Gut–brain axis

The gut–brain axis refers to the biochemical signaling taking place between the gastrointestinal tract and the nervous system, often involving intestinal microbiota, which have been shown to play an important role in healthy brain function.

Brain function
Research suggests that the gut–brain axis, a bidirectional neurohumoral communication system in the human body, functions as a pathway for the gut microbiota to modulate brain function of its host. The postnatal microbial colonization of the gastrointestinal (GI) tract results in a long-lasting impact on the neural processing of sensory information regarding the hypothalamic-pituitary-adrenal stress response. Early postnatal bacterial colonization in germ free (GF) mice promoted the development of a central nervous system. The c-Fos activation in the paraventricular nucleus was rapidly induced by the inoculation of Bifidobacterium infantis. Trytophan metabolism was modulated by Bifidobacterium infantis, suggesting that the normal gut microbiota can influence the precursor pool for serotonin, which is correlated to neurophysiological behavior. Anxiety-like behavior and central neurochemical changes were relieved in GF mice compared with specific pathogen free (SPF) mice. In addition, bacterial species Clostridial were found at an elevated level in the stools of children with autism than the stools of the children without.

Behavioral phenotype
During birth, the immediate microbial colonization contributes to the development of epithelial barrier function, gut homeostasis, angiogenesis, innate adaptive immune function, and common neuro-developmental disorders (autism, schizophrenia). Compared to the specific pathogen free (SPF) mice, the germ free (GF) mice illustrated increased motor activity, reduced anxiety-like behavior, altered expression of synaptic plasticity-related genes, elevated noradrenaline, dopamine, and 5-hydroxytryptamine turnover in the striatum. When exposed to antibiotics, GI infections and stress, sharp changes in diet, the gut homeostasis and the central nervous system becomes imbalanced. Clinically, the introduction of probiotics, beneficial in the treatment of GI symptoms of disorder, help reduce anxiety, stress, and mood of patients with irritable bowel syndrome (IBS) and chronic fatigue. Lactobacillus reuteri, probiotic, is known to modulate the immune system, decrease anxiety, and reduce the stress-induced increase of corticosterone. Other probiotics can lower inflammatory cytokines, decrease oxidative stress, and improve nutritional status.

Gut–brain–liver axis
The liver plays a dominant role in blood glucose homeostasis by maintaining a balance between the uptake and storage of glucose through the metabolic pathways of glycogenesis and gluconeogenesis. In recent studies, it is illustrated that intestinal lipids regulate glucose homeostasis involving a gut-brain-liver axis. The direct administration of lipids into the upper intestine increases the long chain fatty acyl-coenzyme A (LCFA-CoA) levels in the upper intestines and suppresses glucose production even under sub diaphragmatic vagotomy or gut vagal deafferentation. This interrupts the neural connection between the brain and the gut and blocks the upper intestinal lipids’ ability to inhibit glucose production. The gut-brain-liver axis can regulate the glucose homeostasis in the liver and provide potential therapeutic methods to treat obesity and diabetes.