The term “gut–brain axis” is occasionally used to refer to the role of the gut flora in the interplay as well, whereas the term “microbiome–gut–brain axis” explicitly includes the role of gut flora in the biochemical signaling events that take place between the GI tract and CNS.[1][2][3]
Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine and neuroimmune systems, including the hypothalamic–pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, including the enteric nervous system and the vagus nerve, and the gut microbiota.[1][3]
The first of the brain–gut interactions shown, was the cephalic phase of digestion, in the release of gastric and pancreatic secretions in response to sensory signals, such as the smell and sight of food. This was first demonstrated by Pavlov.[4][5]
Interest in the field was sparked by a 2004 study showing that germ-free (GF) mice showed an exaggerated HPA axis response to stress compared to non-GF laboratory mice.[1]
As of October 2016, most of the work that had been done on the role of gut flora in the gut–brain axis had been conducted in animals, or on characterizing the various neuroactive compounds that gut flora can produce.
Studies with humans – measuring variations in gut flora between people with various psychiatric and neurological conditions or when stressed, or measuring effects of various probiotics (dubbed “psychobiotics” in this context) – had generally been small and were just beginning to be generalized.[6]
Whether changes to gut flora are a result of disease, a cause of disease, or both in any number of possible feedback loops in the gut–brain axis, remained unclear.[7][1]
LGS: Leaky-Gut Syndrome.