How the Immune System can Control Your Behavior

If someone you love is experiencing depression or finding less pleasure in social activities, you might want to look deeper.   It is quite possible that hidden infection or inflammatory condition may be causing the changes you observe.  Have compassion...there is often more to it than meets the eye.  I have seen many relationships crumble when one person is suffering from immune dysfunction and social isolation and the other does not see the illness for what it really is.

Our immune system is a powerful force inside each one of us!  This protective system is charged with the job of responding to foreign invaders to keep us in optimal health.  Most of us don't think too much about this system until it is not working correctly.  I treat many patients that suffer from overactive or under-active immune systems due to chronic infections, like tick-borne diseases;  toxic exposures, like mold and mycotoxins; or autoimmune diseases, like multiple sclerosis, lupus or Hashimoto's thyroiditis.  Although many patients understand the important role of the immune system in protection and defense, few people know that it also controls our behavior.  A recent study in Nature discussed the role of cytokines activated when the immune system goes on red alert and the connection to social isolation and autistic behaviors.  It's even plausible that changes in immune function may lead to personality changes!

Sickness and Depression

Perhaps no connection has been more studied than that of immune activation and inflammation and the link to depression.  Systemic infections cause the patient to allocate limited resources, conserve energy and prevent spread of infection.  The resulting sickness behavior is common to most infections, including viruses, bacteria and multi-cellular parasitic infections.  There is a broad spectrum of symptoms – fever, nausea, decreased appetite, malaise, fatigue and achiness – all of which may aid in the fight to conserve resources and increase isolation-type behavior.  In animal models we see sickness associated with a decrease in time  seeking interaction with a other animals as a result of diminished motivation for social exploration.  Symptoms of depression appear after pro-inflammatory cytokines are produced by the body or if they are administered experimentally. The fact that inflammation often leads to later depression suggests a cause–effect relationship.  It indicates that immune activation can precipitate depression. Many symptoms of inflammation-induced depression overlap with sickness behaviors, including fatigue, changes in sleep pattern, lack of interest in daily or pleasurable activities (anhedonia), changes in appetite or body mass and unexplained aches and pains

Inflammatory Cytokines and the Brian

A recent article about inflammatory cytokines and brain signaling discussed inflammation and the brain:

When considering the pathological signaling cascades in immunological disorders of the brain, certain cytokines might be considered of key importance, with their presence determining the course of a particular disease. Interleukin-1 (IL-1), IL-6, IL-17, and TNFα are critical for the pathogenesis of inflammation in certain brain disorders. Targeting these cytokines or their receptors can alter the course of several neurological diseases, but the effects may be beneficial or harmful.

We understand from this article that the inflammatory signals of the immune system (cytokines) have a profound effect on the brain.  Many patients battling systemic inflammatory or autoimmune disorders suffer from an "inflamed brain" and all that goes with it... symptoms like depression, anxiety and insomnia.  The role of cytokines on behavior can be summarized by saying that TNFα (sickness and depression) and IL-1β (sickness) alter behavior by direct actions on neurons of the brain.

Gaba may affect the immune system too...

GABA, an inhibitory neurotransmitter in the brain, has a similar inhibitory effect on the immune system. Antigen presenting cells (APCs) of the immune system have gaba receptors and therefore, gaba can directly inhibit the function of these immune cells. What this means is the neurotransmitter from the brain may have a direct inhibitory effect on the body's immune system.  This article on Gaba and the immune system states....Intricate and reciprocal regulatory relationships exist between the nervous system and the immune system, mediated in part by chemical messengers.

 

Insults to the body, from the outside or from the inside, activate cells of the innate immune system. 

[PHOTO SOURCE HERE]

Mind Altering Microbes: How your gut microbiome may influence your mood

"I've got a gut feeling about this"

While we have certainly heard that appetite and digestion are controlled by the enteric nervous system  (also known as "the master control panel in your gut"), who would've thought that the gut might also control your emotions and mood?  It's no wonder the old sayings, like "I've got a gut feeling about this", "That movie was gut-wrenching", or  "Come on, gut it out!" ring so true.  In fact I'd venture to say when we are trusting our intuition we associate it with having a "gut feeling" about something.

From the research it is now clear that gut microbes have an affect on inflammation, pain, eating behaviors, food cravings, mood and other seemingly unrelated symptoms, such as depression or uncontrolled anxiety.  In addition, it is common for depression and anxiety to co-exsist with disorders such as IBS (irritable bowel disorder).

It goes both ways...

Yes, it's true!  Did you know the gut-brain axis provides a way of communicating both directions using signals, such as neurotransmitters, hormones and cytokines?  This means that your gut bugs actually talk to your brain to influence emotions.  Equally important the emotions you feel and neurotransmitters produced by the brain have a profound effect on the gut as well.  We know that dysfunction in this communication between gut and brain can lead to various diseases, including depression and anxiety.  Who knew that the composition of your gut microbes could play such a great role in your mood?  The next time you get angry at your spouse or are overcome with sadness making you want to curl up in bed you can simply say, "Don't blame me...It's my gut microbes's fault!"  and you may be right on target!

The human gut is populated by more than 100 trillion microbes, which means there is more bugs in your gut than cells in your body.   And the genetic material contained by microbes in your gut is 150X that of the genetic material from human origin.  Most experts agree we have more than 1000 different species in our gut and over 7000 different strains.  We know that as we are exposed to stress, chemicals, antibiotics, and toxins, the diversity of the microbiome decreases and we know that the less diverse or microbiome, the more susceptible we are to illness and disease.

A baby's colonization of the gut first occurs at birth with vaginal exposure to the mother's microflora.  Did you know that c-section baby's have gut microbes more akin to skin flora than gut flora after birth?  And some studies show that throughout the entirety of life, they may never regain the normal diversity of vaginally delivered infants.

These are just a few of the functions of these bugs residing in your gut:

• Development of your immune system function
• Assisting with bowel movements and gut motility
• Maintaining intestinal cell barrier integrity (keeping the the good stuff in and the bad stuff out)
• Aiding in digestion and absorption of specific vitamins and minerals
• Controlling fat absorption and distribution

Pathways involved in communication between the gut microbes and brain.

Microbes and Stress

What is increasingly clear is that there is bi-directional communication between our gut microbes influencing the central nervous system and brain... and the reverse; communication between our brain influencing microbial composition.   Did you know that stress affects the gut microbes, too?

These are the top 3 ways that chronic stress affects the gut:

1. Increases the levels of inflammatory cytokines (IL-6, TNF-alpha) which can changes gut microbe populations.
2. Increases permeability of the gut lining, which is linked to many autoimmune diseases  (Hashimoto's thyroiditis, lupus, rheumatoid arthritis, multiple sclerosis and many others).
3. Allows bacteria to cross over into the bloodstream where the bacterial coating (LPS) can trigger an intense inflammatory response in the body.

So how do the gut microbes contribute to anxiety and depression?

Here are some of the mechanisms by which the gut microbes influence the brain and emotions:

• Altered microbial composition: Both probiotic ("good guys") administration and harmful infectious bacteria ("bad guys") have both shown to have an effect on the brain and emotions.  One study showed supplementation with probiotics decreased anxiety.
• Immune Activation:  Bacteria in the gut have been shown to activate the immune system and increase production of harmful pro-inflammatory cytokines.   There are many studies showing a link between increase in certain cytokines and depression (see below if you want to read more)
• Vagus nerve:  This is one of the main controls of the parasympathetic system that calms our fight or flight response and allows our body to relax and feel calm.  Activation of the vagus nerve and release of acetyl-choline has been shown to have a profoundly calming and anti-inflammatory effect on the body.  Most of the effects of gut microbes on the brain and body have been shown to be dependent on vagal nerve activation.
• Tryptophan metabolism:  Tryptophan is an extremely important amino acid and the raw material needed to make serotonin (think "the happy neurotransmitter") by the body.  There is a pathway, called the kynurinine pathway that involves metabolism of tryptophan and accounts for nearly 95% of the stores of tryptophan in the body.  In the case of pathogenic microbial infections in the gut (bacteria, yeast, or parasites) this pathway may be activated and "steal" from your body's tryptophan stores.  This leads to depletion of serotonin stores and may result in insomnia and depression.
• Microbial metabolites:  Bacteria in the gut help produce bile acids and short chain fatty acids (SCFAs) which are essential for human physical and mental health.
• Neurometabolites: Crazy but true... bacteria have the ability to produce many neurotransmitters and metabolites that have direct action on brain and thought.   Did you know studies show microbes can even influence your food cravings?!
• Bacterial cell wall sugars:  Perhaps most fascinating of all, the outer coatings of bacteria contain sugar molecules that can directly signal immune and hormonal systems into action.  This is the mechanism thought to be responsible for the healthy effects of probiotics on the gut and brain.

The bottom line is there is a growing body of evidence that suggests gut microbes play a large role in regulation in behavior and brain chemistry and are relevant to development of depression and anxiety.

So perhaps the best antidepressant is a healthy whole food diet and a high potency probiotic to fuel a healthy gut microbiome!

Check out Part II - Six Simple Steps to Treat Depression

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Further Reading:

• Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior
• Inflammatory Cytokines in Depression: Neurobiological Mechanisms and Therapeutic Implications
• Cytokine variations and mood disorders: influence of social stressors and social support
• Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut
• Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour
• Stress and the Gut

Health Tips for Anyone with a MTHFR Gene Mutation...

If you haven't seen the popular blog on MTHFR Gene Mutations... What's the big deal about Methylation?, you might want to start by familiarizing yourself with this common genetic mutation that can affect everything from depression and anxiety to risk of heart attack or stroke.

In light of the amount of questions and comments I've gotten, it's about time I write a follow-up blog giving you some helpful hints in dealing with this common genetic SNP that can affect your health in so many various ways.

A little background to bring you up to speed on methylation...

First, I suggest going back to re-read the previous blog article before moving on. For a quick review.... let's define methylation.  Methylation is the act of a carbon and three hydrogens (namely a methyl group) attaching itself to an enzyme in your body. When this methyl group attaches to an enzyme, the enzyme performs a specific action. One thing you might not realize is that methylation is responsible for is the breakdown of histamine. A methyl group is made and then floats around until it finds a specific binding site. In this case, the methyl group binds to histamine. When a methyl group binds to histamine, histamine breaks apart and goes away.   Many patients who have one or more methylation SNPs, like MTHFR have a hard time breaking down histamine, which can wreak havoc on the body in many ways!

If you haven't been tested and want to find out if you have this common genetic mutation, you can ask your doctor to order MTHFR gene mutation testing through LabCorp.   Better yet you can order a genetic profile directly without a physician order online through 23andMe for only $99.

Key functions these donated methyl group are:

• Protecting DNA and RNA.  If DNA is not protected it is susceptible to damage by viruses, bacteria, heavy metals, solvents and other environmental toxins. Over time if this damage becomes significant and could even result in cancer.
• Reducing histamine levels (see this article)  Sometimes the common methyl-donor, SAMe can help reduce histamine levels.
• Protecting cell membranes.    The methyl group donated by SAMe helps build phosphatidylcholine which then gets incorporated into the walls of all your cells.  If these cell membranes become damaged and weak, the cells become fragile and harmful things may enter the cell.  If they are unable to carry in useful nutrients, they will die. Excessive cell membrane damage can lead to serious medical conditions, such as multiple sclerosis.

What are some things I can do if I have the MTHFR gene mutation?

Here's ten tips for you!

1. Avoid taking folic acid blocking or depleting drugs, such as birth control pills or Methyltrexate
2. Avoid taking proton pump inhibitors, like Prilosec or Prevacid or antacids, like Tums, which may block essential Vitamin B12 absorption
3. Have your homocysteine measured, which if elevated may indicate a problem with methylation or a deficiency of B12 or folate.  If your homocysteine is elevated, limit your intake of methionine-rich foods
4. Avoid eating processed foods, many of which have added synthetic folic acid.  Instead eat whole foods with no added chemicals or preservatives.
5. Get your daily intake of leafy greens, like spinach, kale, swiss chard or arugula, which are loaded with natural levels of folate that your body can more easily process.
6. Eat hormone-free, grass-fed beef, organic pastured butter or ghee, and eggs from free-range, non-GMO fed chickens.  
7. Remove any mercury amalgams with a trained biologic dentist.  Avoid aluminum exposure in antiperspirants or cookware.  Avoiding heavy metal or other toxic exposure is important.
8. Make sure you supplementing with essential nutrients, like methyl-B12, methyl-folate, TMG, N-acetylcysteine, riboflavin, curcumin, fish oil, Vitamins C, D, E, and probiotics.  If you are double homozygous for MTHFR mutations, you should proceed very cautiously with methyl-B12 and methyl-folate supplementation as some people do not tolerate high doses.  Introduce nutrients one by one and watching for any adverse reactions.  Use extreme caution when supplementing with niacin, which can dampen methylation.
9. Make time for gentle detox regimens several times per week.  These could include infared sauna, epsom salt baths, dry skin brushing, and regular exercise or sweating.
10. If you have a known genetic mutation, share the information with parents, children and other family members and encourage them to be tested, too!  The easiest way is to order  through 23andMe for only $99 online.

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