HELLP, Preeclampsia, Antiphospholipid Antibodies and Basic Triplets

—-the other 200 posts —-

Clotted RBCs in Capillary

Some of my research involves the unique properties of milk and the development of the immune system, so I talk to medical people, lactation researchers and occasionally discuss the control of inflammation involved in ovulation, fertilization, implantation, gestation, labor and lactation.  It is clear to me that there are a few trends in disruption of these pregnancy processes resulting from the modern increase in inflammation and gut-related problems linked with immune tolerance.  Infertility is increasing, because women are becoming more chronically inflamed.  Miscarriages and premature births/low birth weight are increasing, because chronic inflammation enhances labor.  Pre-eclampsia (high blood pressure and protein leaking into the urine) results from chronic inflammation and omega-3 fatty acid depletion.  Now an even scarier form of pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) is on the rise.  I want to discuss HELLP to put all of these pregnancy-related problems into perspective.

HELLP, Cause and Cure Unknown?

HELLP is an autoimmune disease and I have repeatedly discussed the cause of autoimmune diseases:  1) inflammation, 2) deficiency of Tregs (immune tolerance) and 3) antigen basic triplets (antigen presentation).  When HELLP was recently brought to my attention with a sudden rise in local hospitals, I decided to see if it could be easily explained and cured, just by examining the available medical literature.  Wikipedia indicated that the cause and cure was not known and that was confirmed by local doctors, who just treat the symptoms by early deliveries and long stays for the babies in neonatal intensive care units.  My work was cut out for me.

Autoimmune Disease with Unknown Autoantigen 

An examination of the symptoms, rupture of blood cells (fibrin production), liver damage, clotting (low serum heparin), high blood pressure (capillary apoptosis), proteinuria (low heparan sulfate (HS) to prevent protein loss), pointed to some obvious treatments and the causes.  Infertility is often treated by in vitro fertilization/insemination, supported with aspirin and heparin injections to maintain gestation.  These treatments are consistent with high levels of chronic inflammation that block implantation and stimulate labor.  Infertility is also associated with antiphospholipid antibodies.  A closer look at the antiphospholipid antibodies showed that they were directed against β₂-glycoprotein-I.  So, I expected the β₂-glycoprotein-I protein to be the original target for the antibodies, the initiating antigen, but when I looked up the sequence of that protein, it lacked the expected basic triplet I have found in all  other autoantigens and allergens.  This meant to me that there was a different protein with a related sequence that started the HELLP autoimmune disease.

Attack on P-Selectin Starts Immune Autoimmunity

I checked for other proteins with related sequences and basic triplets (RKR in the carboxy terminal sequence below), and found P-selectin that is produced most abundantly in liver and on the surface of blood cells.  A quick search of the literature showed that P-selectin reacts with anti-phospholipid antibodies and has a pair of basic triplets that enhance immune presentation and make this protein a strong candidate for becoming an autoantigen.  Antibodies against P-selectin will cause clotting as seen in HELLP.

ref|NP_002996.2| P-selectin precursor [Homo sapiens]:

......carboxy terminalGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP

Antibiotics and Liver Damage

I suspect that HELLP is caused by a combination of liver damage and prior exposure to antibiotics (or common drugs that have antibiotic activity) that cause gut dysbiosis, i.e. loss of gut bacteria that stimulate development of the suppressive part of the immune system, e.g. deficiency in regulatory T cells, Tregs.  Examples of the type of liver damage that may lead to HELLP are excessive consumption of alcohol (alcoholic fatty liver) or high fructose corn syrup (non-alcoholic fatty liver).

HELLP from Cause to Cure

• Diet and/or infection causes liver inflammation.
• Antibiotics/drugs and/or processed foods lacking prebiotic fiber produce gut dysbiosis.
• Lack of gut bacteria needed for development of the immune system in the gut produces a deficiency of Tregs and dysfunction of immune tolerance.
• Liver inflammation, deficiency of Tregs and availability of antigens with basic triplets leads to antibodies against liver proteins.
• Chronic inflammation leads to decrease in HS production and leaky kidneys/proteinuria.
• Chronic inflammation/liver damage produces fibrin production.
• Fibrin production and low HS enhances clotting and leads to apoptosis/cell death in capillaries.
• Loss of capillaries leads to high blood pressure.
• Cure of HELLP, anti-phospholipid antibodies and pre-ecampsia, involves lowering chronic inflammation (aspirin and heparin treatment) with an Anti-Inflammatory Diet, fixing vitamin D deficiency, increasing omega 3/6 ratio,  and repairing gut dysbiosis to fix immune tolerance.
• Without these interventions, HELLP symptoms will become more severe, especially in subsequent pregnancies and additional autoimmune diseases will develop.

Gut Microbiome 2014: Diet, Inflammation, Disease, and Repair

---  My other 200 posts here  ---

The year 2014 began with my posts on damage to the gut microbiota caused by antibiotics, processed foods and excess hygiene.  I lamented the inadequacy of information from the media on damage/repair of the gut bacteria and highlighted medical myths with a post on some of Dr. Oz’s own ills that are self-inflicted by his diet and hygiene recommendations.  I also started to discuss how to cure autoimmune diseases by repairing damaged gut flora and by avoiding the antibiotic activity present in many common drugs.

With my 200th post in March, I summarized my thoughts on the causes and cures of common diseases in a series of diagrams on:

Health Diagram I    — Gut Flora and Diet, 

Health Diagram II   — Curing Autoimmunity and Allergies,

Health Diagram III  — Inflammation from Cell to Tissue  

I illustrated the relationships among diet, inflammation and diseases mediated by gut flora that I have discussed, since I started my blog in 2008.  Now after a couple of hundred articles and more than two million visits to my blog, I think that I am starting to grasp some of the major issues that cause inflammatory diseases.  The cures also now seem obvious.

Antibiotics Contribute to Autoimmune Diseases

Some species of gut bacteria are needed for the development of the aggressive half of the immune system and other species are needed for the suppressive half.  Thus, starving or poisoning gut flora leads to immune system problems and diseases.  Antibiotics are a quick way of crippling the immune system.  It seems that the aggressive part of the immune system is less fragile, because in most cases antibiotic treatments produce autoimmune disease due to loss of bacteria that are needed for development of immune cells that block the aggressive half of the immune system from attacking innocuous cells of the body or environment, i.e. antibiotics usually trigger deficient tolerance, and autoimmunity.

Feed the Gut Microbiome for a Healthy Immune System

Diet provides food for the body and flora.  Protein and fat are the macronutrients needed for the body, while the gut microbiota lives off of plant polysaccharides (except starch) that pass through the small intestines undigested into the colon.  The hundreds of plant polysaccharides are hydrolyzed by hundreds of enzymes made by gut flora and produce short chain fatty acids, e.g. acetate and butyrate, that feed colon cells.  Food processing systematically removes polysaccharides that feed gut flora and compromises the components of the immune system dependent on those bacteria.

Repairing the Gut Microbiome by Eating the Missing Bacteria

It is easier to see that eating a diet that lacks food for the gut microbiota will be a problem, than it is to figure out where to find replacements for lost species of gut bacteria.  The only way that bacteria get into the gut is down the throat.  To repair a damaged gut microbiota requires both changing diet and introducing the missing types of bacteria by eating them.  Eating dairy probiotics and fermented vegetables can provide a quick, but only temporary fix.  Most of the needed bacteria are more common in soil than in food.

Phytochemicals Are First and Foremost Antibiotics

I was shocked that my background in phytochemicals didn’t lead more directly to a major culprit causing modern diseases.  The gut microbiota is clearly a major factor in health and sickness.  Antibiotics that kill bacteria, damage the gut microbiota.  It is also unsurprising that processing food to reduce soluble fiber, damages gut flora, by systematically depriving gut bacteria of their major source of food.  The proliferation of antimicrobial products also damages the gut flora.  What I missed in this onslaught of modern lifestyles on the gut microbiota, was the major player in antibiotic resistance — phytochemicals are natural antibiotics. 

I Missed the Antibiotic Activity of Common Medicines

I studied phytochemicals and wrote research articles on their toxic, antibiotic activities, but everyone else was merchandizing phytochemicals as antioxidants, essential oils and superfoods.  This is a major conceptual problem.  Our bodies expend a significant fraction of our energy resources to detoxicify phytochemicals and human cultures have elaborate rituals to avoid phytochemicals and domesticate plants by breeding for the least toxic.  What I missed was the implication that the pharmaceutical industry was repurposing toxic, antibiotic phytochemicals as medicines and then skipping the "antibiotic" label.

Unlabelled Antibiotic Drugs Cause the Rise of Superbugs

Overuse of antibiotics is a problem, because it damages the gut microbiome and contributes to the modern increase in autoimmunity.  Food processing is another culprit and so is the mania for hyperhygiene and the demonization of bacteria.  Unfortunately, the major culprit in the development of multiple antibiotic resistant superbugs is the tons of commonly used pharmaceuticals that systematically attack gut bacteria, but are not labelled as antibiotics.  Most modern drugs were developed from phytochemicals and were initially used in plants to kill bacteria and fungi, i.e. phytoalexins.  Pharmaceutical companies acknowledge the antibiotic activities of common drugs, by sponsoring research conferences to develop existing drugs as new classes of antibiotics for treatment of superbugs.

Fermented Vegetables Repair Gut Flora

---the other 200 posts---

Fermented Vegetables is your most valuable investment in health.  Kirsten and Christopher Shockey (The Fermentista's Kitchen) have assembled a do-it-yourself guide that makes fermenting your own vegetables fast, simple, fool proof and delicious.  Importantly, their crock ferments provide a rich source of probiotics and prebiotics (soluble fiber) that can go a long way toward repairing the epidemic of damaged gut flora (microbiome) and inflammatory diseases.  Yes, you can cure autoimmune diseases and allergies.

Old Friends Become Fermentista

I have known the Shockeys, since we homeschooled our kids together, they started their homestead farm in Oregon and  they began to ferment.  I got interested in diet, inflammation and disease mediated by gut flora, and they got interested in growing food for their family and feeding their gut flora.  I was trying to figure out how to repair gut flora and they were figuring out how to make gut flora food.

Fermented Vegetables are a Source of Gut Flora

It took me a while to realize that my crock-crazed friends had provided the answer to my gut flora repair problem.  It was a modern approach to a traditional answer.  Fermentation is a natural solution to the problem of food spoilage.  Crushing vegetables in just the right amount of salt provides the sugars needed for lactic acid fermentation and inhibits spoilage microbes.  The lactic acid bacteria convert the sugars to lactic acid and the mild acid and salt stop other bacteria and fungi from growing.  The result is tasty, crunchy vegetables with the pleasant sour and mouth feel of lactic acid.  The removal of the vegetable sugars leaves the low-glycemic, complex polysaccharides, a.k.a. soluble fiber or prebiotics, that are the major food for gut flora.

The Guide to Fermentation

I was so excited when the Shockeys were starting a fermented veggies business and began writing Fermented Vegetables.  As my readers may have noticed, I tend toward the terse and scientifically esoteric.  They just cut to the taste and tell you how to make your crocks work miracles.  I struggle with the BIG picture and they just make the next meal delicious, so their kids (now adults) want more kraut and kimchi.

Fermented Vegetables is Available Now (bottom)

All of the Answers to Fermenting Vegetables

Fermented Vegetables is divided into four parts that simply, but thoroughly explain 1) what happens in a fermenting crock, 2) how krauts, brines and kimchi works, 3) how to make every kind of fermented veggie, and 4) how to cook with them.  It is all in the book.  Approachable.  Safe.  Delicious.  For beginners, cooks, chefs, kraut connoisseurs.  I have made a quick, tasty  cabbage kraut starting with knife, salt and Ball jar in 15 minutes, plus three days of waiting in a cool, dark place.  They tell you how to get great results with what is already in your kitchen, or how to use specialty water-seal crocks, onggi pots, tampers, followers, mandolines, etc., etc.  From pint jars to multi-gallon crocks, the how-to is there.  All of the details to slice, shred, salt, submerge, seal and sample are in the book, along with lots of food porn pictures to tempt you into making your first crockful of kraut or rhubarb infused with ginger and cardamom.  Just to make you feel comfortable, they also have an appendix on scum, the yucky, but harmless, fungal mat that can form where air meets the brine.

Health Diagrams II -- Curing Autoimmunity and Allergies

The Cure for Damaged Gut Flora and Inflammatory Diseases

I have written hundreds of posts that link modern inflammatory diseases to diet and damaged gut flora.  The immune system develops in the intestines in response to gut flora and without those bacteria and fungi, the regulatory function of the immune system is lost and disease begins.  Autoimmune diseases and allergies are caused by damaged gut flora.  Repair of that damage will cure the diseases, but repair requires adding back the missing bacteria.  [Drugs to treat symptoms have antibiotic activity that further damage the gut flora.]  Some of the missing bacteria are present in each batch of homemade fermented vegetables and eating krauts and kimchi can fix gut flora.  Homemade is better than commercial, because batches made from the bacteria clinging to vegetables have more diverse bacteria than commercial krauts made with starter cultures of just a few species of bacteria.  It should also be obvious that cooking, heating or canning fermented vegetables eliminates the desired, live fermenting bacteria.

Dr. Oz Diet and Gut Flora Myths

….All 190 posts here….

I just watched a Dr. Oz program on health myths, including corrections, such as recognition of the high fructose content of agave syrup (especially bad for diabetics.)  So I thought I would go ahead and correct some of the perspectives on his show that I don't think are supported by biomedical research.

The Big Truth about Diet and Gut Flora

Health results primarily from a matched Diet AND Gut Flora, with minor contributions by exercise, personal genetics, environmental toxins, etc.  You can eat the extremes of just meat or only vegetables or any mixture and be healthy, as long as your gut flora is made up of about two hundred different species of bacteria that can fully digest the soluble fiber in your diet.  Health requires a gut flora adapted to your diet.  Those bacteria, the gut flora, produce all of your needed vitamins, eliminate constipation, block inflammation and control the development of your immune system, which takes place in the lining of your intestines in response to gut bacteria.

Assorted Health Truths

Truth:  Saturated fats are healthy, but polyunsaturated omega-6 vegetable oils are inflammatory.  Oz can't bring himself to read the literature and acknowledge the heart benefits of saturated fats and meat.

Truth:  Soluble fiber, e.g. pectin in fruit or inulin in leeks or chondroitin in meat, is healthy food for gut flora, but insoluble fiber, such as in whole grains is a scam and just sucks out micronutrients.  Oz could really help the public by explaining that the hundreds of different polysaccharides produced by plants, i.e. soluble fiber, are digested by hundreds of different enzymes in gut flora.  Gut flora digest soluble fiber into sugars that are converted into short chain fatty acids that feed intestinal cells.

Truth:  GMOs have been studied intensively, are relatively boring and healthy, but organically grown veggies have not been shown to provide any additional health benefits over conventional.  Oz adheres to a very political line and attacks GMOs without any reasoned arguments and touts organic veggies without reference to supporting research.

Truth:  Grass grown beef has healthier fats with more omega-3 oils, but omega-3 plant oils, such as ALA in flax, provide only minor benefits and can't substitute for the long chain DHA and EPA in fish/algae oil.  Oz keeps pushing flax seed even though the benefits are minimal and the problems of high insoluble fiber have not been tested.

Truth:  Constipation is a sign of unhealthy gut flora and can lead to autoimmune disease, allergy or food intolerance, but laxatives such as magnesium only fix the symptoms and not the missing essential gut bacteria.  Oz is really confused about constipation and focuses on dehydration rather than the bacterial content of stools.

Truth:  Antibiotics may be essential for surgery or life threatening bacterial diseases, but antibiotic-damaged gut flora must be repaired (not just probiotics) or the immune system will be compromised.  Antibiotics are major contributors to autoimmune disease and I don't think that Oz realizes the damage that he starts or continues by not repairing gut flora after he repairs hearts.

Truth:  Dairy probiotics, e.g. Lactobacillus or Acidophilus, can provide a quick fix for some functions of gut flora, but these limited probiotic bacteria do not survive in the gut and do not substitute for normal gut bacteria.  I think that Oz still sends his patients home with yogurt after heavy antibiotic treatment and leaves his patients with damaged gut flora and long term disease risk.

Truth:  An Anti-Inflammatory Diet can reduce sources of inflammation that is the foundation for cancer, autoimmunity, allergy and most diseases, but adding new bacteria (not dairy probiotics) through social contacts and live fermented foods is essential for a healthy gut and immune system.

Truth:  All needed vitamins are supplied by healthy gut flora (as biofilm chemical signals) and healthy people do not benefit from multivitamin supplements, but people with damaged gut flora, e.g. because of antibiotic use or autoimmune disease, may require specific vitamins.

Truth:  Antioxidants are just plant defense chemicals, i.e. plant antibiotics, that are unimportant in general health, but they may alter gut flora in unpredictable ways.  Oz likes all antioxidants, but can't explain why these generally toxic chemicals are not used by plants as antioxidants.

Truth:  All of the vitamin D that we need is supplied by minimal skin exposure to sunlight, but most Americans are vitamin D deficient, because chronic inflammation blocks solar production of vitamin D in the skin.  Oz doesn't seem to understand the role of inflammation in vitamin D deficiency.

Truth:  We don't need Grains and other sources of starch, but grains also typically cause health problems, e.g. sensitivity, intolerance or celiac, for most people and can cause inflammation of the gut and disruption of the gut flora that can lead to autoimmune diseases.  Most thyroid disease and back problems are autoimmune diseases that start with celiac.  Oz still promotes whole grains even though added bran lowers nutritional quality and many people are healthier without grains.  He also seems to ignore the relationship between grain, antibiotics and autoimmune disease.

Truth:  Breakfast is not a necessary meal and there are health benefits to lengthening the time between the last and first meal of the day, but if breakfast is eaten, it should be low in sugar and starch, i.e. avoid cereal, since cereal causes a severe spike in insulin when eaten after a fast.  Breakfast makes you hungry, because even protein in the morning will raise insulin and cause an eventual abrupt drop in blood sugar that is experienced as hunger.  Why does Oz believe in breakfast?

Truth:  Food intolerances and allergies (rare) are due to missing species of gut bacteria, but these eating problems cannot be fixed by diet alone, since new bacteria (other than dairy probiotics) must be eaten.  Dairy probiotics are only useful to cure lactose intolerance.

Truth:  Hygiene should be minimal, because most people repair damaged gut flora due to antibiotics, for example, by intimate contact with friends and pets.  Antimicrobial soaps and sterile home surfaces prevent gut flora repair, because the vast majority of bacteria killed by hygiene are beneficial.  Appropriate hygiene is a real problem for Oz and he is obsessed with closing toilet covers.

Truth:  Cardiovascular disease starts with inflammation and is aggravated by fat deposits, but statins and lowered serum cholesterol only reduce heart attack risk, because statins have a weak side effect of lowering inflammation.  Diet changes and repair of gut flora, e.g. my Anti-Inflammatory Diet, fish oil supplements and wild fermented foods, are much more effective at reducing inflammation and curing cardiovascular disease without the severe risks of statins.  Oz is slowly becoming skeptical of statins, but still hasn't read the research literature critically.

Truth:  Poor health and most diseases have only minor genetic risk factors, but diet and gut flora are "inherited" directly and shared by the whole family.  When your doctor asks what diseases run in your family, she is asking about your shared gut flora.  Oz still gives the impression that genes are significant in disease and for example asks audience members if relatives have had heart disease.  He should tell them to repair their gut flora!

Summary Diet Truths

Truth:  There is nothing magic about healthy foods.  All that is needed are protein (meat, fish, eggs, dairy, beans, etc.; plant and animal proteins are equivalent), fats (from leaf and meat, not omega-6-rich seeds) and soluble fiber (to feed gut flora) from their original sources to retain naturally abundant micronutrients (vitamins, except C, are usually unimportant.)  That is my Anti-Inflammatory Diet and supplements should not be needed.  Natural, local foods are healthy, but there are no super foods and exotic does not mean better.  Variety does not compensate for low quality.  Your gut flora needs time to adjust, especially to new soluble fiber, so just change foods with the seasons, not daily, and make sure that you are sampling new bacteria in live fermented foods to make your gut community adaptable.

Transglutaminase, Gluten, Celiac, Inflammation, Autoimmunity

The point of this post is that the intestines produce an enzyme, transglutaminase (TG) that normally protects the gut from toxic plant proteins, such as grain gluten, but modern food processing and antibiotics corrupt digestion of gluten to produce intestinal inflammation and a series of related autoimmune diseases including celiac, thyroiditis, diabetes, baldness and atherosclerosis. 

Transglutaminase Links Proteins Enzymatically

Transglutaminase is a ubiquitous enzyme produced in the intestines, thyroid, heart, skin, hair follicles, etc.  This enzyme attaches to a protein (TG + ProA ~~> TG-ProA) via amino groups extending from some of the protein's amino acids, e.g. lysine or glutamine, and then the enzyme replaces itself by another protein leaving the two proteins crosslinked (TG-ProA + ProB ~~> TG + ProA-ProB).  Another alternative reaction is to leave the original glutamine without its amino group to yield glutamic acid residues.

Linking Proteins Makes Connective Tissue Tough

Transglutaminase is useful to crosslink the proteins in connective tissue.  Proteins in basement membranes form a matrix by binding to the heparan sulfate sidechains of another basement protein, perlecan.  The heparin-binding domains consist of basic amino acids that TG can react with to crosslink the proteins.

Linking Pathogen Proteins

Transglutaminase is also produced to crosslink the DNA/heparin/matrix polysaccharide-binding domains of pathogenic bacteria leading to aggregation, localization and death of the bacteria.  Inflammation resulting from activation of the inflammatory transcription factor, NFkB, stimulates production of TG.

Gluten is a Plant's Way of Saying "Don't Eat Me!"

Gliadin is a protein component of gluten that contains long stretches of glutamine residues, i.e. it is a polyglutamine protein similar to the protein that causes Huntington's disease.  Gliadin is an advantage as a storage protein for grain, because it is aggregated by the TG that protects the lining of the intestines of herbivores, such as humans, makes the animal sick and thereby discourages eating the grain.  Aggregation of gliadin/gluten inhibits digestion of the grain protein and can leave TG bound to gliadin.  Conversion of the polyglutamine stretches to polyglutamic acid stretches that are negatively charged, produces proteins that will bind to the positively charged heparan sulfates that circulate along the surface of intestinal cells leading to damage and inflammation.

Basic Triplet Leads to Antibody Production

Transglutaminase is also transported into cells, because it contains a region with a triplet of basic amino acids (...EPKQKRKLVA...).  This internalization probably contributes to enhanced presentation of TG to the immune system for subsequent antibody production.

Transglutaminase is Inflammatory

Transglutaminase interaction on the surface of cells also activates, NFkB, the transcription factor responsible for inflammation. Thus, TG turns on inflammation and part of inflammation is the activation of the innate immune system that includes production of TG.  This circular activation may produce autoinflammation that is associated with various forms of inflammatory bowel diseases.

Gluten Sensitivity is Normally Controlled By Gut Flora

Gluten sensitivity expressed by most people, is the intestinal response to the toxicity of gluten as it interacts with TG and causes inflammation.  This inflammation will also result in immune presentation of both gliadin and TG, and production of antibodies to both. Antibody production will normally be controlled by regulatory T cells of the immune system, unless spreading inflammation in the gut and/or antibiotics destabilizes the gut flora and compromises regulatory T cell development in the intestines.  

Anti-Glutaminase Antibodies Attack the Gut

Celiac results from uncontrolled production of antibodies to gliadin and TG with attack by the immune system on the aggregated gliadin/TG on the surface of the intestinal epithelium.  Celiac flare ups in response to eating even small quantities of gluten lead to further inflammation of the gut and further disruption and simplification of gut flora.

Celiac Leads to Thyroiditis and Much More

Transglutaminase is also produced by the thyroid and celiac will develop into a more generalized autoimmune disease that results in Hashimoto's thyroiditis.   TG production in the skin can result in skin rashes and may contribute to rosacea.  The base of hair follicles contains TG involved in hair production, and may contribute to some forms of hair loss.  Another substantial worry about the sequelae of celiac and gluten intolerance is the presence of TG in coronary arteries.

Antibiotics are Part of the Gluten Problem

Celiac and gluten sensitivity seem to be increasing with modern processing of grains and increased use of antibiotics.  Wheat has been gradually changed by traditional breeding, but genetic engineering has not yet been developed for wheat.  So, at least in this case, GM wheat cannot be part of the problem.  Many recent studies show that antibiotics profoundly and permanently alter gut flora.  As a result, the immune system, which is dependent on gut flora diversity is compromised, and various forms of autoimmunity and allergies develop.

Super Fine Flour Damages Gut Flora

Germ and bran are removed from all wheat before it is ground.  This is true even for whole grain flours, which have some of the germ and bran added back after milling.  Modern milling may be part of the gluten problem, because the flour is ground so fine that the grains of starch are broken.  Broken starch grains are digested by pancreatic amylases in the upper intestines, whereas some of the starch from intact grains is digested by gut flora in the colon.  Thus, modern wheat flour fails to feed gut flora like soluble fiber to produce short chain fatty acids, e.g. proprionic acid that supports Treg development; modern superfine flour supports autoimmune diseases and allergies.

Cultural Practices Make Gluten Safe

Wheat has been bred to produce bread as fast as possible from superfine flour.  This rapid bread production eliminates the exposure of gluten to enzymes from both germinating wheat seed and fermenting bacteria, which are part of traditional bread making.  Coarsely milled, traditional flour responds to soaking in water by activating enzymes that partially digest gluten, since gluten is a storage form of amino acids destined for the seedling.  Sour dough starter, a mixture of bacteria that can ferment the starch and gluten into short chain fatty acids and bubbles of carbon dioxide, has been used traditionally to provide leavening and flavor to bread.  Both flour and bacterial enzymes modify the structure of gluten to render it less toxic to the intestines.  Cultural traditions insured that gluten would be systematically detoxified by enzymes during hydration and fermentation of dough prior to baking.  Modern processing leaves wheat gluten in bread unmodified and toxic.

Prevention and Cure:  Eliminate or Detoxify Wheat and Add Bacteria

Preventing and curing diseases associated with gluten and transglutaminase is simple.  Eliminating wheat would do the trick.  Unfortunately, wheat is the mainstay in many parts of the world.  Fortunately, gluten intolerance is not uniformly observed where wheat is eaten.  This indicates that there are potentially safe ways to eat wheat and bread.  I gained insight into how to eat wheat safely from two books that were recently published:  Cooked by Michael Pollan and Artisan Bread in Five Minutes a Day by Jeff Hertzberg, MD and Zoë François.

Michael Pollan has recently become interested in gut flora and his book revealed how he built up a healthy gut flora eating homemade fermented food and compromised his work with antibiotics.  The major breakthrough that I made by reading Cooked was based on his experiments in baking whole wheat bread.  He hydrated the flour first and then used sour dough starter for lengthy fermentation.  This was the same process that I had used to make great loaves of bread (photo above) using Jeff Hertzberg’s directions in Artizan Bread in Five Minutes a Day.

The answer to gluten intolerance and most autoimmune diseases amounts to eliminating wheat or treating wheat in a safe, traditional process that inactivates the toxic properties of gluten; and maintaining a healthy gut flora (probiotics are not enough) with hundreds of different species of bacteria that promote the development of the suppressive immune system mediated by regulatory T cells:

Safe Traditional Bread 

• Remove bran and discard as toxic insoluble fiber.
• Grind wheat to retain starch grain structure.
• Soak flour to hydrate and activate wheat enzymes to start digestion/detox of gluten.
• Ferment dough with bacteria (sour dough starter) to continue digestion/detox of gluten.
• Bake.

Develop Healthy Gut Flora and Suppressive Immune System

• Avoid antibiotics that kill bacteria.
• Avoid hygiene practices, e.g. antibacterial soaps, bleaching surfaces, closing toilet covers, etc. that eliminate sources of healthy bacteria.
• Kiss your loved ones and pets, and encourage everyone to garden/play in the soil (an excellent source of thousands of different species of bacteria.)
• Recruit healthy gut bacteria by eating a variety of homemade fermented vegetables. My most highly recommended source is my friends at: http://www.fermentista.us
• Remember that cooked or pasteurized foods do not contain useful bacteria.
• Remember that dairy probiotic bacteria cannot live in the human gut and can only provide a temporary help to the immune system.
• Limit the variety of foods that are consumed and gradually change with the seasons to avoid rapid changes in nutrients to which gut flora cannot adapt.  Food intolerances indicate maladapted gut flora.
• Constipation indicates dysfunctional gut flora and a compromised immune system.

Baldness Cure: Low Dose Naltrexone?

Naltrexone can be used to block opioids and provide the basis for treatment for drug abuse, but in low doses (LDN) it provides a paradoxical increase in natural endorphins that reverses inflammation and provides an effective treatment for autoimmune diseases, e.g. MS.

Receptors
A recent anonymous post brought the role of cannabinoid and opioid receptors in baldness to my attention. The relationship between these receptors, inflammation and autoimmunity is very complex. The heat and cold sensors, which also bind capsaicin and menthol, appear to be mediated by endorphins. Acupuncture also seems to function by similar mechanisms and is inhibited by high dose Naltrexone.

Low Dose Naltrexone
A side effect of high dose Naltrexone (e.g. 50 mg/d) is hair loss. Low dose Naltrexone (e.g. 1 mg/day, taken at night) appears to stimulate hair production and it may reverse the effects of Finasteride, since LDN improves libido.

Endorphin-Suppressed Inflammation
I would expect hair loss to be prevented/reversed by topical treatments that block inflammation and autoimmune attack on hair follicles. Curcumin, from turmeric, blocks NFkB and appears to help hair loss. Capsaicin can block inflammation via endorphin production and also helps hair loss. I would also expect that topical menthol and castor oil would reduce hair loss.

Anti-Inflammatory Diet
The anti-inflammatory diet that I recommend, may not be sufficient to block hair loss, but it may provide a good foundation for other anti-inflammatory treatments. In fact, other topical treatments may not be effective unless chronic, diet-based inflammation is eliminated. It may also be important to reduce oxidative stress by optimizing glutathione and vitamin C.

I would appreciate comments by others who may have experience with LDN and balding.

Contagious Health

Healthy gut flora: bacteria from family, friends, Fido and food provide the foundation for the complex microbial community of the intestines, which controls the immune system.  Antibiotics and hygiene are detrimental to gut flora and health.

Gut Flora Are Complex

Recent studies of the gut flora, e.g. the human gut biome, show that each individual maintains more than 150 different species of bacteria.  Worldwide, that means that about a thousand different bacterial species are common residents of the human gut and together those gut bacteria use more than 1 million different genes.  Many of those genes code for the enzymes used by gut bacteria to digest plant polysaccharides, i.e. soluble fiber.

Hygiene Isolates People from Healthy Sources of Gut Flora

Every time we speak, we release a mist of bacteria from our lungs, mouth and GI tract.  These bacteria are on our skin, clothes and personal items, and provide a source of the bacteria that make us healthy.  Parents and older siblings pass these bacteria on to younger children.  These donated bacteria are essential for the development of a healthy immune system and children growing up with healthy relatives and exposed to soil bacteria via pets, farm animals, etc. are healthier than children who are more isolated.  

In this sense, hygiene is unhealthy, because an individual is isolated from new sources of bacteria that could replace those lost by limited diets, antibiotics, etc.  Otherwise, health is contagious, since gut bacteria from healthy individuals can spread among the population.  Washing hands and food is unnatural and unhealthy.

Few Bacteria Make You Sick, but Many Are Essential for Good Health

Food intolerance can result from “good” family hygiene, limited diets and exposure to antibiotics.  A common intolerance results from the absence of bacteria that produce an enzyme to digest dairy lactose, i.e. lactose intolerance.  Lactose intolerance can be readily cured by eating a dairy product, such as yogurt, that contains both lactose and live bacteria (probiotics) that can digest the lactose.  Simply eating moderate amounts of live yogurt daily for a couple of weeks resupplies the gut flora with bacteria that can digest lactose, and the intolerance is gone.

Soluble Fibers Are Plant Polysaccharides that Are Digestible by Bacterial Enzymes

Humans only produce enzymes to digest one polysaccharide, starch.  All of the other hundreds of polysaccharides present in plants are only digestible by bacterial (and fungal) enzymes of the gut flora.  If the bacteria and enzymes needed to fully digest a particular food polysaccharide are absent, then digestive problems ensue and the polysaccharide can act as a laxative.  Continual eating of the problem food with a new source of diverse bacteria, e.g. lightly rinsed vegetables right from the garden, then the gut flora will incorporate new bacteria that can digest the problem polysaccharide and the gut is happy.  

Soluble fiber feeds the gut bacteria that convert it into short chain fatty acids that nourish the colon. Constipation results from the absence of the bacteria needed to digest dietary fiber and to produce the large volume of bacteria that make up well hydrated stools. 

Gut Bacteria Are Needed for Healthy Immunity

Cells of the human immune system are stored predominantly in the lining of the intestines.  Intensive study of the interaction of the gut bacteria with the gut has revealed that both the aggressive half of the immune system that attacks pathogens and the suppressive half that protects the body itself from attack, develop in the gut in response to particular types of bacteria.  Thus, the absence of one type of bacteria can cripple responses to infection, while other bacteria are needed to block autoimmune diseases and allergies.  Most diseases are caused by disruption of the normal interactions between gut bacteria and the immune cells developing in the gut.

Antibiotics Lead to Autoimmunity

Antibiotics have dramatic and lasting impact on gut flora.  Cattle treated with antibiotics and a high carbohydrate diet have an altered metabolism (obesity) that leads to rapid fat accumulation in their tissues.  This is good for making tasty beef, but the same approach in people produces the suite of diseases in affluent societies.  

Children treated with an antibiotic for a simple ear infection, are much more likely to return to pediatricians for treatments of subsequent obesity, infections and diseases.  Compromised gut flora can take years to return to normal function after antibiotic treatment.  Loss of the appendix, which is the normal source of bacteria to replenish gut flora after diarrhea, results in an increased risk of abnormal gut flora and numerous autoimmune diseases.  It is likely that most autoimmune diseases are preceded by prior treatment with antibiotics that disrupted normal gut flora and permanently altered the immune system.

Interventions to Treat Disease:  the Anti-Inflammatory Diet and Fecal Transplants

It should be obvious that a disrupted or unhealthy gut flora will compromise the immune system and contribute to disease.  Treatment of diseases is complicated by the use of drugs that also impact the gut flora and produce additional side effects.  An alternative approach would be to support the healthy gut flora and normal development of the gut immune system.  As always, the answer is a supportive diet and a source of gut bacteria.  The diet is obviously the Anti-Inflammatory Diet that provides support for almost anything that ails you.  Probiotics are not retained in the gut, but they can contribute a few of the genes needed for a healthy gut flora. The source of bacteria for a  healthy gut flora may range from minimally washed garden vegetables, to the more aggressive total replacement of gut flora with a fecal transplant from a healthy donor.  

Aging Gut Flora

Diet selects for the bacteria that grow in the GI track and control the development of the immune system.  Diet-based inflammation produces aging symptoms.

Returning to the Subject of Aging

I want to return to the subject of aging.  A year and a half ago I wrote, “You don’t wear out, you flame out.”  I still think that is true, but I need to update that idea of inflammation and aging to include diet, gut flora and immune system development.  So here is my old article with a new focus on the gut.

Wearing Out Only Happens with Inflammation

I don’t think that aging happens -- most symptoms associated with aging are just medically mismanaged chronic inflammation.  The major observations are that older people have more degenerative/autoimmune diseases and they suffer from fewer infectious diseases.  The typical explanation is that the bodies of older people have figured out infections with an experienced immune system and that mechanical damage takes its toll over time -- joints wear out.  I think that there may be a minor amount of truth in this cultural perspective, but there is something more profound at work, sarcopenia combined with a compromised gut flora.

Replacing Muscle with Visceral Fat Is Inflammatory

Sarcopenia (muscle loss) is the gradual loss of muscle and replacement by fat.  Thus, by age fifty most people are physically less active and even if they appear to have the same weight and shape as in their active youth, the muscle of their abdomens and limbs has been partially replaced with fat.  This fat, as in those who are obese, releases inflammatory cytokines into the circulation and the body reacts as if it has a low grade infection.

Chronic Inflammation Taxes Immune System

Senior citizens are constantly expending energy and taxing their immune system by chronic inflammation.  As a result they get fewer infections, but the chronic inflammation provides the foundation for cancer and autoimmune diseases.  Their bodies aren’t mechanically wearing out, but they are wearing out by over use of the immune system.  

Aging Symptoms Are Inflammation Symptoms

Those seniors who are physically active and eat an anti-inflammatory diet, do not appear to age as fast as those who are sedentary, obese and display the typical symptoms of chronic inflammation, the metabolic syndrome.  Most of the characteristics associated with advancing years are merely symptoms of poorly managed chronic inflammation that can be reversed by an anti-inflammatory diet and exercise.

Diet Determines Gut Flora

Diet also contributes to aging, because diet controls development of gut flora and gut flora control development of the immune system.  The gut flora of an individual reflect the bacteria that have entered the GI tract, nutrients available to the bacteria in previous meals, bacterial growth regulators released by the gut, exposure to antibiotics, exposure to phytochemicals and gut transit time.

Gut Flora Is Diverse and Adaptable

Gut flora appears to be amazingly diverse from individual to individual with thousands of bacterial species inhabiting humans worldwide and about 150 species in each individual.  The same species remain in an individual for long periods of time regardless of diet.  The dominance of particular species depends on recent diet.  Major changes can result from antibiotics or gut diseases, e.g. Crohn’s.

Constipation Means Dysfunctional Gut Flora

Bowel stools are made up predominantly of bacteria and not undigested plant parts, i.e. fiber.  Fiber is made up of plant polysaccharides that are not digested by salivary, stomach or pancreatic enzymes, e.g. proteases and amylases that degrade proteins and starch.  Fiber polysaccharides pass into the colon where they are digested by gut flora.  People with constipation usually have disrupted gut flora, e.g. wiped out by antibiotics, and so the minimal volume of remaining undigested fiber is all that passes out in compact, dehydrated lumps.  If gut flora have been exposed to a particular type of fiber and bacteria having the needed enzymes have been brought into the gut previously, then the fiber is digested to sugars that feed the gut bacteria.  The increased population of bacteria is what makes up normal, hydrated bowel stools.

Gut Flora Changes Slowly to New Foods (Polysaccharides)

Bacteria grow quickly and with ample nutrients gut bacteria can double in number in about an hour.  Bacterial species are usually defined by the ability to utilize various carbohydrates or polysaccharides as nutrients.  Depending on the food eaten, nutrients favor the growth of particular bacterial species and the gut flora population changes dynamically.  New species are incorporated into the gut flora only if they find their way into the gut on food, e.g. riding on fresh, uncooked vegetables, and food provides nutrients that can permit the new bacteria to grow.  It will take several meals for new bacteria to reach appreciable numbers.  In the mean time the new fiber may be partially degraded and produce chemicals that disrupt other gut flora and cause bloating symptoms of food intolerance.  This is not an allergic reaction of the immune system.  It just takes time and persistence to permit the gut flora to adapt.  Most people systematically make themselves intolerant to particular foods by over-reacting to initial maladaption of their gut flora to the new food.  If they persisted with progressive exposure to diverse foods, their gut flora would adapt.

Simplified Aging Gut Flora Contributes to Inflammation

People of increasing age who maintain a diverse, anti-inflammatory diet and maintain muscle mass by weight-bearing exercise, avoid age-related inflammation and disease, i.e. they age more slowly.  Conversely, those who simplify their diets by eating processed foods high in starch and vegetable oils, show symptoms normally associated with advanced age, even when young.  The aging diet is inflammatory and it also produces a gut flora which is different from the youthful.

Aging Gut Flora Contributes to Disease

Constipation is an extreme example of dysfunctional gut flora and since gut bacteria are needed for the normal development of the immune system that is located in the lining of the small intestines, constipation is also an indicator of a compromised immune system.  Aging is frequently accompanied by digestive problems with one extreme being constipation.  It should not be surprising that individuals with compromised immune systems also develop numerous degenerative diseases indicative of a lack in the immunological tolerance systems that develop in the gut in response to normal gut flora.  Constipation and digestive problems are not normal signs of aging.

Eliminate Symptoms of Aging by Cultivating Gut Flora

A healthy diet, healthy gut flora, and a competent immune system are all tightly connected.  The typical symptoms of aging merely reflect an unhealthy diet and lifestyle that leads to chronic inflammation, a compromised immune system and disease.  The process of aging can be slowed by attention to the next meal.  Most people who fail to be healthy and active well into their 80’s are simply victims of bad choices (or of bad medical advice.)

Antibiotics, Gut Flora, Food Intolerance and Disease

Cattle Are Finished by Selective Killing of Gut Flora.  The Sickened Animals Store Fat that Grills Great.  People Get Metabolic Syndrome.

The likening of modern humans to potatoes sacked out on a couch is misleading.  The obesity epidemic linked to diets of processed foods more closely resembles the stumbling progression of cattle to abattoir.  Antibiotics and diet systematically lead in both feedlot and food court to gut dysbiosis, immune system failure, hormone disruption, rampant fat accumulation, physical inactivity, depression and the modern suite of chronic diseases.  Healthcare costs escalate, but vet bills, in contrast, are forestalled by a captive bolt pistol.

Background Observations

• Antibiotics kill bacteria and not humans, because the bacteria have different machinery for making proteins, nucleic acids and cell walls.
• Antibiotics kill bacterial pathogens and not viruses or fungi.
• Antibiotics kill helpful bacteria in the gut (gut flora) even more readily than pathogens.
• Antibiotics are used in meat production to alter gut flora to change animal metabolism;  e.g. cattle treated with antibiotics gain fat.  Protection from disease is secondary.
• Simple diet means simple gut flora.  Processed foods are simplified foods that simplify gut flora.
• Probiotics can replace only a small fraction of the gut flora diversity.
• Gut bacteria control the immune system development in the lining of the gut.
• Chronic antibiotic use permanently simplifies gut flora and compromises the immune system.
• The appendix stores gut bacteria as a reserve to replenish gut flora following diarrhea.
• Diseases based on inflammation and immune system intolerance result from gut dysbiosis (inadequate gut bacteria).

Antibiotics Kill Good Bacteria

This is a rant about antibiotics, not about humane actions.  Humane actions are not the point here, since I am talking about health care and not treatment of agricultural animals.  I am pleading for the rights of gut flora everywhere and antibiotics are the casual killers.  Compromised gut flora is collateral damage in attempting to eliminate bacteria characterized as pathogens.  Every time the pediatrician treats the mother by acceding to her pleas for an antibiotic prescription to silence a howling ear ache and get a good night’s sleep, or the dermatologist treats teen acne with antibiotics, billions and billions of domesticated bacteria die.

Constipation Is a Sign

Countless hours are wasted waiting, because antibiotic-depleted gut flora cannot hydrate and form normal stools.  Probiotics are gulped down, but they supply only a handful of the hundreds of bacterial species that are needed for health.  Yeasts and other fungi that are naturally resistant to antibiotics quickly replace the lost beneficial bacteria in the gut, vagina and on other body surfaces.  Surcease for simple sorrows leads to lingering and lasting laminations.  Don’t mess with mother nurture.

Damage of Antibiotic Use Is Slow

Most of the impact of antibiotic annihilation of bacteria normally present in humans is unobserved, because the deleterious effects lag months behind the initial treatment.  After all, cattle treated with antibiotics to restructure their gut flora to induce bovine obesity, appear to thrive as they rapidly gain weight and avoid symptoms of infectious diseases.  Humans on antibiotics also display fewer dental and incidental infections.  Constipation is not a high price to pay for a better mirror image.  

Antibiotics Compromise the Immune System

Unfortunately, allergies, autoimmune diseases, degenerative diseases and cancers are not usually linked to prior use of antibiotics.  There is no evidence that gut flora recovers  after antibiotic treatment, but constipation as a consequence of chronic antibiotic use is a common indicator of gut dysbiosis, collapse of normal gut flora bacterial communities.  The harbingers of inflammatory and degenerative diseases are present, but are usually discounted, because they are a common consequence of the Western diet.

Food Intolerance Reveals Inadequacies in Gut Flora

Food intolerance is a sign of depleted gut flora diversity.  Gut flora have hundreds of genes that can break down a huge diversity of polysaccharides derived from plant cell walls.  Gut flora of Japanese who routinely consume kelp have specialized enzymes to hydrolyze unusual algal sulfated polysaccharides.  Essentially all of the polysaccharides in plant fiber can be consumed by bacteria in the anaerobic environment of the colon.  Inability of individuals to digest particular food components usually results from a deficiency of the gut flora and an indication of a history of dietary simplification and antibiotic use.  Lactose intolerance, for example, results from depletion of lactose-degrading bacteria from the gut flora and can be remedied by simply eating lactose with probiotics for a couple of weeks.  Gut flora can adapt, but they need persistent exposure to diverse, i.e. non-processed, food.

Antibiotic Allergies Are Natural

Allergies develop from a combination of inflammation and compromised immunological tolerance.  Inflammation heightens processing of antigens for presentation to the immune systems, whereas loss of immunological tolerance means that aggressive immune responses are inadequately controlled.  Thus, innocuous environmental molecules are incorrectly recognized as pathogen components.  Allergies to antibiotics, such as penicillin, make sense, because the antibiotic is used to treat inflammatory infections and the antibiotic treatment eliminates the gut bacteria that are needed to develop gut lymphocytes (Tregs) to produce tolerance.  Antibiotics lay the foundation for immune system dysfunction that is central to many chronic diseases.

Healthy gut flora and a healthy immune system require:

• avoidance of antibiotics
• systematic (not simply eating yogurt) rebuilding of gut flora following diarrhea or antibiotic use; lack of an appendix means gut flora reservoir is gone
• eating a variety of vegetables; avoiding processed food
• using herbs and spices
• don’t overdo hygiene; gut flora diversity derives from bacteria that you eat and those that rub off acquaintances
• eat seasonally to increase diversity