axis, thereby increasing glucocorticoid production. This may reduce activity in the prefrontal cortex and suppress higher-order thinking and decision-making. We discuss how signaling molecules produced by gut bacteria influence the limbic system (thalamus, amygdala, hypothalamus, and hippocampus), primarily involved in emotions, memory, and motivation. The HPA axis and the gut microbiota-oligodendrocyte axis (GMOA) are discussed in more detail. We ask whether interactions between signaling molecules produced by gut bacteria and the limbic system can affect human intelligence, cognition, consciousness, and decision-making, coordinated by the cerebrum (cerebral cortex), prefrontal cortex, and parietal lobe.
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