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]

The Biology of Food Addiction

The Calorie Hypothesis
Current view: Obesity is just lack of will power ...eat less, exercise more

This model fails because:

1. Our body's wise compensatory mechanisms defend against weight loss by decreasing energy expenditure and increasing appetite as we diet
2. High glycemic carbohydrates (like added refined sugars, sugar-sweetened beverages, refined grains, and starches) light up the nucleus accumbent - the brain's addiction center - promoting compulsive overeating of processed high glycemic foods
3. Multiple other factors actually regulate metabolism: dietary composition, gut microbiome, toxic exposures, infections, allergens, nutrient status, mitochondrial dysfunction, and imbalance of hormones and neurotransmitters.

"Caloric-restricte traditional "diets" exacerbate metabolic dysfunction and actually lead to OVEREATING over the long-term"

A more accurate view...

1. Poor diet quality, not calories is drive of obesity
2. All calories not created equal
3. Food is more than calories... it is information that programs genetic expression and changes metabolic state
4. Diets don't work because they are not addressing fundamental drivers of excess caloric intake: physiologic addiction to refined carbs and sugar! 

Sugar is eight times more addictive than cocaine!

Experimental research reveals a commonality between addition to sugar and cocaine.

• Both sweet taste and drugs of abuse, such as cocaine, stimulate release of dopamine in ventral stratum, critical in the process of reward-processing and learning
• Cross-tolerance and dependance are seen in both sugar consumption and drugs of abuse. This means that over time it takes more and more of each to get the desired effect.
• In one study, rats preferred saccharin over IV cocaine. In another, they chose sucrose over cocaine.

Compulsive Overeating Can Resemble Drug Addiction

Visceral Fat is "hungry" and may drive overeating behavior

• Visceral fat is fat that is stored around your organs
• These visceral fat cells are metabolically active and suck fuel out of your blood stream, making you eat more!
• They secrete hormones and cytokines that promote weight gain and inflammation
• Hormones such as adiponectin, insulin, resisting, leptin and MSH
• Cytokines such as IL-6, TNF-alpha, and other pro-inflammatory molecules
• Insulin release surges in response to high glycemic foods, creating more inflammation and obesity-promoting metabolism, more visceral fat storage = vicious cycle

Dietary composition more important than calories...

• In this large European study, increase in protein content and a reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss.
• Another study shows a low-glycemic diet higher in fat and protein improves metabolic rate and energy.
• Mice fed high-GI diet had almost twice the body fat of those on the low-GI diet after 9 weeks.
• Athletes on ketogenic, high-fat diet had better performance, less fatigue

Bottom line: Latest research indicates that sugar consumption is an independent risk factor for many, if not ALL, chronic disease.

Do you need more reasons to stop eating sugar now?

Here are my recommendations for optimal health and weight:

1. Quality of foods is essential... low glycemic load, high micronutrient and phytonutrient and fiber content = eat a rainbow of colors in your foods.
2. Choose organic, pastured meats and wild fish
3. Eat more vegetables and low-glycemic fruits, like berries and green apples
4. Avoid all packages, processed foods - if it has more than 3-4 ingredients don't buy it!
5. Limit high glycemic starchy foods, like white potatoes and white rice
6. Eliminate gluten if you're sensitive and avoid ALL refined processed grains
7. Avoid all hydrogenated and trans fats. Use organic butter, ghee, coconut oil, olive oil, avocado and other healthy fats freely
8. Avoid genetically modified foods, like corn, soy, canola.

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Zonulin & Leaky Gut: A discovery that changed the way we view inflammation, autoimmune disease and cancer!

An amazing discovery a few years ago revolutionized our ability to understand the gut and permeability and how this impacts a wide range of health conditions from cancer to autoimmune disease to inflammation and food sensitivities. 

This little molecule, zonulin, has quite a story...

Zonulin is the "doorway" to leaky gut

Zonulin opens up the spaces between the cells of the intestinal lining. That normally occurs, in order for nutrient and other molecules to get in and out of the intestine. However, when leaky gut is present, the spaces between the cells open up too much allowing larger protein molecules to get into the bloodstream where an immunologic reaction can take place. Once that happens, the body is primed to react to those proteins each and every time they appear.  It can also cause leakage of intestinal contents, like bacteria into the immune system creating inflammation and overloading the liver's ability to filter out this garbage.

Triggers that open the zonulin doorway

Based on Dr. Fasano's research, we know that the two most powerful triggers to open the zonulin door are gluten and gut bacteria in the small intestine.  Gliadin causes zonulin levels to increase both in those people who have celiac disease and those who do not.  As the zonulin level rises, the seal  between the intestinal cells diminishes, opening up spaces between cells that allow all sorts of things to pass right through.  This is called "leaky gut".  Its as if the security guard that keeps the bad guys out is taking a nap! Sometimes large food molecules will pass through to the immune system.  The immune system thinks they are foreign invaders and will mount an immune response leading to food sensitivities.  In addition this immune activation leads to more damage to the intestinal cells (called enterocytes) and the gut becomes more inflamed and more permeable or "leaky".  As the damage continues, the microvilli that line the intestines and absorb nutrients become damaged, leading to other nutrient deficiencies.  

Top causes of increased zonulin and development of leaky gut:

1. Overgrowth of harmful organisms, like bacteria or yeast in the intestine 
1. SIBO = small intestinal bacterial overgrowth
2. Fungal dysbiosis or candida overgrowth
3. Parasite infections
2. Gliadin in the diet (gluten containing foods)

Gliadin is a protein in wheat, that like gluten, is a trigger for people with celiac disease. However, a study published in the Scandiavian Journal of Gastroenterology in 2006 clearly showed that gliadin can affect zonulin even in people without the gene for celiac. The researchers concluded that

Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

The significance of this is that gluten affects intestinal permeability in all persons to different extents.  It also means that 100% of patients with autoimmune disease or leaky gut could potentially benefit from a gluten-free diet.

Elevated zonulin levels and leaky gut are also associated with the following:

1. Crohn's disease
2. Type 1 Diabetes
3. Multiple Sclerosis
4. Asthma
5. Glioma
6. Inflammatory Bowel Disease

In conclusion the article states: 

Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food-derived environmental triggers or changes in gut microbiota all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer. This new theory implies that [once this path is activated] it can be... reversed by preventing the continuous interplay between genes and the environment.

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Alessio Fasano

Abstract:
The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

The Gut Immune System Connection - An Animated Video

The gut mucosa connects with the largest population of immune cells in the body!  Is it any wonder that in functional medicine we assess your gut function as one of the initial steps in cases of allergies, asthma, autoimmune disease, eczema, crohn's disease, ulcerative colitis, IBS, celiac disease, arthritis and more?  

It’s often the first point of exposure to pathogens.   Many microbes use it as a entry point into the rest of the body. The gut immune system therefore needs to be ready to respond to pathogens but at the same time it is constantly exposed to harmless environmental antigens, food particles and commensal microflora which need to be tolerated. Misdirected immune responses to harmless antigens are the underlying cause of food allergies and debilitating conditions such as inflammatory bowel disease. This animation introduces the key cells and molecular players involved in gut immune connection and disease.



By checking your gut's microbial environment and taking a functional medicine approach to health and wellness, we can actually modulate some of the underlying immune dysregulation and eliminate your symptoms!

Nature Immunology homepage: http://www.nature.com/ni/index.html