By Pam Conboy

The gut-brain axis is a communication network that links the central nervous system (CNS) with the enteric nervous system. The anatomical network includes the brain and spinal cord (CNS), autonomic nervous system (ANS), hypothalamic-adrenal-pituitary (HPA) axis, and innervation of the GI tract, or enteric nervous system. Both neural and hormonal routes of communication allow the brain to influence intestinal activities, including activity of functional effector cells (i.e., immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells, etc.). Gut microbiota also influence the central nervous system both directly and indirectly by supporting epithelial barrier function, modulating immune function, supporting healthy inflammation metabolism, and directly altering circulating neurotransmitter levels. All of this gut-brain chatter has a remarkable influence on mood.

Gut-Brain Axis

Microbiota Mechanisms of Action

  • Intestinal epithelial barrier strengthening
  • Immunity and inflammation modulation
  • Hormone and neurotransmitter modulation

Although most of the research linking mood and the microbiota has come from animal models, clinical trials have begun to validate the cognitive impact of probiotics, or, psychobiotics.1,2

In a randomized, triple-blind, placebo-controlled trial of 40 adults, participants received a multi-strain probiotic formula (Ecologic BARRIER, Winclove, Amsterdam) at a dose of 5 billion CFU per day. Over the four-week period, the treatment group reported significant improvements in cognitive reactivity to sad mood as evidenced by a reduction in aggressive and ruminative thoughts (LEIDS-r scale). Of particular note in this study is the use of a probiotic as first-line clinical support for mental wellbeing.

A more recent, systematic ten-study review by Wallace and Milev assessed probiotic influence on mood, stress, and cognition.4 Although, most of the studies demonstrated positive results on measures of mood, they were heterogeneous in terms of probiotic strain, dosing, and duration of treatment. The authors therefore concluded that further randomized controlled clinical trials are warranted.

Nonetheless, there seems no doubt that manipulation of the gut microbiota is a promising mental health intervention. As neuroscientist, Jane Foster, PhD of McMaster University states, “It might be time to start thinking about treating [sad mood] from the bottom up instead of the top down. The evidence is there that the brain is responding to the gut. Let’s make that the therapeutic pathway.”5

  • Fond G, Boukouaci W, Chevalier G, Regnault A, Eberl G, Hamdani N, et al. The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: a systematic review. Pathol Biol (Paris). 2015;63:35-42.
  • Evrensel A, Ceylan ME. The Gut-Brain Axis: The missing link in depression. Clin Psychopharmacol Neurosci. 2015;13(3):239-244.
  • Steenbergen L, Sellaro R, van Hemert S, et al. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun. 2015 Aug;48:258-64.
  • Wallace CJK, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017;16:14. DOI 10.1186/s12991-017-0138-2.


About the Author:

Majored in biology and trained as a medical technologist, Pam left the laboratory bench early on to pursue a career in marketing. In vitro diagnostics was the initial focus, where she began as a product manager. After more than a decade working for companies large and small, she spent nearly 15 years as an independent marketing consultant serving bio/pharma, medical device, and animal health companies worldwide. Today, Pam is the Director of Marketing for Klaire Labs (SFI USA) I Reno, NV.