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.

Dr. Oz’s Pain: Constipation and Bursitis

Dr. Oz has complained several times about his constipation and the pain he feels in his shoulders during surgery.  He has recommended numerous treatments.  Since I feel a friendly affection toward Mehmet after talking/shouting at his image on the screen for hours, I think that I should give him some advice to relieve his pain.

Hot, Cold, Topical Treatments Are Effective, but Don’t Penetrate Themselves

Dr. Oz keeps talking about how various topical applications penetrate the skin.  He has even recommended the use of an electrical system to carry pain relieving steroids into his tissue by what looks to be electrophoresis.  This is dubious.  I would recommend that he stick to the topical chemicals, e.g. capsaicin, menthol, that target the hot and cold sensors of the superficial layers of the skin and result in deep penetrating nerve signals that trigger anti-inflammatory responses in the underlying bursa.

Constipation Is Caused by Damaged Gut Flora or Dysbiosis

Dr. Oz, like most physicians, does not usually explain the causes of diseases, such as bursitis.  Unfortunately, when he tries to explain problems, such as constipation, he overlooks important aspects of the problem for a facile physical model.  In the case of bursitis, it is important to realize that the patient, Dr. Oz, is also constipated.  Constipation can be aggravated by dehydration or “holding it”, but in Dr. Oz’s case, the combination of bursitis, an autoimmune disease, with constipation (and gas) suggests the more complete explanation of dysbiosis or damaged gut flora.  Dysbiosis is what causes constipation, because bowel stools, poop, is mostly packed, hydrated bacteria that grow in the colon by digesting soluble fiber.  If you eat an apple a day, there is enough pectin and other plant polysaccharides, i.e. soluble fiber, to increase the volume of the stools to make one regular.  [Don’t be confused by the misconception promoted by Dr. Oz that the volume of stools results from insoluble fiber, such as in whole grains.  The husk part of whole grains is useless or unhealthy and grains in general are not needed for a healthy diet.]  

Flush Toilet Hero

Dr. Oz’s constipation suggests a damaged gut flora.  Since he is a physician, one would suspect that he has used antibiotics in the past few years and wiped out essential types of gut bacteria.  Dr. Oz probably followed his own advice and attempted to patch up his damaged gut flora with probiotics.  Unfortunately, as I have repeatedly explained, dairy probiotics don’t survive in the gut and cannot repair damaged gut flora.  But Dr. Oz is even harder on his gut flora.  He has recommended the use of colloidal silver throat spray when he has been exposed contagious germs.  Silver, although ineffective for its intended use, is very toxic to gut flora after it is swallowed.  Dr. Oz also subscribes to numerous approaches to house and body hygiene, which are probably occupational hazards for surgeons.  Hygiene is the enemy when it comes to ingesting bacteria lost to antibiotics.  The atomizing flush toilet is my gut flora hero for spreading contagious health.

Damaged Gut Flora = Damaged Immune System

Constipation is bad enough, but damaged gut flora can mean that some of the bacteria needed for the gut-based development of cells regulatory T-cells (Tregs) that keep the immune system under control, are missing.  Constipation can lead to deficient Tregs and that means a major predisposition to autoimmune disease and allergies.  [Fecal transplants cure autoimmune diseases and allergies.]  Antibiotics, silver, hygiene excesses and constipation suggest to me that Dr. Oz has been cruising toward some rude immunological sequelae.

Autoimmunity Results From Antibiotics, Dysbiosis and Compromised Tregs

Autoimmune diseases result when a trifecta of inflammation, compromised Tregs and appropriate antigens occurs.  Normally physical damage, such as abusive shoulder exercise, results in inflammation as the first step in healing.  The inflammation can rev up the immune cells in the local area of tissue damage and some of the proteins, such as lubricin, which lubricates the bursa, may have basic triplet amino acid sequences that lead to presentation to immune system cells.  But no antibodies against self tissues are produced, because the Tregs stop the process.  Healthy gut flora produce healthy Tregs and block autoimmunity.

Dr. Oz abuses his shoulder bursa during surgery, but it can’t heal properly, because he has damaged his gut flora and compromised his Tregs.  The result is the autoimmune bursitis from which he now suffers.  He can reduce the symptoms and inflammation with topical anti-inflammatory natural chemicals, but he needs to repair his gut flora to repair his Tregs and reduce autoimmunity.  In the mean time, he is contaminating his local environment, family and friends with his unhealthy bacteria.  I wonder if Dr. Oz’s friend, Dr. Mike Roizen also suffers from autoimmune diseases?

Prescription to Repair Gut Flora:  Anti-Inflammatory Diet, Soluble Fiber, Fermented Vegetables, Less Hygiene

KEEP YOUR TOOTH BRUSH NEAR THE OPEN TOILET 

Antibiotics, Gluten, Hashimoto's Thyroiditis and Baldness

My impression is that Hashimoto's is caused by a combination of an initial immune attack on the thyroid and incompetent regulatory T cells.  In most cases the immune attack on the thyroid is a secondary consequence of celiac/gluten intolerance, in which anti-transglutaminase antibodies attack transglutaminase bound to gluten in the intestines.  Transglutaminase  is an enzyme that is also produced by the thyroid (and hair follicles) and attack by celiac antibodies can enhance or inhibit thyroid hormone production (or baldness.)  Both Hashimoto's and celiac do not occur if the suppressive part of the immune system, i.e. regulatory T cells, is functioning.  

Antibiotics Compromise the Immune System

The major point here is that antibiotics disrupt normal bacterial biofilms that line the intestines and these healthy gut bacteria are required for development of regulatory T cells.  Compromise of Tregs leads to autoimmune diseases, e.g. celiac, Hashimoto’s and baldness, and also allergies.

Antigens/Allergens Have Basic Amino Acid Triplets

The antigens targeted in autoimmune diseases, e.g. tTG, anti-nuclear, TPO, and allergies form an obvious pattern.  All of these antigens and allergens have simple amino acid sequences (rare patches of three basic/positively charged amino acids) that enhance their presentation to the immune system to produce antibodies.  Nuclear proteins, for example, are frequent autoantigens and most of these proteins interact with nucleic acids (negatively charged) and have predictable patches of positively charged amino acids (arginine and lysine).  Other common autoantigens have basic amino acid (arg/lys) patches, because they interact with phospholipids (also negatively charged.)  Proteins with basic patches, e.g. HIV-TAT or heparanase, are also readily transported into cells and nuclei.  Peptides with these sequences are produced by action of stomach enzymes on proteins, e.g. milk lactoferrin, and are antimicrobial.

Allergies / Autoimmune Diseases Are a Predictable Consequence of Antibiotics

Doctors treat with antibiotics, but they fail to repair damage that they cause to gut flora.  The gut flora of most patients treated with antibiotics, especially those who are most fastidiously hygienic, never fully recover.  Constipation is a common symptom of severe dysbiosis and related immunoincompetence.  Probiotics are gut flora bandaids and do not survive as components of gut flora.

Gut bacteria are also needed for development of the aggressive part of the immune system.  Thus, autoimmune diseases can be treated with even more intense use of antibiotics, that will eliminate the rest of the immune system.  Since all vitamins are produced by gut flora as quorum sensing signals, antibiotics can also produce the exotic symptoms of vitamin deficiencies.

Antibiotics are essential to many therapeutic approaches, e.g. surgical procedures or therapy for chronic Lyme disease, but they must be used responsibly and treated patients must be subsequently tested to ensure a repaired gut flora and a functional immune system have been reestablished after antibiotics.  Long term antibiotic use needs special attention, e.g. deliberate Repair of Gut Flora or a fecal transplant.

Thus, I think that it is most likely that ever increasing antibiotic exposure and processed foods, coupled with obsessive hygiene have led to crippled gut flora (as observed in the simplified gut microbiomes of Americans), a net decline in suppressive Tregs and the observed increase of autoimmunity and allergies.  The competence of the immune system may be a major determinant in the course of infection with a pathogen that can produce chronic infections.

Vitamin C, Guinea Pigs, Limeys and Gut Worms

Scurvy and the Need for Vitamin C

Old timey sailors got the symptoms of scurvy, defective collagen and connective tissue, presumably because they stopped eating leafy greens that contained the needed vitamin C, aka ascorbic acid.  Primates/humans and guinea pigs are among the few animals that lack the ability to make their own ascorbic acid and therefore must eat a diet with a minimum amount of the vitamin to avoid a deficiency disease.  This is the conventional wisdom partially based on observation and experiment, but also founded on conjecture.

Parasitic Gut Worms Were the Natural Source of Vitamin C

I don't believe that vitamins are essential ingredients of a healthy diet, but rather I contend that all of the necessary nutritional chemicals are produced by the microorganisms of the gut.  I have previously discussed the gut flora (bacteria and fungi) as the source of most vitamins.  I wish to expand vitamin production to include gut fauna (animals).  I think that it is likely that intestinal worms are the historically natural source of human vitamin C.

Gut Bacteria Control the Development of the Immune System

The human gut actively communicates with the biofilms of bacteria and fungi that form a lining for the healthy gut.  The aggressive cells of the immune system that attack invading pathogens, develop in response to chemical signals from filamentous gut bacteria, and the suppressive cells of the other half of the immune system, which prevents attack on innocuous food antigens (to avoid allergies) or the human body itself (autoimmunity), develop in response to Clostridium ssp.  Thus, the immune system can be highly compromised, if the gut flora bacteria are damaged, e.g. by antibiotics.

Vitamins are Signaling Chemicals of Gut Biofilms

The communities of bacteria in gut biofilms are self-regulating by exchanging chemicals called quorum sensing signaling molecules.  Different species of bacteria and fungi in the biofilms produce and detect different chemical signals.  Since the biofilms are in intimate contact with the cells that line the gut and absorb dietary nutrients, it is not surprising that the biofilm signaling molecules are also absorbed by intestine cells.  Many of these biofilm signal molecules are vitamins, e.g. the B vitamins.  Gut bacteria are the natural source of most vitamins and healthy gut flora eliminates the need for eating vitamins in food or supplements.  Vitamin deficiencies are a symptom of a damaged gut flora.  Antibiotics and vitamin supplements can damage healthy gut biofilms.

Dietary Soluble Fiber Feeds Gut Flora

The human gut flora consists of a couple of hundred different species of bacteria in each person.  Those bacteria in aggregate can produce about a hundred thousand different proteins that focus on the digestion of food molecules that the upper gut cannot digest and absorb.  Since the upper gut can only digest proteins, fats and starch/sugars, that means that the gut flora eat the rest, undigested plant/animal polysaccharides.  Soluble fiber is the plant polysaccharides, e.g. inulin and pectin, that are digested and feed the gut flora.  The undigested polysaccharides include cellulose.  Lignin and some other plant polymers also pass through the gut and are eliminated.  The undigested stuff is called insoluble fiber and it also has bound phytate, which drags some metals such as zinc out with it.  That is why insoluble fiber, such as wheat bran, is not nutritious or healthy.  Insoluble fiber is also a minor contributor to the bulk of stools, which are made up predominately of the gut bacteria that have grown on soluble fiber.

Sea Voyages Damage Gut Organisms

The hundred of different species of bacteria in the gut change in proportions to adapt to different foods in each meal.  If the diet is fairly constant, then the diversity of the population gradually increases, just as the diversity of species in a tropical rain forest is greater than in a temperate forest.  This also explains why gut flora diversity is far less in the USA than in other parts of the world.  Americans are encouraged to eat diverse diets in the search for vitamins and superfoods.  Each dramatic change in diet makes it hard for the gut flora to adapt and the remaining bacteria are those that are generalists.  It might also be expected that early sailors who changed their diets dramatically when they went to sea, ended up with a highly compromised ship-board gut flora (and fauna.)

The Perils of Hygiene

I have a fascination for stories involving the potential of rampaging tigers.  Images of a tiger attempting to drag a hunter from his seat on an elephant or the need of a colleague to employ an armed bodyguard when capturing crabs from Malaysian Mangrove roots at night, linger in my imagination.  I still think about the report of Wallace guarding his derrière while collecting beetles in Bukit Timah, Singapore, in “The Malay Archipelago.”  Humans tend to be incompatible with lions and tigers and bears, and we wipe them out.  We do the same with bacteria, fungi and worms.  We wash our hands, flush the toilet, use hand sanitizers, kill weeds, spray pesticides, grow meticulous lawns/crops, dose ourselves with antibiotics and cleanse.  We are free of the threat of tigers, but we failed to see what else was lost during their extermination.

Probiotics Don’t Fix the Damage of Antibiotics

Antibiotics ravage gut flora.  It is no surprise that a course of antibiotics frequently leads to diarrhea or constipation, since normal stools require normal gut flora.  What is surprising is that physicians, e.g. Dr. Oz, seem to think that antibiotic decimated gut flora can be fixed with probiotics.  Sure, probiotics can provide a temporary bandaid, since Lactobacilli that would normally live on milk in the gut of newborns, are able to provide most of the functions of an adult gut flora.  But probiotics don’t survive in the adult gut and probiotics to not repair damaged gut flora.

Changes to Gut Flora are Permanent, Unless....

Gut bacteria are like wolves in Idaho.  If you don’t bring in new wolves and stop hunting them, you never again have wolves in the wilderness.  If you don’t bring in new bacteria and feed them, damaged gut flora does not repair.  Antibiotic treatment that wipes out the bacteria needed for development of the suppressive immune system will lead to autoimmune disease.  However, repairing the gut flora by flushing in new bacteria (fecal transplant) or gradually reintroducing new diverse bacteria with fermented foods, can also reverse autoimmune diseases as the immune system is repaired.

Parasitic Worms Were Lost at Sea

We think that vitamin C is only provided by plants that we eat, because we didn’t notice what was lost when we cleaned out the worms that typically inhabit the human gut.  Who would have thought that those inconvenient creatures were there for our own good?  We unknowingly compensated for the lost vitamin C production of the worms by incorporating foods rich in vitamin C in our diets.  Shipboard diets that eliminated bowel worms were augmented with limes rich in ascorbic acid.

Guinea Pigs Also Need Worms

It is interesting to note that the experimental animal used to replicate human nutritional requirements for vitamin C is the guinea pig, which is one of the few animals (in addition to bats and primates) that doesn’t make its own.  It is also interesting that guinea pigs (and bats?) commonly have intestinal worms that have to be purged from their bowels before they are used in the lab. 

Gut Flora and Fauna Provide Vitamins

My bottom line is that a normal, healthy gut contains all of the bacteria, fungi and worms to supply all of the needed vitamins.  I do, however, think that dietary vitamin C is a good replacement for one function of intestinal worms, even though I will be watching for other benefits ( Helminth therapy?) that were lost with the removal of these parasites.

Some points:

•   Many vitamins are signal molecules for gut biofilm quorum sensing.
•   Intestinal worms are the typical source for human vitamin C.
•   Vitamin D is a hormone produced in the skin in response to sunlight.
•   Vitamin supplements are unnecessary (problem?), if gut flora and fauna are healthy.
•   Modern diets and hygiene eliminate gut parasites, so food needs to supply vitamin C.
•   Chronic inflammation consumes vitamin C and eliminates production of vitamin D.

Dr. Oz on Gut Flora Repair

---  the other 200 posts  ---

Where is the hippo? Trying to repair a complex community of a couple of hundred different species of bacteria by just changing diet, is like a zoo trying to add hippos by building a new enclosure and supplying it with fodder. You can wait and wait, but you can't add new species without adding new species. Hippos don't appear by spontaneous generation and neither does E. coli or other gut bacteria. You have to ship in hippos from other zoos and after antibiotic-induced extinction of gut bacteria, you have to introduce or eat missing species of bacteria. Also just adding probiotics will not provide a lasting fix for damaged gut flora any better than adding more elephants or giraffes will improve the diversity of a zoo lacking hippos.

I am amazed that Dr. Oz and the medical industry can encounter symptoms of dysfunctional gut flora, e.g. constipation, food intolerance, autoimmunity, allergy, that are preceded by antibiotic treatment and not address the compromised species diversity of the gut. The involvement of gut bacteria in immune system function is documented in the biomedical literature. The lasting impact of antibiotics on gut bacteria is known. Then why do Dr. Oz and the rest of the medical industry just recommend probiotics, a half dozen different species of bacteria found in fermenting dairy products (think elephants and giraffes), to repair a decimated gut bacterial community? They seem to be perplexed and ask, "Where is the hippo?"

Generalizations about Gut Bacteria

Each healthy human maintains a subset of a couple of hundred of the couple of thousand different species of bacteria found in humans around the globe. The diverse community in each individual may differ in species, but has approximately the same complement of genes in people sharing the same diet.

• 1-200 different species of bacteria per person
• 1-2000 different species of human gut bacteria
• 1 million different genes among the different bacteria
• Most genes are involved in digesting plant carbohydrates, i.e. soluble fiber: inulin, pectin, fructans, algal sulfated polysaccharides, etc.
• Diet diversity, e.g. the Modern American Diet, reduces the diversity of the gut bacterial community, presumably because the rapid change in foods permits survival of only generalist bacteria that can digest many different foods.
• Simple diets produce gut flora diversity, but only if there is access to diverse bacteria.
• Health may result from diverse gut flora developed from a simplified diet and ample bacterial resources.
• Obesity and other diseases may result from simplified gut flora developed from a changing, complex diet and a sterile environment/isolation.
• Vegan and paleo extremes can lead to healthy gut flora diversity, if the gut bacterial community is permitted to adjust to the diet composition by avoiding rapid changes and providing diverse bacterial sources.
• Meat contains complex polysaccharides, e.g. glycosaminoglycans, such as chondroitin sulfate and heparan sulfate proteoglycans, which are bacterial fodder equivalent to soluble fiber.
• Probiotics are unique bacterial species that do not persist in the gut of adults, but dominate the gut of milk eating babies and stimulate development of the gut and immune system.
• Probiotic bacteria can temporarily provide developmental signals for immune system development that are normally provided by a healthy gut flora.
• Antibiotics cripple gut flora needed for development of the immune system.
• Common medicines have significant antibiotic activity and modify gut flora.

Damage to Gut Flora is Not Repaired by Diet Alone
There is little or no effort being made by the medical industry to develop approaches to repair gut flora damaged by disease, unhealthy diets or medical procedures. This is similar to a surgeon stepping away from removal of a diseased organ without closing the wound. Antibiotics leave a gut flora that will remain permanently damaged without systematic, monitored repair. It might also be suspected that disruption of gut flora by antibiotics and the introduction of large amounts of new foods, such as high fructose corn syrup and vegetable oils may contribute to or cause the modern prominence of obesity. After all, gain or loss of weight changes gut flora, obese individuals have damaged gut flora, and trading gut flora between fat and lean animals, trades weight gain/loss behaviors.

Sources of Bacteria to Repair Damaged Gut Flora

• We must eat new bacteria in order to replace bacterial species lost by antibiotics or unhealthy diets.
• Probiotics -- bacteria that aide gut function, commercially from dairy fermentation
• Fresh vegetables -- bacteria are on the surfaces of plants unless the vegetables are cleaned or cooked
• Fermented foods -- Bacterial growth leading to acid or alcohol production has beed used in the preparation and storage of many foods and provides a rich bacterial resource.
• Environment -- Bacteria are transferred to our hands and face from other people, pets and surfaces, unless hands and the body are continually washed. Sanitizers and frequent washing of hands and surfaces eliminate acquisition of environmental bacteria to repair damaged gut flora. Social isolation and hygiene block repair of gut flora.
• Replacement -- experimental replacement of damaged with healthy gut flora (fecal transplant) has been very effective in curing many diseases without significant risks, but is restricted by the medical industry.

Dr. Oz on Sweeteners: Sugar, Fructose, Insulin/Resistance, AGE, FattyLiver

….All 190 posts here….

I was shocked when Dr. Oz recommended a snack made with agave syrup. I had seen a previous program by America's representative of the medical industry in which he revealed the hazards of agave syrup as a new source of fructose. Now he just skipped over the use of this fructose syrup as a "natural" sweetener, even though it is even less healthy than high fructose corn syrup, HFCS. There seems to be a lot of deliberate confusion about sweeteners and since I am trained as a carbohydrate chemist, I will try to tell it as I see it.

General Information 

• Carbohydrates are not needed in your diet, since your liver can make all the blood sugar that you need from protein. Most diabetics can benefit from a low carbohydrate diet. 
•  Glucose, the blood sugar, is primarily responsible for turning on insulin production, so sweeteners (glucose, sucrose, HFCS, corn syrup) or dietary carbohydrates (starch, e.g. cereal, rice, pasta, potatoes, bananas) that are readily converted to glucose, cause blood insulin levels to rise. 
•  Fructose in any form (HFCS, sucrose, agave syrup) contributes to liver damage. Fructose is the most chemically reactive sugar. 
•  Artificial sweeteners, especially in soft drinks, do not contribute dietary calories, but they apparently increase insulin production and contribute to hunger, eating and obesity. 
•  Insulin production removes glucose from the blood, i.e. lowers blood sugar, by increasing glucose transport into fat cells. If glucose is in your blood, but insulin is not present, e.g. type I diabetes, then you get thin. If glucose is in your blood and insulin is present, then you get fat. If you are fat and glucose is still high in the blood and insulin is present, then the fat cells will die unless they shut off the insulin response, i.e. insulin resistance. Lowering the amount of carbohydrates, sweeteners/starch, in your diet makes it easier to control blood sugar levels and avoid hunger. 
•  Decreasing dietary carbohydrates means that calories have to be present in some other form and the answer is saturated fat. Most polyunsaturated fats, e.g. vegetable oils, except olive oil, are not healthy. The fats in meat, butter, eggs and coconut oil are the healthy choices supported by the biomedical literature, and along with vegetables, form the foundation of a healthy, anti-inflammatory diet. 

Central Metabolism Started with Fructose not Glucose 
All organisms convert sugars through a common series of enzymatic steps, called central metabolism, to a simple, three-carbon compound called pyruvate. Pyruvate can be used as a source of energy in mitochondria in the presence of oxygen or converted into alcohol or acids in various forms of fermentation. No matter what sugars are used, e.g. glucose, galactose, mannose, they are all converted in cells into derivatives of fructose. Thus, fructose is common to all organisms and can be considered to be the most primitive. So why is glucose usually considered to be the the start of central metabolism and why is dietary fructose dangerous?

Fructose is too Reactive to Transport 
The first cells used fructose as the starting material to make the building block molecules of cells, e.g. carbs, proteins, fats, nucleic acids, and energy in the form of ATP. Multicellular organisms, such as animals and plants had to move sugars from cell to cell. It would be obvious to transport fructose, since all other molecules could be converted into fructose, but the problem is that fructose is too chemically reactive, i.e. it reacts with proteins to form AGE. It is for that reason that fructose is converted by cells into glucose, which is less than one tenth as chemically reactive. In plants, the reactive groups of glucose and fructose are bonded together to produce sucrose, table sugar, which is much less reactive and can be transported in plant vessels at very high concentrations.

High Blood Sugar is Bad, High Fructose is Worse (AGE-ing) 
High levels of blood sugar, glucose, react with proteins to produce advanced glycation end products, AGE. Fructose in the blood produces these inflammatory compounds more than ten times faster. That is why fructose is a bad sweetener for diabetics. Eating fructose, e.g. agave syrup or sucrose, doesn't directly raise blood sugar/glucose levels, since it raises blood fructose levels, which is worse.

Fructose Fattens Livers 
Fructose is rapidly absorbed in the intestines and transported to the liver. The blood vessels of the liver remove fructose from the blood and it is rapidly converted into fat. Fructose in sweeteners has now surpassed alcohol as the major source of liver disease.

Sweeteners
Fructose is ten times sweeter than glucose, and that is why cheap forms of glucose, such as corn syrup, are treated with enzymes to convert some of their glucose into fructose to produce high fructose corn syrup. Corn syrup is not as sweet as pure glucose, because the syrup contains a mixture of short chains of glucose of different lengths, and the chains decrease in sweetness with length. By changing some of the glucose into fructose, the HFCS can be made as sweet as table sugar, sucrose. Corn subsidies keep corn syrup cheap and make HFCS very profitable. Unfortunately, the HFCS contains fructose and therefore it has the liver toxicity and AGE-forming inflammation of fructose.  Agave syrup is like HFCS on steroids.

Agave Syrup is Fructose 
Agave syrup contains fructose produced by industrial processing of the fructose polysaccharides, inulin, in agave extracts. I cannot understand why anyone would use this commercially processed fructose as a sweetener. It doesn't raise blood sugar as much as sucrose, because there is much more fructose than sugar (like very high fructose corn syrup) it raises blood fructose levels instead, which is much, much worse.

Sugar Makes You Hungry 
The human body can only use simple sugars, e.g. glucose, fructose, sucrose, or starch. Body enzymes convert sucrose into fructose + glucose, and starch into glucose. Other carbs, such as soluble fiber, are only digested by gut bacteria in the colon. The conversion of starches to glucose begins with enzymes in saliva in the mouth and is completed in the upper part of the digestive tract. Starch should be considered as a simple sugar, because it causes a rapid rise in blood sugar, just like glucose. It may actually be faster than table sugar. The rapid rise of blood sugar causes a rapid increase in blood insulin, which in turn rapidly removes sugar into fat cells. The rapid rise and fall of blood sugar provides the experience of hunger. That is why cereal, e.g. oat meal, in the morning produces intense hunger just a few hours later. Actually, oat meal is not quite as unhealthy as most cereals, because it also has some soluble fiber to feed gut flora. A protein and fat breakfast, e.g. bacon and eggs, does not produce rapid hunger, because it does not produce a large insulin rise and glucose fall.

Insulin Resistance is Better than Death by Glucose 
As fat cells accumulate glucose as a result of blood sugar transported into the cells in response to insulin, more and more of the glucose is converted into fructose and on to pyruvate. The pyruvate accumulates in mitochondria and ATP production is saturated. This is potentially lethal for the cells, because the conversion of pyruvate into ATP is accomplished by removing high energy electrons as the pyruvate is converted to carbon dioxide. The high energy electrons accumulate in the inner membranes of the mitochondria and if they are not systematically converted to low energy electrons and dumped onto oxygen to produce water, reactive oxygen species, ROS are produced and the result is inflammatory oxidative stress. Antioxidants would be needed to protect from major cellular and organ damage. The cells protect themselves by responding to the accumulation of high energy electrons on the mitochondria by shutting down the response to insulin and blocking further intracellular glucose accumulation. This is insulin resistance.

Carbs: Never too Low 
Dietary carbs, such as sugars and starches are not needed, because the liver can convert protein into glucose. Thus, diabetics, who have a hard time balancing their dietary intake of carbs with the insulin that they inject, can simplify the process by routinely eating less carbs spread through many meals and triggering some glucose production by the liver. Craving for carbohydrates/sweets can be dramatically reduced simply by eating fewer carbs and avoiding insulin production that can lead to more dramatic swings of blood sugars and hunger. Using this strategy, I am hungry less than once a week.

Healthfulness of Sweeteners 
 --from Most Healthy....

• Stevia - is a diterpene glycoside (I previously made the silly error of listing it as a protein) (erythritol, another simple sugar alcohol is added to make the stevia granular) that is sweet, doesn't raise blood sugar, no insulin spike and no AGE 
• Glucose - raises blood sugar, spikes insulin and produces AGE 
• Xylitol - is a sugar alcohol that inhibits dental bacteria, doesn't raise blood sugar, no insulin spike or AGE 
• Corn Syrup - raises blood sugar, spikes insulin, produces AGE, low sweetness  
• Sucrose - raises blood sugar, spikes insulin and produces AGE, and liver damage 
• Honey - is half fructose and half glucose, raises blood sugar, spikes insulin, produces high AGE and may damage liver  

• Artificial Sweeteners, aspartame, sucralose, saccharin, etc. - don't raise blood sugar or produce AGE, but may have other risks, including hunger 

• HFCS - is high fructose corn syrup, raises blood sugar and spikes insulin, produces very high AGE and causes liver damage 
• Fructose - doesn't raise blood sugar or spike insulin, produces very high AGE and causes liver damage,  does not produce satiety and may encourage consumption of other sugars 
• Agave Nectar - is mostly fructose, doesn't raise blood sugar or spike insulin, produces very high AGE and causes liver damage 

 ...to Least Healthy or Health Risk--

Milk Casein, Amyloid, Pasteurization, Homogenization

Milk is a very special food for mammalian babies. It provides essential nutrients; stimulates development of the gut; promotes the growth of the unique neonate gut flora; and kills everything else. Milk is anti-bacterial, anti-fungal and anti-viral. It is used in fruit orchards as a pruning tool dip to prevent the spread of disease between trees, and it is used as a foot dip after ceremonial walking on hot coals. But is cow's milk healthy for adult humans and is milk compromised by pasteurization and homogenization?

Mother's Milk is Fierce
Milk as it is transferred from breast to baby is loaded with molecular weapons for the protection of the baby's respiratory and digestive systems. Cells from the mother are transferred along with the milk and quickly spread out on the surface of the mouth and digestive system to patrol for pathogens. The mother's immune system detects potential risks as the baby's mouth contacts the mother's lymphatic system at the breast, and the antibodies that are subsequently produced are transferred into the milk. Enzymes in the milk digest bacterial cell walls and other milk proteins are converted into anti-bacterial peptides in the baby's stomach before ultimately being digested into amino acid nutrients. Many of the fat/lipid nutrients in milk are also anti-bacterial or anti-viral. Most of the carbohydrate in milk is the simple disaccharide lactose that most bacteria can't use for food. The remaining 10% of the carbohydrates are extensions of the lactose to make galacto-oligosaccharides (GOS, a.k.a. bifidus factor) that are toxic to all but the few bacterial species that make up the highly specialized microbial community of the human baby gut flora. (Cow's milk has an entirely different composition, e.g. lacks bifidus factor, and supports a different gut flora.)

Milk is Liquid Fat
It is hard to transport fat in water, because it isn't soluble. That is true for blood or milk. We have all heard about good and bad cholesterol, LDL and HDL, and the problems of transporting blood lipids from gut to liver to tissues. Specialized carrier proteins are needed for lipid transport in blood and the same is true for milk. Caseins are the milk proteins that coat droplets of fats that make milk white and then form digestible curds in response to the baby's stomach acid and digestive enzymes. We exploit the natural curd forming response of milk proteins and lipid droplets to form yogurts and cheeses.

Pasteurization and Homogenization Put Milk in the Dairy Case
Milk behaves optimally when immediately transferred from the mother's mammary tissue to the baby's digestive tract. Bacteria that contaminate breast milk are quickly killed by cellular and molecular defenses of the milk itself. Thus, breast milk has a long storage life at room temperature, chilled or frozen. The natural defenses of milk also permit regional milk banks, where donated milk is minimally processed and screened, for subsequent use by hospitals to avoid problems, such as necrotizing colitis, associated with the use of artificial feeding substitutes. Commercial preservation of cow's milk in stores has resulted in attempts to extend the shelf-life by heat treatment (pasteurization) to provide additional protection from microbial contamination and homogenization to prevent curd formation.

Milk is for Babies
So why isn't milk the perfect food? Part of the reason may come from the highly specialized and essential role of milk for mammals like people. Millions of years of extreme selection pressure have made sure that every woman produces ample milk for all of her babies. Until very recently, if the baby could not successfully nurse, it would die. That made breast milk the perfect food for babies and milk was integral to the development of the baby gut, baby gut flora and baby immune system. But that didn't mean that cow's milk would be a healthy commercial food for human adults.

Milk Processing May Accentuate Casein Amyloid Fiber Formation
Proteins are made of a long sequence of a thousand amino acids. At each of those thousand positions there is one of twenty different amino acids. Some of the amino acids are hydrophilic and bind to water, whereas other amino acids are hydrophobic and bind only to lipids. Proteins in water fold and unfold in thousands of alternative configurations until the final shape is reached in which there is not enough energy in the molecular vibrations and movements of the water molecules to knock the protein into an alternative shape.

Heating/pasteurization and torturous mixing/homogenization can force milk casein and fats into new configurations that make the proteins stackable into fibers/amyloids. These milk protein fibers may be of interest, because protein fibers are important in many diseases, e.g. type I diabetes, Alzheimer's disease. The problem with amyloids, is that these fibers form a natural repetition of the same amino acid on each of the stacked proteins. This repetitive amino acid, e.g. positively charged lysine or arginine, can provide a binding site for a similarly spaced, oppositely charged molecule, such as heparin, which is involved in dragging molecules from the surface into cells. Beta amyloid fibers with positively charged amino acids in a band along their edges are what kills nerve cells in Alzheimer's disease.

Research has recently demonstrated that milk casein forms amyloid fibers in response to pasteurization and homogenization. It would be interesting to know if these fibers bind to heparin and if these fibers are toxic to intestinal cells.

I have raw cream from grass fed cows in my morning coffee and my three daughters never tasted formula.

Dr. Oz, Pain, Hot/Cold Receptors

The production of endorphins in tissues in response to nerve stimulation relieves inflammation and pain. Dr. Oz and the medical community seem to forget that hot and cold receptors in the skin can be readily triggered by natural products in foods, to stimulate the release of endorphins and treat inflammation in nearby tissues.

Hot and Cold Don't Easily Penetrate the Skin
Athletic trainers commonly apply hot and cold packs to avoid swelling and inflammation from injuries, and they are always discussing the virtues of various hot/cold regimens. They ignore the extraordinary efficiency of the circulatory system in regulating tissue temperatures and avoiding temperature changes. They also ignore the fact that chemical "hot and cold" salves and ointments are effective without actually changing the temperature of the skin. The essential observation is that triggering hot and cold sensing nerves is more important than changing the temperature of the damaged tissues.

Common Food Molecules Activate Hot/Cold Nerve Receptors
Peppers are hot, because they contain capsaicin that binds to protein receptors on nerves in the skin, which results in the brain sensation of heat. Camphor and castor oil bind to the same receptors. Menthol binds to corresponding cold receptors. Vicks Vaporub has both menthol and camphor, and therefore stimulates both hot and cold sensors. Vicks is also an effective treatment for tissue inflammation.

Vicks and Castor Oil are Effective Treatments for Pain and Inflammation
A bee sting or a burn on a finger will produce reddening, swelling and pain, that can be quickly alleviated by applying Vicks to the wrist. The hot and cold sensors of the wrist would be stimulated and the returning nerve signals would be generally detected in the whole hand and produce endorphins that would calm the inflammation and sooth the injured finger. In a similar way, an inflamed joint can be treated by topical menthol and castor oil, and lower abdominal discomfort can be alleviated by castor oil applied to the belly.

Tendonitis can be Treated with Peppermint Soap
I have treated a persistent tendonitis in my shoulder by applying Dr. Bronner's Peppermint Soap liberally to my shoulder and waiting a few minutes before continuing my shower. This gentle, persistent treatment produced relief within a week. This was a cure for this persistent inflammation and pain. It also works on joints.

What Dr. Oz needs to communicate is that there are simple ways to stimulate hot/cold receptors that have nothing to do with changing the temperature of deeper tissues, but these treatments are very effective in stimulating general endorphin production that reduces troublesome inflammation and pain. As an addendum, vagal stimulation, i.e. through yoga postures such as shavasana or the Valsalva maneuver, can produce a reduction in general inflammation.

New Antibiotics, Biofilm Inhibitors, Vitamin Deficiency

I was not expecting my recent reading of an article on femtosecond reaction kinetics to produce another discussion of quorum sensing, biofilms and vitamins. The idea behind the article was to identify new targets for drug design based on the ephemeral transition states that occur as enzymes bind substrates, stabilize transition states and yield product molecules. Drugs that mimic the transition states make good enzyme inhibitors. One of the target enzymes for the control of disease is an enzyme, MTAN, involved in the synthesis of quorum sensing molecules that orchestrate the construction of common biofilms. The idea is to inhibit MTAN and also avoid selection for antibiotic resistance. Unfortunately, targeting quorum sensing molecules also may produce vitamin deficiencies, since many of these molecules, in this case vitamin K, are also quorum sensing molecules.

Drugs have too many Side Effects
Specificity in the binding of molecules to the thousands of proteins that are coded by the ca. 20,000 human genes depends on a very tight fit between the molecular "key" and the binding site "lock" of the protein. Just as in physical world, a small key/drug molecule with limited surface detail is not as safe/specific as a larger key with many surface features, and a larger lock/enzyme active site that is harder to pick/has fewer interactions with random enzymes. Unfortunately, most drugs are small molecules with limited surface features that make them like molecular skeleton keys that produce many side effects by interacting with unintended proteins/enzymes.

Transition States are more Specific
A recent focus on drug research is to exploit molecular computation and modeling to design molecules that will bind to the part of an enzyme that actually participates in binding substrates and catalyzing chemical reactions. These designed molecules can interact with an expanded region of the enzyme and bind more strongly than the normal substrate. The designed molecules can be very effective inhibitors that will not react as nonspecifically as inhibitors identified by trial an error, e.g. statins.

Biofilm Inhibitors are Targets for Antibiotic Development
The enzymes involved in the synthetic pathways of biofilm quorum sensing signals have been identified and powerful inhibitors of some of these enzymes have now been designed and synthesized. These inhibitors are very effective in inhibiting biofilm formation by some common bacterial pathogens (and essential gut flora.)

Biofilm Inhibitors will also Block Vitamin Production in Gut Biofilms
The new biofilm inhibitor antibiotics may have enhanced specificity, but they target enzymes that also provide essential functions in biofilms that are needed for healthy gut and immune system function. Many of the vitamins that are produced by gut flora are also quorum sensing signal molecules in healthy gut biofilms. Thus, blocking MTAN to block biofilm formation of a pathogen, will also block gut synthesis of vitamin K, which is made in gut bacteria using the MTAN pathway. These inhibitors would be expected to be particularly damaging to the specialized gut flora of breastfed babies, since these gut bacteria are known producers of vitamin K.

Genetics of Food Intolerance

Food intolerance is based on missing bacteria in the the gut rather than inadequacy of human enzymes, e.g. lactase, or altered immune system.

I make the extreme statement that food intolerance is not genetic, to emphasize that the vast majority of intolerance can be cured by changing the bacterial composition of the gut's microbiological community, the gut flora, rather than attempting to accommodate a permanent deficiency. The two common "intolerances" that are offered by my readers to invalidate my sweeping statement are lactose and gluten (celiac) intolerance.

Lactose Intolerance is Not Due to Inadequate Lactase
Everybody has the same gene for lactase, but some people have altered upstream control elements and continue to express lactase in their intestinal cells after infancy, whereas others don't. The racial pattern of adult lactase expression is an interesting note on human evolution, but is irrelevant with respect to an individual's ability to tolerate the lactose sugar in dairy products.

Lactose is the major sugar present in milk and the ability of the intestines to utilize lactose directly like glucose is a selective advantage for human evolution. Absent that ability, lactose would just pass through the gut without impact. However, bacteria in the colon also have lactose digesting enzymes. These bacteria produce hydrogen and methane gases, and these products in turn can feed other bacteria. If all of the products are consumed, then the lactose has been treated as a soluble fiber and the result is more gut bacteria and a happy gut. If some of the bacteria are missing, then the lactose acts as a laxative, e.g. lactulose, and the bowels are not so happy.

All that is needed to cure lactose intolerance, as in all food intolerances, is to provide the gut bacteria that are missing to fully metabolize the offending sugars or polysaccharides. Just continuing to eat dairy without also eating or introducing new species of bacteria into your gut, will just provide more symptoms, but eating yogurt still containing live probiotic bacteria (Read the label. Any live bacteria listed will work.) that have the enzymes to ferment lactose, will lead to a rapid cure. (See reference below.) As the fermenting bacteria grow in the gut, they transfer their genes to gut bacteria in the biofilms lining the gut and these new species of bacteria keep the lactose out of trouble.

The point is that having a food intolerance means that the aggregate of all of the genes in all of your gut microorganisms is lacking the genes/enzymes needed to completely digest a food component. In the case of lactose intolerance, the missing genes are present in typical probiotics, bacteria that grow on milk/lactose.

Celiac is not a Typical Food Intolerance
Celiac is a complex interaction between major toxic proteins in wheat (gliadin), detox gut enzyme (tissue transglutaminase, tTg) and antibodies. Gliadin is a wheat protein adapted to attack the intestines of herbivores. Herbivores, such as insects and humans, can in turn protect themselves from gliadin and other polyglutamine proteins with the enzyme transglutaminase. tTg binds to glutamines in gliadin and converts them to glutamic acids. Unfortunately, while the gliadin is bound to the tTg, inflammation can predispose the gut to present these proteins to the immune system for processing to trigger antibody production. This is the start of the autoimmune disease.

The major histocompatibility antigens (MHAs) code for the proteins that display fragments of proteins on cell surfaces for antigen presentation and immune response. There is a lot of MHA variation and evolutionary adaptation. Some MHAs favor antibody production to gliadin and tTg. This just shows that celiac and grain/gluten intolerance is not a typical food intolerance, which will be remedied by simply altering gut bacteria, even though establishing gut bacteria that metabolize gliadin or that reduce autoimmunity, may be part of the cure.


Enhancing Gut Flora is Part of the Cure for all Autoimmune Diseases
There are rare food allergies, even though the majority are misdiagnosed intolerances. The production of antibodies to food antigens is a symptom of the breakdown in communication between the gut immune system and gut flora. Particular species of bacteria are responsible for the development of both the aggressive and suppressive components of the immune system, which occurs in the lining of the gut. Loss of the suppressive cells, Tregs, can result from unhealthy diets and exposure to antibiotics, and results in autoimmune disease, in which the aggressive immune system is out of control and attacks self antigens.

Symptoms of all autoimmune diseases can be improved by reestablishing normal control of the aggressive part of the immune system via healthy gut flora. Clostridium species of bacteria normally induce healthy development of the suppressive immune system and these types of bacteria are common in soil clinging to fresh vegetables prior to extensive washing. Which of the bacteria that are eaten become established in the gut flora is unpredictable, because the bacteria interact with each other, food and cells lining the gut. The only safe and simple procedure currently available is the fecal transplant. Some experimental fecal transplants are facilitated by the use of encapsulated freeze-dried gut flora. There is great resistance to this simple, safe, cheap approach from the medical industry.

Reference:
Almeida CC, Lorena SL, Pavan CR, Akasaka HM, Mesquita MA. 2012. Beneficial Effects of Long-Term Consumption of a Probiotic Combination of Lactobacillus casei Shirota and Bifidobacterium breve Yakult May Persist After Suspension of Therapy in Lactose-Intolerant Patients. Nutr Clin Pract., 27(2):247-51.

Dr. Oz, Vitamins, Biofilms

Vitamins supplement enzyme action, but they are produced by gut flora for biofilm communication.

Dr. Oz and the general biomedical community promote the idea that vitamin supplements or in foods are needed or improve health. Of course, several research studies show that typical multivitamin supplements or the levels of vitamins in "enriched" foods do not provide improvements in health. Since gut flora produce all of the needed vitamins, this should be no surprise. But why do gut bacteria release vitamins needed for the normal functions of the human body?

Vitamins are Enzyme Cofactors

Vitamins are small molecules that bind to particular cellular enzymes and provide functions that can't be provided by proteins. Enzymes are linear strings, polymers, of about a thousand amino acids. The 23,000 human genes code for the sequence of amino acids in as many enzymes. The amino acid strings fold up systematically into three dimensional balls that bring together chemical groups of the amino acids that can catalyze biochemical reactions. The twenty different amino acids in proteins are limited in the scope of their reactions. Binding of some metabolic products, such as vitamins, expands the types of reactions possible. Vitamins are enzyme cofactors. Bacteria can synthesize all of the vitamins needed for metabolism, but humans can't.

Vitamin D is a Hormone

Vitamin D is not a typical vitamin.  It is not an enzyme cofactor, but rather it is a steroid hormone that is produced in the skin from cholesterol through the action of ultraviolet light. The production of antibacterial peptides in the small intestines, for example, is a response of intestinal cells to vitamin D. Exposing arms and legs to sunlight produces about 10,000 IU of vitamin D per minute. (Typical supplements contain only 1,000 IU.) Production of vitamin D is reduced by skin pigmentation, sunscreen and inflammation. People exposed to daily sunlight for hours in San Diego, for example, may still be deficient in vitamin D, if their production of vitamin D has been shut down by chronic inflammation, as indicated by typical inflammatory conditions, such as arthritis, allergies, inflammatory bowel diseases, obesity, dental/oral infections, prostatitis, thyroiditis and other autoimmune diseases.

Vitamins are Produced by Gut Biofilms

People with healthy, diet-adapted gut flora, can subsist on very limited diets without vitamin deficiency diseases, because all of the vitamins can be obtained from bacteria growing in films coating the lining of the gut. These biofilms are complex communities of dozens of different bacteria and fungi. The bacteria synthesize polysaccharides in which these and other bacteria and fungi become embedded. The biofilms release vitamins that are taken up by intestinal cells to provide the needs of the body.

Vitamins are Chemical Signals for Biofilm Assembly

Bacteria, such as E. coli, do not form biofilms, if they are just grown at low concentrations on laboratory nutrients. If the concentrations of bacteria become very high, however, the bacteria respond by activating genes that coordinate biofilm formation. Bacteria detect the presence of other bacteria by releasing and detecting chemical signals in a process called quorum sensing. The chemical signals used in quorum sensing and biofilm maintenance are vitamins. Thus, human intestines are adapted to exploit the presence of biofilms and vitamin secretion. Humans need not synthesize vitamins, because they are always produced by gut biofilms as an essential biofilm function.

Antibiotics and Multivitamin Supplements

Antibiotic use is known to disrupt gut flora and produce vitamin deficiencies. Killing off healthy gut biofilms with casual use of antibiotics should be anticipated. The medical industry is remiss, however, in not repairing gut flora after medically mandated antibiotic use. Probiotics can temporarily supply some of the functions of the hundreds of bacterial species in each healthy individual, but they do not replace complex biofilms.

 The vitamin production of some of the bacterial species eliminated from the gut by antibiotics can be replaced by vitamin supplements, but supplements may disrupt the normal vitamin/quorum sensing communication and further disrupt biofilms. Thus, vitamin supplements may be unhealthy, if they disrupt biofilms that are necessary for healthy function of the gut-based immune system, which is needed to avoid, for example, allergies and autoimmune diseases.

Major Points about Vitamins, Biofilms and Health

• Health requires gut biofilms to supply vitamins and control the immune system.
• Biofilms produce and use vitamins for maintenance of biofilms.
• Eating vitamins may disrupt normal biofilm formation.
• Antibiotics disrupt gut biofilms and cause vitamin deficiencies and immune system disfunction.
• Biofilm repair requires ingestion of missing bacterial species (150 total) and may be inhibited by excessive hygiene.

Dr. Oz, Constipation, Soluble Fiber, Food Intolerance

--- all 200 posts here ---
The medical industry doesn't seem to understand the basics about the interaction of gut flora with food and the immune system.

I respect Dr. Mehmet Oz for creating a media personality to communicate medical information for public consumption and I know that there are many constraints placed on his freedom to discuss his personal and professional insights on health. That said, it seems to me that the public Dr. Oz, the voice of mainstream medicine and to some extent the food industry, fails to understand some essential features of the transformation of food to poop.

Dr. Oz has described on his television series, the impact of major disease on diagnostic changes in the color and appearance of poop, but he doesn't seem to understand that poop is mostly bacteria that have grown in the gut. The major implication of the predominance of gut bacteria in poop is seen in constipation. The pounds of bacteria in the colon provide the bulk and hydration of the poop, and when the bacteria are not abundant, the result is compacted, undigestible dietary fiber, which is the hard poop of constipation. That is why antibiotics, which have the major effect of killing gut bacteria, result in constipation. Chronic use of antibiotics, or frequently even a single use, can produce prolonged constipation.

The impression that I get from listening to Dr. Oz discuss soluble fiber, is that these food polysaccharides pass through the small intestines and then contribute to the texture/hydration of poop. This would be the case, if there were not bacteria in the gut, because the only polysaccharides/carbohydrates digested by human enzymes in the gut are starch and sucrose. Plants (and animals) produce hundreds of other types of polysaccharides that can only be digested by bacterial (and fungal) enzymes. All of the types of polysaccharides, abundantly present in fruits and vegetables, that can be digested by gut bacteria are called soluble fiber. (Undigestible fiber, such as grain fiber, is of no benefit.) Soluble fiber is the main source of food for gut bacteria and is also converted into the short chain fatty acids, e.g. acetic acid, that are the major nutrients for the human cells that line the colon. Thus, soluble fiber, such as the inulin in leeks or the pectin in apples, is essential for healthy poop and intestines.

Dr. Oz advises eating dairy and fermented foods with their live bacteria to supplement gut flora and to compensate for antibiotic treatments. This suggests that providing just a few different species of fermenting bacteria, probiotics, can produce a healthy community of gut bacteria. Unfortunately, each human gut requires hundreds of different species of bacteria that are not present in common dairy products, such as yogurt. The hundreds of different types of bacteria needed for a healthy gut are normally acquired from other people and animals, and from uncooked, raw vegetables. Cooking and excessive sanitation eliminates the exchange and acquisition of healthy bacteria. Exposure to antibiotics can lead to a lasting deficiency of gut bacteria that is unrecognized by modern medicine.

Dr. Oz recommends that people who have trouble eating certain foods or have good intolerances, should avoid the problem foods. This suggests that the problem is somehow in the intolerant person, even though there are no genes for food intolerance and very few cases of food intolerance result from an immune reaction. Food intolerance is actually the inability of an individual's incomplete gut flora to digest certain types of food. Antibiotics, for example, can kill off species of bacteria that are needed to completely digest certain types of soluble fiber or other plant products, phytochemicals, so instead of producing the needed short chain fatty acids, other irritating molecules are produced and the digestive system is upset. Simple intolerances, such as lactose intolerance, can be remedied by just eating small amounts of yogurt containing fermenting bacteria, probiotics, that have the genes for enzymes that can digest lactose. In a couple of weeks, most people are permanently able to tolerate lactose. More complex intolerances may require more persistent pursuit of the missing bacterial species by eating many different types of raw vegetables with clinging soil bacteria. The medical community has failed to acknowledge the need to repair gut flora compromised by antibiotics and to provide simple guidelines for reacquiring missing gut bacteria.

Dr. Oz provides a great service by promoting some healthy ideas, but it would be even better if he helped the public to understand how the gut and gut flora produce healthy poop.

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.