447 – Gut Health & Mental Health: The Impact of the Second Brain
Dr. Dawn-Elise Snipes PhD, LPC-MHSP, Executive Director: AllCEUs.com
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Disclaimer
~ This is for educational purposes only and not intended to replace medical advice. Always have clients discuss any nutritional changes or supplements with a Registered Dietician or their primary care physician.
Objectives
~ BREIFLY review the findings from the research identifying the connection between the brain and the gut
~ Differentiate gut health from proper nutrition
~ Identify signs and consequences of poor gut health
~ Explore the bidirectional relationship between the brain and the gut (second brain)
~ Identify promising alternative approaches to treating mood (and other) disorders.
Overview
~ Depression is the leading cause of disability in the world according to the World Health Organization. The effectiveness of the available antidepressant therapies is limited.
~ Data from the literature suggest that some subtypes of depression may be associated with chronic low grade inflammation.
~ The uncovering of the role of intestinal microbiota in the development of the immune system and its bidirectional communication with the brain have led to growing interest on reciprocal interactions between inflammation, microbiota and depression.
~ The intestinal microbiota: A new player in depression? Encephale. 2018 Feb;44(1):67-74
Overview
~ Gut microbiota appear to influence the development of emotional behavior, stress- and pain-modulation systems, and brain neurotransmitter systems
~ Microbiota changes caused by illness, dietary changes, probiotics and antibiotics impact endocrine and neurocrine pathways (bottom up)
~ The brain can in turn alter microbial composition and behavior via the autonomic nervous system (âstressâ) (top down)
~ Even mild stress can change the microbial balance in the gut, making the host more vulnerable to infectious disease and triggering a cascade of molecular reactions that feed back to the central nervous system
Overview
~ Exposure to chronic stress decreased the relative abundance of Bacteroides species and increased the Clostridium species in the caecum; and caused activation of the immune system (i.e. inflammation)
~ Children with Autism Spectrum Disorder treated with oral vancomycin âantibiotic to reduce Colostridiumâ had significant improvement in behavioral, cognitive and GI symptoms
~ Acute and chronic stress increase GI and BBB permeability through activation of mast cells (MCs)
Gut Inflammation and Mood
~ Inflammation of the GI Tract places stress on the microbiome through the release of cytokines and neurotransmitters.
~ Coupled with the increase in intestinal permeability, these molecules then travel systemically.
~ Elevated blood levels of cytokines TNF-a and MCP (monocyte chemoattractant protein) increase the permeability of the blood-brain barrier, enhancing the effects of rogue molecules from the permeable gut.
~ Their release influences brain function, leading to anxiety, depression, and memory loss.
Gut-Brain Connection
~ The vagus nerve is one of the biggest nerves connecting your gut and brain. It sends signals in both directions
~ In mice it was found that feeding them a probiotic reduced the amount of cortisol in their blood. However, when their vagus nerve was cut, the probiotic had no effect
~ Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5
Overview
~ Alterations in the gut microbial community have been implicated in multiple host diseases such as obesity, diabetes, and inflammation, while recent evidence suggests a potential role of the microbiota-gut-brain axis in neuropsychiatric disorders, such as depression and anxiety.
~ Research has found that tweaking the balance of gut bacteria can alter animalâs brain chemistry and lead it to become either more bold, anxious or depressed.
Overview
~ A healthy gut absorbs nutrients sufficiently to support brain health.
~ A healthy gut prevents bacteria and inflammation causing agents to âleakâ into the bloodstream
~ A healthy gut can adequately produce neurotransmitters
~ Gut bacteria manufacture about 95 percent of the body's supply of serotonin
Gut and Neurotransmitters
~ Lactobacillus and Bifidobacterium synthesize gamma-aminobutyric acid (GABA) from monosodium glutamate
~ E. coli, Bacillus and Saccharomyces produce norepinephrine
~ Candida, Streptococcus, Escherichia and Enterococcus produce serotonin
~ Bacillus and Serratia produce dopamine.
Gut and Neurotransmitters
~ Mucosal 5-HT (serotonin precursor) plays a direct role in the regulation of intestinal permeability
~ Norepinephrine (NE), epinephrine (E), dopamine (DA), and serotonin are able to regulate and control not only blood flow, but also affect gut motility, nutrient absorption, gastrointestinal innate immune system, and the microbiome
What is Leaky Gut
~ Leaky gut is when the cells lining your gut arenât stuck together as tightly as they could be, allowing proteins, viruses, bacteria, and more to leak out of the gastrointestinal tract and into the bloodstream.
~ âLeaky gut' syndrome, is often described as an increase in the permeability of the intestinal mucosa, which could allow bacteria, toxic digestive metabolites, bacterial toxins, and small molecules to âleak' into the bloodstream.
Leaky Gut
~ Lipopolysaccharide (LPS) is an inflammatory toxin made by certain bacteria.
~ TNF-alpha is an inflammatory cytokinine also made in the gut, which has been linked with depression and a reduction in serotonin production Inflammation and high LPS in the blood have been associated with a number of brain disorders including severe depression, dementia and schizophrenia
~ These molecules increase inflammation and which trigger the HPA-Axis
~ The HPA-Axis releases cortisol and suppresses serotonin and sex hormones.
Leaky Gut
~ When inflammatory agents âleakâ into the bloodstream it also increases the permeability of the Blood-Brain-Barrier letting potential inflammatory molecules into the brain.
~ Inflammation is associated with major depressive disorder (MDD) and suicidal behavior.
~ Those with MDD and a recent suicide attempt had higher levels of gut permeability markers. Leaky gut biomarkers in depression and suicidal behavior. Acta Psychiatr Scand. 2018 Oct 22
Gut-Brain Connection
Interventions
~ âPsychobioticsâ, which are live organisms, when ingested may produce health benefits in patients suffering from mood disorders
~ In a study of 124 healthy volunteers (mean age 61.8 years), those who consumed a mix of specific psychobiotics (Lactobacillus helveticus and bifidobacterium longum) exhibited less anxiety and depression
~ Children with ADHD were substantially improved on either an AFC-free diet, or by dietary supplementations with polyunsaturated fatty acids (PUFA), iron and zinc
Interventions
~ Nutrition activates hormonal, neurotransmitter and signaling pathways in the gut which modulate brain functions like appetite, sleep, energy intake, reward mechanisms, cognitive function and mood.
~ In a study of older adults it was found that healthy nutrition can reduce the incidence of depression from 40-50%
~ Healthy foods such as olive oil, fish, fruits, vegetables, nuts, legumes, poultry, dairy and unprocessed meat (no nitrates or nitrites, hormone and steroid free) have been inversely associated with depression risk
Interventions
~ Magnesium, calcium, iron and zinc are inversely associated with depression
~ Chromium leads to a secondary synthesis of serotonin, norepinephrine and melatonin and have been associated with reductions in depression
~ Vitamin C was also found to have an equivalent effect as amitriptyline (antidepressant)
~ Folate, B12 and B6 combine to enhance cognitive performance and reduces the risk of depression
~ Vitamin D is also associated with reduced depression
~ Calcium and copper
Interventions
~ Several medications (metformin, gram-negative antibiotics), showed a certain potential to treat depression
~ Lactobacillus acidophilus induced the expression of the cannabinoid 2 and Îź-opioid 1 receptors in the colonic epithelium
~ Lactobacillus farciminis inhibited stress-induced visceral hypersensitivity
~ Ingestion of Lactobacillus casei Shirota, Lactobacillus and B. Longum reduced anxiety and depressive symptoms and cortisol levels
~ Prebiotics result in lower cortisol levels and improved attention to positive stimuli (lactose, fiber)
Interventions
~ Lactobacillus helveticus is a type of lactic acid bacteria thatâs naturally found in the gut. Itâs also found naturally in certain foods, like:
~ Italian and Swiss cheeses (e.g., Parmesan, cheddar, and Gruyère)
~ Milk, kefir, and buttermilk
~ Fermented foods (e.g., Kombucha, Kimchi, pickles, olives, and sauerkraut)
Interventions
~ Elevated hypothalamic-pituitary-adrenal (HPA) axis response and depression in GF rats can be reversed by administering a single bacterium, Bifidobacterium infantis
Interventions
~ Increase Bifidobacteria
~ Take probiotics esp. Lactobacillus and Bifidobacteria
~ Eat high-fiber foods such as apples, artichokes, blueberries, almonds and pistachios to feed the good bacteria
~ Eat prebiotic foods (carbs that help healthy bacteria grow). Onions, garlic, bananas and chickory root
~ Eat polyphenols from foods such as cocoa, green tea and red wine
~ Eat whole grains such as oats and barley
~ Eat fermented foods such as yogurt and kimchi
~ Exercise
Summary
~ How does anxiety or depression perpetuate itself via the gut-brain axis?
~ How do gut disorders like IBS or Chronâs impact mood?
~ How do autoimmune disorders contribute to depression and anxiety?
~ How does HPA-Axis dysregulation contribute to leaky gut?
Insulin Resistance
~ Insulin resistance is when cells in your muscles, fat, and liver donât respond well to insulin and canât easily take up glucose from your blood.
~ This can eventually lead to higher than normal blood glucose levels or âprediabetesâ
~ obesity, especially too much fat in the abdomen and around the organs, called visceral fat, is a main cause of insulin resistance
~ belly fat makes hormones and other substances that can contribute to chronic, or long-lasting, inflammation in the body.
~ Risk factors
~ Obesity
~ Sedentary lifestyle
~ Sleep issues
~ Neuroimmune imbalances have been found as potential biomarkers of stress, anxiety, depression, systemic inflammation and leaky gut, which may result in the imbalance between regulatory and proinflammatory T cells
~ Methods Mol Biol. 2018;1781:77-85. Neuroimmune Imbalances and Yin-Yang Dynamics in Stress, Anxiety, and Depression
~ Chapter Fifteen â The Importance of Diet and Gut Health to the Treatment and Prevention of Mental Disorders International Review of Neurobiology Volume 131, 2016, Pages 325-346
~ Perturbations of the gut microbial community have already been implicated in multiple host diseases such as obesity, diabetes, and inflammation, while recent evidence suggests a potential role of the microbiota-gut-brain axis in neuropsychiatric disorders, such as depression and anxiety. Microbes and mental health: A review. Brain Behav Immun. 2017 Nov;66:9-17
~ Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the âleaky gut hypothesis', increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes. gut Those with MDD and a recent suicide attempt had higher levels of gut permeability markers. Leaky gut biomarkers in depression and suicidal behavior. Acta Psychiatr Scand. 2018 Oct 22
~ âVarious afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, essential metabolites, all convey information about the intestinal state to the CNS. Conversely, the HPA axis, the CNS regulatory areas of satiety and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions appear to influence the pathogenesis of a number of disorders in which inflammation is implicated such as mood disorder, autism-spectrum disorders (ASDs), attention-deficit hypersensitivity disorder (ADHD), multiple sclerosis (MS) and obesity.
~ Neuro/immune-active substances derived from the intestinal lumen can penetrate the gut mucosa, be transported by blood, cross the blood-brain-barrier (BBB) and affect the CNS
~ Gut microbiota can influence CNS function through their ability to synthesize or mimic a range of host-signaling neuroactive molecules s, such as acetylcholine (Ach) gamma-aminobutyric acid (GABA), histamine, melatonin and 5-hydroxytryptamine (5-HT, serotonin)16.
~ âPsychobioticsâ, which are live organisms, when ingested may produce health benefits in patients suffering from mood disorders. In a study of 124 healthy volunteers (mean age 61.8 years), those who consumed a mix of specific psychobiotics (Lactobacillus helveticus and bifidobacterium longum) exhibited less anxiety and depression
~ Children with ADHD were substantially improved on either an AFC-free diet67, or by dietary supplementations with polyunsaturated fatty acids (PUFA), iron and zinc68
~ Recent studies revealed new mediators of both energy homeostasis and mood changes (i.e. IGF-1, NPY, BDNF, ghrelin,leptin, CCK, GLP-1, AGE, glucose metabolism and microbiota)
~ CCK
~ is a gut hormone that is released in the small intestine when fats and proteins are eaten.
~ One of the most powerful panic inducers
~ Ghrelin
~ Increased by the consumption of carbohydrates
~ Regulates CNS development
~ Exerts an antidepressant effect
~ Displays dopaminergic properties
~ Leptin
~ Triggered by a high concentration fructose diet
~ Highly associated with depressive symptoms, sleep disturbances and decreases in feeding-stimulated dopamine release
~ Triggers increased food intake
~ Seems to regulate response to psychiatric medications
~ Intranasal IGF (Insulin growth factor-1) administration has been shown to have comparable effects to SSRIs
~ Insulin resistance has been linked to PI3K signaling which is central in the development of depressive symptoms
~ The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Diet rapidly and reproducibly alters the human gut microbiome Nature volume505, pages559â563 (23 January 2014)