How Our Microbiome Influences Our Mental Health

How Our Microbiome Influences Our Brain Development, Sense of Well-Being, Mood, Cognition, Stress Tolerance, Social Engagement, Aging Process & Conditions Such as ADHD, Autism & Alzheimer's.

Our gut microbiome is a thriving ecosystem consisting of trillions of microbes (bacteria, viruses, archaea, and fungi) belonging to thousands of species, many of which were here before we were.

Despite the emergence of research into the microbiome in the last twenty years, our ancestors recognized the link between digestion and emotions, mood, and behavior. Fecal transplants date back to Ancient Greece and 4th century China.

The gut-brain axis was already a thing by the 18th century. 19th century, physicians appreciated the impact of the gastrointestinal (GI) tract on the mind. In the 20th century, however, we took a step backward when scientists reversed this understanding, saying instead that it was the mind that influenced the gut.

Finally, in the 21st century, it was realized that we can hold two truths at the same time. The brain influences the gut (via the autonomic nervous) AND, the gut influences the brain through the microbiome.

But how does the gut microbiome impact the brain beyond freeing up nutrients from our food? It appears to come down to three main mechanisms (each with endless complexity…I won’t attempt to share):

1. Microbes make products /soluble substances (neurotransmitters, hormones, metabolites) that can cross the gut-blood barrier and thus move into the bloodstream. These substances can directly influence nerve cells. Some can cross the blood-brain barrier. They can also impact immune cells, which affect our nervous system.

2. Microbes can send signals via nerves (of the enteric nervous system and the vagus), which connect the brain and gut. The enteric nervous system is a mesh-like system of neurons of our GI tract that connects to our autonomic (“automatic”) nervous system.

3. Microbes stimulate the immune system cells in the gut's wall, communicating with the brain through cytokines or chemical messengers. In this way, they can be involved in neuroinflammation (brain inflammation).

In short, some microbes make things that make us feel good and support our health, and some make things that make us feel bad and contribute to illness.

Research using mostly mouse models and some human studies examines what happens to brain symptoms when we increase or decrease certain microbial populations. The goal is to develop treatment interventions that target the microbiome. Psychobiotics, for example, would be probiotics/ microbial populations aimed at treating mental health conditions.

If you pull back and consider the bigger picture, however, you’ll realize that the goal for all of us is to improve microbial diversity, which has decreased due to our modern lifestyle. We don’t necessarily need deep research to do that.

Brain Development

The effects of the microbiome are already occurring as our brain is developing. The gut microbes play a role in the early development of neurons, which means they leave lasting impacts on the brain and, potentially, our behaviors.

But what microbes was our brain being influenced by before we were born? Our mother's gut microbiome was making its metabolites that crossed the placenta. One example is short-chain fatty acids (SCFAs), which impacted the development of our brain cells.

To give you a sense of the research into the gut microbiome-brain axis and what is being learned, I’ll share a sampling of studies….

Wellbeing

Many brain-related conditions have been associated with changes in our microbiome, such as a reduced amount of certain bacteria, especially those that produce short-chain fatty acids (SCFA’s) when they break down the fiber. Buyrarate is one example of an SCFA believed to improve brain function.

• A 2019 study found a correlation between the amount of butyrate-producing bacteria and well-being. That doesn’t mean we know if one is causing the other. Are the microbes providing a sense of well-being, or is a content brain and thus less stressed physiology a more welcoming environment for some microbe? Maybe both.

Anxiety

• Research shows that “germ-free” mice (without a microbiome due to being reared in sterile conditions) are prone to anxiousness and are less sociable than those with an intact microbiome.

Depression

• The bacteria Lactobacillus rhamnosus JB1 appears to improve the mood of anxious and depressed mice. This doesn’t happen when the vagus is blocked, suggesting that signaling of the vagus is the mechanism of action.

• A 2019 randomized, double-blind, placebo-controlled trial (meaning the researchers and participants didn't know who was getting the treatment and who was not) studied the effects of a multi-species probiotic. Those in the probiotic group experienced a significant subjective improvement in mood compared with the placebo group.

Cognition

• Another study found that giving probiotics to people with psychotic conditions (with residual cognitive symptoms) had improved cognitive function.

• One study found that those who had used antibiotics for over two months scored lower on cognitive tests such as learning, working memory, and attentional tasks.

Stress Control

• One small study (45 participants) showed that those on a diet high in fiber, prebiotics, and fermented food reported feeling less stressed than the control group.

ADHD

• Germ-free mice (and those given antibiotics) have also been found to be hyperactive, prone to risky behavior, and less able to learn or remember.

Autism Spectrum

Those with autism have higher rates of GI disorders.

• A 2013 study found that mice with a model version of autism had thinner and more permeable gut walls than normal mice. When analyzing the gut microbiome composition, researchers found abnormally low levels of a bacteria called Bacteroides fragilis and a 46 times higher 4-ethylphhenylsulfate in their blood (relative to control mice). A very similar chemical, para-cresol sulfate, is found at high levels in the blood of people with ASD.

  When researchers injected the non-ASD mice wth 4-ethylphenylsulfate, it induced autism-like behaviors. Giving the mice with ASD-like symptoms B. fragilis appeared to restore levels of 4-ethylphenylfsulfate to normal and improved their behavior and gastrointestinal symptoms.

Sociability

• While research suggests that the gut microbiome contributes to autistic behavior, it also appears to contribute to the differences in social behavior in the general population. Numerous types of autism-associated bacteria are also related to differences in sociability in the general population.

Aging & Alzheimer’s

• Aging mice have lower SCFAs (again, good for the brain) and dysregulated, hyperactive microglia (inflammatory cells in the brain). Giving a high-fiber diet changed the types of bacteria in the gut microbiome, increased the production of SCFA’s, and reduced the expression of certain genes that control inflammation in the brain.

  • A follow-up study found that the high-fiber diet shifted most of the microglia out of a dysregulated state and back to the normal healthy state seen in younger adult mice.

• It is known that people with Alzheimer's have more inflammation-promoting gut bacteria. Research shows that these changes occur even before the brain changes, which means it could be a target of intervention.

As you can see, most of the research looks at bacteria. I wish fungi were also being considered, as many of us see candida (and mold) clinically wreaking havoc on the gut-brain axis. I’ve previously shared a post on research showing evidence of candida and mold in the brains of those with Alzheimer’s.

Impacts

The microbiome is difficult to study because of the differences in our baseline microbiome. Our early experiences can even impact that baseline. One study found that adults who had been formula-fed as children had a less diverse microbiome in adulthood. Children delivered by cesarean section have microbiomes that differ from those born vaginally. They also have a higher risk of early-life infections, inflammatory conditions, and allergies.

Our genetics, diet, social interactions, and exposures to toxins, EMF, and stress can impact our microbiome. Microbes (like the rest of us) can change when they feel threatened. In their case, by multiplying and becoming more virulent. This has been studied in bacteria exposed to EMF.

Increasing Microbial Diversity

Regardless of our differences, it seems that a diversity of microbes is key. Ways to promote diversity for most people (and not necessarily those who are sensitive to certain foods or food families):

• Diet

  • a high-fiber diet (as opposed to a highly processed diet)

  • organic when possible

  • prebiotic foods: e.g., garlic, onions, asparagus, cabbage, beans, leak, banana

  • fermented foods: yogurt, kefir, saurekraut, and other fermented vegetables. Many people I see with histamine intolerance, mast cell activation or certain snps (DAO, MAOA) may have difficulty tolerating these very high histamine foods.

  • probiotics - despite the plethora of options, we don’t have it all figured out

  • a more adventurous diet (again for those who tolerate such adventures). Even international travel has been shown to increase microbial diversity, possibly due to novel microbes and different diets

• avoiding things that decrease the diversity of our microbiome (sugar, toxins, overuse of antibiotics, nonsteroidal anti-inflammatory medication).

• exercise, but not to an extreme, which lowers diversity

• meditation (or other practices that lower stress)

• being socially active, which results in exchanging microbes (I hope to explore this fascinating research in a future newsletter)

• getting outside in the natural, unsanitized world

• And because I am a fan of zinc, I’ll mention it here again…. Zinc deficiency can alter the microbiome, and zinc supplementation has been shown to protect the gut microbiome from pathogens and toxins. Keep in mind, however, that too much zinc can also have negative impacts on the microbiome).

I hope I’ve given you a deeper understanding of the wonders of the microbial world living within each of us and how we can support it so it can support us.

Until next time,

Courtney

CourtneySnyderMD.com

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Medical Disclaimer:

This newsletter is for educational purposes and is not intended or implied to be a substitute for professional medical advice, diagnosis, or treatment for yourself or others, including but not limited to patients you are treating (if you are a practitioner). Consult your physician for any medical issues that you may be having.