Our specialists regularly review advancements in health and wellness, ensuring our articles are updated with the newest information as it becomes accessible.
Recent Updates
June 12, 2024
Our specialists regularly review advancements in health and wellness, ensuring our articles are updated with the newest information as it becomes accessible.
The concept of the gut as the “second brain” first emerged with the discovery of the enteric nervous system (ENS) in the gastrointestinal (GI) tract. The ENS has its own extensive network of neurons that can function somewhat independently of the central nervous system (CNS), controlling processes like the movement of food through the GI tract, digestive enzyme secretion, and regulating blood flow. This concept garnered even more momentum as researchers explored the bidirectional communication, known as the “gut-brain axis,” that exists between the gut and the CNS.
Gut health issues are linked to the development of psychiatric, neurodevelopmental, neurological, and cognitive diseases, underscoring the importance of this axis. Statistics show that approximately 2 out of every 3 Americans will experience some level of cognitive decline by age 70. In addition, it's estimated that anxiety will affect around 30% of individuals, while approximately 20% will contend with mood disorders during their lifetime. The gut-brain axis serves as an important avenue for interventions and therapies to help optimize cognition and improve mental health.
[signup]
The Intricacies of the Gut-Brain Connection
The ENS is the largest and most complex unit of the peripheral nervous system, containing approximately 400-600 million neurons, and is located within the walls of the GI tract. Although it does receive CNS input through the vagus nerve and spinal cord, it is also able to act independently due to local reflex circuits.
The gut is not only responsible for digestion but also influences our cognition and mood through its communication with the brain. The vagus nerve plays a vital role in the bidirectional connection between the two systems. Signals from the gut, such as neurotransmitters and information about gut microbiota, are transmitted via the vagus nerve to the brain. In return, the brain also uses the vagus nerve to influence gut function, allowing it to modulate gastrointestinal activities in response to stimuli like psychological stress or anticipation of a meal.
The gut-brain axis not only includes direct neural connections but also indirect connections facilitated through the endocrine and immune systems. The GI tract produces its own hormones that communicate with the brain. For instance, ghrelin, which is produced in the stomach, signals to the brain that it’s time to eat when you are hungry. In turn, the brain initiates hormonal responses that exert influence over gut functions.
An example of this is the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus, a gland in the brain, senses when our body is under stress and triggers a cascade of events that result in the release of hormones, such as cortisol, by the adrenal glands. Cortisol interacts with various cell types in the gut, including epithelial cells and immune cells, allowing it to regulate transit time, intestinal barrier function, and the composition of the microbiome - the community of microorganisms that reside in the gut.
Around 70% of our immune system resides in the gastrointestinal tract, specifically in gut-associated lymphoid tissue (GALT). The GALT interacts with the gastrointestinal tract directly, coordinating immune system activity in response to exposure to gastrointestinal contents. In response to exposures like infection or inflammation, immune cells in the gut release signaling molecules called cytokines. These cytokines can enter the bloodstream and even enter the brain, thereby impacting its functions.
The Microbiome: A World Within
The gut microbiome refers to the trillions of microorganisms, including bacteria, fungi, and archaea, that reside within the gastrointestinal tract. Each person has a unique microbiome that is shaped by multiple factors. Genetic and early lifestyle exposures, such as delivery and infant feeding methods, set the foundation. Lifestyle practices, throughout the course of our lives, continue to shape the composition of our microbiome, including diet, medications, alcohol consumption, smoking, physical activity, and sleep patterns. The microbiome has many functions, including:
Digestion
The microbiome assists in breaking down complex carbohydrates, fibers, and other food components we cannot digest on our own. This breakdown allows for the absorption of essential nutrients as well as the production of short-chain fatty acids (SCFAs) that play a role in gut health.
Protection From Pathogens
Beneficial gut bacteria can help prevent the growth and colonization of harmful pathogens, thereby protecting against infections.
Synthesis of Vitamins
Some microorganisms in the gut can synthesize essential vitamins, such as vitamin K and certain B vitamins. These vitamins are then absorbed and contribute to various physiological functions in the body.
Immune System Regulation
The gut microbiome plays a crucial role in developing and modulating the immune system. It helps distinguish between harmful pathogens and beneficial microorganisms, preventing unnecessary immune responses and inflammation.
Neurotransmitter Production
Gut bacteria can produce neurotransmitters, including serotonin, dopamine, glutamine, and GABA, which can impact mood and mental health.
Gut Barrier Function
The microbiome helps maintain the integrity of the gut barrier, preventing potentially harmful substances from entering the bloodstream, where they can trigger inflammation.
Detoxification
Certain gut bacteria are involved in the metabolism of hormones and environmental exposures, like toxins and drugs, aiding in their elimination from the body.
All of these important functions not only play a role in optimizing gut health but also brain function, such that dysbiosis has been associated with disruption to the gut-brain axis. Dysbiosis refers to an imbalance in bacterial composition, activity, or distribution within the gut. This can occur when there is a loss of beneficial bacteria, an overgrowth in potentially pathogenic organisms, a loss of overall diversity, or conditions like small intestinal bacterial overgrowth (SIBO) where colon bacteria have migrated into the small intestine.
Gut Microbiome and Brain Health
While the connection might not be immediately obvious, the microbiome can be at the root of cognitive symptoms such as depression, anxiety, and brain fog. Brain fog is a term used to describe a constellation of symptoms including forgetfulness, difficulty concentrating, dissociation, excessive cognitive effort, difficulty communicating, and fatigue. In dysbiosis, the changes to the microbiome composition result in changes to its metabolic functions, like its ability to produce neurotransmitters and SCFAs, that ultimately impact the gut-brain axis.
Neurotransmitters play a pivotal role in regulating mood and cognition, and neurotransmitter imbalances have been associated with cognitive impairment, anxiety, depression, memory, and concentration. Certain bacterial strains in the gut produce enzymes that synthesize and metabolize neurotransmitters and their precursors, such as glutamate, GABA, serotonin, dopamine, and tryptophan. Carbohydrate fermentation by gut bacteria also results in the production of short-chain fatty acids. SCFA’s modulate neurotransmitter and neurotrophic factor production in the brain. Neurotrophic factors include nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor (BDNF), which regulate the neurons and microglia, immune cells, in the brain. In psychiatric and neurodegenerative conditions, changes to the microbiome are commonly identified in which lower SCFA-producing strains of bacteria and higher levels of inflammatory gram-negative bacteria are seen.
Inflammation: The Silent Enemy
The microbiome has an important role in regulating the immune system and barrier functions. Dysbiosis disrupts these processes, leading to systemic and neural inflammation, both of which are fundamental factors at the root of cognitive dysfunction. (13, 43, 68)
Beneficial commensal bacteria in the microbiome regulate immune responses by supporting the development of immune cells called regulatory T cells that prevent unnecessary inflammation. In dysbiosis, immune system activation is triggered, which increases proinflammatory signals. (4)
The microbiome also plays a role in maintaining the integrity of the gut barrier. The gastrointestinal tract is the body’s largest contact point with the outside world. A well-functioning intestinal barrier is crucial for preventing pathogens, toxins, and poorly digested food particles from entering the bloodstream. When this barrier breaks down, in a condition known as intestinal permeability or “leaky gut," it allows for the gastrointestinal contents to enter the bloodstream, triggering the immune system and increasing inflammatory responses.
Certain beneficial bacteria increase the production of mucus-tight junction proteins, and SCFAs strengthen the intestinal barrier. In dysbiosis, an overabundance of gram-negative bacteria, which contain endotoxins or lipopolysaccharides (LPS), can damage the intestinal lining, leading to intestinal permeability. Some microorganisms also increase the production of a protein called zonulin, which regulates tight junction proteins. Higher levels of zonulin are associated with intestinal permeability. (11) Intestinal permeability is associated with cognitive decline, as well as psychiatric conditions such as anxiety and depression. (55)
SCFAs not only exert a protective influence over the intestinal barrier but also the blood-brain barrier (BBB). The BBB functions similarly to the intestinal barrier, controlling the passage of substances from the bloodstream into the brain tissue. BBB dysfunction or permeability, just like intestinal permeability, is associated with inflammation in the brain and cognitive dysfunction. (38)
Functional Medicine Tests for Gut-Brain Health
Functional medicine tests are useful tools in identifying the root causes of cognitive changes by evaluating the health of the gut-brain axis.
Cyrex Intestinal Permeability
The Array 2 by Cyrex Laboratories measures specific biomarkers related to the intestinal barrier, such as antibodies to zonulin and tight junction proteins. This provides information about the integrity of the intestinal barrier and whether intestinal permeability exists.
Organic Acids
The Organic Acids test (OAT) by Mosaic Diagnostics measures organic acids in the urine, which are metabolic byproducts made as the body processes nutrients, neurotransmitters, and other molecules. The levels of these organic acids provide information about neurotransmitter imbalances, oxidative stress, and dysbiosis.
Blood-Brain Barrier
Cyrex’sArray 20 measures antibodies against proteins related to the blood-brain barrier. Immune responses to these proteins can indicate increased blood-brain barrier permeability.
Nutritional Pathways to a Healthier Gut and Mind
What we consume not only fuels our bodies and brains but also regulates gut-brain health, influencing the composition and metabolism of the gut microbiota, the integrity of the intestinal lining, and inflammation. As a result, dietary choices can ultimately impact our mood, cognition, and even our susceptibility to neurological and psychiatric conditions.
Western diets are characterized by high amounts of processed foods, refined carbohydrates, salt, saturated fats, and trans fats, as well as less than desired amounts of fiber, important nutrients, and antioxidants. Some of the prominent foods in the Western diet can stimulate inflammation directly or indirectly through their influence on the microbiome composition. (51) Diets high in sugar have been shown to decrease microbial diversity and increase intestinal permeability, while diets high in plant-based foods and fiber, such as a Mediterranean diet, support the growth of beneficial commensal bacteria that inhibit inflammatory responses. (40)
Food sensitivities, which involve the immune system's reactions to specific food proteins, influence intestinal permeability. They do so by increasing inflammation or stimulating zonulin production. (62) Collaborating with a functional medicine practitioner to either conduct food sensitivity testing or navigate an elimination diet can be helpful in personalizing dietary recommendations to steer clear of potentially harmful foods for your gut.
Prebiotics and probiotics, acquired either through dietary sources or supplements, aid in optimizing the microbiome composition. Prebiotics, non-digestible dietary compounds typically from carbohydrates or fiber, serve as a source of nutrition for beneficial gut bacteria, promoting their growth and activity. These compounds are found naturally in certain foods like fruits, vegetables, whole grains, and legumes or can also be taken in supplemental form. Common prebiotic supplements available include inulin, fructooligosaccharides, resistant starch, and galactooligosaccharides. Probiotics are living beneficial microorganisms, usually yeast or bacteria, that are found in fermented foods, such as yogurt, sauerkraut, and kimchi. Incorporating more fermented foods into your diet or using oral probiotic supplements have both been found to improve microbial composition and reduce inflammation.
Lifestyle Choices that Promote Gut and Brain Health
The gut-brain axis is shaped not only by our dietary choices but also by the lifestyle practices we engage in. Physical activity, stress management, and sleep all have a profound impact on both the gut and the brain, thereby influencing the intricate relationship between the two.
Physical Activity
Exercise habits influence the microbiome and gut inflammation. Over-exercising has a negative impact on the composition of the microbiome and increases intestinal permeability. On the other hand, regular, lower-intensity exercise exerts protective effects, improving the microbiome composition and increasing SCFA production.
Exercise also directly influences brain health and neuroplasticity by stimulating the release of neurotrophic factors like BDNF, increasing blood flow, and improving glucose and lipid metabolism, which aids in delivering necessary fuel to the brain. Studies show it helps to improve cognitive functions, such as memory and attention, and also helps to prevent cognitive decline.
Stress Management
Stress negatively impacts the gut-brain axis through its effects on the nervous, endocrine, and immune systems. Under stress, the brain uses the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis to send signals to the gut. Research shows that stress changes intestinal permeability, intestinal motility, intestinal secretions, microbiome composition, and intestinal inflammation. (29) Psychological stress is also associated with decreased cognitive functioning, cognitive decline, depression, and anxiety.
Mind-body therapies stimulate the body’s relaxation response to counteract the negative neuroendocrine effects of stress. Some of these techniques include mindfulness, meditation, yoga, deep breathing, progressive muscle relaxation, and biofeedback. Mindfulness practices, for example, have been used to improve cognitive function, treat gastrointestinal symptoms, and improve mood.
Sleep
Sleep plays a vital role in supporting cognitive health through memory consolation, hormone balance, and detoxifying the brain. Sleep disruption changes microbiome composition as well as increasing inflammatory cytokines. These underlying mechanisms contribute to its association with decreased cognitive ability, depression, and anxiety.
Good sleep hygiene practices to implement to improve sleep quality include sticking to a consistent sleep schedule, getting exposure to natural light during the day, ensuring the room you sleep in is cool, dark, and quiet, limiting screen exposure in the evenings, and avoiding heavy meals and caffeine too close to bedtime.
[signup]
Why The Gut is The Second Brain: Key Takeaways
Recognizing the critical role of the gut-brain axis in cognitive health is essential. Microbiome composition and activity, intestinal permeability, and inflammation all significantly disrupt this axis. Functional medicine tests are invaluable in gaining insight into the function of the gut-brain axis, guiding individuals towards tailored diet and lifestyle choices. By embracing the gut-brain connection and proactively nurturing this connection, individuals are empowered to enhance their overall well-being.
The concept of the gut as the “second brain” first emerged with the discovery of the enteric nervous system (ENS) in the gastrointestinal (GI) tract. The ENS has its own extensive network of neurons that can function somewhat independently of the central nervous system (CNS), controlling processes like the movement of food through the GI tract, digestive enzyme secretion, and regulating blood flow. This concept garnered even more momentum as researchers explored the bidirectional communication, known as the “gut-brain axis,” that exists between the gut and the CNS.
Gut health issues are linked to the development of psychiatric, neurodevelopmental, neurological, and cognitive challenges, underscoring the importance of this axis. Statistics show that approximately 2 out of every 3 Americans will experience some level of cognitive decline by age 70. In addition, it's estimated that anxiety will affect around 30% of individuals, while approximately 20% will contend with mood disorders during their lifetime. The gut-brain axis serves as an important avenue for interventions and therapies to help optimize cognition and support mental health.
[signup]
The Intricacies of the Gut-Brain Connection
The ENS is the largest and most complex unit of the peripheral nervous system, containing approximately 400-600 million neurons, and is located within the walls of the GI tract. Although it does receive CNS input through the vagus nerve and spinal cord, it is also able to act independently due to local reflex circuits.
The gut is not only responsible for digestion but also influences our cognition and mood through its communication with the brain. The vagus nerve plays a vital role in the bidirectional connection between the two systems. Signals from the gut, such as neurotransmitters and information about gut microbiota, are transmitted via the vagus nerve to the brain. In return, the brain also uses the vagus nerve to influence gut function, allowing it to modulate gastrointestinal activities in response to stimuli like psychological stress or anticipation of a meal.
The gut-brain axis not only includes direct neural connections but also indirect connections facilitated through the endocrine and immune systems. The GI tract produces its own hormones that communicate with the brain. For instance, ghrelin, which is produced in the stomach, signals to the brain that it’s time to eat when you are hungry. In turn, the brain initiates hormonal responses that exert influence over gut functions.
An example of this is the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus, a gland in the brain, senses when our body is under stress and triggers a cascade of events that result in the release of hormones, such as cortisol, by the adrenal glands. Cortisol interacts with various cell types in the gut, including epithelial cells and immune cells, allowing it to regulate transit time, intestinal barrier function, and the composition of the microbiome - the community of microorganisms that reside in the gut.
Around 70% of our immune system resides in the gastrointestinal tract, specifically in gut-associated lymphoid tissue (GALT). The GALT interacts with the gastrointestinal tract directly, coordinating immune system activity in response to exposure to gastrointestinal contents. In response to exposures like infection or inflammation, immune cells in the gut release signaling molecules called cytokines. These cytokines can enter the bloodstream and even enter the brain, thereby impacting its functions.
The Microbiome: A World Within
The gut microbiome refers to the trillions of microorganisms, including bacteria, fungi, and archaea, that reside within the gastrointestinal tract. Each person has a unique microbiome that is shaped by multiple factors. Genetic and early lifestyle exposures, such as delivery and infant feeding methods, set the foundation. Lifestyle practices, throughout the course of our lives, continue to shape the composition of our microbiome, including diet, medications, alcohol consumption, smoking, physical activity, and sleep patterns. The microbiome has many functions, including:
Digestion
The microbiome assists in breaking down complex carbohydrates, fibers, and other food components we cannot digest on our own. This breakdown allows for the absorption of essential nutrients as well as the production of short-chain fatty acids (SCFAs) that play a role in gut health.
Protection From Pathogens
Beneficial gut bacteria can help manage the growth and colonization of harmful pathogens, thereby supporting the body's defense against infections.
Synthesis of Vitamins
Some microorganisms in the gut can synthesize essential vitamins, such as vitamin K and certain B vitamins. These vitamins are then absorbed and contribute to various physiological functions in the body.
Immune System Regulation
The gut microbiome plays a crucial role in developing and modulating the immune system. It helps distinguish between harmful pathogens and beneficial microorganisms, preventing unnecessary immune responses and inflammation.
Neurotransmitter Production
Gut bacteria can produce neurotransmitters, including serotonin, dopamine, glutamine, and GABA, which can impact mood and mental health.
Gut Barrier Function
The microbiome helps maintain the integrity of the gut barrier, preventing potentially harmful substances from entering the bloodstream, where they can trigger inflammation.
Detoxification
Certain gut bacteria are involved in the metabolism of hormones and environmental exposures, like toxins and drugs, aiding in their elimination from the body.
All of these important functions not only play a role in supporting gut health but also brain function, such that dysbiosis has been associated with disruption to the gut-brain axis. Dysbiosis refers to an imbalance in bacterial composition, activity, or distribution within the gut. This can occur when there is a loss of beneficial bacteria, an overgrowth in potentially pathogenic organisms, a loss of overall diversity, or conditions like small intestinal bacterial overgrowth (SIBO) where colon bacteria have migrated into the small intestine.
Gut Microbiome and Brain Health
While the connection might not be immediately obvious, the microbiome can be at the root of cognitive symptoms such as feelings of sadness, worry, and brain fog. Brain fog is a term used to describe a constellation of symptoms including forgetfulness, difficulty concentrating, dissociation, excessive cognitive effort, difficulty communicating, and fatigue. In dysbiosis, the changes to the microbiome composition result in changes to its metabolic functions, like its ability to produce neurotransmitters and SCFAs, that ultimately impact the gut-brain axis.
Neurotransmitters play a pivotal role in regulating mood and cognition, and neurotransmitter imbalances have been associated with cognitive impairment, anxiety, depression, memory, and concentration. Certain bacterial strains in the gut produce enzymes that synthesize and metabolize neurotransmitters and their precursors, such as glutamate, GABA, serotonin, dopamine, and tryptophan. Carbohydrate fermentation by gut bacteria also results in the production of short-chain fatty acids. SCFA’s modulate neurotransmitter and neurotrophic factor production in the brain. Neurotrophic factors include nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor (BDNF), which regulate the neurons and microglia, immune cells, in the brain. In psychiatric and neurodegenerative conditions, changes to the microbiome are commonly identified in which lower SCFA-producing strains of bacteria and higher levels of inflammatory gram-negative bacteria are seen.
Inflammation: The Silent Enemy
The microbiome has an important role in regulating the immune system and barrier functions. Dysbiosis disrupts these processes, leading to systemic and neural inflammation, both of which are fundamental factors at the root of cognitive challenges. (13, 43, 68)
Beneficial commensal bacteria in the microbiome regulate immune responses by supporting the development of immune cells called regulatory T cells that help manage inflammation. In dysbiosis, immune system activation is triggered, which increases proinflammatory signals. (4)
The microbiome also plays a role in maintaining the integrity of the gut barrier. The gastrointestinal tract is the body’s largest contact point with the outside world. A well-functioning intestinal barrier is crucial for preventing pathogens, toxins, and poorly digested food particles from entering the bloodstream. When this barrier breaks down, in a condition known as intestinal permeability or “leaky gut," it allows for the gastrointestinal contents to enter the bloodstream, triggering the immune system and increasing inflammatory responses.
Certain beneficial bacteria increase the production of mucus-tight junction proteins, and SCFAs strengthen the intestinal barrier. In dysbiosis, an overabundance of gram-negative bacteria, which contain endotoxins or lipopolysaccharides (LPS), can damage the intestinal lining, leading to intestinal permeability. Some microorganisms also increase the production of a protein called zonulin, which regulates tight junction proteins. Higher levels of zonulin are associated with intestinal permeability. (11) Intestinal permeability is associated with cognitive decline, as well as psychiatric conditions such as anxiety and depression. (55)
SCFAs not only exert a protective influence over the intestinal barrier but also the blood-brain barrier (BBB). The BBB functions similarly to the intestinal barrier, controlling the passage of substances from the bloodstream into the brain tissue. BBB dysfunction or permeability, just like intestinal permeability, is associated with inflammation in the brain and cognitive challenges. (38)
Functional Medicine Tests for Gut-Brain Health
Functional medicine tests are useful tools in identifying the root causes of cognitive changes by evaluating the health of the gut-brain axis.
Cyrex Intestinal Permeability
The Array 2 by Cyrex Laboratories measures specific biomarkers related to the intestinal barrier, such as antibodies to zonulin and tight junction proteins. This provides information about the integrity of the intestinal barrier and whether intestinal permeability exists.
Organic Acids
The Organic Acids test (OAT) by Mosaic Diagnostics measures organic acids in the urine, which are metabolic byproducts made as the body processes nutrients, neurotransmitters, and other molecules. The levels of these organic acids provide information about neurotransmitter imbalances, oxidative stress, and dysbiosis.
Blood-Brain Barrier
Cyrex’sArray 20 measures antibodies against proteins related to the blood-brain barrier. Immune responses to these proteins can indicate increased blood-brain barrier permeability.
Nutritional Pathways to a Healthier Gut and Mind
What we consume not only fuels our bodies and brains but also supports gut-brain health, influencing the composition and metabolism of the gut microbiota, the integrity of the intestinal lining, and inflammation. As a result, dietary choices can ultimately impact our mood, cognition, and even our susceptibility to neurological and psychiatric conditions.
Western diets are characterized by high amounts of processed foods, refined carbohydrates, salt, saturated fats, and trans fats, as well as less than desired amounts of fiber, important nutrients, and antioxidants. Some of the prominent foods in the Western diet can stimulate inflammation directly or indirectly through their influence on the microbiome composition. (51) Diets high in sugar have been shown to decrease microbial diversity and increase intestinal permeability, while diets high in plant-based foods and fiber, such as a Mediterranean diet, support the growth of beneficial commensal bacteria that help manage inflammatory responses. (40)
Food sensitivities, which involve the immune system's reactions to specific food proteins, influence intestinal permeability. They do so by increasing inflammation or stimulating zonulin production. (62) Collaborating with a functional medicine practitioner to either conduct food sensitivity testing or navigate an elimination diet can be helpful in personalizing dietary recommendations to steer clear of potentially harmful foods for your gut.
Prebiotics and probiotics, acquired either through dietary sources or supplements, aid in optimizing the microbiome composition. Prebiotics, non-digestible dietary compounds typically from carbohydrates or fiber, serve as a source of nutrition for beneficial gut bacteria, promoting their growth and activity. These compounds are found naturally in certain foods like fruits, vegetables, whole grains, and legumes or can also be taken in supplemental form. Common prebiotic supplements available include inulin, fructooligosaccharides, resistant starch, and galactooligosaccharides. Probiotics are living beneficial microorganisms, usually yeast or bacteria, that are found in fermented foods, such as yogurt, sauerkraut, and kimchi. Incorporating more fermented foods into your diet or using oral probiotic supplements have both been found to support microbial composition and help manage inflammation.
Lifestyle Choices that Promote Gut and Brain Health
The gut-brain axis is shaped not only by our dietary choices but also by the lifestyle practices we engage in. Physical activity, stress management, and sleep all have a profound impact on both the gut and the brain, thereby influencing the intricate relationship between the two.
Physical Activity
Exercise habits influence the microbiome and gut inflammation. Over-exercising has a negative impact on the composition of the microbiome and increases intestinal permeability. On the other hand, regular, lower-intensity exercise exerts supportive effects, improving the microbiome composition and increasing SCFA production.
Exercise also directly influences brain health and neuroplasticity by stimulating the release of neurotrophic factors like BDNF, increasing blood flow, and improving glucose and lipid metabolism, which aids in delivering necessary fuel to the brain. Studies show it helps to support cognitive functions, such as memory and attention, and also helps to manage cognitive decline.
Stress Management
Stress negatively impacts the gut-brain axis through its effects on the nervous, endocrine, and immune systems. Under stress, the brain uses the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis to send signals to the gut. Research shows that stress changes intestinal permeability, intestinal motility, intestinal secretions, microbiome composition, and intestinal inflammation. (29) Psychological stress is also associated with decreased cognitive functioning, cognitive decline, depression, and anxiety.
Mind-body therapies stimulate the body’s relaxation response to counteract the negative neuroendocrine effects of stress. Some of these techniques include mindfulness, meditation, yoga, deep breathing, progressive muscle relaxation, and biofeedback. Mindfulness practices, for example, have been used to support cognitive function, help manage gastrointestinal symptoms, and improve mood.
Sleep
Sleep plays a vital role in supporting cognitive health through memory consolation, hormone balance, and detoxifying the brain. Sleep disruption changes microbiome composition as well as increasing inflammatory cytokines. These underlying mechanisms contribute to its association with decreased cognitive ability, depression, and anxiety.
Good sleep hygiene practices to implement to improve sleep quality include sticking to a consistent sleep schedule, getting exposure to natural light during the day, ensuring the room you sleep in is cool, dark, and quiet, limiting screen exposure in the evenings, and avoiding heavy meals and caffeine too close to bedtime.
[signup]
Why The Gut is The Second Brain: Key Takeaways
Recognizing the critical role of the gut-brain axis in cognitive health is essential. Microbiome composition and activity, intestinal permeability, and inflammation all significantly disrupt this axis. Functional medicine tests are invaluable in gaining insight into the function of the gut-brain axis, guiding individuals towards tailored diet and lifestyle choices. By embracing the gut-brain connection and proactively nurturing this connection, individuals are empowered to enhance their overall well-being.
The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
Learn More
No items found.
Lab Tests in This Article
Array 2
by
Cyrex Laboratories
Serum
The Array 2 Intestinal Antigenic Permeability Screen™ is an important initial screening test for patients with multiple chronic GI and neurologic symptoms, suspected food sensitivities, chemical intolerances, or a history of pathogen-induced autoimmune conditions. Array 2 differentiates transcellular versus paracellular intestinal permeability, epithelial barrier dysfunction in the form of actomyosin antibodies, and immune reactivity to lipopolysaccharides (LPS). These types of immune reactivity can lead to imbalances of the gut-brain axis and disruption of the blood-brain barrier.
Organic Acids (OAT)
by
Mosaic Diagnostics (formerly Great Plains)
Urine
The Organic Acids Test (OAT) provides a comprehensive metabolic analysis of a patient's overall health, including intestinal yeast and bacteria, vitamin and mineral levels, oxidative stress, neurotransmitter levels, and oxalates.
Array 20
by
Cyrex Laboratories
Serum
The Array 20 panel measures blood-brain barrier permeability and evaluates breaches of the blood-brain barrier by stress, trauma, or environmental triggers. It can help investigate contact sports-related traumatic brain injuries, as well as assess the risk of developing neurodegenerative disorders.
Anderson, S. (2022, May 3). 9 possible causes of persistent brain fog. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-brain-fog
Barisano, G., Montagne, A., Kisler, K., Schneider, J. A., Wardlaw, J. M., & Zlokovic, B. V. (2022). Blood–brain barrier link to human cognitive impairment and alzheimer’s disease. Nature Cardiovascular Research, 1(2), 108–115. https://doi.org/10.1038/s44161-021-00014-4
Beam, A., Clinger, E., & Hao, L. (2021). Effect of diet and dietary components on the composition of the gut microbiota. Nutrients, 13(8), 2795. https://doi.org/10.3390/nu13082795
Belkaid, Y., & Hand, T. W. (2014). Role of the microbiota in immunity and inflammation. Cell, 157(1), 121–141. https://doi.org/10.1016/j.cell.2014.03.011
Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018). Vagus nerve as modulator of the brain–gut axis in psychiatric and inflammatory disorders. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00044
Burk, J. A., Blumenthal, S. A., & Maness, E. B. (2018). Neuropharmacology of attention. European Journal of Pharmacology, 835, 162–168. https://doi.org/10.1016/j.ejphar.2018.08.008
Cloyd, J. (2023, May 4). A functional medicine SIBO protocol: Testing and treatment. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-sibo-protocol
Cloyd, J. (2023, August 15). A root cause medicine protocol for patients with generalized anxiety: Comprehensive lab testing, therapeutic diet, and supplements. Rupa Health. https://www.rupahealth.com/post/a-root-cause-medicine-protocol-for-patients-with-generalized-anxiety-comprehensive-lab-testing-therapeutic-diet-and-supplements
DeCesaris, L. (2022, August 30). 10 signs you should try an elimination diet. Rupa Health. https://www.rupahealth.com/post/how-to-do-an-elimination-diet
DeGruttola, A. K., Low, D., Mizoguchi, A., & Mizoguchi, E. (2016). Current understanding of dysbiosis in disease in human and animal models. Inflammatory Bowel Diseases, 22(5), 1137–1150. https://doi.org/10.1097/mib.0000000000000750
Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R., & Scaldaferri, F. (2023). Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review. Internal and Emergency Medicine. https://doi.org/10.1007/s11739-023-03374-w
Diorio, B. (2022, August 11). If you experience anxiety, GI discomfort, or irritability you may have a neurotransmitter imbalance. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-understanding-neurotransmitters-101
Dunn, G. A., Loftis, J. M., & Sullivan, E. L. (2020). Neuroinflammation in Psychiatric Disorders: An introductory primer. Pharmacology Biochemistry and Behavior, 196, 172981. https://doi.org/10.1016/j.pbb.2020.172981
Fleming, M. A., Ehsan, L., Moore, S. R., & Levin, D. E. (2020). The enteric nervous system and its emerging role as a therapeutic target. Gastroenterology Research and Practice, 2020, 1–13. https://doi.org/10.1155/2020/8024171
Greenan, S. (2021, November 17). The 8 most common signs of a food sensitivity. Rupa Health. https://www.rupahealth.com/post/a-functional-medicine-approach-to-food-sensitivities-testing-and-treatment
Hale, J. M., Schneider, D. C., Mehta, N. K., & Myrskylä, M. (2020). Cognitive impairment in the U.S.: Lifetime risk, age at onset, and years impaired. SSM - Population Health, 11, 100577. https://doi.org/10.1016/j.ssmph.2020.100577
Henry, K. (2023, February 21). An integrative medicine approach to Depression. Rupa Health. https://www.rupahealth.com/post/an-integrative-medicine-approach-to-depression
Huang, F., & Wu, X. (2021). Brain neurotransmitter modulation by gut microbiota in anxiety and depression. Frontiers in Cell and Developmental Biology, 9. https://doi.org/10.3389/fcell.2021.649103
Jandhyala, S. M. (2015). Role of the normal gut microbiota. World Journal of Gastroenterology, 21(29), 8787. https://doi.org/10.3748/wjg.v21.i29.8787
Kalmbach, D. A., Arnedt, J. T., Song, P. X., Guille, C., & Sen, S. (2017). Sleep disturbance and short sleep as risk factors for depression and perceived medical errors in first-year residents. Sleep, 40(3). https://doi.org/10.1093/sleep/zsw073
Kamiński, J., Mamelak, A. N., Birch, K., Mosher, C. P., Tagliati, M., & Rutishauser, U. (2018). Novelty-sensitive dopaminergic neurons in the human substantia nigra predict success of declarative memory formation. Current Biology, 28(9). https://doi.org/10.1016/j.cub.2018.03.024
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry, 62(6), 593. https://doi.org/10.1001/archpsyc.62.6.593
Khakham, C. (2023, October 9). Physical activity and sleep: The relationship on cognitive health in the geriatric population. Rupa Health. https://www.rupahealth.com/post/physical-activity-and-sleep-the-relationship-on-cognitive-health-in-the-geriatric-population
Konstantopoulou, G., Iliou, T., Karaivazoglou, K., Iconomou, G., Assimakopoulos, K., & Alexopoulos, P. (2020). Associations between (sub) clinical stress- and anxiety symptoms in mentally healthy individuals and in major depression: A cross-sectional clinical study. BMC Psychiatry, 20(1). https://doi.org/10.1186/s12888-020-02836-1
Kulshreshtha, A., Alonso, A., McClure, L. A., Hajjar, I., Manly, J. J., & Judd, S. (2023). Association of stress with cognitive function among older black and white us adults. JAMA Network Open, 6(3). https://doi.org/10.1001/jamanetworkopen.2023.1860
Lobionda, S., Sittipo, P., Kwon, H. Y., & Lee, Y. K. (2019). The role of gut microbiota in intestinal inflammation with respect to diet and extrinsic stressors. Microorganisms, 7(8), 271. https://doi.org/10.3390/microorganisms7080271
LoBisco, S. (2022, September 16). How food affects your mood through the gut-brain axis. Rupa Health. https://www.rupahealth.com/post/gut-brain-axis
Logsdon, A. F., Erickson, M. A., Rhea, E. M., Salameh, T. S., & Banks, W. A. (2017). Gut reactions: How the blood–brain barrier connects the microbiome and the brain. Experimental Biology and Medicine, 243(2), 159–165. https://doi.org/10.1177/1535370217743766
Madison, A., & Kiecolt-Glaser, J. K. (2019). Stress, depression, diet, and the gut microbiota: Human–bacteria interactions at the core of psychoneuroimmunology and Nutrition. Current Opinion in Behavioral Sciences, 28, 105–110. https://doi.org/10.1016/j.cobeha.2019.01.011
Maholy, N. (2023a, February 22). Improving gut health with exercise. Rupa Health. https://www.rupahealth.com/post/improving-gut-health-with-exercise
Maholy, N. (2023b, April 14). How to reduce stress through mind-body therapies. Rupa Health. https://www.rupahealth.com/post/how-to-reduce-stress-through-mind-body-therapies
Maholy, N. (2023c, June 29). The role of probiotics and prebiotics in Gut Health: An integrative perspective. Rupa Health. https://www.rupahealth.com/post/the-role-of-probiotics-and-prebiotics-in-gut-health-an-integrative-perspective
Maholy, N. (2023d, July 17). Top labs to run bi-annually on your patients experiencing sleep disorders. Rupa Health. https://www.rupahealth.com/post/top-labs-to-run-bi-annually-on-your-patients-experiencing-sleep-disorders
Mandolesi, L., Polverino, A., Montuori, S., Foti, F., Ferraioli, G., Sorrentino, P., & Sorrentino, G. (2018). Effects of physical exercise on cognitive functioning and wellbeing: Biological and psychological benefits. Frontiers in Psychology, 9. https://doi.org/10.3389/fpsyg.2018.00509
McWhirter, L., Smyth, H., Hoeritzauer, I., Couturier, A., Stone, J., & Carson, A. J. (2022). What is brain fog? Journal of Neurology, Neurosurgery & Psychiatry, 94(4), 321–325. https://doi.org/10.1136/jnnp-2022-329683
Mitrea, L., Nemeş, S.-A., Szabo, K., Teleky, B.-E., & Vodnar, D.-C. (2022). Guts imbalance imbalances the brain: A review of gut microbiota association with neurological and Psychiatric Disorders. Frontiers in Medicine, 9. https://doi.org/10.3389/fmed.2022.813204
Monda, V., Villano, I., Messina, A., Valenzano, A., Esposito, T., Moscatelli, F., Viggiano, A., Cibelli, G., Chieffi, S., Monda, M., & Messina, G. (2017). Exercise modifies the gut microbiota with positive health effects. Oxidative Medicine and Cellular Longevity, 2017, 1–8. https://doi.org/10.1155/2017/3831972
Morris, G., Fernandes, B. S., Puri, B. K., Walker, A. J., Carvalho, A. F., & Berk, M. (2018). Leaky brain in neurological and psychiatric disorders: Drivers and consequences. Australian & New Zealand Journal of Psychiatry, 52(10), 924–948. https://doi.org/10.1177/0004867418796955
Mou, Y., Du, Y., Zhou, L., Yue, J., Hu, X., Liu, Y., Chen, S., Lin, X., Zhang, G., Xiao, H., & Dong, B. (2022). Gut microbiota interact with the brain through systemic chronic inflammation: Implications on neuroinflammation, neurodegeneration, and aging. Frontiers in Immunology, 13. https://doi.org/10.3389/fimmu.2022.796288
Nagpal, R., Shively, C. A., Register, T. C., Craft, S., & Yadav, H. (2019). Gut microbiome-mediterranean diet interactions in improving host health. F1000Research, 8, 699. https://doi.org/10.12688/f1000research.18992.1
Naliboff, B. D., Smith, S. R., Serpa, J. G., Laird, K. T., Stains, J., Connolly, L. S., Labus, J. S., & Tillisch, K. (2020). Mindfulness‐based stress reduction improves irritable bowel syndrome (IBS) symptoms via specific aspects of mindfulness. Neurogastroenterology & Motility, 32(9). https://doi.org/10.1111/nmo.13828
Ohtsuka, Y. (2015). Food intolerance and mucosal inflammation. Pediatrics International, 57(1), 22–29. https://doi.org/10.1111/ped.12546
Ownby, R. L. (2010). Neuroinflammation and cognitive aging. Current Psychiatry Reports, 12(1), 39–45. https://doi.org/10.1007/s11920-009-0082-1
Rundek, T., Roy, S., Hornig, M., Cheung, Y. K., Gardener, H., DeRosa, J., Levin, B., Wright, C. B., Del Brutto, V. J., Elkind, M. SV., & Sacco, R. L. (2021). Gut permeability and cognitive decline: A pilot investigation in the northern Manhattan study. Brain, Behavior, & Immunity - Health, 12, 100214. https://doi.org/10.1016/j.bbih.2021.100214
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023). Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis. Frontiers in Endocrinology, 14. https://doi.org/10.3389/fendo.2023.1130689
Saffouri, G. B., Shields-Cutler, R. R., Chen, J., Yang, Y., Lekatz, H. R., Hale, V. L., Cho, J. M., Battaglioli, E. J., Bhattarai, Y., Thompson, K. J., Kalari, K. K., Behera, G., Berry, J. C., Peters, S. A., Patel, R., Schuetz, A. N., Faith, J. J., Camilleri, M., Sonnenburg, J. L., … Kashyap, P. C. (2019). Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-09964-7
Schreiner, I., & Malcolm, J. P. (2008). The benefits of mindfulness meditation: Changes in emotional states of depression, anxiety, and stress. Behaviour Change, 25(3), 156–168. https://doi.org/10.1375/bech.25.3.156
Scott, A. J., Webb, T. L., Martyn-St James, M., Rowse, G., & Weich, S. (2021). Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials. Sleep Medicine Reviews, 60, 101556. https://doi.org/10.1016/j.smrv.2021.101556
Scott, S. B., Graham-Engeland, J. E., Engeland, C. G., Smyth, J. M., Almeida, D. M., Katz, M. J., Lipton, R. B., Mogle, J. A., Munoz, E., Ram, N., & Sliwinski, M. J. (2015). The effects of stress on cognitive aging, physiology and emotion (ESCAPE) project. BMC Psychiatry, 15(1). https://doi.org/10.1186/s12888-015-0497-7
Sevinc, G., Rusche, J., Wong, B., Datta, T., Kaufman, R., Gutz, S. E., Schneider, M., Todorova, N., Gaser, C., Thomalla, G., Rentz, D., Dickerson, B. D., & Lazar, S. W. (2021). Mindfulness training improves cognition and strengthens intrinsic connectivity between the hippocampus and posteromedial cortex in healthy older adults. Frontiers in Aging Neuroscience, 13. https://doi.org/10.3389/fnagi.2021.702796
Shi, Z., Wu, X., Santos Rocha, C., Rolston, M., Garcia-Melchor, E., Huynh, M., Nguyen, M., Law, T., Haas, K. N., Yamada, D., Millar, N. L., Wan, Y.-J. Y., Dandekar, S., & Hwang, S. T. (2021). Short-term western diet intake promotes il-23‒mediated skin and joint inflammation accompanied by changes to the gut microbiota in mice. Journal of Investigative Dermatology, 141(7), 1780–1791. https://doi.org/10.1016/j.jid.2020.11.032
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020a). The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00025
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020b). The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00025
Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., Parikh, E., Lopez, J. V., & Tartar, J. L. (2019). Gut microbiome diversity is associated with sleep physiology in humans. PLOS ONE, 14(10). https://doi.org/10.1371/journal.pone.0222394
Stevens, B. R., Goel, R., Seungbum, K., Richards, E. M., Holbert, R. C., Pepine, C. J., & Raizada, M. K. (2017). Increased human intestinal barrier permeability plasma biomarkers zonulin and fabp2 correlated with plasma LPS and altered gut microbiome in anxiety or depression. Gut, 67(8). https://doi.org/10.1136/gutjnl-2017-314759
Sweetnich, J. (2023, February 22). How stress affects our gut health. Rupa Health. https://www.rupahealth.com/post/how-stress-affects-our-gut-health
Sweetnich, J. (2023, February 22). How stress affects our gut health. Rupa Health. https://www.rupahealth.com/post/how-stress-affects-our-gut-health
Tafet, G. E., & Nemeroff, C. B. (2016). The links between stress and depression: Psychoneuroendocrinological, genetic, and environmental interactions. The Journal of Neuropsychiatry and Clinical Neurosciences, 28(2), 77–88. https://doi.org/10.1176/appi.neuropsych.15030053
Ticinesi, A., Lauretani, F., Tana, C., Nouvenne, A., Ridolo, E., & Meschi, T. (2019). Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. PubMed, 25, 84–95. https://pubmed.ncbi.nlm.nih.gov/30753131
Vighi, G., Marcucci, F., Sensi, L., Di Cara, G., & Frati, F. (2008). Allergy and the gastrointestinal system. Clinical and Experimental Immunology, 153(Supplement_1), 3–6. https://doi.org/10.1111/j.1365-2249.2008.03713.x
Vita, A. A., Zwickey, H., & Bradley, R. (2022a). Associations between food-specific IGG antibodies and intestinal permeability biomarkers. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.962093
Wang, X., Zhang, P., & Zhang, X. (2021). Probiotics regulate gut microbiota: An effective method to improve immunity. Molecules, 26(19), 6076. https://doi.org/10.3390/molecules26196076
Wastyk, H. C., Fragiadakis, G. K., Perelman, D., Dahan, D., Merrill, B. D., Yu, F. B., Topf, M., Gonzalez, C. G., Van Treuren, W., Han, S., Robinson, J. L., Elias, J. E., Sonnenburg, E. D., Gardner, C. D., & Sonnenburg, J. L. (2021). Gut-microbiota-targeted diets modulate human immune status. Cell, 184(16). https://doi.org/10.1016/j.cell.2021.06.019
Weinberg, J. L. (2022, November 16). 4 science backed health benefits of the Mediterranean diet. Rupa Health. https://www.rupahealth.com/post/4-science-backed-health-benefits-of-the-mediterranean-diet
Weinberg, J. L. (2022, December 19). How short chain fatty acids affects our mood, digestion, and metabolism. Rupa Health. https://www.rupahealth.com/post/how-short-chain-fatty-acids-affects-our-mood-digestion-and-metabolism
Yang, Z., Zou, Y., & Wang, L. (2023). Neurotransmitters in prevention and treatment of alzheimer’s disease. International Journal of Molecular Sciences, 24(4), 3841. https://doi.org/10.3390/ijms24043841
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023). Role of neuroinflammation in neurodegeneration development. Signal Transduction and Targeted Therapy, 8(1). https://doi.org/10.1038/s41392-023-01486-5
Thanks for subscribing!
Oops! Something went wrong while submitting the form.
Thanks for subscribing!
Oops! Something went wrong while submitting the form.