“We are what we eat”. These well-known words, widely used by nutritionists, date back to Ludwig Feuerbach, a German philosopher of XIX century that focused on the needs of the human body to be properly fed, in contrast with the dominant way of thinking of his age that gave priority to feed the souls. May be appear surprising, but the modern neurological science has gained evidence that a good nutrition connects directly with the functionality of the Central Nervous System (CNS).
With the term gastrointestinal (GI) microbiota, we refer to the microorganisms settled across the gut – above all, more than 100 species of bacteria. The GI microbiota accomplishes several tasks, many of them beneficial, like the degradation of indigestible fibers, the protection against pathogenic bacteria, and the synthesis of essential nutrients that the humans are not able to produce, like the vitamin K and the amino acid tryptophan.
The GI microbiota has not only a protective function. It also has a key role in the bidirectional communication between the gut and the CNS: the so-called “gut-brain axis”. The signals between gut and brain travel through neurons such as the vagus nerve, which transmit the feedback of the gut, and hormones. For example, in the presence of stressful situations, the brain releases cortisol, which reaches the gut and affects his permeability by altering the composition of the microbiota.
On the other side, in the gut-to-brain direction, the tryptophan released by the GI microbiota bacteria undergoes some biochemical modifications that lead to two different class of molecules that act in opposite ways on a receptor of the brain cells, called N-methyl-D-aspartate receptor (NMDAR). The up- or down-regulation of the NMDAR has direct consequences in some neurological disorders, as explained below.
Gut microbiota and psychiatric disorders
Diseases like depression, anxiety, autistic spectrum disorder or schizophrenia depend on a variety of genetic and environmental factors. The GI bacteria represent one of these factors. For example, children with the autism spectrum disorder have a different bacterial composition in the gut with respect to healthy individuals: the Bifidobacteria composition decreases, while Lactobacilli and Bacteroidetes species increase. Although is not known whether this is a cause or a consequence of this condition, there is a clear correlation between the microbial composition of the gut and the autism.
A typical marker of the schizophrenia is the impairment of the immune system due to an increase of inflammatory cytokines. Normally, the GI microbiota regulates the release of both pro- and anti-inflammatory cytokines from the gut to the rest of the body in a balanced way. In the schizophrenic subjects, there is an imbalance favorable to the pro-inflammatory cytokines, which, with an indirect effect, affects the brain function. These cytokines regulate the production of the Brain-Derived Neurotrophic Factor (BDNF) that acts on the NMDARs of the brain. Generally, a decrease of the BDNF levels is associated with cognitive problems, schizophrenia and depression.
Therefore, the biochemical communication throughout the gut-brain axis can be outlined with the following, simplified cycle: the microbial population of the gut produces and releases several chemicals (neurotransmitters, short chain fatty acids, tryptophan, etc.) that act at the brain level. One of the most relevant molecule of the brain affected by the biomolecules coming from the gut is the BDNF, which acts on the NMDAR, which turns on/off a series of pathways. Among other effects, there is an increase or a decrease of the symptoms of neurological disorders such as schizophrenia, and the modification of the composition of the GI microbiota.
Final remarks
The general findings here described highlight the importance of the GI microbiota in the regulation of some brain processes. From here, it seems important taking care of the nutrition, because the food ingested have a direct effect on the health and composition of our intestinal microbiota.
The design of a personalized diet as a complementary tool in the treatment of neurological diseases is far to be achieved, because of the high complexity of the microbiota, and of the unique microbial pattern of every person. Meanwhile, the dietary supplementation of probiotics (for example, live strains of Bifidobacterium) or prebiotics (soluble sugars used by GI microbiota) may help to improve the composition of the gut microbiota, thus better regulating the transmission of the signals in the gut-brain axis.
Reference:
Maqsood R and Stone TW. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders. Neurochem Res (2016) 41:2819–2835
The elaboration of this post has been financed by the project PI15/01082, as a part of the National Plan of I+D+I and co-financed by the ISCIII – General Deputy Direction for Evaluation and Development of Health Research – and the European Regional Development Fund (ERDF).
