The concept of a second brain emerged several years ago with the discovery of neurons that are embedded in the walls of the GI tract. In addition to these neurons, there are other cells that are designated interstitial cells of Cajal, named after Santiago Ramón y Cajal, a Spanish pathologist, histologist, neuroscientist, and Nobel laureate. These cells are found intertwined among neurons embedded within the smooth muscles lining the gut. According to the early studies of Cajal, these cells served as the generator and pacemaker of the slow waves of contraction that move material along the GI tract, thus mediating neurotransmission from motor nerves to smooth muscle cells. In other words, in the days of Cajal, at the turn of the nineteenth century, it was hypothesized that the neurons in the GI tract only served to move the products of digestion through the intestine and that they were subjugated to the influence of the brain that it is inside our heads.

It has been known for some time that mood influences the function of the GI tract. Many people suffer stomach distress when they are anxious or stressed. However, until recently, it was only hypothesized that the GI tract simply responded, in a sort of passive way, to the inputs that came from inside our heads. The neurons of the GI tract were considered mere executors of the orders that came from above, with no ability whatsoever to generate anything that could be defined as “thought” or “emotions.”

After the pioneering work of Cajal, it was discovered that in the GI tract, there are about one hundred million neurons. That is one-thousandth of the number of neurons in the brain inside our heads, and essentially the same number of neurons as are in the spinal cord. Therefore, the concept of a “second brain” embedded in the walls of our GI tract, began to emerge. In fact, those neurons not only are interconnected with each other, but they are also interconnected with the neurons inside our heads and, after decades of neglect, it was hypothesized that their role could go well beyond that of simply “obeying” the orders that came from above. In other words, in the past decade, it has been first hypothesized and then demonstrated that the flux of information within the body is not unidirectional, from the head to the gut, but bi-directional, and the neurons in the GI tract influence the behavior of those in the brain and vice-versa.

It was the discovery of the complexity of these neural networks that led to the concept of the second brain. It should be said, however, that the denomination “second brain” might not be anatomically correct. In fact, in all pair organs, we do not describe them as first and second; instead, we talk of left and right kidneys or lungs.

As far as the brains (plural) are concerned, we should envision the neurons in the GI tract, the so-called “second brain” (simply because it was discovered millennia after the first one) just as another anatomical part of the brain. In other words, we should describe the second brain simply as another anatomical part of the brain, just like the frontal or parietal lobes or the cerebellum. And just like those other parts of the brain inside our heads, the second brain can operate autonomously or in conjunction with the other parts of the brain.

It normally communicates with the neurons inside our heads through the vagus nerve and sympathetic system, and for these communications, it makes use of more than thirty neurotransmitters, most of which are identical to the ones found in the neurons inside our heads, such as acetylcholine, dopamine, and serotonin. Oddly enough, more than 90% of the body’s serotonin lies in the gut, as well as about 50% of the body’s dopamine, which is currently being studied to further our understanding of its function in the brain. There are further similarities with the brain inside our heads; there are cells that are similar to the astroglia of the brain, a sort of connective tissue, and a diffusion barrier around the capillaries surrounding ganglia that is similar to the blood-brain barrier of cerebral blood vessels.

With the increase in knowledge about the anatomy and physiology of the second brain, novel interpretations concerning its function were hypothesized. This led to the writing of books and articles to divulge the concept that we have an extension of our brain inside our gut that sometimes works in a manner that was not envisaged before. For example, Scientific American 2010 published an article entitled “Think Twice: How the Gut’s “Second Brain” Influences Mood and Well-Being” describing “The emerging and surprising view of how the enteric nervous system in our bellies goes far beyond

just processing the food, we eat”. On the other side of the Atlantic, BBC news in 2012 published an article by Michael Mosley, entitled “The second brain in our stomachs”, which states that, “… new research is revealing the surprising ways in which our guts exert control over our mood and appetite”.

Apart from the number of articles and books published on the subject, researchers in the fields of psychiatry, neurology and development look seriously into the function of the second brain to elucidate the pathogenesis of diseases that, until recently, were supposed to be diseases of the brain inside our heads. For example, a scientific article published in 2010 by researchers in psychiatry in the authoritative journal “Brain Behavior and Immunity” (2010 Jan; 24(1):9-16) and aptly entitled “Mood and gut feelings”, concludes stating that “It may be that we need to change the focus from the brain and look at the role of the gut in what has traditionally been thought of as brain-based disorders”.

According to another review on the subject:

“The concept that the gut and the brain are closely connected, and that this interaction plays an important part not only in gastrointestinal function but also in certain feeling states and in intuitive decision making, is deeply rooted in our language. Recent neurobiological insights into this gut-brain crosstalk have revealed a complex, bidirectional communication system that not only ensures the proper maintenance of gastrointestinal homeostasis and digestion but is likely to have multiple effects on effect, motivation, and higher cognitive functions, including intuitive decision-making.

Moreover, disturbances of this system have been implicated in a wide range of disorders, including functional and inflammatory gastrointestinal disorders, obesity and eating disorders”.2

Therefore, we may summarize that our brain is partly inside our skull and partly outside our heads, notably in the walls of the GI tract, and all the parts of our brain cooperate in our processes of thought. But this is only the tip of the iceberg. In fact, both the brain inside our head and in the GI tract are made of human neurons; that is, they are made of cells that pertain to the human part of our body and therefore can be aptly designated our “human brains.” The instructions for the functioning of those human neurons are encoded in our human DNA, which contains approximately 22,000 genes, many of which regulate the behavior of those neurons.

Those 22,000 human genes are only one-hundredth of the genes that are within our (not-so-) human body. In fact, altogether, the mass of commensal or symbiotic microbes in our body, the microbiota, according to the NIH Microbiome Project, contains more than 360 times the total genetic material contained in all the cells in the human body, and therefore we are forced to acknowledge the existence of a third brain that this time is not only an extension or another anatomical part of the brain inside our head but something completely different. It is a non-human brain that plays a role as important as the human brain in determining who we are and why we are doing what we are doing.

2.  Nat Rev Neurosci. 2011 Jul 13; 12(8):453-66)


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