Author: Tina Zhou
Microbes in the human body outnumber human cells at approximately a 10:1 ratio. There are 100 trillion microbes living in the intestines alone; these microscopic communities can account for as much as 6 pounds of a person’s body weight. Gut microbes have been known to promote healthy digestion, but recent research uncovered these microbes’ influence on the body’s immune and nervous system, as well as potential implications in therapies for patients with Autism Spectrum Disorder (ASD).
Gut bacteria, such as Lactobacillus rhamnosus, produce a variety of neurotransmitters that can reach the brain through nerves that connect the gastrointestinal tract to the central nervous system. Some of these microbe-produced neurotransmitters include GABA, which helps regulate inhibitory signals in the brain and other nerve cells, as well as serotonin, a vital excitatory neurotransmitter that plays a role in happiness, anxiety, and depression. A 2013 experiment in Ireland showed the connection between the microbiome and the serotonergic system, as well as various other connections between the effects of the microbiome on neurodevelopment and behavior.
In addition, various studies show increasing evidence for the connection between the microbiome and stress-related behaviors. A study in rhesus monkeys showed that stress was connected to changes in the composition and diversity of the primates’ gut microbiota; similar studies on mice, rats, and zebrafish all produced similar results. Specifically, mice raised from birth in germ-free conditions, devoid of microbes, exhibited more stress than non-sterile mice. These germ-free mice also exhibited deficiencies in serum serotonin levels and elevated serum tryptophan levels, demonstrating their inability to convert tryptophan, an amino acid serotonin precursor, to serotonin. Normal mice showed no such abnormalities compared to these mice, suggesting that gut microbes regulate serum (or peripheral) serotonin levels by producing the essential neurotransmitters in large quantities.
With strong scientific evidence demonstrating the relationship between gut microbial activity and brain health, applications of the laboratory research grabbed the attention of clinicians and researchers conducting pre-clinical and translational studies. In 2011 Dr. Cryan – of the Irish laboratory – found that mice that ate a particular probiotic were more relaxed than those who did not eat the supplement[1,2]. Patients with gastrointestinal disorders who exhibit stress and anxiety are referred to psychologists by gastroenterologists, who recognize the relationship between gut health and mental health. A stressed microbiome can also cause these patients to be more sensitive to any type of pain, and mental stress and anxiety can further exacerbate these pain signals. In addition to mental health, scientists are studying the gut microbiome’s influence on neurodevelopmental disorders such as ASD; these studies focus on exploring the microbiome’s ability to regulate the body’s serotonin levels.
A recent study on the connection between gut serotonin levels and ASD found that serotonin may be the center of the gut-brain microbiome axis. In addition to being an excitatory neurotransmitter, serotonin also regulates critical aspects of brain development such as myelination, axonal growth, and neuronal migration[5,6]. With the gut epithelia being one of two major reservoirs of serotonin in the body, it is clear that the healthy development of the neural system relies upon the gut’s ability to produce and regulate serotonin levels, a process in which gut microbes play a major role. The study discovered that upon treating mice with microbial abnormalities with a microbe called Bacteriodes fragilis, both gastrointestinal defects and ASD-associated behaviors improved.
Gut microbiota have received increasing amounts of scientific attention in recent decades due to their regulation of several essential processes in the body. Medical applications of this research range from correcting dysbiosis and gastrointestinal problems via fecal transplants to therapies that can deliver probiotic treatment to patients with disorders ranging from immune-related gut-inflammation to psychological and neurodevelopmental conditions. These new potential treatments and therapies may undermine conventional methods such as surgery and traditional drug therapies in treating disease in patients.
4 Fast Facts about the Gut-Brain Connection. (2017, September 24). Retrieved from https://nccih.nih.gov/news/events/IMlectures/gut-brain
Clarke, G., Grenham, S., Scully, P., Fitzgerald, P., Moloney, R. D., Shanahan, F., . . . Cryan, J. F. (2012, June 12). The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Retrieved October 9, 2018, from https://www.nature.com/articles/mp201277
Harvard Health Publishing. (n.d.). The gut-brain connection - Harvard Health. Retrieved October 9, 2018, from https://www.health.harvard.edu/diseases-and-conditions/the-gut-brain-connection
Israelyan, N., & Margolis, K. G. (2018, March 31). Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders. Retrieved October 9, 2018, from https://www.sciencedirect.com/science/article/abs/pii/S1043661817316869
Jameson, K. G., & Hsiao, E. (2018, June 19). Linking the Gut Microbiota to a Brain Neurotransmitter. Retrieved October 9, 2018, from https://www.sciencedirect.com/science/article/pii/S0166223618300869?via=ihub
Kim, D., & Camilleri, M. (2000, October 01). Serotonin: A mediator of the brain–gut connection. Retrieved October 9, 2018, from https://www.nature.com/articles/ajg20001422
The Brain-Gut Connection. (n.d.). Retrieved from https://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection
The Gut-Brain Connection. (n.d.). Retrieved from https://my.clevelandclinic.org/health/treatments/16358-gut-brain-connection