Category Archives: intestinal permeability

Functional Medicine: Getting to the Root Causes of Illness, A cure for Alzheimer’s

Today I watched a great TED talk by Dr. Rangan Chaterjee discussing his own journey in the discovery and implementation of a functional medicine approach to caring for his patients. The concept of using basic science and clinical science to diagnose and treat the root causes of illness, rather than treating symptoms, has been around for more than two decades.  This approach has recently started to attract more attention, especially within the community of younger physicians who have become more dissatisfied with the frustrations of traditional allopathic medicine.

Here is the talk. Dr. Chatterjee covers lots of ground in a passionate and informative talk.

Enjoy this talk. If you would like to learn about how a functional medicine approach can CURE ALZHEIMER’S DISEASE then watch this video of Dr. Bredesen who gave this lecture at a meeting of the American College of Nutrition.

Doctor Bredesen, an acclaimed neuroscientist, researcher, and more recently a brilliant clinician, has been criticized by the academic research community for implementing a clinical research protocol that addresses more than one variable at a time! Unfortunately, medical science has been handcuffed by the drug-model of clinical research wherein only one variable (drug vs. placebo for example) is studied. But if an illness has many potential contributing root causes, changing only one variable is doomed to failure, as Dr. Bredesen explains in this lecture.

Sleep well, eat clean, get outdoors every morning to help keep your circadian rhythm and biological clock in order.

Bob Hansen MD

Babies born with more than 200 toxic chemicals in their blood

The  Environmental Working Group (EWG) is a non profit organization devoted to protecting the public from one of our greatest health threats, pollution in all of it’s forms. The EWG supported a study in which newborn infants were tested for known industrial and agricultural toxic chemicals. All of the infants had > 200 and some up to 300 toxic chemicals found circulating in their blood at birth. These babies were not born to parents living in or near toxic waste dumps, or working in dangerous industrial environments. They were born to parents living like you and me. You can read about this and many other issues here.

The 1976 Toxic Substances Control Act grandfathered >70,000 industrial and agricultural chemicals already in use as “safe” and provided for no effective standardized testing requirements for the introduction of new chemicals. Heather White, Executive Director of the EWG was recently interviewed for an  Autoimmune Summit. I have attended this health related summit on-line while recovering from my surgery and was shocked to hear and then read about out environmental exposure and lack of protection.

We often think about pollution and environmental toxins as contributing to cancer, birth defects, asthma and similar problems but auto-immunity is another problem with links to our toxic exposure.

During the Auto-Immune Summit Aristo Vojdani, Ph.D., M.Sc., M.T. scientist and editor of a peer-reviewed journal on auto-immunity, estimated that 60% of auto-immune diseases are “triggered” by environmental toxins, 30% triggered by dietary components, and 10% triggered by infectious disease. He distinguished triggers from predisposing factors which represent the physiologic milieu that leads to auto-immunity. This terminology of triggers vs. predisposing factors may seem confusing and arbitrary. In a nutshell, underlying the molecular mimicry theory of auto-immunity is “leaky gut”.  The “gateway to autoimmunity” is “leaky gut” (increased intestinal permeability) which allows foreign substances to cross the intestinal barrier, enter the circulation and challenge our immune system. Leaky gut  has many contributing factors including but not limited to diet, stress, gut dysbiosis and infections.  Although the % of auto-immune disease that is “triggered by” environmental toxins (versus diet and infections) remains speculative, there is mounting evidence that all of these factors contribute to greater or lesser degrees in various patients.

The paleo community has often stressed the importance of eliminating specific foods and replacing sugar laden flour foods with nutrient dense foods. But emphasis has also been placed on eating organic foods to avoid pesticides, herbicides and hormones.

Dr Vojdani has suggested that in addition to the gut-immune related mechanisms of molecular mimicry, environmental toxins, especially heavy metals, BPA and organic solvents,  act not only has foreign invaders stimulating the immune system but also stimulate the immune system by causing tissue damage directly and thereby presenting damaged or transformed tissue to the immune system as foreign. Environmental toxins do not require a leaky gut to enter our bodies. Many are absorbed through our lungs and skin, and many are directly absorbed through our guts even in the absence of a “Leaky gut”. Heavy metals including mercury, lead and cadmium do not require a leaky gut for intestinal absorption, nor do pesticides, herbicides or hormones administered to the animal we consume. They wreak havoc not only by directly damaging our organs but also by altering our immune system.

Dr Noel Rose, Director of Center for Autoimmune Research (John’s Hopkin’s University) and Dr. Ahmet Hoke, Director, Division of Neuomuscular Disease (John’s Hopkins NIMH Center) opine that our rising rates of auto-immune disease are the result of our “unsuccessful adaptation to new environmental agents”. (See Forward written in Last Best Cure | Donna Jackson Nakazawa.)

The  Government Accountability Office (GAO) is the Federal Government’s internal watchdog agency. A GAO report ( U.S. GAO – Environmental Justice: EPA Needs to Take Additional Actions to Help Ensure Effective Implementation) revealed that 85% of the new chemicals introduced into our environment are not accessed for safety. The  Environmental Protection Agency receives 90 days notice prior to the introduction of new chemicals (industrial, agricultural, etc). Industry does not have the burden of proof relative to safety. Instead, the EPA must determine, within 90 days, if a new chemical is “safe”. Shouldn’t it be the other way around?

Beyond that issue we have the problem of multiple  low grade simultaneous exposures. If a given level of toxin is “safe” based on short term studies of animals or humans, how do we know that a combination of hundreds or thousands of toxins over many years are “safe”. Likewise, if  air concentrations or water concentrations of a single toxin are deemed “safe” how can we possible test the combined effects of hundreds and thousands of environmental toxins in our air, water, soil and food?

The EPA, created under the Nixon administration, was decimated during the Bush administration when budget cuts resulted in the loss of > 50% of it’s senior scientists. With that executive action most of the EPA’s institutional memory was lost and along with it many of the already limited safeguards we had in place.

The concept of “eating clean” minimizes exposure to the potentially harmful effects of anti-nutrients  and immune stimulants (harmful plant lectins and saponins, excess phytic acid, excess omega 6 fatty acids) and more importantly encourages the consumption of nutrient dense foods (lots of colorful vegetables, grass fed meats, wild seafood). But “eating clean” also requires avoiding environmental toxins, including pesticides and herbicides.

To achieve that goal within a budget you can consult the EWG’s lists of foods that have the most and the least amount/variety of pesticides/herbicides. These lists are called the “dirty dozen” and the “clean fifteen”.

To avoid heavy metal exposure (especially mercury) eat seafood that is low on the food chain (less opportunity to accumulate mercury in their tissue). Many people do not realize that most of the mercury in our seafood comes from burning coal. Multiple heavy metals are present in coal. When coal is burned to generate electricity the heavy metals are released into the air and are then washed into our rivers, streams, lakes and oceans where they can accumulate in fish. As the heavy metals work up the food chain they accumulate in tissues. The best/safeest sources of healthy omega three fats are in smaller cold water fish (sardines, anchovies, small mackeral, salmon, trout). And do not forget oysters, scallops,  mussels,  and clams which may have less amounts of omega 3 fats but are safe with respect to heavy metals being low down on the food chain.

The concept of “living clean” involves more than being selective about food and cooking techniques. It involves avoiding exposure to toxic chemicals which can be found in our water (drinking and bathing), air, soil, clothing, furniture, make-up, deodorant, toothpaste and household cleaners. You can learn about these exposures at the EWG’s website. Consumer Guides | Environmental Working Group

Here is a fact that might get your attention, 90% of red lipstick has mercury in it. That’s right, 90%. Every day women around the world are painting their lips with lipstick that has mercury. The average American uses 10-12 personal care products per day which exposes us to 120 or more toxic ingredients. The law that regulates personal care products was written in 1938 (after a woman became blind from using mascara). It needs to be updated and there is much lobbying against better regulation (lots of money in personal care products an make-up). In the meantime we need to be more aware about what we put on and in our bodies.

Our environment is filled with “endocrine disruptors” which mimic and interfere with our hormones. The most common one is BPA (plastic) which has estrogen like effects.

What are our greatest exposures to BPA? Answer: plastic lids on coffee/tea to-go cups, plastic bottles of soda and plastic bottles containing citrus juices. Heat and acid both leech BPA (and probably other toxins) out of plastic into the liquids we drink. The most acidic beverage by far is SODA (as low as pH 2.2). So toxic chemical exposure is yet another reason to avoid soda. Do not serve your guests soda or water in plastic containers at parties. Set an example. Store your foods in glass containers and especially do not put warm or hot food into plastic containers. Get a water filter for your drinking water. Some even go so far as to get a water filter for their showers and baths.

Finally, flame retardants (furniture and clothing) required by law represent major health hazards by filling the air of our homes and exposing our skin to toxic substances. Mothers and toddlers have an estimated 3 times greater risk for this exposure which has been linked to neuro-development disorders, ADHD and endocrine disruption. Firefighters have very elevated levels of toxic chemicals derived from flame retardants. Some patients with a variety of illnesses have seen improvement in symptoms by having their furniture re-upholstered with coverings that do not contain flame retardants (anecdotal reports). Consider getting a HEPA air filter for your home and office. Remember hurricane Katrina? Remember the great number of illnesses reported by families made homeless by Katrina who were relocated to live in temporary portable housing. Those buildings were releasing formaldehyde and other toxic chemicals and produced illness within just a few days.

In my next post I will provide the “dirty dozen” and “clean fifteen” lists to help you make decisions about organic food purchases if you cannot afford to purchase 100% organic. In the meantime check out the EWG website. Also coming soon is a recipe for tumeric-ginger tea/marinade as an anti-inflammatory alternative to NSAIDs.

Live Clean and Prosper

Bob Hansen MD.

A Paleo physician’s journey through major surgery

At age 46 I had a total hip arthroplasty (THA). Metal and plastic components replaced my hip joint (the stem, ball and socket of the hip). I am convinced that if I had adopted a Paleo lifestyle at age twenty instead of age 58 I would have not needed that surgery. But more about that another time.

On Monday I underwent a revision of that surgery to replace some components, scrape out bad bone, remove inflamed joint lining, flush out plastic debris, and place some bone grafts into areas where bone cysts had formed. The surgery was necessary because the plastic debris from my first artificial joint had stimulated my immune system in a way that caused my macrophages (white blood cells) and osteoclasts (a special kind of bone cell) to start destroying the bone around my hip socket. This process is called osteolysis.

Our immune cells evolved to destroy and consume bacteria and viruses, not plastic powder. So as the plastic liner of my hip prosthesis wore down, the plastic debris provided a constant source of inflammation, stimulating my immune system to get rid of a foreign invader. The bone around my prosthesis got caught in friendly fire. This problem does not seem to occur since a newer form of plastic, having only 10% the wear rate of the old plastic has been introduced. Time will tell if that proves to be true.

To prepare for surgery I reviewed my Paleo behavior with respect to diet, sleep, exercise, stress reduction and outdoor time. My exercise routine was already very reasonable. I had been strictly avoiding grains (except for occasional white rice) and legumes but did include some fermented dairy (kefir and cheese) and wine. So I eliminated all dairy and all alcohol. Sleep has always been an issue because as a physician I take call and sometimes work through the night with emergency cases.

My last call night was 3 weeks before surgery and I was up all night. The next day I flew to NJ for two important events (a reunion and a wedding) both of which were definitely not Paleo environments. A flight cancelation required more sleep deprivation in order to reach my first event on time. That sleep deprivation in combination with the changes in time zone disrupted my circadian rhythm so upon returning home two weeks before surgery I knew I had to play catch-up to be ready for surgery. I avoided alcohol except for a few drinks at my brother’s wedding and violated the wheat prohibition once with a piece of wedding cake.

When I returned to California I was 6 pounds heavier and jet lagged. I promptly got an upper respiratory infection (probably acquired on my flight home) which started in my throat and nose and went to my lungs.

So now I am jet-lagged and infected just two weeks from surgery. Not a good situation.

Thereafter I was strictly Paleo in diet, sleep, and stress reduction (yoga and meditation) but had to limit exercise to yoga and walking in order to fight the infection and prepare for surgery. I spent as much time walking outdoors as was feasible and focused on eight hours sleep each night. After one week I was beating the URI so I decided to do two 30 minute sessions of resistance training during the last week before surgery.

By the day of surgery the URI was completely cleared and I was down 6 pounds to my baseline.

I self administered my own pre-operative medication protocol (designed to mitigate post operative pain) and received a spinal anesthetic from my friend and colleague using a combination of local anesthetic and a small dose of spinal morphine. The latter can provide pain reduction for up to 24 hours after surgery.

So here is the amazing result.

5 hours after surgery I walked without pain using a walker bearing full weight on the surgical leg. I walked again that evening without pain. I knew this was the honeymoon period because the spinal morphine was still protecting me.

The next morning the honeymoon was over but I was still able to walk with full weight bearing without any pain medications and subsequently walked several times up and down the hospital halls during the first three post operative days. Although I had pain with movement I had no pain at rest.

On the day after surgery my CRP (C reactive protein) was 0.2 mg/dl. CRP is a measure of inflammation in the body. Normal range is zero to 0.5. I was elated. One day after a major traumatic event which typically initiates an inflammatory cascade, I did not have excess inflammation throughout my body as measured by CRP. My WBC (white blood cell count) was also normal.

A paleo lifestyle will not prevent pain after surgery but being in a low inflammatory state before surgery certainly helped with recovery.

My walking ability immediately after surgery and during the next three days astounded the physical therapists and nurses. They all stated I had set records.

My colleagues in the Anesthesia Department could not believe that I received no opiate or NSAID pain medications during my recovery. It is now five days since surgery. I have taken no opiate pain killers or NSAIDs except for low dose aspirin (starting yesterday) to help prevent blood clots

I avoided NSAIDs because NSAIDs increase intestinal permeability (which leads to an inflammatory response) and also because NSAIDs increase risk of cardiovascular events (heart attack, stroke, blood clots in the legs which can travel to the lungs and cause death in severe cases)

I can attribute my success to many factors including an excellent anesthetic, a great surgeon, an optimal pre-operative medication protocol, the superb nursing and therapy staffs and the Paleo lifestyle. In preparing for surgery I was able to make an effective come back from a stressful travel week, two successive nights of sleep deprivation and an upper respiratory infection only because of the Paleo approach.

As I walked my laps around the orthopedic unit I noticed that most patients spent the entire day in bed except for a few laps each day with PT. Many factors contribute to that problem. Our PT department is very aggressive but post operative pain, obesity, inflammatory diets and sedentary lifestyles all contribute to slow recovery. The hospital menu is highly inflammatory thick with processed-carbohydrates, pro-inflammatory grains, legumes, and refined vegetable oils, and yes,  even some trans fats. A strictly Paleo menu would be very helpful. But most of those patients have been living the Standard American Lifestyle (inflammatory diet, chronic sleep deprivation, inadequate exercise, poor stress management, etc.)  for a lifetime prior to surgery and it can take months to years of a Paleo lifestyle to mitigate a lifetime of self abuse. Even then some damage is permanent (like my hip).

I ate the hospital’s fresh fruit, vegetables and wild seafood, the rest was delivered from home by my loving spouse. Kathie is my anchor in the storm and my guiding light when I become lost. The importance of love and human physical contact is well recognized by the Paleo community so it is appropriate that I end with an expression of gratitude to Kathie and the host of friends who visited me during recovery. Hugs and kisses are as important as an anti-inflammatory diet.

Live clean and prosper.

Bob Hansen MD

Chronic Pain Reduced by the Paleo Lifestyle

I spend 50% of my clinical time treating chronic pain patients. A paleolithic diet which consists of pastured grass-fed meat, free range poultry and eggs, fresh seafood, fresh vegetables, fruits and nuts decreases inflammation by eliminating major sources of dietary induced inflammation.

Yesterday I saw a patient one month after he started a paleolithic lifestyle (paleo diet, 8 hours of sleep per night- cycling with the sun, regular exercise including a prescribed spine rehab program).

Within 30 days his pain  has decreased by more than 50%, He feels  more energetic. He stated “I have started to dream again and get a full night’s sleep”. He has lost 12 pounds in one month and his blood pressure is down. He is ready to return to work after not working for eight months (with some activity restrictions). He is not taking any opiate pain medication.

His MRI scan and X-rays of the spine will not demonstrate any improvement. He still has degenerative disc disease, one or more tears in a disc annulus (outer wall of the disc) and arthritis in the facet joints of his neck (cervical spine) and lower back (lumbar spine). But the lifestyle elements that have contributed to his chronic inflammation have been significantly reduced in just 30 days and he has benefited “tremendously” in his own words.

There are many mechanisms involved with chronic inflammation. Most patients with chronic pain have an inflammatory component. Many patients with chronic pain are overweight or obese. Excess visceral adiposity (fat around the internal organs) creates a state of chronic inflammation by constantly producing inflammatory chemicals called chemokines and cytokines. These inflammatory mediators are produced by the fat cells and by the white blood cells (macrophages) that reside alongside the fat cells. They contribute to a process called central sensitization where the brain and spinal cord nerves that mediate pain  become sensitized and over-react to sensory input. Interleukin 6 is one of these mediators. Increased levels are associated with fatigue, depression and a state of hyperalgesia where painful stimuli are amplified. Tumor necrosis factor alpha is another important inflammatory mediator produced in excess when excess fat accumulates around the internal organs. Weight loss is essential to decease systemic inflammation, particularly in the setting of chronic pain when someone is overweight or obese.

Pro-inflammatory foods can also increase inflammation by altering intestinal flora and increasing intestinal permeability. These mechanisms have been discussed in previous posts and in the manifesto page of this website.

Few patients follow my dietary and lifestyle advice. Most seem to prefer taking pills, getting injections and other interventional pain procedures. In other words, they prefer to “be-fixed” rather than  take lifestyle initiatives that are likely to not only decrease their pain but also improve their general health. As an interventional pain practitioner I encourage patients to take full advantage of the pharmacology and interventional procedures that are likely to help. But without significant changes in bad dietary habits, poor sleep hygiene and without adopting a rehabilitation exercise program the pills and injections/procedures are much less effective and the prognosis is poor.

Stress reduction is also essential for health in general and for pain reduction in particular. Yet despite repeated recommendations to utilize an inexpensive stress reduction workbook, few patients ever bother to take this important step to reduce pain, anxiety and suffering.

Our culture is one in which patients expect to “be fixed” rather than to be led down a path which leads to healing and functional improvement by actively participating in their own rehabilitation and healing. Our culture is also one in which  major organizations provide bad dietary advice, particularly with respect to encouraging increased consumption of grains and legumes which have pro-inflammatory components and anti-nutrients. We evolved over a few million years without consuming grains, legumes, refined vegetable olis or dairy. Our evolutionary biology and physiology thrive when these foods, particularly processed foods are eliminated from the diet and we consume only those whole natural foods we have evolved to eat.

Modern medicine provides many remarkable drugs, surgeries and procedures that can be life saving and life altering. But application of this technology without addressing the fundamental determinants of health (proper nutrition, restorative sleep, judicious exercise, stress reduction, and restoration of circadian rhythm) yields much less benefit. Ultimately, unless we remove from our lives the destructive components of modern society and culture we cannot heal and instead continue to suffer from chronic degenerative diseases that cause pain, loss of intellect and loss of mobility.

No references tonight, just comments and reflection. References have been provided in previous posts.

Peace, health, and happiness.

Dr. Bob

The bacteria in your gut are essential to your health Part II, obesity, metabolic syndrome and dysbiosis

I have discussed the evidence linking the mix of bacteria in your gut (gut flora) to health and disease in Part I. The Bacteria in your Gut are essential to your health Part I | Practical Evolutionary Health

Today I will discuss the evidence related specifically to  obesity and metabolic syndrome (the constellation of obesity, insulin resistance, high blood pressure, and abnormal blood lipids). My discussion will follow closely the evidence and theory presented in research and review papers authored by Dr. Cani and colleagues. The first one is titled:

Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.”

You can find the full text of this article here .

I have had the pleasure of corresponding with Dr. Cani by e-mail regarding her many publications investigating the relationship between gut flora, obesity, and metabolic syndrome.

“Recently, we and others have identified several mechanisms linking the gut microbiota with the development of obesity and associated disorders (e.g. insulin resistance, type 2 diabetes, hepatic steatosis).”

Explanation: The gut microbiota are the bacteria, viruses and other “bugs” that reside in our intestines. Insulin resistance can occur in various parts of the body, wherever insulin has an effect including fat cells, liver, muscle, brain. When higher amounts of insulin are required to achieve an effect this is called insulin resistance. In Type 2 diabetes, the pancreas is still able to make insulin but insulin is less effective in controlling blood sugar. In Type I diabetes the pancreas no longer produces insulin. Hepatic Steatosis means fatty liver disease. The liver accumulates fat and this can lead to cirrhosis, liver failure and death. Alcohol consumption can cause this but when alcohol is not involved this is called Non-Alcoholic-Fatty-Liver Disease (NAFLD). Our nation presently has an epidemic of not just obesity but also NAFLD. Evidence points to  excess carbohydrate consumption and excess consumption of vegetable oils (linoleic acid)  as contributing factors in NAFLD.  Carbohydrate restriction and consumption of saturated fat, particularly medium chain fats (as found in coconut) can protect against NAFLD. But the gut flora also play a role. The mechanisms involved are many.

“Among these, we described the concept of metabolic endotoxaemia (increase in plasma lipopolysaccharide levels) as one of the triggering factors leading to the development of metabolic inflammation and insulin resistance.”

Endotoxemia occurs when a toxin from certain kinds of bacteria circulates in the blood. This endotoxin enters our blood through our intestines under conditions in which the protective barrier of the intestines is compromised. The compromise of the intestinal barrier is variously referred to as ” leaky gut” or “increased intestinal permeability”. Wheat gluten-gliadin  causes increased intestinal permeability (especially in celiac disease) as can other plant lectins. In this discussion, the gut bacteria also contribute in the setting of “dysbiosis” (the beneficial effects of helpful bacteria are overwhelmed by the harm-causing bacteria when a healthy balance is not present)

Lipopolysaccharide (LPS) comes from the outer wall membrane of certain bacteria. Blood plasma is the liquid part of blood in which the blood cells circulate. So an “increase in plasma lipopolysaccharide” simply means that there is more LPS circulating in the blood. That is a bad thing. Depending on how much is circulating this alone can cause organ failure and death and is a major part of the physiologic changes involved in septic shock. But lower levels of LPS circulating in the blood can cause chronic low grade inflammation and insulin resistance. Obesity is associated with chronic inflammation and increased LPS circulating in the blood and being distributed to various organs where it wreaks havoc.

“Growing evidence suggests that gut microbes contribute to the onset of low-grade inflammation characterizing these metabolic disorders via mechanisms associated with gut barrier dysfunctions.”

“We have demonstrated that enteroendocrine cells (producing glucagon-like peptide-1, peptide YY and glucagon-like peptide-2) and the endocannabinoid system control gut permeability and metabolic endotoxaemia.”

That is a mouth-full. Over thirty different kinds of hormone producing cells have been found in the human intestine. These cells are called enteroendocrine cells. The hormones produced by these cells have many effects. You can find a great review of these cells and their effects here .

In Dr. Cani’s review article she describes how some of these hormones produced in the gut can increase intestinal permeability and allow more of the toxic, inflammation producing LPS to enter the bloodstream. But these hormonal effects are just part of the picture. Another part relates to endocannabinoids.

The  Endocannabinoid system in humans is complex and relates to hunger, satiety, energy metabolism, and yes gut permeability. Endocannabinoid refers to our internal (endo) production of cannabis like substances. Pot smoking people get the munchies because of the appetite stimulating effects of marijuana. But endocannabinoids have many other physiologic effects including the modulation of pain, mood, immune function and memory.

Dr. Cani describes in great detail the evidence supporting the roles that the gut flora play in influencing intestinal permeability mediated through the effects of various hormones and endocannabinoids. In animal and human studies changing the gut flora produces changes in these hormones and endocannabinoids which in turn can increase or decrease intestinal permeability and increase or decrease circulating LPS.

It turns out that specific  Prebiotics can produce growth of beneficial gut bacteria and through the series of steps outlined above, reduce inflammation in the body, improve blood sugar, improve insulin sensitivity, and decrease fat,

Oh, and similar to the endocannabinoid system, there is an “apelinergic system” in our bodies that also plays a role. If you want to read more about these systems you should read the original article and the other links below to related articles.

I have discussed in the past that fecal transplants have been used to treat the specific dysbiosis that occurs with C Difficile colitis. But fecal transplants have many potential beneficial uses.

The Fatlose 2 trial is presently studying the effects of fecal transplants on insulin resistance and related problems in human volunteers. I will let you know when the results are published, Studies conducted in rodents have demonstrated significant weight loss and improved insulin sensitivity when obese rodents receive fecal transplants from lean rodents.

In summary: dysbiosis represents an unhealthy mix of bacteria in the gut

  • dysbiosis causes increased intestinal permeability (leaky gut)
  • increased intestinal permeability leads to increased circulating LPS, which is bad
  • elevated levels of circulating LPS create a chronic state of inflammation which contributes to obesity and metabolic syndrome
  • the mechanisms that link dysbiosis to intestinal permeability include hormonal disruption (enteroendocrine cells) and the endocannabinoid system. Other mechanisms are also likely in play.
  • prebiotics and probiotics can mitigate dysbiosis, reduce intestinal permeability, reduce inflammation, and offer potential therapy for obesity and metabolic syndrome
  • fecal transplantation offers a potential for treatment for obesity and metabolic syndrome, research is underway

Our ancestors lived and evolved for a few million years prior to the relatively brief ten thousand years of agriculture and one hundred years of industrialization. The overuse of antibiotics in medicine and animal husbandry have contributed to dysbiosis. Other factors include stress, disruption of circadian rhythm, sleep deprivation. Cesarean delivery and avoidance of breast feeding conspire to dysbiosis. Processed foods feed unfriendly bacteria in our guts at the expense of beneficial bugs. Agricultural foods have introduced dietary lectins which also increase intestinal permeability and thereby contribute to chronic inflammation. The further we stray from our evolutionary niche, the more problems we experience.

This discussion just touches the surface of gut flora, dysbiosis, health and disease. We have yet to explore the gut-brain axis. Our gut and microflora communicate with and effect the function of our brain and other organs as well.

We will continue to explore health and disease from an evolutionary perspective.

Below are links to articles related to our discussion.

Peace, health and happiness.

BOB

Gut microbiota controls adipose tissue expans… [Benef Microbes. 2014] – PubMed – NCBI

Glucose metabolism: Focus on gut microbiota, … [Diabetes Metab. 2014] – PubMed – NCBI

Probiotics, prebiotics, and the host microb… [Ann N Y Acad Sci. 2013] – PubMed – NCBI

Crosstalk between the gut microbiota a… [Clin Microbiol Infect. 2012] – PubMed – NCBI

Gut microbiota and its possible relationship … [Mayo Clin Proc. 2008] – PubMed – NCBI

Enteroendocrine Cells: Neglected Players in Gastrointestinal Disorders?

Stomach bacteria can cause and worsen heart disease

A recent study from Italy (1) has identified a relationship between the bacteria that causes stomach ulcers and heart disease. H Pylori is a bacteria that can colonize the lining of the stomach and remain there for a lifetime unless diagnosed and eliminated with antibiotics. This bacteria was demonstrated to be a major cause of stomach ulcers by two physicians ( Dr. Barry Marshall and Dr. Robin Warren) who won the Nobel Prize for their finding.

Atherosclerosis the formation of plaque in the walls of arteries, is in large part an inflammatory process (2,3). The coronary arteries supply oxygenated blood to heart muscle and heart valves. A heart attack (myocardial infarction) occurs when a plaque  ruptures or tears, sending debris downstream in a coronary artery. That debris and/or the exposed ruptured plaque causes  a blood clot that obstructs blood flow to a portion of the heart and if the clot remains untreated a heart attack (muscle damage) occurs within minutes to hours. This process can also result in a fatal abnormal heart rhythm (ventricular fibrillation).

A major source of inflammation that is known to contribute to atherosclerosis and heart attacks is infection (2). Many patients suffer heart attacks following an acute infection or severe emotional stress.  Inflammation is involved in forming plaques, creating unstable plaques, causing plaque to tear or rupture and inflammation is involved in the dynamic process that leads to a heart attack (3). To quote the authors of this study:

Ischaemic heart disorders are the consequence of an atherosclerotic process. A concomitant cause of atherosclerosis is inflammation. Infections represent the single most frequent determinant of inflammation. In case of H pylori infection, the organism colonises the human stomach for life (if infection is not properly treated); therefore, the trigger is continuous and inflammation lasts for a lifetime.

The authors of this study found that a certain subset of H Pylori bacteria carry a protein that is similar to two or more very important and essential proteins in heart muscle. Those proteins are called human tropomyosin and cardiac ATPases. Both types of proteins are essential to the ability of the heart muscle to pump blood through the heart.

The authors postulate a mechanism called molecular mimicry. Because H Pylori proteins are very similar to certain proteins in the heart, colonization or infection in the GI tract by H Pylori results in an immune response directed against these foreign proteins which are very similar to proteins in heart muscle. The immune system”mistakes” these heart muscle proteins for the foreign proteins in H Pylori and mounts an immune response against the heart muscle. The study found that patients infected with certain H Pylori strains had higher circulating levels of inflammatory markers and BNP . BNP is associated with heart failure, (loss of heart muscle contracting ability) and loss of heart muscle function results in a poorer prognosis in patients with coronary artery disease.

Thus this study supports a direct link between bacterial infection in the GI tract and heart disease, mediated through the immune system.

This sort of molecular mimicry has been recognized in medicine as it relates to two very well known diseases caused by infections with a species of streptococcus (as in strep throat). Those diseases are rheumatic heart disease (also called rheumatic fever)  and glomerulonephritis, Either of these can occur as a complication of strep infections, ergo the importance of diagnosing and treating strep throat.

H Pylori represents one of many examples of the interplay between bacteria in our GI tract, the immune system and disease causation. Intestinal dysbiosis (imbalance between healthy and disease causing bacteria that reside in our gut) has been associated with a  multitude of disease processes including obesity, diabetes, psychiatric disorders and cancer (5,6,7,8,9,10).

An essential component of this process is the entry of foreign proteins or other antigens (immune stimulants) across the gut wall into the body where the immune system gets activated. Intestinal Permeability is a term that describes the ability of substances to cross the GI barrier (intestinal wall) and enter the circulation (blood or lymph glands). I have discussed this before. There are many potential causes of increased intestinal permeability (leaky gut) including small intestinal bacterial overgrowth (a specific kind of dysbiosis) dietary sources such plant lectins and saponins found in grains and legumes, stress, sleep deprivation and medications such as NSAIDS. When an individual suffers from leaky gut (increased intestinal permeability) the probability that toxic substances can enter the blood stream increases. Endotoxin (produced by pathogenic bacteria in the gut) has been related to many inflammatory disease processes wreaking havoc when it penetrates the intestinal barrier.

Intestinal permeability, auto-immune disease, molecular mimicry, and gut dysbiosis are topics often discussed in the Paleo community. These topics represent physiologic processes that relate to humans deviating from our evolutionary habits, diets and lifestyles.

References are below.

Peace.

BOB

(1)  Cross-sectional Study: CagA–positive Helicobacter pylori Infection, Acute Coronary Artery Disease and Systemic Levels of B-type Natriuretic Peptide Journal of Clinincal Pathology. 2014;67(3):251-257.

(2) 11. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 1999;100:e20–8.

(3)  Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999;340:115–26

(4)  Mayr M, Kiechl S, Mendall MA, et al. Increased risk of atherosclerosis is confined to CagA-positive Helicobacter pylori strains: prospective results from the Bruneck study. Stroke 2003;34:610–5.

(5) Diabetes, obesity and gut … [Best Pract Res Clin Gastroenterol. 2013] – PubMed – NCBI

(6) Involvement of gut microbiota in the de… [Gut Microbes. 2012 Jul-Aug] – PubMed – NCBI

(7) Crosstalk between the gut microbiota a… [Clin Microbiol Infect. 2012] – PubMed – NCBI

(8) [The role of gut microbiota in… [Postepy Hig Med Dosw (Online). 2013] – PubMed – NCBI

(9) [Research advances in th… [Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2013] – PubMed – NCBI

(10) The gut microbiota, obesity and insulin resi… [Mol Aspects Med. 2013] – PubMed – NCBI

Intestinal Permeability, Food and Disease

In medical school I learned some fundamental concepts about nutrition and digestion that turn out to be wrong. For example, we were taught that proteins in our diet are completely broken down into single amino acids in the gut, then absorbed through the wall of the intestine as individual amino acids. Turns out that not all proteins are completely digested in this manner and that fragments of proteins that are several amino acids long can be absorbed through the gut and enter our blood. Examples of such proteins include wheat gluten and bovine serum albumin (found in cows milk and whey protein) to name a few. The problem with absorbing such nutrients into our bloodstream is that these protein fragments are “foreign” and can be recognized by our immune systems as foreign, triggering an immune (inflammatory) response.

Some peptides (short chains of amino acids) in bovine serum albumin have structural similarity to peptides in human tissues. This foreign protein has been implicated in autoimmune diseases such as Multiple Sclerosis, Rheumatoid Arthritis and Type 1 Diabetes.

Other substances such as bacterial endotoxin similarly can be absorbed into the blood and cause trouble. Endotoxin, also called LPS or  Lipopolysaccharide, is a major component of the outer membranes of certain kinds of bacteria (gram negative bacteria such as E-coli) that live in the  Lumen of our gut. High levels of endotoxin circulating in the blood occur during septicemia and can result in death from septic shock. Lower levels of circulating endotoxin have been demonstrated to contribute to alcoholic and non-alcoholic liver disease, both of which can cause liver failure and death.

Intestinal wall permeability is governed by many factors. There are regulatory proteins that open and close the gaps (tight junctions) between the cells that line the walls of our intestines, thereby allowing more and larger foreign substances to enter our blood. This mode of entry is referred to as “paracellular” since it does not involve the usual absorption mechanism through the walls of the cells that line the intestines.

Substances regularly consumed by Americans known to increase intestinal permeability include gluten (the sticky protein found in wheat, barely, rye, oats), alcohol, non-steroidal anti-inflammatory drugs  like ibuprofen (Motrin, Advil), naprosyn (Alleve), and aspirin.  Refined “vegetable oils” that are high in a specific Polyunsaturated fatty acid called linoleic acid (examples of these vegetable oils include corn oil, soy oil, cottonseed oil) have also been demonstrated to increase intestinal permeability.

Vegetable oils have also been found to enhance the liver inflammation and destruction caused by  alcohol which is at least in part mediated by absorption of endotoxin and ultimately also caused by oxidative stress.

The same applies to non-alcoholic liver fatty liver disease. (Progression of alcoholic and non-al… [Drug Metab Pharmacokinet. 2011] – PubMed – NCBI)

Interestingly, consumption of saturated fat (as found in beef tallow, coconut oil, butter and cocoa butter-the oil of dark chocolate) protects the liver from inflammation and destruction caused by alcohol, while polyunsaturated fat consumption (vegetable oils)  do the opposite. (References above and below)

There is growing evidence for a link between auto-immune disease and Alterations in intestinal permeability. Increased intestinal permeability (IP) has been observed in a substantial percentage of individuals with Type I diabetes. It is commonly observed in populations at high risk of developing Crohn’s disease and has been observed in patients who subsequently develop Crohn’s disease. Patients with ankylosing spondylitis have increased IP and although these patients are typically treated with NSAIDs which increase IP, the effects of NSAIDS have been isolated from a primary defect in IP which is shared by relatives without the disease.

“increased intestinal permeability is observed in association with several autoimmune diseases. It is observed prior to disease and appears to be involved in disease pathogenesis.”

A paleolithic diet avoids all sources of gluten (paleo is grain-free) and it also avoids refined “vegetable oils”. These food items present a double hit relative to inflammation. First, they increase IP which increases circulating levels of various “foreign” proteins and other foreign macromolecules which can stimulate the immune system. The second hit from these food items represents their direct inflammatory effects once absorbed into the body. I have previously discussed the  inflammatory response to excess omega six fats here.

An excellent review of the importance of the ratio of omega six fats found in “vegetable oil”  to omega three fats found in fish oil can also be found here ,  here   and  here.

The potential inflammatory response and anti-nutrient effects of cereal grains and in particular the gliadin portion of wheat gluten has been discussed and reviewed in multiple papers including:

Do dietary lectins cause disease?

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

BMC Medicine | Full text | Spectrum of gluten-related disorders: consensus on new nomenclature and classification

BMC Medicine | Abstract | Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity

Bioactive antinutritional peptides derived from cere… [Nahrung. 1999] – PubMed – NCBI

Antinutritive effects of wheat-germ agglutinin and… [Br J Nutr. 1993] – PubMed – NCBI

This discussion just scratches the surface of the effects of intestinal permeability and health. Future discussion will address how the micro-flora (bacteria and viruses that live in our GI system) affect intestinal permeability, our brains, our immune system and our health.

Avoiding foods that we have not evolved to eat will result in decreased inflammation and will often reduce the symptoms of auto-immune and other inflammatory diseases. Many present day diseases are considered by evolutionary biologists to represent a mismatch between our culture, food, and our evolutionary biochemistry. These diseases were likely rare or non-existent  before the advent of agriculture and the subsequent industrialization of society with highly processed foods.

Eat only pastured meat, free range poultry and eggs, wild seafood, fresh vegetables, fruit and nuts and you will avoid the problems discussed above as well as a host of other problems to be discussed in future posts.

Peace,

Bob Hansen MD