The bidirectional routes of communication between the brain and the gut microbiota. These include the vagus nerve, short-chain fatty acids, tryptophan, cortisol and cytokines. The figure also proposes a mechanism by which the gut microbiome could alter central neurochemistry in patients with schizophrenia.
Gut microbiota affects the blood-brain barrier
【LWBS 2015 05 26 A】(Pan Li edited from Mol Psychiatry and Sci Transl Med)
Within our bodies resides a large population of symbiotic microbiota. The microbiome is composed of approximately 10^14 bacteria, containing 100 times the number of genes of the human genome. The gut microbiota weighs approximately the same as the human brain. It has been suggested that the gut microbiota plays a key role in maintaining the life and good health of the host. Gut microbiota protects against invading pathogens, help metabolize dietary nutrients and drugs, and influence the absorption and distribution of fat. Not only does the gut microbiota important in the gastrointestinal tract, but it also plays a key role in the development and functioning of the central nervous system (CNS). The gut microbiota produces substances including the key central neurotransmitters, which exert their functions not only in the enteric nervous system, but also in the brain.
Dating back from the 19th and the early 20th century, scientists thought that waste accumulated in the colon triggers “auto-toxication”. The infection resulting from the poisons in the gut, in turn leads to depression, anxiety and psychosis. Research suggests that microbiota inhabited in one’s gut may affect one’s state of mind. The gut-brain axis is bidirectional. The brain acts on the gastrointestinal and immune systems, regulating the composition of the gut microbiota, while the neuroactive compounds secreted by the gut microbiota, including neurotransmitters and metabolites, also act on the brain.
Blood-brain barrier (BBB)
Blood-brain barrier separates the circulating blood from the brain extracellular fluid in the central nervous system (CNS) and, is formed by brain endothelial cells. Blood-brain barrier is higher selective in the substances that go across it. Only gases, glucose and other small molecules can pass it, while blood-brain barrier prevents the entry of large or potentially harmful substances.
Gut microbiota affect the permeability of blood-brain barrier
Recently, Viorica Branistea, PhD, et al. from the Karolinska Institute in Sweden found that gut microbiota affect the permeability of the blood-brain barrier. They took advantage of two types of mice: “germ-free (GF)” mice and “specific pathogen-free (SF)” mice. GF mice were born in sterile conditions, and were fed with sterile food and water since birth, hence the gastrointestinal tract is completely sterile with no live microbes. While SF mice are the regular mice for scientific research and they are free from specific pathogen, but microbes inhabit in their guts.
The permeability of the blood-brain barrier in normal individuals is pretty low, preventing the penetration of harmful and large molecules into the brain. However, the research group found that in the adult GF mice free of gut microbes, the blood-brain barrier is highly permeable, compared with adult SF mice, suggesting that the gut microbiota plays a role in maintaining the integrity of the blood-brain barrier. They also observed that although the CNS vascular density of GF and SF mice are similar, yet the expression of brain endothelial tight junction proteins, occludin and claudin-5, are significantly decreased. Colonization of GF mice with SF mice rescued, at least in part, the elevated permeability of the blood-brain barrier and decreased expression of brain endothelial tight junction proteins in GF mice. Thus, restoring intestinal microbiota can improve the integrity of blood-brain barrier.
Uptake of the substance Raclopride in the brain of germ-free versus conventional mice. Credit: Miklos Toth.