Gut–brain axis

The gut–brain axis is the two-way biochemical signaling that takes place between the gastrointestinal tract (GI tract) and the central nervous system (CNS).^[2] The term "microbiota–gut–brain axis" highlights the role of gut microbiota in these biochemical signaling.^[3][2] Broadly defined, the gut–brain axis includes the central nervous system, neuroendocrine system, neuroimmune systems, the hypothalamic–pituitary–adrenal axis (HPA axis), sympathetic and parasympathetic arms of the autonomic nervous system, the enteric nervous system, vagus nerve, and the gut microbiota.^[2]

Chemicals released by the gut microbiome can influence brain development, starting from birth. A review from 2015 states that the gut microbiome influences the CNS by "regulating brain chemistry and influencing neuro-endocrine systems associated with stress response, anxiety and memory function".^[4] The gut, sometimes referred to as the "second brain", may use the same type of neural network as the CNS, suggesting why it could have a role in brain function and mental health.^[5]

The bidirectional communication is done by immune, endocrine, humoral and neural connections between the gastrointestinal tract and the central nervous system.^[4] More research suggests that the gut microbiome influence the function of the brain by releasing the following chemicals: cytokines, neurotransmitters, neuropeptides, chemokines, endocrine messengers and microbial metabolites such as "short-chain fatty acids, branched chain amino acids, and peptidoglycans".^[6] These chemical signals are then transported to the brain via the blood, neuropod cells, nerves, endocrine cells,^[7][8] where they impact different metabolic processes. Studies have confirmed that gut microbiome contribute to range of brain functions controlled by the hippocampus, prefrontal cortex and amygdala (responsible for emotions and motivation) and act as a key node in the gut-brain behavioral axis.^[9]

While Irritable bowel syndrome (IBS) is the only disease confirmed to be directly influenced by the gut microbiome, many disorders (such as anxiety, autism, depression and schizophrenia) have been reportedly linked to the gut-brain axis as well.^[6][10][7] According to a study from 2017, "probiotics have the ability to restore normal microbial balance, and therefore have a potential role in the treatment and prevention of anxiety and depression".^[11]

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 through Nobel prize winning research in 1904.^[12][13]

As of October 2016, most of the work done on the role of gut microbiota in the gut–brain axis had been conducted in animals, or on characterizing the various neuroactive compounds that gut microbiota can produce. Studies with humans – measuring variations in gut microbiota 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.^[14] Whether changes to the gut microbiota are a result of disease, a cause of disease, or both in any number of possible feedback loops in the gut–brain axis, remain unclear.^[15]