The Gut-Brain Axis

Annu Rev Med. 2022 Jan 27:73:439-453. doi: 10.1146/annurev-med-042320-014032. Epub 2021 Oct 20.


Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Alterations in gut-brain-microbiome interactions have been identified in rodent models of several digestive, psychiatric, and neurological disorders. While alterations in gut-brain interactions have clearly been established in irritable bowel syndrome, a causative role of the microbiome in irritable bowel syndrome remains to be determined. In the absence of specific microbial targets for more effective therapies, current approaches are limited to dietary interventions and centrally targeted pharmacological and behavioral approaches. A more comprehensive understanding of causative influences within the gut-brain-microbiome system and well-designed randomized controlled trials are needed to translate these exciting preclinical findings into effective therapies.

Keywords: gut–brain–microbiome interactions; interoception; irritable bowel syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Brain
  • Brain-Gut Axis
  • Gastrointestinal Microbiome*
  • Humans
  • Irritable Bowel Syndrome* / therapy
  • Microbiota*