The gut-brain axis
Physics teaches us that in complex systems the relationships between different elements generate new properties not related to those of the individual elements themselves. Although the human body is certainly a complex system, this approach has not been applied much in medicine, that, until now, with a botanical approach, has divided the body into organs independent from each other.
Yet, a banal evidence of the bowel-brain connection is in nutrition. Some of the neurotransmitters, among the molecules essential for brain functions, derive from essential amino acids, namely those that derive exclusively from the demolition of dietary proteins. For example, brain serotonin is synthesized from the amino acid tryptophan, dopamine, noradrenaline and adrenaline from tyrosine, while the decarboxylation of histidine results in histamine, which is uptaken by the brain.
All dietary amino acids are decarboxylated by intestinal microbiota. A dysbiotic flora decarboxylates excessively them, tryptophanand tyrosine; this reduces their brain uptake and, as a consequence, the synthesis of neurotransmitters of which are the precursors. Furthermore, these amino acids all compete for the same access to the brain, so the chance for them to be captured depends on their plasmatic concentration ratio. So a greater decarboxylation of tryptophan favors the uptake of tyrosine, in this waythe tryptophan dysbiosis is essential for our survival: in case of danger the decreasing in brain tryptophan uptake, that make us anxious decreasing brain serotonin synthesis, carry out to an increasing of brain tyrosine uptake. In this way anxiety is a positive response to stressors, because increases brain dopamine , which makes us more skillful, of norepinephrine which makes us smarter, and of adrenaline which makes us stronger, then more capable of facing danger.
It is evident as the Acute Phase Reaction to a stressor (APR) is a positive response, but if the dysbiosis becomes chronic – in other words if the bowel, like a worn out spring, fails to restore the initial conditions – the person falls into a Chronic Phase Reaction (CPR), which has been called the “mother of all diseases”[1]. The cause of this fragility is that tryptophan controls also the brain synthesis of NPY[2], a neuropeptide that controls the processes of neurogenesis and synaptogenesis, thus the brain’s ability to self-repair[3]. Tryptophan controls also immune response, which in women decreases cyclically to avoid an antibody attack to a possible fetus[4].
The corresponding decrease of serotonin leads to the well-known pre-menstrual syndrome. The women’s intestine is therefore forced to work more than the men’s, and it wears out more easily. If this happens, the level of tryptophan cannot return to normal levels, which reduces brain NPY, thus the plasticity of the central nervous system. Besides, tryptophan controls also cell death by apoptosis[5]. Our survival is based primarily on the ability of our body to repair damages from external environmental causes. For example, we can repair DNA directly or indirectly damaged by radiation thanks to the well-known free radicals. This task is assigned to the intestinal microbiota, an army 10 times as many as us. The microbiota generates “tailor” molecules, capable of detecting DNA damage and repairing it[6]. If this action does not occur, cellular degeneration is induced, to allow rapid identification of the problem and to let the antibodies eliminate the deteriorated cells by apoptosis[7]. Nowadays, anti-cancer therapies are based on the control of degeneration: perhaps restoring the rifle of apoptosis would be more effective.
Lymphocyte production takes place in a causal way: we produce antibodies against nothing, against ourselves, and against real enemies. Then, in the process of maturation, we test them and discard the wrong ones, which are 97% of the production. We eliminate them inducing their death by apoptosis. The loss of this ability to clean up the antibodies becomes a big problem especially in subjects with high intestinal permeability, since they have a high production of antibodies. Then many auto-antibody will remain in the circulation.
So the higher incidence of autoimmune diseases in women is not due to a greater propensity of their immune system to “go crazy”, but to a reduced capacity to clear the antibody production from antibodies produced against ourselves.
Despite the fact that we know a lot about it, nowadays the bowel is considered as a postal system, as precise as the Swiss one, able to get what we want where we want (e.g. melatonin to the brain, branched chain amino acids to the muscles, collagen to the joints). The new drugs, even if they will be orally administered, are studied by injecting them into the veins or the peritoneum of animals, and their mechanisms of action are evaluated on isolated cells, using drug concentrations significantly higher than what would arrive at that tissue when the drug is orally administered .
Yet we know how that the intestine is complex, capable of reacting to stimuli/nutrients and activating complex endogenous response. Recent works show how tissue inflammation is the cause of several diseases, from cancer to neurological and behavioral ones. The inflammation of the brain is reported to be the pathogenic cause, not a predisposing factor, for epilepsy[8], depression, multiple sclerosis, Parkinson’s, Alzheimer’s[9], autism[10] and so on. The inflammation of the sexual organs is reported to be the cause of their dysfunctions. But Riazi demonstrates how an intestinal inflammation can migrate to other organs[11], [12]. So reducing an intestinal inflammation, even by introducing a “simple” diet, may reduce symptoms of different diseases apparently unrelated to each other[13], [14], [15], [16], [17]. To put in consideration the axes of communication of the complex system of the human body highlights how diseases are not so much due to the exposure to new pathogens, as to the decreased ability to repair the damage that these continually cause to us.
The endogenous processes of self-repair start mainly from the intestine; keeping it efficient is the greatest form of prevention.
The author
Paolo Mainardi works in neurochemistry, mainly on epilepsy, since 1981, the year of his graduation in Chemistry. For some years he has been proposing a milk serum protein, the alpha- lactalbumin, for use in the control of seizures. Thanks to the results obtained in both clinical and animal testing, this research entered the NIH screening program for new drugs (USA). The current president of ILAE (International League Against Epilepsy) Professor Perucca, is also part of this project. Studies on animals have been performed by the group of Professor De Sarro in Catanzaro; clinical studies have been and are conducted by Dr. Pasquale Striano, awarded the under 40 prize for the largest scientific production at European level at the European ILAE congress in 2013.
The research on this protein led Dr. Mainardi to re-evaluate the role of the gut-brain axis in different neurological diseases, as well as in psychiatric and behavioral issues. Lately he has been participating as a speaker or scientific manager in trainings for gynecologists, neonatologists and urologists to present the role of bowel inflammation in sexual dysfunctions and infertility.
