Our Second Brain

Unfortunately, many articles have been written which perpetuate the myth that men and women can be easily differentiated based on their brain structure, as well as intelligence and other mental characteristics^1,2. This myth is based in part on reductionist thinking and the idea that we are machines that are hard-wired at conception by the genes we inherit from our parents^3,4. That is, many people think that the DNA we inherit from our parents is the blueprint for life⁵. It is also based in part on the myth that all of our decisions are made by the brain that is in our skull.

This is in contrast with systems thinking, which recognizes that the human body is an ecosystem that contains not just human cells, but also bacteria⁶. Most of these bacteria reside in the gut and contain about 100 times more protein-coding DNA than our human cells⁷. The gut microbiome extends from the esophagus to the lower intestines⁶. These enteric bacteria interact with the central, autonomic and peripheral nervous systems (CNS, ANS and PNS, respectively) as part of the microbiota-gut-brain axis. Interactions go both ways in a bidirectional network of communication. This network connects the emotional and cognitive centers of the brain with intestinal functions through the neural, endocrine and immune systems⁶. So, our gut microbiome affects our behavior, health, intelligence and emotions.

The composition of bacteria in our gut is not hard-wired. It depends on what our mothers eat when we are in utero and what we eat after we are born, as well as our exposure to antibiotics. Our intelligence and behavior are subject to change through training, education, exposure to environmental toxins and even our diet (which affects our gut microbiome). So, it is ridiculous to claim that our brains are hard-wired or are innately different between men and women. We have neurons not just in the brain in our skull, but also in our gut. The gut microbiome is not hard-wired (nor is the brain or any other part of one’s body, when one considers epigenetics).

There are also neurons in the gut or enteric system. This is called the enteric nervous system (ENS). The ENS is a separate branch of the ANS⁸¹. It exists throughout the length of the gastrointestinal tract (GIT). The GIT is densely innervated by a network of 200–600 million neurons. These neurons innervate all regions of the GIT. The ENS influences the physiology and function of the GIT, while communicating with the CNS by both parasympathetic and sympathetic vagal pathways⁸. Sometimes, the ENS is called our second brain because it contains many types of neurons and glial cells that are linked in complex circuitry, similar to the brain in our skull⁹. The ENS regulates many systems in the bowel while coordinating digestive and defensive functions in the gut. Defects in its development in utero and/or subsequent damage after birth can cause vomiting, abdominal pain, constipation, IBS, Hirschsprung disease, growth failure, and early death. At the same time, the ENS can produce new neurons in postnatal and adult lives, thus affecting our health and behavior throughout life¹⁰.

Many of the enteric neurons relay sensory information in the gut to the CNS. Enteric glial cells are also important in the ENS⁹. Like glial cells in the CNS, enteric glial cells were originally thought to have merely supportive roles, but are now known to be actively involved in the ENS. They link enteric nerves, enteroendocrine cells, immune cells, and epithelial cells. Enteric glial cells also link the nervous and immune systems, while playing important roles in gastrointestinal (GI) disorders⁹.

Moreover, the placenta contains bacteria that colonize the fetal gut⁶. This establishes a gut microbiome that is important in the healthy development of the baby’s brain and immune system^8,11. Once the baby is born, breastfeeding can help the baby develop a healthy microbiome. Bacteria in the gut produce short chain fatty acids that help prevent cancer¹². So, the gut microbiome has been described not only as a second brain, but also our personal oncologist, and an essential part of our neuroendocrine immune systems (or network) ^13,14.

Bacteria in the gut also activate the vagus nerve¹⁵. It is the tenth cranial nerve. It innervates the pharynx, larynx and visceral organs. It is the main afferent pathway from the gut to the brain. The vagus nerve can affect health and behavior. This includes lethargy, depression, anxiety, loss of appetite and sleepiness. All of these factors can affect one’s intelligence, aggressiveness and ability to communicate (which some claim are different in men and women). Moreover, the gut microbiome affects the ENS, as well as the brain and behavior. For example, improper regulation of inflammation that occurs in major depressive disorders may be caused (at least in part) by imbalance in the gut microbiome. This is an extension of the hygiene hypothesis. It states that the large increases in neurodegenerative diseases, autoimmune diseases and allergies are due in part to the large-scale eradication of bacteria in clean, modern, indoor environments¹⁵. Certainly, depression, autoimmune diseases and allergies can also affect one’s intelligence, aggressiveness and ability to communicate.

Dysbiosis in the gut microbiota-gut-brain axis plays important roles in aberrant social behavior as well as the etiology of several neurodegenerative diseases, including anxiety, depression, autism and Parkinson’s disease^16-22. Neurodegenerative diseases can certainly affect one’s intelligence and emotions, which are not hard-wired by our human genes. The gut microbiome and ENS also play important roles in maintaining homeostasis and the production of energy as well as influencing obesity^23-25. As a result, the ENS is also an important factor in diabetes, inflammatory diseases, colorectal cancer, chronic kidney disease, atherosclerosis and heart disease^26-28. The human gut microbiota also produces melatonin, which helps cause the gut to have circadian rhythmicity (the 24-hour cycle that affects sleep and many physiological processes) ²⁹.

The gut microbiota and ENS can be thought of as an entero-endocrine organ that has many more cells and protein-coding DNA than rest of the human body^30-32. It is part of the GIT, which is the largest endocrine organ in the human body. The GIT is also a hub in the communication network in the human body. It contains the highest concentration of immune cells in the body. It is a network consisting of 200-600 million neurons and trillions of viruses, Bacteria, Archaea and Eukarya that make up the human gut microbiota³³. The gut microbiome helps to regulate intestinal function and interacts with the rest of the body to maintain good health. The gut microbiota has been called the conductor of communication between the immune and neuroendocrine network¹². That is, the microbiota produces and secretes hormones, responds to hormones secreted by human eukaryotic cells and regulates their expression³⁴. Many of the biosynthetic pathways that produce neuroendocrine hormones are found in bacteria as well as human eukaryotic cells. So, the gut microbiota produces and responds to neurohormones that are secreted in response to a neuronal input. Microbiota can modulate behavior through neurohormones such as serotonin, dopamine and norepinephrine. At the same time, these neurohormones can alter growth, motility, biofilm formation and/or virulence of bacteria. Serotonin may be a major neurotransmitter in the brain, but 90% of it is located in the intestines. It is a key signaling molecule in both the gut and the brain. Moreover, the microbiota, hormones and the human Eukaryotic cells all work together to help maintain a healthy immune system. Diet, exercise, mood, overall health, stress and gender can change the concentrations of hormones that can affect the gut microbiome. The opposite also occurs. A healthy gut microbiota can help keep a person calm because bacteria affect the concentrations of stress hormones (corticosterone and adrenocorticotropic hormone, or ACTH). On the other hand, dysbiosis in the gut microbiome can contribute to autoimmune diseases, including type-1 diabetes^30-32. This inter-kingdom form of communication has been called microbial endocrinology³². For example, the stress-mediated excretion of neurohormones can alter the expression of genes in pathogenic bacteria in the gut³². Hormones and neurotransmitters affect many aspects of behavior, which is not simply hard-wired in the brain that is in one’s skull. Our health and behavior also depend in part on the gut microbiome – our second brain. As a result, our behavior and mental skills are influenced by our lifestyle, diet and exposure to antibiotics. They are not hard-wired by the genes we inherit upon conception.

So, the ENS forms a complex, neural network³⁵. The gut microbiome has been called the brain’s Geppetto because it controls (or puppeteers) neural function and human behavior³⁵. Actually, the brain affects the gut just as much. Still, the expression “thinking with my gut” has taken on a new meaning. Moreover, the expression “you are what you eat” is more significant than once thought. That is, our diet greatly affects the composition of microbes in our gut, which plays a major role in shaping our feelings and behavior. This is starting to change our idea of what it is to be human³⁵.

Modern neuroscience is also trying to change our idea of what it is to be human as it fights against the myths of neurosexism². Our brains, intelligence, skills and health are continually changing. Even if a study were to find a statistically significant difference between the brains of men and women or their skills, this does not mean that the differences are due to genetics. From the day we are born, we are bombarded with stereotypes and social conditioning. Gender is a social construct, even though sex is not. Still, a gendered world can produce a gendered brain². At the same time, we can obtain new skills, change our attitudes and become more intelligent through training and social interactions. We are not hard-wired. A mother defending her young can be far more aggressive than any man. Even men are not hard-wired, We don’t have to be sexist. We can make a conscious choice to recognize that women’s rights are human rights and behave accordingly.

The topic of next month’s article will be the myth of gender differences in the brain, which was described elegantly and thoroughly in the book, The Gendered Brain, by Gina Rippon². At birth, the brain is no more gendered than the lungs or kidneys. Moreover, to be an environmentalist is to be a feminist. The same sexist attitudes that treat women as commodities also treat the environment as a commodity to be used and often abused. One of the most important things that we can do to reverse Global Climate Change is to provide girls with the same educational opportunities as boys, women with job training and equal pay for equal work³⁶.

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² Rippon, G. The Gendered Brain. Penguin Books, New York, 2019.
³ Goldman, B. Two Minds. The Cognitive Differences between Men and Women. Stanford Medicine, 2017.
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²⁸ Felice, V.D. et al. Microbiota-Gut-Brain Signalling in Parkinson's Disease: Implications for Non-Motor Symptoms. Parkinsonism & Relational Disorders, Volume 27, pp. 1-8, 2016.
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