24/10/2025
The gut-brain axis integrates 4 primary streams of signals:
🧠 1. Neural Pathway
The vagus nerve and enteric nervous system (ENS) transmit afferent signals from the gut to the brain. Microbial metabolites and host-derived neurotransmitters (e.g., serotonin, dopamine, GABA) influence mood, cognition, and stress responses. Enteroendocrine and enterochromaffin cells release neuroactive compounds in response to microbial cues.
🧬 2. Endocrine Pathway
The gut microbiota modulates HPA axis activity through changes in gut barrier integrity, circulating metabolites, and stress hormones. Cortisol, released from the adrenal cortex, affects both systemic inflammation and brain function. Microbiota-regulated hormones such as GLP-1, CCK, and ghrelin further influence appetite, mood, and behavior.
🦠 3. Immune Pathway
Microbial antigens (PAMPs) and metabolites interact with intestinal immune cells (e.g., Th1, Th17, dendritic cells), influencing systemic and neuroinflammatory tone. Elevated cytokines like TNF-α, IL-1, and IL-6 have been linked to blood-brain barrier disruption, depression, and cognitive impairment.
🔁 4. Metabolic Pathway
The gut microbiota ferments dietary components (e.g., fiber, protein, bile acids) into signaling molecules including:
-SCFAs (butyrate, propionate)
-Secondary bile acids
-Branched-chain amino acids (BCAAs)
These metabolites affect energy regulation, neurotransmission, and epigenetic signaling within the CNS and peripheral tissues.