10/11 The connection between your gut and your brain
Video:
View our lesson online. Bridget Wright created this 30 minute video on the lesson. View it here.
Introduction to the connection between your gut and your brain
We have all experienced the brain-gut connection. If you have ever delivered a public speech and were feeling “butterflies”, or so upset you were nauseous. Many emotions are associated with symptoms in the gut. But how well do you understand the connection?
This lesson will look at the connection between the brain and the gut, looking at emotions, neurotransmitters, and mental illnesses. It will then look at microbiomes, and how they have been shown to contribute to certain brain related diseases and some suggestions on how to improve your own microbiomes.
The brain which controls your gut
(The Brain-Gut Connection, 2016) (The Abdominal Brain- Enteric Nervous System, 2016) (Ardizzone, 2017)
Hidden in the walls of the digestive system is your “second brain” or “brain in your gut”. It is called the enteric nervous system (ENS) by scientists and is two thin layers of more than 100 million nerve cells lining your gastrointestinal tract from esophagus to rectum. This extensive network of neurons is widely dispersed throughout the gut, and coordinate gastrointestinal events such as blood flow, secretion and absorption. Interestingly, the ENS can function on its own, even disconnected from the brain. Other ways that the ENS resembles a brain:
• Glial cells to support the neurons in the gut
• Contains 500 million neurons
• Uses 40 (and possibly many more) neurotransmitters
• Produces 50% of the body’s dopamine
• Produces 95% of the body’s serotonin
• Has a barrier resembling the blood-brain barrier
• May even have its own memory
The brain and gut are connected by the vagus nerve, which also connects with most of the organs and is prominent in activating the parasympathetic nervous system. Around 90% of the signals passing through the vagus nerve come from the ENS to the brain, allowing one of the most effective ways for the brain to learn more about the environment.
The main purpose of the ENS is to control digestion, from swallowing to the release of enzymes that break down food, to the control of blood flow that helps with nutrient absorption and elimination. It may trigger the big emotional shifts experienced by people who suffer from irritable bowel syndrome (IBS) and other functional bowel problems like constipation, diarrhea, bloating, pain and stomach upset. In the past, doctors thought that anxiety and depression contributed to these symptoms. But studies now suggest that irritation in the gastrointestinal system may send messages to the central nervous system (CNS) to trigger mood changes.
This is particularly interesting because a higher than normal percentage of people with IBS and functional bowel disorders develop depression and anxiety, given the fact that up to 30 to 40% of the population have functional bowel problems at some point in their life.
This helps to explain why antidepressants and mind-body therapies like cognitive behavioral therapy (CBT) also help reduce gastrointestinal symptoms. The brains “talk to each other” so therapies like this may help one to help the other. So, a gastroenterologist may prescribe antidepressants for IBS because these medications calm symptoms which are acting on the nerve cells in the gut. Similarly, CBT may help improve communication between the two brains.
Video:
The Vagus Nerve is crucial in connecting the brain to the gut. Watch this 4 minute video which describes how it works.
Stress and your stomach
(The gut-brain connection, 2016)
It is no surprise that the brain influences the stomach. Just thinking about food gets the stomach’s juices flowing. The connection can go the other way as well, as the troubled intestine sends signals to the brain. So, problems in the gut can be the cause or the product of anxiety, stress or depression. This is especially evident in cases with gastrointestinal problems and no obvious physical cause. In this case, you would have to look deeper for the role of stress and emotion on the gut.
These problems are not “all in your head”. Instead, psychology combines with physical factors to cause pain and other bowel symptoms. Psychosocial factors can influence the physiology of the gut, as well as the symptoms.
So, stress (or depression or anxiety) can affect movement and contractions of the GI tract, make inflammation worse and may even make you more susceptible to infection.
Research has also suggested that some people with functional GI disorders may perceive pain more acutely than other people because their brains cannot properly regulate pain signals from the GI tract. Stress can make the pain even worse.
But can reducing stress or treating anxiety or depression improve GI conditions? A review of 13 studies showed that patients that used psychologically based approaches had greater improvement in digestive symptoms than those who only used conventional medical treatment. (The gut-brain connection, 2016)
Serotonin and the gut
(Kim, 2000)
Serotonin is a brain neurotransmitter that is related to depression, migraine, and other neuropsychiatric illnesses. It is also found in the gut. In fact, it is estimated that about 95% of serotonin is found in the GI tract. Research is still in the early stages. However, as mentioned above, serotonergic antidepressants are used in IBS, and other selective serotonin agonists and antagonists are being proposed to treat gut disorders because of their direct effect on the gut, rather than the CNS.
Gut-Brain connection and mental illness and disease
(Deans, 2014)
How does the gut-brain connection work? Here is a brief description:
1. The body responds to stress via the hypothalamic-pituitary-adrenal axis. Think of the fight and flight response. Your heart pounds, pupils dilate, hair stands on end, steroids and adrenaline flood your system to give you an extra burst of speed. Even your blood platelets change shape as they become stickier, which means you are less likely to bleed out if you are attacked. This is wonderful for those times when the tiger attacks you, but not so great with chronic stress. With chronic stress, there are mental issues such as anxiety or depression and also physical symptoms like chronic gut problems, headaches, high blood pressure and more.
2. The immune system is also involved. When under stress, the body releases inflammatory cytokines, which are little chemical messengers that bring the immune system into high alert. So, with chronic stress, our body responds as though it is experiencing a chronic infection. Chronic levels of this inflammatory response can lead to other types of chronic diseases such as depression, high blood pressure, atherosclerosis, and autoimmune diseases. It may also influence whether we develop cancer. In this way, our gut can make the difference between whether we are sick or well, mentally or physically.
3. Next, there is bacteria in the gut which interact with the immune system to cause the release of inflammatory cytokines, stress steroids and the stress response we see when attacked by a tiger. It can even influence pain response (unfavorable gut bacteria can mean that you are more sensitive to pain). You can also have good bacteria in the gut, which can keep the bad bacteria low and can turn off the chronic stress response in the immune system. The good bacteria can also turn off the cortisol and adrenaline response on the hormonal level.
Let’s learn more about bacteria in the gut.
Video: Learn more about inflammation and the difference between acute inflammation (injury) and chronic inflammation (stress)
Bacteria in the gut
(Rogers, 2016)
Microbiome is a term that describes the genome (the DNA) of all microorganisms living in and on vertebrates (humans and animals). The gut microbiome is comprised of microbes inhabiting the gut including bacteria, archaea, viruses, and fungi.
The human intestine has trillions of bacteria, with the largest concentration and diversity in the colon. In the past, it was difficult to culture the gut microbiomes, but technology has improved this research. The human microbiome project instituted in 2007 by the National Institutes of Health has identified microbiota at various services of the human body. (Microbiota refers to the micro-organisms and viruses in the human gastrointestinal (GI) tract, while microbiome refers to the genetic make-up of all microbiotas.) This microbiota can change with environmental changes, such as childbirth and maturation.
Everyone has a unique microbiota, although about a third are common among most humans. Factors including hygiene, diet, location, and genotype will influence intestinal microbiota. In addition, there may be a role of sex hormones and age as well.
Below, you can see a map of the diversity in the human microbiome, from the Human Microbiome Project.
Exploring the stools of mice
(Zimmer, 2019)(Fecal Transplantation, 2019)
Fecal transplantation is a transfer of stool from a healthy donor into the gastrointestinal tract. It is currently used for the treatment of recurrent colitis but is being explored for other uses. It works with colitis to restore the “good” bacteria in the digestive tract which has been killed off by antibiotics.
Fecal transplants can help determine these links between an unusual microbiome and bacteria. Rob Knight, a microbiologist at UC San Diego, discovered some hints of the links. They took stool from mice with a genetic mutation that caused them to eat a lot and put on weight. They transferred the stool to mice that had been raised without gut microbiomes since birth. The germ-free mice got hungry and put on weight.
But they also discovered that germ-free mice became loners and stayed away from other mice. They looked at the amygdala (the emotional part of the brain) and found that germ-free mice made unusual sets of proteins, referred to as clumps which changed the connections they had with other cells.
Expanding this study, stool was tranferred from ordinary mice into germ free mice which had received antibiotics. Once their microbiomes were restored, the antibiotic-treated mice began developing clumps again (seen originally in the germ free mice). This led researchers to assume that bacteria are driving this.
Researchers are now looking at specific strains of bacterial species to see if they have an effect. Research on autism in mice found a mutated gene which cause mice to groom themselves repeatedly and avoid contact with other mice. In another mouse strain, feeding mothers a high-fat diet made it more likely their pups will behave that way. When these mice were studied, it was found that they lacked a bacterium called Lactobacillus reuteri (L. reuteri). When they added this to their diet, the animals became social again.
Evidence was discovered that this bacterium (L. reuteri) releases compounds that send a signal to nerve endings in the intestines. The vagus nerve sends these signals from the gut to the brain, where they may alter the production of oxytocin (a hormone that promotes social bonding). Other microbial species send signals along the vagus nerve, and other communicate via the blood stream.
It is also possible that microbiomes are influenced in utero, as it has been shown that the pregnant mother’s microbiome releases molecules that enter the fetal brain. Mothers also provide microbiomes during breast feeding.
Video:
Learn how fecal transplantation is used as treatment in a hospital setting.
Video:
Here is a longer video, a Ted Talk, which explains microbiomes and how they can affect you.
Connecting the brain to the gut
(Zimmer, 2019)
Going back to those germ-free mice, scientists measured the strength of connections between the amygdala (the emotional processing part of the brain) and other regions of the brain. Babies with a lower diversity of species in the gut have stronger connections, suggesting that low diversity microbiomes may make babies more fearful.
Another test of microbiomes put the germ-free mice with epilepsy on a ketogenic diet and found that there was no relief from seizures. But, when they gave the germ-free mice stool from mice on a ketogenic diet, seizures were reduced. Researchers found that two types of gut bacteria thrive in a ketogenic diet. They may be providing the hosts with neurotransmitters that stop electrical activity in the brain (thus decreasing epilepsy symptoms). It is conceivable that in the future, a pill containing the bacteria can treat epilepsy symptoms.
Sarkis Mazmanian, a microbiologist at Caltech has identified a single strain of bacteria that triggers symptoms of Parkinson’s disease in mice. He is working on a compound that may block signals the microbe sends to the vagus nerve.
The problem with the research is that people will take the findings and assume that probiotics and microbes might be marketed, even before scientists are sure of the findings.
Video:
This 10-minute YouTube video explains the microbes in your gut and how it affects your mental health. It mentions the ENS and the way it communicates with the CNS, mentions the vagus nerve and even the blood brain barrier. It describes the studies with mice and stress and changes in the bacteria which occur. A great video because it does pull everything together.
Video:
This five-minute video describes the human microbiome in a cute animated way. It gets the message across! (Produced by NPR).
Gut microbiome and Brain Health
(Wanucha, 2018)
While these microbiomes help digest food, process nutrients, make vitamins B and K and produce immune molecules which fight inflammation and heal wounds, the value may extend beyond the gut and into the brain.
There is a direct line of communication, set up by special nerve cells and immune pathways called the gut-brain axis. In the gut, bacteria make neuroactive compounds which include 90% of serotonin (a neurotransmitter associated with emotions) and in the brain, signals are sent to the GI system to stimulate or suppress digestion.
Our microbiome is unique and shaped by early life, diet and environment. But genetics influences how bacteria function in the human gut. Also, bacteria may express different genes and make proteins that will predispose certain people to gut inflammation or other conditions.
A diverse microbiome is a healthy one. Diversity protects one from dominating and causing trouble in the gut and beyond. Certain conditions such as inflammatory bowel disease, autism and blood cancers have been shown to be related to shifts in the microbiome. Researchers are also working to see if the disrupted microbiome can contribute to Alzheimer’s disease and related conditions.
Example: Alzheimer’s disease and microbiomes: (Wanucha, 2018)
Advanced tools allow researchers to identify species in the human gut and analyze bacterial genes and protein products that affect brain health. Recently, research at the Wisconsin Alzheimer’s Disease Research Center examined the microbiomes of people with Alzheimer’s disease to identify the bacteria present and assess the richness and diversity of the microbiome.
They found that people with Alzheimer’s had a unique and less diverse community of gut microorganisms. Specifically, they found significant increases and decreases in common gut bacteria and were able to link the abnormal levels of these microbes to the amount of Alzheimer’s disease proteins in spinal fluid.
The results suggest that the unique microbiome of people with Alzheimer’s can be contributing to the progression of the disease, through the gut-brain axis. A possible conclusion might be that restoring healthy gut bacteria composition could prevent or slow down Alzheimer’s in at-risk populations.
Example: Parkinson’s disease and microbiomes: (Wanucha, 2018)
In another study funded by NIH, it was suggested that Corynebacterium might help cause Parkinson’s disease, but only in people with a certain genotype. They discovered that every person who had that genotype and Corynebacterium in the gut had Parkinson’s disease. Corynebacterium is a common bacterium on human skin, and researchers do not know how it enters the gut.
This research implicates the importance of genetics in studying the microbiome. It suggests that a combination of factors (types of bacteria in their gut, interactions between the bacteria and the genes, as well as the risk of disease) may determine why some develop Alzheimer’s disease or Parkinson’s, and that understanding the impact of genetic factors may benefit the understanding of these diseases.
Example: Microbiomes and Infant boys (Species of Gut Bacteria Linked to Enhanced Cognition and Language Skills in Infant Boys, 2021)
A University of Alberta research team recently followed more than 400 infants from the CHILD Cohort Study (CHILD). Boys with a gut bacterial composition high in the bacteria Bacteroidetes at one year of age were found to have more advanced cognition and language skills a year later. This finding was specific to male children.
Researchers suggested that there are subtle differences between male and female gut microbiota, but that girls at early are more likely to have more of these Bacteroidetes. So, they suspect that girls have a sufficient number of Bacteroidetes and that is why their scores surpass those of boys.
According to the researchers, Bacteroidetes are one of a very few bacteria that produce metabolites called sphingolipids, instrumental in the formation and structure of neurons in the brain. Caesarean birth is one factor that can significantly deplete Bacteroidetes. Factors which may benefit gut microbiota composition in infants include breastfeeding, living a high fiber diet, living with a dog and being exposed to nature and green spaces.
Although the findings do not mean that children with a lower proportion of Bacteroidetes will lag behind their peers, researchers do believe that this study provides a way to potentially identify children at risk of neurodevelopmental disorders.
This research replicated similar findings from another study that also found positive associations between Bacteroidetes in late infancy and neurodevelopment in boys but not girls. (Tamana, 2021)
Research backed ways to improve gut health (and ultimately your brain health)
(Leonard, 2019)
For a summary, Medical News Today has listed 10 scientifically supported ways which may improve gut microbiome and enhance overall health.
Probiotics and fermented foods: May support a healthy gut microbiome and prevent gut inflammation.
Prebiotic fiber: Probiotics feed on nondigestible carbohydrates called prebiotics. Prebiotics may help probiotics to become more tolerant to environmental conditions. Suggestions include asparagus, banana, garlic, onions and whole grains
Less sugar and sweeteners: A 2015 study suggested that sugar and fat negatively affect gut microbiomes, while another study reported artificial sweetener aspartame increases some bacterial strains linked to metabolic disease. They may also increase blood sugar even though they are not actually sugar.
Reduce stress: Stressors affecting gut health may include psychological stress, environmental stress (heat, cold, noise), sleep deprivation and disruption of the circadian rhythm. Try meditation, deep breathing, and progressive muscle relaxation.
Avoid antibiotics when possible: They damage gut microbiota and immunity, and some research has reported long term loss of beneficial bacteria.
Exercise regularly: Recommended amounts are at least 150 minutes of moderate intensity exercise a week, along with two or more days of muscle strengthening activities.
Sleep: Irregular sleep may negatively affect guy flora. Adults should get at least 7 hours of sleep a night.
Disinfectant cleaning products: Babies were studied in homes where people used disinfectant products at least once a week. They were found to have higher levels of Lachnospiraceae gut microbes associated with type 2 diabetes and obesity. At age 3, these infants had a higher body mass index as well.
Stop smoking: Research over a 16-year period found that smoking alters the intestinal flora by increasing potentially harmful microorganisms and decreasing the levels of beneficial ones. This may increase the risk of intestinal and systemic conditions such as inflammatory bowel disease.
Consider a vegetarian diet: Studies have shown a significant difference between the gut microbiomes of vegetarians versus those who eat meat. This may be due to the high levels of prebiotic fiber. It may also help to lose weight.
Summary
There is a strong connection between our gut and our brain. And like the relationship between the heart and brain, what is healthy for one is healthy for the other. So, approaching this from both angles (good diet, stress reduction techniques) will be the best solution.
Works Cited
Ardizzone, T. (2017, March 5). The Gut-Brain Connection - How it affects your life. Retrieved from organiclifestylemagazine.com: http://www.organiclifestylemagazine.com/the-gut-brain-connection- how-it-affects-your-life
Deans, E. (2014, April 6). The Gut-Brain Connection, Mental Illness, and Disease. Retrieved from psychologytoday.com: https://www.psychologytoday.com/blog/evolutionary- psychiatry/201404/the-gut-brain-connection-mental-illness-and- disease
Kim, D. e. (2000). Serotonin: A mediator of the Brain-Gut Connection. American Journal of Gastroenterology. Retrieved from https://search.proquest.com/openview/0913f5f1ab00bb75672e259937 367f88/1?pq-origsite=gscholar&cbl=2041977
Leonard, J. (2019, May 28). 10 ways to improve gut health. Retrieved from medicalnewstoday.com: https://www.medicalnewstoday.com/articles/325293.php
Rogers, Y. a. (2016, February). Genomic Technologies in Medicine and Health: Past, Present, and Future. Medical and Health Genomics, pp. 15-28. Retrieved from https://www.sciencedirect.com/science/article/pii/B9780124201965000022
Species of Gut Bacteria Linked to Enhanced Cognition and Language Skills in Infant Boys. (2021, July 13). Retrieved from neurosciencenews.com: https://neurosciencenews.com/boys-bacteria-cognition-language-18911/
Taylor, A. (2014, March 3). Bacteria’s Role in Bowel Cancer. Retrieved from the-scientist.com: https://www.the-scientist.com/daily-news/bacterias-role-in-bowel-cancer-37854
The Abdominal Brain- Enteric Nervous System. (2016, March 31). Retrieved from lumennatura.com: https://www.lumennatura.com/2016/03/31/the-abdominal-brain- enteric-nervous-system/
The Brain-Gut Connection. (2016, June). Retrieved from hopkinsmedicine.org: https://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/the-brain-gut-connection
The gut-brain connection. (2016, March). Retrieved from health.harvard.edu: https://www.health.harvard.edu/diseases-and- conditions/the-gut-brain-connection
Wanucha, G. (2018, October 4). The Gut Microbiome and Brain Health. Retrieved from washington.edu: http://depts.washington.edu/mbwc/news/article/the-gut-microbiome-and-brain-health
Zimmer, C. (2019, January 28). Germs in Your Gut Are Talking to Your Brain. Scientists Want to Know What They’re Saying. Retrieved from nytimes.com: https://www.nytimes.com/2019/01/28/health/microbiome-brain-behavior-dementia.html