10/30: Gut & the Brain
Lesson recording
In this 30 minute video, Bridget Wright provides a lesson on the Gut and the Brain. She makes this very easy to understand!
The Brain-Gut Connection
Your gut and brain are in constant communication. If you’ve ever experienced a “gut feeling” you’ve experienced this communication. It’s the feeling of “butterflies” in your stomach or that “gut wrenching” experience. The gastrointestinal tract is sensitive to emotions - anger, anxiety, sadness, elation - all these feelings can trigger symptoms in the gut. And these feelings in your gut can influence decision-making (e.g., “going with your gut feeling”)
In this lesson we will define some terms like the gut, microbiome, microbiota and the brain-gut axis. Then, we will learn about probiotics, fermented foods and prebiotics and their impact on health and brain health. And finally, we will define and discuss the keto diet and the recent research findings on neurodegenerative conditions and health in general.
What is the Gut in the Body?
The gut refers to your gastrointestinal (GI) system. The GI tract is a series of hollow organs joined in a long, twisting tube from the mouth to the anus. The hollow organs that make up the GI tract are the mouth, esophagus, stomach, small intestine, large intestine, and anus. The solid organs include the liver, pancreas, and gallbladder.
What is the Gut Microbiome? What is Microbiota?
The gut microbiome is:
● A collective name that includes the gut microbiota, the genes they express, proteins, chemical messengers (pro- or anti-inflammatory) as well as vitamins, acids, and gasses produced by the microbiota.
● In humans, the term is often used to describe the microorganisms that live in or on a particular part of the body, such as the skin or gastrointestinal tract.
● Alterations in the microbiome have been observed in many health conditions and may be implication in some disease pathology (including conditions related to the brain)
Microbiota:
● The bacteria, yeast and viruses present in the gut, which produces everything that make up the gut microbiome.
● Your body contains 38 trillions of microbes that make up your microbiota and assist in keeping you healthy.
● These groups of microorganisms are dynamic and change in response to a host of environmental factors, such as exercise, diet, medication, and other exposures.
● Bacteria that live in your gut help in the digestion of food.
● Each person has an entirely unique network of microbiota that is originally determined by one’s DNA.
How Does our Microbiota Benefit the Body?
Microbiota helps with
● digestion – specifically, they digest prebiotic fiber to produce short chain fatty acids, which are important for gut health.
● stimulating the immune system
● synthesizing certain vitamins and amino acids, including the B vitamins and vitamin K. For example, the key enzymes needed to form vitamin B12 are only found in bacteria, not in plants and animals.
● brain health – new research suggests that the gut microbiome may affect the central nervous system, which controls brain function.
In a bit, we are going to talk about foods that can affect and support the microbiota for a healthy gut, including probiotics, fermented foods and prebiotics. But first let’s take a closer look at that brain-gut connection.
Video: How the body uses the bacteria within our body to influence behavior and health. Great introduction to the topic.
Gut-Brain Axis: How is the Gut Connected to the Brain?
The gut-brain axis (GBA) consists of bidirectional communication between the central nervous system (brain and spinal cord) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions (Carabotti, et al, 2015).
The ENS is one of the main divisions of the autonomic nervous system and consists of a mesh-like system of neurons that controls the function of the gastrointestinal tract. The autonomic nervous system also includes the parasympathetic nervous system and sympathetic nervous system that regulates involuntary physiologic processes including heart rate, blood pressure, respiration, digestion, and sexual arousal.
The vagus nerve (of the parasympathetic nervous system) - connects the gut and brain through the gut-brain axis. It communicates information from the gut to the brain using neurotransmitters such as serotonin and dopamine.
● About 90% of serotonin is produced in the gut (Appleton, 2018)
● About 50% of dopamine is produced in the gut (Eisenhofer et al., 1997)
Last week we learned how certain foods containing tryptophan and tyrosine play a role in serotonin and dopamine production respectively. Dopamine and serotonin are neurotransmitters that send signals throughout the body; these neurotransmitters affect how we feel. When dopamine is released in our brain, we feel a sense of temporary pleasure. Serotonin creates a long-lasting feeling of happiness or well-being. Both neurotransmitters act as hormones that help coordinate different functions and processes in our bodies like growth, metabolism, emotions and sleep.
Many recent studies have implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease (Cyan et al., 2019). The National Institute on Aging (NIA) of the National Institutes of Health is dedicated to investigating how the gut microbiome may be associated with disease, including Alzheimer’s disease and other neurodegenerative diseases. As we age, the bacteria living in our gut changes as well. The microbiota tends to become less diverse, meaning there are fewer types of bacteria. This loss of diversity could make room for opportunistic bacteria to move in, and these bacteria are often associated with illness. Researchers are exploring whether age-related changes in the gut microbiome can be reversed to slow or prevent the effects of neurodegenerative disease. To learn about the role of the gut microbiome in the different stages of Alzheimer’s, NIA is funding the Alzheimer’s Gut Microbiome Project.
Feeding the Gut
You need three types of substances to feed your gut:
Probiotics
Fermented foods
Prebiotics
Video: Watch how the food we eat affects our guts. Good introduction to the following sections. And a plug for fiber!
Probiotics
Probiotics
The International Scientific Association for Probiotics and Prebiotics defines “probiotics” as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. These microorganisms, which consist mainly of bacteria but also include yeasts, are naturally present in some fermented foods, may be added to other food products, and are available as dietary supplements. However, not all foods and dietary supplements labeled as “probiotics” have proven health benefits.
Probiotic foods may contain a variety of microorganisms. The most common are bacteria that belong to groups called Lactobacillus, Bifidobacterium and Streptococcus thermophilus (yogurt cultures). Probiotics may have a variety of effects in the body, and different probiotics may act in different ways.
Research has shown that probiotics can support health in a variety of different ways. In general, they may assist with your immune function, aid your digestion, keep harmful microorganisms in check, produce vitamins, and aid in nutrient absorption. Specifically, there’s evidence that certain probiotics can:
● Reduce antibiotic-associated diarrhea
● Treat infectious pediatric diarrhea
● Improve some digestive symptoms, including those caused by mild to moderate irritable bowel syndrome
● Help manage symptoms associated with poor digestion of lactose
● Reduce colic symptoms in infants
● Decrease some common infections, including those of the respiratory tract, gut, and vaginal tract
Probiotic foods include yogurt and some kefir (check the nutrition label for ingredients)
Fermented Foods
Fermented foods (McFarland et. al., 2021, van der Schoot et al., 2022; Dimidi et. al., 2020; Poras-Garcia et al., 2023)
Fermented foods are made through the growth and metabolic activity of a variety of live microbial cultures (microbes). Many of these foods are rich sources of live and potentially beneficial microbes but we don’t know how much and if they confer a health benefit to be classified as a probiotic food (more research needed). Therefore, some fermented foods like yogurt are also probiotic foods, but not all fermented foods can be classified that way. Some fermented foods, such as sourdough bread, chocolate, and most commercial pickles, are processed after they are fermented and do not contain live cultures in the form in which they are consumed.
Fermented foods that contain live cultures but do not typically contain proven probiotic microorganisms include many cheeses, kimchi (a Korean fermented napa cabbage dish), kombucha (a fermented tea), sauerkraut (fermented cabbage), miso (a fermented soybean-based paste), picked foods (onions, carrots, mango etc.), and raw unfiltered apple cider vinegar made from fermented apple sugars.
Health benefits: The consumption of fermented foods helps to introduce a variety of beneficial bacterial strains which helps to create diverse gut microbiome. A diverse gut microbiome is associated with better digestive function, and protection against gastrointestinal conditions. Specifically, diversity has been linked to reduced inflammation, and specific strains of probiotics can help reduce the risk of conditions such as irritable bowel syndrome (IBS) and constipation. Fermented foods may also play a role in supporting our immune system. It is theorized that fermented foods produce tryptophan—a building block for serotonin. And a recent review published in June 2023 found that daily consumption of fermented foods has neuroprotective effects and slowed cognitive decline in older adults.
Possible side effects:
Although fermented foods can be healthy in introducing beneficial bacteria which may decrease inflammation and alleviate gut problems, as well as benefit brain health through increased production of serotonin, there can be effects from too much fermented foods. They include:
Gas and bloating: Fermented foods, which have live microorganisms (microbes), can cause gas and bloating. Microbes produce gas when fed prebiotics (coming up in the next section). Some fermented foods such as kimchi and sauerkraut contain both the microbes and the prebiotic fibers that feed their growth, resulting in a little extra gas and bloating.
Histamine intolerance: Some people may find that consuming fermented foods, specifically aged or matured foods, can be higher in histamine. This is a compound that can cause inflammation or an allergic reaction.
Increase in salt consumption: Many fermented foods are high in salt to preserve the food or to promote the growth of the bacteria.
Prebiotics
Prebiotics
Prebiotics are found in foods (typically high-fiber foods) and act as food for gut microbiota. Prebiotics are used with the intention of improving the balance of these microorganisms and therefore play a key role in optimal digestive system health.
Prebiotics are found in many fruits and vegetables, especially those that contain complex carbohydrates, such as fiber and resistant starch.
Here are some prebiotics and their food source:
• Galactooligosaccharides: dairy products, beans, and certain root vegetables
• Fructooligosaccharides: onion, chicory, garlic, asparagus, banana, artichoke
• Oligofructose: wheat, onion, chicory, bananas, garlic
• Inulin: Asparagus, Bananas, Burdock, chicory, Dandelion root, Garlic, Jerusalem artichokes, Leeks, Onions
• Chicory: endive, radicchio, escarole, frisée, chicory root
Resistant Starch: Resistant starch is a carbohydrate that resist digestion in the small intestine and ferments in the large intestine. As the fibers ferment they act as a prebiotic and feed the good bacteria in the gut. There are several types of resistant starch. They are classified by their structure or source. More than one type of resistant starch can be present in a single food.
When starches are digested, they typically break down into glucose. Because resistant starch is not digested in the small intestine, it doesn’t raise glucose. Gut health is improved as fermentation in the large intestine makes more good bacteria and less bad bacteria in the gut. Healthy gut bacteria can improve glycemic control. Other benefits of resistant starch include increased feeling of fullness, treatment and prevention of constipation, decrease in cholesterol, and lower risk of colon cancer. Resistant starch is fermented slowly so it causes less gas than other fibers.
Foods that contain resistant starch include:
■ Plantains and green bananas (as a banana ripens the starch changes to a regular starch)
■ Beans, peas, and lentils (white beans and lentils are the highest in resistant starch)
■ Whole grains including oats and barley
■ Cooked and cooled rice
The amount of resistant starch changes with heat. Oats, green bananas, and plantains lose some of their resistant starch when cooked. Another type of resistant starch is made in the cooking and cooling process. For example, cooked rice that has been cooled is higher in resistant starch than rice that was cooked and not cooled.
Health benefits of resistant starch https://www.sciencedirect.com/science/article/abs/pii/S0924224421006385
Probiotic Supplements and Brain Health
(Office of Dietary Supplements of the National Institutes of Health, updated June 2, 2022)
There is a growing body of evidence from animal studies supporting the potential role of probiotics and prebiotics in reducing the risk of neurodegenerative diseases. Recent evidence from human studies suggests that there is an association between microbiota and cognitive functioning, which we’ve learned to be the microbiome-gut-brain axis. Probiotic bacteria consumption can alter human microbiota; therefore, probiotic supplementation may affect the gut microbiota dynamics and influence cognitive function.
There are quite a few rigorous studies on probiotic supplementation in human trials however, the sample sizes are small and the number of strains tested is limited. According to one meta-analysis of randomized control trials, probiotic supplementation had a highly significant effect on cognitive function in people with cognitive impairment or Alzheimer's disease (AD). The researchers found that for people without cognitive impairment, probiotic supplementation may be ineffective (Lui et. al., 2023). In meta-analysis and systematic literature review, the findings suggested that dietary supplementation with probiotics improves cognitive function, especially in people with mild cognitive impairment (MCI) (Zhu et. al, 2021). Another review found that most studies involving AD, MCI, or healthy older adults showed cognitive improvement in subjects treated with probiotics for 12-24 weeks (Handajani et. al., 2023). While the research is promising, more research is needed with larger sample sizes and testing the wide variety of probiotic strains.
Probiotics available as dietary supplements (in capsules, powders, liquids, and other forms) contain a wide variety of strains and doses. These products often contain mixed cultures of live microorganisms rather than single strains. The effects of many commercial products containing “probiotics” have not been examined in research studies.
Current labeling regulations only require manufacturers to list the total weight of the microorganisms on probiotic products’ Supplement Facts labels; this cellular mass can consist of both live and dead microorganisms and, therefore, has no relationship with the number of viable microorganisms in the product. Probiotics must be consumed alive to have health benefits and they can die during their shelf life; therefore, consumers should look for products labeled with the number of CFU at the end of the product’s shelf life, not at the time of manufacture.
Disclaimer: If you’re considering a probiotic dietary supplement, consult your health care provider first. This is especially important if you have chronic health conditions. Anyone with a serious underlying health condition should be monitored closely while taking probiotics.
The Gut Microbiota and Ketogenic Diets
(Zhu et al., 2022)
What is the Keto Diet?
The ketogenic (or keto) diet is a rapidly growing dietary trend for weight loss and was initially designed in the United States in the 1920s for treatment of a condition called refractory epilepsy. The ketogenic (keto) diet changes the way your body uses food. Typically, carbohydrates in your diet provide most of the fuel your body needs. The keto diet reduces the number of carbs you eat and teaches your body to burn fat for fuel instead. According to the Institute of Medicine of the National Academies, the Acceptable Macronutrient Distribution Range for carbohydrates is 45-65%, for fat is 20-35%, and for protein is 10-35% of the energy intake for adults. A ketogenic diet primarily consists of high fat intake, moderate protein consumption, and low carbohydrate intake. The macronutrient distribution typically ranges from approximately 55% to 60% fat, 30% to 35% protein, and 5% to 10% carbohydrates. Many nutrient-dense foods also contain carbohydrates. This includes plant-based proteins (lentils, beans), whole grains, fruits and vegetables which also contain prebiotics for gut health. Carbs from all sources are restricted on the keto diet. When your carb intake is very low, glucose stores are minimal. Since your body and brain still require energy, it looks for another source and starts to burn fat instead. As your body breaks down fat, it produces a compound called ketones. The ketones, or ketone bodies, become your body and brain’s main source of energy.
Can the Keto Diet be Neuroprotective?
Results from a 2020 systematic review of 10 randomized controlled trials indicated that among adults with mild cognitive impairment and/or Alzheimer disease, adherence to an acute or long-term (45-180 days) ketogenic therapy (ketogenic diet, medium chain triglyceride-based, or ketogenic formulas/meals) improved both acute and long-term cognition (Grammatikopoulou et al., 2020). In Alzheimer disease, a ketogenic diet regulates brain metabolism, mitochondrial homeostasis, and inflammation by increasing mitochondrial function and reducing oxidative stress. (Masood et al., 2023)
Nutritional ketosis has promise for treating Parkinson’s disease. However, only three studies explored the use of a ketogenic diet in cohorts with Parkinson’s disease, and, while not conclusive, the data suggest non-motor symptom benefit (Choi et al., 2021). A pilot randomized controlled trial compared the effect of a low-fat diet versus the ketogenic diet in Parkinson's disease. The study had 47 patients, and both groups showed a decrease in the Movement Disorder Society Unified Parkinson Disease Rating Scale. However, the group on the ketogenic diet showed a more significant reduction than the low-fat diet group. Also, the ketogenic group showed more significant improvements in nonmotor symptoms. (Phillips et al., 2018)
Studies of a ketogenic diet in neurometabolic degenerative disorders including Alzheimer’s disease and Parkinson’s Disease consistently demonstrated improved learning and memory. Further rigorous studies with quantitative measures is needed to confirm preliminary supportive evidence for benefits on mood, mobility, and specifically in Parkinson’s Disease of executive and processing speed, pain, tremor, rigidity, and urinary frequency (Choi et al., 2021). The good news is that the body of research in this area is growing.
Keto and Issues of Concern in the long term (Masood et al., 2023, Attaye et. al., 2022)
The ketogenic diet's short-term effects (up to 2 years) are well-reported and established. However, the long-term health implications are unknown due to limited literature. Long-term adverse effects include hepatic steatosis (or fatty liver disease, extra fat deposited in the liver), hypoproteinemia (low protein in the blood), hypocitraturia (less urinary citrate excretion), hypercalciuria (excess calcium in the urine), kidney stones, and vitamin and mineral deficiencies. A ketogenic diet affects the gut microbiota which in turn affects other aspects of health. Specifically, the ketogenic diet has been shown to influence multiple domains of metabolic health, such as obesity, insulin resistance, and dyslipidemia; however, other health issues may result from long term use of this dietary pattern.
● Nutrient deficiencies: Keto diets are very restrictive and can lead to inadequate intake of essential vitamins, minerals, and phytochemicals.
● Digestive issues: High-fat, low-fiber diets can cause digestive problems, such as constipation, diarrhea, and bloating.
● Liver problems. With so much fat to metabolize, the diet could make any existing liver conditions worse.
● Kidney stones: A high-fat, low-carbohydrate diet can increase the risk of developing kidney stones.
● Heart disease: A ketogenic diet can increase the risk of heart disease due to its high saturated fat content and lack of fiber.
● Muscle loss: Rapid weight loss on a ketogenic diet can lead to muscle loss
● Constipation. The keto diet is low in fibrous foods like grains and legumes.
● Fuzzy thinking and mood swings
● Cognitive decline: The effects of low-carbohydrate diets on brain metabolism can potentially lead to cognitive decline.
Bottom line: If you are considering the keto diet, please consult with your primary care physician. The research findings are not conclusive, and one must consider the keto diet’s effect on the gut microbiome that could result in health implications at the individual level.
Summary
Your gut microbiome is made up of trillions of microbiotas: bacteria, fungi and other microbes. The gut microbiome plays a very important role in your health by helping control digestion, and benefiting your immune system and can also affect brain health. The communication system between your gut and brain is called the gut-brain axis and consists of bidirectional communication via the vagus nerve between the central nervous system (brain and spinal cord) and the enteric nervous system. Short chain fatty acids (SCFAs) are produced by the gut microbiota in the colon. SCFAs may have different beneficial effects on anti-inflammatory pathways, energy metabolism, including glucose, lipid, and cholesterol metabolism. To help support your microbiome and microbiota, you can eat a variety of probiotic foods, fermented foods and prebiotics found in foods with fiber (fruits and vegetables), whole grains and resistant starch.
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