Stress & the gut-brain axis: Regulation by the microbiome

Abstract

The importance of the gut-brain axis in regulating stress-related responses has long been appreciated. More recently, the microbiota has emerged as a key player in the control of this axis, especially during conditions of stress provoked by real or perceived homeostatic challenge. Diet is one of the most important modifying factors of the microbiota-gut-brain axis. The routes of communication between the microbiota and brain are slowly being unravelled, and include the vagus nerve, gut hormone signaling, the immune system, tryptophan metabolism, and microbial metabolites such as short chain fatty acids. The importance of the early life gut microbiota in shaping later health outcomes also is emerging. Results from preclinical studies indicate that alterations of the early microbial composition by way of antibiotic exposure, lack of breastfeeding, birth by Caesarean section, infection, stress exposure, and other environmental influences - coupled with the influence of host genetics - can result in long-term modulation of stress-related physiology and behaviour. The gut microbiota has been implicated in a variety of stress-related conditions including anxiety, depression and irritable bowel syndrome, although this is largely based on animal studies or correlative analysis in patient populations. Additional research in humans is sorely needed to reveal the relative impact and causal contribution of the microbiome to stress-related disorders. In this regard, the concept of psychobiotics is being developed and refined to encompass methods of targeting the microbiota in order to positively impact mental health outcomes. At the 2016 Neurobiology of Stress Workshop in Newport Beach, CA, a group of experts presented the symposium "The Microbiome: Development, Stress, and Disease". This report summarizes and builds upon some of the key concepts in that symposium within the context of how microbiota might influence the neurobiology of stress.

Fig. 1

Key communication pathways of the microbiota–gut–brain axis. There are numerous mechanisms through which the gut microbiota can signal to the brain. These include activation of the vagus nerve, production of microbial antigens that recruit immune B cell responses, production of microbial metabolites (i.e. short-chain fatty acids [SCFAs]), and enteroendocrine signaling from gut epithelial cells (e.g., I-cells that release CCK, and L-cells that release GLP-1, PYY and other peptides). Through these routes of communication, the microbiota–gut–brain axis controls central physiological processes, such as neurotransmission, neurogenesis, neuroinflammation and neuroendocrine signaling that are all implicated in stress-related responses. Dysregulation of the gut microbiota subsequently leads to alterations in all of these central processes and potentially contributes to stress-related disorders. 5-HT serotonin, CCK cholecystokinin, GABA γ-aminobutyric acid, GLP glucagon-like peptide, IL interleukin, PYY peptide YY, TNF tumour necrosis factor.