How to Enhance Your Gut Microbiome for Brain & Overall Health

Gut-​​Brain Communication

• Gut and brain communicate bi-directionally
• Gut includes the entire digestive tract, not just the stomach
• Neurons and taste receptors are located all along the digestive tract
• Gut-​​brain axis includes the central nervous system (brain, spinal cord, and neural retinas)

Gut’s Influence on the Brain

• Gut communicates with the brain through neurons and neurochemicals (e.g., dopamine, serotonin)
• Neurons in the intestines can impact thoughts, feelings, and behaviors
• Gut microbiome (trillions of bacteria) affects metabolism, immune system, and brain function

Brain’s Influence on the Gut

• Brain impacts the entire digestive tract, including digestion speed and gut chemistry
• Stress, social challenges, and happiness can affect gut chemistry
• Gut chemistry, in turn, can change brain function

Tools for Gut Health

• Athletic Greens (AG One): all-​​in-​​one vitamin, mineral, probiotic, and prebiotic drink
• Element: electrolyte drink with sodium, magnesium, and potassium
• Inside Tracker: personalized nutrition platform analyzing blood and DNA data for health goals

Upcoming Guest Episode

• Dr. Justin Sonnenberg, a world expert in gut microbiome, will discuss gut microbiome complexity and actionable tools for gut health
  Gut-​​Brain Axis and the Nervous System

• Central nervous system: retinas, brain, and spinal cord

• Peripheral nervous system: components outside the central nervous system
• Gut communicates with the brain through peripheral nervous system components

Structure of the Gut

• Digestive system begins at the mouth and ends at the anus
• Series of sphincters separate chambers of the digestive tract
• Variation in acidity (pH) creates microenvironments for different microbiota
• Digestive tract is approximately 9 meters long

Microbiota and Microbiome

• Microbiota: actual bacteria
• Microbiome: bacteria and their genes
• Humans carry about 2–3 kg (over 6 pounds) of microbiota
• Microbiota reside along the entire digestive tract, within microvilli, and in niches
• Microbiota constantly turnover, being born and dying off

Influences on Microbiome

• Diet strongly influences microbiome
• Social interactions, environment, and contact with animals also impact microbiome
• Microbiota contribute to digestion and metabolism of neurotransmitters

Functions of Microbiota

• Produce enzymes for digestion and fermentation
• Change brain function by metabolizing or facilitating metabolism of neurotransmitters, such as GABA

• GABA is an inhibitory neurotransmitter, involved in suppressing the action of other neurons and reducing anxiety and epilepsy symptoms
  Gut-​​Brain Communication

• GABAergic neurons can be disrupted, leading to runaway excitation and seizures

• Microbiota in the gut can influence brain function, immune system function, and digestion
• Neurons are present throughout the body, including the gut
• Neuropod cells, discovered by Diego Bohórquez’s lab, are activated by sugar, fatty acids, and amino acids 
  • Particularly sensitive to sugars
  • Part of the sweet sensing system
• Neuropod cells communicate with the brain through the vagus nerve 
  • Nodo’s ganglion: cluster of neurons near the neck, connected to the gut and the brain
• Experiments show that humans and animals seek out sweet foods even if they can’t taste them 
  • Gut sensation plays a role in the desire for particular foods

• Neuropod cells adjust the release of neuromodulators like dopamine

  • Dopamine is associated with motivation, craving, and pursuit
  • Contributes to seeking out and consuming more of certain foods
    Gut-​​Brain Signaling

• Neuropod: neuron sensing of sweet foods, fatty acids, and amino acids in the gut

  • Communicates to the brain via the vagus nerve
  • Stimulates seeking out foods that deliver nutrients
• Hormone pathways in the gut also involve neurons 
  • Example: Ghrelin
    • Increases with fasting
    • Stimulates feeling of wanting to seek out food
    • Impacts neural circuits within the brain, including brain stem autonomic centers
• Fast and slow routes to drive eating behavior 
  • Fast route: nutrients in the gut stimulate seeking out food
  • Slow route: hormone-​​related system originating in the gut impacts the brain
  • Both routes operate in parallel
• Glucagon-​​like peptide‑1 (GLP‑1)
  • Made by neurons in the gut and brain
  • Inhibits feeding and reduces appetite
  • Can be stimulated by certain foods (e.g., nuts, avocados, eggs) and substances (e.g., Yerba Mate tea)
  • Impacts activity of neurons in the hypothalamus, which are involved in feeding behavior
• Gut is constantly communicating with the brain, influencing decisions and behaviors

Free Will and Gut-​​Brain Signaling

• Debate on whether free will exists or if decisions are determined by biological events below conscious detection
• Neurons and hormones in the gut influence brain decisions in areas below conscious perception (e.g., hypothalamus, nucleus of the solitary tract)

• The body may be shaping the decisions the brain makes without conscious awareness
  Gut-​​Brain Communication

• Chemical and mechanical signaling

  • Chemical: nutrients and neurotransmitters (e.g. dopamine)
  • Mechanical: distension of the gut or lack of distension
• Direct and indirect signaling 
  • Direct: neurons in the gut communicating with neurons in the brain stem, hypothalamus, and prefrontal cortex
  • Indirect: gut microbiota influencing metabolic events and synthesizing neurotransmitters themselves

Dopamine and Vomiting

• Dopamine involved in motivation, reward, and movement
• Area postrema (vomit center) in the brain stem is full of dopamine receptors
• High dopamine levels can trigger vomiting, as seen in Parkinson’s treatment drugs

Gut Microbiota and Neurotransmitters

• Gut microbiota can create neurochemicals that impact the brain indirectly

• Example: Bacillus and Seratia can synthesize dopamine, increasing baseline levels in the brain and body
  Gut Microbiome and Mood

• Gut microbiota can influence mood and well-being

• Certain gut microbiota support the production of dopamine and serotonin 
  • Elevated levels of dopamine and serotonin enhance mood
• Baseline levels of serotonin affect overall mood, while individual events influence serotonin levels in specific neural circuits
• 90–95% of serotonin is manufactured in the gut 
  • Gut microbiota can raise baseline levels of dopamine and serotonin
  • Neural circuits within the brain also release dopamine, serotonin, and GABA

Establishing a Healthy Gut Microbiome

• Exposure to diverse microbiota in the first three years of life is crucial for long-​​term outcomes 
  • Factors influencing gut microbiome diversity include: 
    • Method of delivery (C‑section vs. vaginal birth)
    • Breastfeeding vs. bottle feeding
    • Exposure to household pets
    • Number of caregivers
    • Premature birth and restrictive environments
• Antibiotic treatment in early life can be detrimental to establishing a healthy gut microbiome 
  • Doctors are more cautious about prescribing antibiotics to children and adults

Gut Microbiome and Brain Health

• Studies show that a healthy gut microbiome can enhance mood and well-being
• Research on mouse models of autism spectrum disorder found that certain microbiota can help offset symptoms of autism 
  • L. reuteri treatment corrects social deficits in autism models by activating the vagus nerve and stimulating dopamine and oxytocin release

• Fecal transplants have shown potential in treating colitis and certain psychiatric illnesses

  • Transplanting stool from healthy individuals to those with a condition can improve or rescue the condition
  • Examples include obesity and some rare metabolic disorders
    Fecal Transplants and Microbiota

• Fecal transplants from healthy weight individuals can lead to weight loss in recipients

  • Indicates the power of microbiota in bodily health
• Microbiota can create positive or negative outcomes depending on the donor
• Most people aim to create a healthy gut microbiome for immune system and brain function

Microbiota and Mental Health

• Studies show a correlation between diverse microbiomes and lower incidence of loneliness
• Emotional wellbeing and gut microbiome profiles can be linked 
  • Gut microbiome diversity generally considered a good thing
• Probiotics and prebiotics can improve mood, digestion, and immune system 
  • Mainly established in the context of post-​​antibiotic treatment or recovering from illness
• Excessive intake of probiotics can lead to brain fog and other issues

Improving Gut Microbiome

• Stress can negatively impact gut microbiome
• Fasting can negatively impact microbiome but may lead to compensatory proliferation of healthy gut microbiota after eating
• Fiber is important for feeding microbiome, but low-​​fiber diets can also improve certain microbiota species
• Probiotics can indirectly support the proliferation of good microbiota by changing the environment in the gut

Takeaways

• Fecal transplants show the power of microbiota in impacting health
• Microbiota diversity is linked to mental health and emotional wellbeing

• Balancing probiotics, prebiotics, and diet can help improve gut microbiome health
  Fasting, Diets, and the Microbiome

• Fasting and specific diets may not be inherently good or bad for the microbiome

• Certain foods can enhance the microbiome and make it healthier

Probiotics and Prebiotics

• Ingestion of probiotics can be useful for improving microbiota diversity
• Maintaining a healthy gut microbiome involves ingesting certain types of foods and possibly augmenting the microbiota system through prebiotics or probiotics
• High doses of prebiotics or probiotics may be useful under conditions of dysbiosis (e.g., after antibiotics) or when the system is stressed

Supporting Gut-​​Brain Axis Health

• Focus on foundational aspects of health, such as sleep, hydration, social interactions, nutrition, and stress management
• Ingesting fermented foods consistently over time can improve gut microbiome diversity and reduce inflammation

Fermented Foods Study

• Study by Sonnenberg Lab and Gardner Lab at Stanford
• Two groups: high fiber diet and high fermented food diet
• High fiber diet did not lead to increased microbiota diversity in all cases
• High fermented food diet resulted in increased microbiome diversity and decreased inflammatory signals and activity
• Duration of ingesting fermented foods was a stronger predictor of improvements than the number of servings

Low Sugar Fermented Foods

• Examples: plain yogurt, kimchi, sauerkraut, kefir, natto
• Must contain live active cultures for optimal benefits

• Avoid sugary versions of fermented foods
  Fermented Foods and Gut Microbiome

• Consuming fermented foods can improve gut microbiome, brain-​​body health, and reduce inflammation

• Examples of fermented foods: kefir, plain yogurt, sauerkraut, kombucha
• Spread fermented food intake throughout the day to limit gastric distress
• Brine, the liquid surrounding sauerkraut, contains active live cultures and may improve microbiota diversity

High Fiber Diet

• High fiber intake can increase the number of enzymes that digest fiber
• This can lead to less gastric distress and better utilization of fiber
• High fiber diet did not have the same positive effects on microbiota diversity as fermented foods

Homemade Fermented Foods

• Making fermented foods at home can be a low-​​cost way to improve gut microbiome
• Examples: homemade sauerkraut, kombucha
• Tim Ferriss’s book “The Four Hour Chef” has a recipe for homemade sauerkraut

Gut-​​Brain Health

• Inflammatory markers in the body can signal deleterious events in the brain
• Consuming fermented foods can have a positive effect on gut-​​brain function
• Animal data suggests that a hyperactivated immune system can lead to neural tissue damage

Fiber and Artificial Sweeteners

• Increasing fiber intake can enhance the capacity for the microbiome to degrade complex carbohydrates in fibrous foods

• Artificial sweeteners may have an impact on gut microbiome, but this has only been established in animal models (mouse) so far
  Effects of Artificial Sweeteners on Gut Microbiome

• Studies show disruptions in gut microbiome in animals consuming large amounts of artificial sweeteners (e.g., saccharine, sucralose)

  • No equivalent studies in humans yet
  • No data on plant-​​based low-​​calorie sweeteners (e.g., stevia, monk fruit) or aspartame
• Controversial topic: some argue that negative effects are only shown in animal models
• Individual choice to consume artificial sweeteners or not

Neurons in the Gut and Artificial Sweeteners

• Recent study (February 2022) shows that gut neurons (neuropod cells) can distinguish between real sugars and artificial sweeteners 
  • Different signaling patterns for real sugar vs. artificial sweeteners
• Unclear how this relates to humans, but likely that similar processes occur in human gut neurons

Gut-​​Brain Axis Overview

• Structure and function of the gut-​​brain axis
• Digestive pathway and gut microbiota
• Direct and indirect pathways of gut-​​brain communication
• Healthy vs. unhealthy microbiome
• Impact of fasting, stress, and antibiotics on gut microbiome
• Prebiotics and probiotics
• Fermented foods and homemade options