Billions of years ago, as our planet Earth was slowly forming to its current state, rocks were constantly hitting the planet, causing massive plate shifts as well as magma eruption from the core. Eventually, water started to appear, and single-celled organisms began to colonize the planet. There are many theories on how these organisms evolved on our planet, still from these organisms, branches of life sprouted. These branches are known as Archaea, Eukarya and Bacteria. As bacteria first started to develop and live on the planet, they had to adapt to significant changes, in a sometimes, harsh environment. These climatic factors included periods of time when the planet experienced extreme weather, such as ice ages resulting in harsh freezes to volcanic periods, that lasted millions of years. To this day, bacteria continue to evolve as the planet gets older. As the branch of Eukarya started to evolve, billions of years ago, bacteria soon developed a symbiotic relationship with these organisms to continue their survival while maintaining a healthy intake of energy. A common example of the symbiotic relationship within eukaryotic cells and bacteria can be seen with mitochondria, which is present in all eukaryotic cells and helps these cells generate energy. The mitochondria itself generates ATP or energy for the cell via oxidative phosphorylation ² However, the organelle of the mitochondria cell is different from other organelles since it contains different genetic material from the eukaryotic cell. Another example of how bacteria developed a symbiotic relationship with cells would be chloroplast which is present in plant cells. Plants use energy from sunlight and their chloroplasts, in turn, generate oxygen and carry electrons. These chloroplasts evolved from ancient cyanobacteria and are semi autonomous organelles due to the presence of their own genome ³ Along with mitochondria, chloroplasts are unique because they do not contain the same DNA as plant cells. Instead, chloroplasts contain DNA that is more related to photosynthetic or ancient cyanobacteria, showing that they probably were engulfed by early eukaryotic cells ⁴ As these primitive eukaryotic cells laid the groundwork for the formation of other animals, such as humans, bacteria started receiving significant roles in the ecosystem. As humans evolved into modern man, bacteria had already colonized the human mouth, as well as other areas of the body to include the intestines. For example, bacterial colonization of the mouth is what causes breath odor when humans speak. Moreover, bacteria in the intestines primarily functions to break down various food compounds while simultaneously producing vitamins that are essential for humans, such as vitamin A and K, which play a role in many coagulation factors ⁵ Thus, bacteria in the intestines allows humans to receive vital vitamins that promote health and bacteria receives the nutrients that the food provides for them. However, these bacteria may release certain chemicals signaling the human nervous system response, which in turn may cause the brain to release certain chemicals, to alter mood or behavior.

The human intestine is comprised of various bacterial species as well as archaea. There are approximately 400 to 500 million species of bacteria that are located within the human intestines⁷ The presence of these different species helps form a gut microbiome. The origin of these bacteria species in humans is primarily passed by mothers to their infants during gestation while the infant is being developed and has the umbilical cord attached, as well as being present within the uterus of the mother along with various cytokines and chemokines ⁸ These bacteria eventually help infants later in life as they start eating different varieties of food, such as meats or vegetables, rather than drinking breast milk or formula. The main intestinal species that belong in this microbiome are Salmonella typhimurium, Escherichia coli ⁹ While some strains of these bacteria are relatively harmless, others are known to cause serious diseases in humans. For example, S. typhimurium are known to have specific toxins that may cause the illness known as typhoid fever in humans. This illness can cause diarrhea and can spread very easily through contaminated drinking water, without treatment, may lead to death. The bacteria E. coli, and a particular strain known as H-157, may be found in contaminated foods, to include, partially cooked meats, and may cause severe illness in people, such as, bloody diarrhea coupled with severe cramping which could ultimately lead to death ¹⁰ Moreover, if S. typhimurium and E. coli are present outside of the intestines, in other areas of the human body, and can spread easily, they have the potential to cause widespread illness. However, when these toxins are found inside of the intestines, they have a symbiotic relationship with the human body and greatly assist in food digestion, as well as, keeping the intestinal tract blocked from other foreign bacteria or pathogens by living there and taking up possible living space ¹¹ All in all, while these bacteria may be harmful if found outside of the intestinal tract, they still benefit humans in many ways, by providing vitamins, as well as nutrients for the varied functions of the human body.

The human nervous system is linked throughout the entire body and is composed of the peripheral and the central nervous system. The central nervous system makes up the brain and the spinal cord. Whereas the peripheral nervous system communicates to all the organs in the body as well as the different limbs. The peripheral nervous system is responsible for sending signals throughout the body and receiving responses from different stimuli. Some of the stimuli received by peripheral nervous system include pain signals or other sensations to help humans interact with the world around them. The nervous system is also highly interlinked with the endocrine system which is responsible for sending hormones throughout the body. These hormones signal the body to coordinate different functions such as development and growth. For example, various sex hormones as well as antioxidants and cytokines and sent throughout the body at a very fast pace to properly respond to an event ¹² The nervous system may receive or send messages quickly, consequently, manifested by running faster or trying to lift a heavy object. The enteric nervous system is the nervous system which makes up the intestinal track, and is, a subset of the main nervous system. The enteric nervous system is very complex as it resembles part of the central nervous system, specifically, it is structured and has numerous and diverse cells ¹³ The enteric nervous system may also collect different chemicals which bacteria produce and may send these chemicals to the brain.

These bacteria, which are present within the intestinal microbiota, have been shown to play a role within certain psychological disorders. The vagus nerve is a nerve that extends through the body and controls involuntary movements in different areas, such as the digestive system, and may also play a role in assisting with depressive disorders as well as various diseases ¹⁵ The vagus nerve receives several different signals from nerves present within the small and large intestines due to chemical input. In more recent studies, scientists have discovered that some bacteria within the nervous system may play a specific role in regulating a particular emotional response of the body by altering pathways and sending distinct chemicals to the brain. While scientists were examining infants within the first few months of their lives, they observed that some of these bacteria produced different compounds such as HDAC ¹⁶ This compound stands for histone deacetylase inhibitor, which plays a role in inhibiting histones by the process of deacetylation. High levels of the HDAC compound can be very dangerous in the human body. HDAC is known to contribute to many neurological disorders such as Parkinson’s disease and schizophrenia ¹⁶ Parkinson’s disease is a progressive, debilitating, and damaging disease as it can cause severe shaking in an individual and lead to dementia. The way Parkinson’s disease leads to dementia is by eroding certain brain matter, making the individual highly susceptible to dementia. Parkinson’s erodes away at the frontal and temporal lobes of the brain. This disease mainly occurs in the nigra pars region of the brain ¹⁸ HDAC is known to be associated with the CREB transcription factor. This is a transcription factor that may activate certain genes. This compound may inhibit the CREB transcription factor, which is known to play a role in phosphorylating processes that stop neurodegeneration and contributes to the onset of Parkinson’s disease ¹⁹ Once Parkinson’s has led to an individual having dementia, the brain eventually shuts down leading to death in the individual. Another interesting area that scientists have been examining is how a propionate ester might cross the GI barrier and act as a potential neurotoxin that can cause autism ⁷ In addition increased levels of cytokines, particularly within the cerebral fluid of the brain has been identified in patients on the autism spectrum, demonstrating a possible link between autism and cytokine levels in the body ²¹ Further research is critical so that scientists can examine the role that these bacteria have in causing autism in young children. Certain bacteria within the gut, such as E. Coli, produce levels of serotonin that may be secreted across the GI barrier again and transported ¹⁶ The hormone serotonin is instrumental in different functions to include digestion, wound healing, sleep, and mood. However, lowered levels of Serotonin may lead to forms of depression. The way this may work is that the body contains certain receptors located on cells that regulate the uptake of serotonin. These SERT receptors promote serotonin uptake and help in the regulation of tryptophan hydroxylase one and two, which regulate serotonin in the enteric region of the body ¹⁶ If the gut wall became impermeable, or bacteria in the region started to decrease, serotonin levels in turn may be altered, affecting an individual’s mood.

Bacteria that are present within the intestinal microbiota may elevate anxiety levels in addition to depression and other moods ²⁴ Some microorganisms in the human intestine are known to produce cytokines that may cause inflammation. Scientists have also been examining how these bacteria cause inflammation within the human GI tract which leads to increased levels of stress within the body, that may add stress to the brain itself ¹⁶ Schizophrenia is a disease that presents symptoms of disturbing thoughts as well as a slowed thinking process. This disease may also interfere with how well people are able to remember things. Scientists have also discovered that the bacteria, known as Proteobacteria, may influence cytokine production and again alter the intestine balance thus, leading to levels of increased inflammation. In addition to schizophrenia, increased dominance of firmicutes over Proteobacteria within the salivary glands may lead to a disorder known as Sjogren’s syndrome. This disease causes disfunction within the salivary in the oral and ocular glands and may lead to dryness in these cavities ²⁶ Bipolar disorder is another disorder which affects a person’s mental health. The person with bipolar disorder may begin to have altered moods which can lead to episodes of violence. It is very similar to depression and schizophrenia and overtime may lead to mania, where an individual experiences highs and lows for weeks to months on end ¹⁶ In the case of bipolar disorder, the bacterium known as Flavonifractor was shown to be in high abundance in the intestinal wall making it more permeable ¹⁶ This shows how a certain bacterium can cause inflammatory properties within the GI tract. The bacteria has the ability to cleave a certain flavonoid known as quercetin, which has anti-inflammatory properties ²⁹ Bifidobacterium spp. Also may play a role inflammatory bowel disease, which causes severe inflammation of the intestines ¹⁶ Meanwhile, other anti-inflammatory factors that prevent the GI tract from swelling were shown to be less abundant ¹⁶ This illustrates how important gut microbiota are to the person’s health. Obsessive Compulsive Disorder, (OCD), may cause a person to have very ritualistic behavior/fixations. Again, certain bacteria were shown to be present profusely, and were therefore, leading to more inflammation causing the alteration of a pathway ¹⁶ People may suffer from these disorders for the rest of their lives.

In addition to bacteria playing a role in affecting the body’s mood, certain trace amines may also affect the body as well. These amines are normally found in food and are degraded by microorganisms. One of the more studied amines, TAAR1, has been shown to have a role in regulating, dopaminergic, serotonergic, and glutamatergic transmission ¹⁶ Therefore, by utilizing this compound for therapy, it may be able to treat ailments such as depression and schizophrenia by altering dopamine and serotonin uptake and thus helping the body to be in an overall better mood. Within the brain, and the body there may be a deficiency known as AADC or Aromatic l-amino acid decarboxylase deficiency which is regulated by glutamate dopamine and serotonin ¹⁶ Furthermore, when there is not much uptake of these neurotransmitters, there is not a lot of tyrosine present, which may alter brain activity and function ¹⁶ Another possible solution to combatting these ailments of depression and schizophrenia could be by designing a drug which could alter tyrosine levels within the brain in order to increase neurotransmitter uptake. In addition to this, there has also been studies on CCK, or Cholecystokinin, which is a brain neuropeptide that is found in foods with high amounts of protein. This peptide can be found within the hypothalamus and production of this peptide may stimulate bile within the gall bladder and bind gastrin, to cause gastric acid to be produced which may also increase anxiety ¹⁶

All in all, bacteria play many different roles in the environment. They can help decompose organisms and regulate certain biological functions. Bacteria may also help in the creation of certain medications and vaccines while also being considered for use in cloning and gene therapy. Another field that is relatively new, but shows great promise, is how bacteria may help heal tissue and increase food production. In addition, another application of bacteria is to use them to clean up oil spills, help maintain nitrogen, and breakdown matter within the soil. Surprisingly, bacteria can perform photosynthesis while living in extreme climates, even today, such as deep thermal vents in the depths of the ocean or cold climates. We know bacteria help eukaryotic cells with certain processes such as photosynthesis or cellular respiration, which are very important for energy use and production. Most importantly, when bacteria are present within the human body, particularly the intestines, rather than causing a respiratory illness such as a cold or flu, they can alter mental behavior and completely change one’s lifestyle. Unfortunately, in the extreme case where this might lead to schizophrenia or autism, it can greatly impact a person’s life. While there is still much research to be done in this field, examination of exactly how bacteria can influence the pathways of the brain, the research that has already been done shows that there is a clear connection with bacteria and the chemicals they produce. Moreover, these chemicals can have a drastic effect on how the brain functions. With continued research in this area, scientists will be able to help combat mental illness by prescribing drugs that stop bacteria from producing certain chemicals or by blocking their transition past the GI barrier.