Gut–brain axis

The gut–brain axis is the biochemical signaling that takes place between the gastrointestinal tract (GI tract) and the central nervous system (CNS). 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. The gut–brain axis is the biochemical signaling that takes place between the gastrointestinal tract (GI tract) and the central nervous system (CNS). 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. 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. 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. 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. 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. 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. The gut flora is the complex community of microorganisms that live in the digestive tracts of humans and other animals. The gut metagenome is the aggregate of all the genomes of gut microbiota. The gut is one niche that human microbiota inhabit. In humans, the gut microbiota has the largest numbers of bacteria and the greatest number of species compared to other areas of the body. In humans the gut flora is established at one to two years after birth, and by that time the intestinal epithelium and the intestinal mucosal barrier that it secretes have co-developed in a way that is tolerant to, and even supportive of, the gut flora and that also provides a barrier to pathogenic organisms. The relationship between gut flora and humans is not merely commensal (a non-harmful coexistence), but rather a mutualistic relationship. Human gut microorganisms benefit the host by collecting the energy from the fermentation of undigested carbohydrates and the subsequent absorption of short-chain fatty acids (SCFAs), acetate, butyrate, and propionate. Intestinal bacteria also play a role in synthesizing vitamin B and vitamin K as well as metabolizing bile acids, sterols, and xenobiotics. The systemic importance of the SCFAs and other compounds they produce are like hormones and the gut flora itself appears to function like an endocrine organ, and dysregulation of the gut flora has been correlated with a host of inflammatory and autoimmune conditions. The composition of human gut flora changes over time, when the diet changes, and as overall health changes. The enteric nervous system is one of the main divisions of the nervous system and consists of a mesh-like system of neurons that governs the function of the gastrointestinal system; it has been described as a 'second brain' for several reasons. The enteric nervous system can operate autonomously. It normally communicates with the central nervous system (CNS) through the parasympathetic (e.g., via the vagus nerve) and sympathetic (e.g., via the prevertebral ganglia) nervous systems. However, vertebrate studies show that when the vagus nerve is severed, the enteric nervous system continues to function.