Gut-Brain Axis

Definition

A bidirectional communication network connecting the gastrointestinal tract and the central nervous system. It operates via neural, immune, endocrine, and microbial pathways, with the vagus nerve serving as the primary neural route.

Neural, immune, microbial, and endocrine channels

The gut-brain axis describes the complex, two-way signaling between the digestive system and the brain. The gut contains its own extensive nervous system — the enteric nervous system — sometimes called the "second brain," with approximately 500 million neurons.

Communication along the gut-brain axis occurs through multiple channels:

  • Neural – The vagus nerve transmits signals in both directions between gut and brainstem. The vast majority (~80%) of these are afferent — carrying information from the gut to the brain.
  • Immune – Gut-associated immune cells release cytokines and mediators that influence brain function and vice versa.
  • Microbial – The gut microbiome produces neuroactive molecules — including short-chain fatty acids and neurotransmitter precursors — that influence nervous system function.
  • Endocrine – Gut hormones affect appetite, mood, and brain signaling.

Disruptions in gut-brain axis communication are associated with irritable bowel syndrome, inflammatory bowel disease, depression, and anxiety. The vagus nerve's central role in this axis is one reason researchers are interested in vagus nerve stimulation for both gut and mental health applications.

Reviewed by

Ulf Andersson

Professor of Pediatric Rheumatology, Karolinska Institutet

Worked at Karolinska for five decades as a clinician and a basic scientist focusing on inflammation. Co-discoverer of HMGB1 as the prototype alarmin molecule. Honorary doctor at Hofstra University in New York. Highly Cited Clarivate Researcher Web of Science awards.

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