Tag Archives: autoimmune disease

Stomach bacteria can cause and worsen heart disease

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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

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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