Neuropsychopharmacology Reviews

Neuropsychopharmacology (2017) 42, 178–192; doi:10.1038/npp.2016.103; published online 13 July 2016

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

Timothy G Dinan1,2 and John F Cryan1,3

  1. 1APC Microbiome Institute, University College Cork, Cork, Ireland
  2. 2Department of Psychiatry & Neurobehavioural Sciences, University College Cork, Cork, Ireland
  3. 3Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

Correspondence: Professor TG Dinan, Department of Psychiatry, Biosciences Institute, University College Cork, Cork IE0000, Ireland, Tel: +353214901759, Fax: +3534922584; E-mail:

Received 7 April 2016; Revised 26 May 2016; Accepted 13 June 2016
Accepted article preview online 20 June 2016; Advance online publication 13 July 2016



There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs or diet or perhaps fecal microbiota transplantation may positively impact mental health.

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