Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:
Anti-Inflammatory Diet and Lifestyle.
There are over 190 articles on diet, inflammation and disease on this blog
(find topics using search [upper left] or index [lower right]), and
more articles by Prof. Ayers on Suite101 .

Thursday, January 22, 2015

Essential Oils, Phytoalexins, Drugs Are All Antibiotics

---  the other 200 posts  ---
Superbug multidrug resistant plasmid
A recent, informative article by Tori Rodriguez for The Atlantic suggests that,

I want to discuss other ramifications of using essential oils as antibiotics to avoid multiple antibiotic resistant superbugs.

The logic for using essential oils in place of medical antibiotics is compelling: 
  • Essential oils are extracts of plants, which have myriad traditional uses, including food.
  • Most antibiotic use is to increase livestock production. 
  • Antibiotics selectively kill gut bacteria in livestock and make them obese.
  • Antibiotic resistance occurs within a week of use in livestock (or people.)
  • Medical antibiotics are quickly losing efficacy.
  • Antibiotic resistance genes quickly move from agriculture to superbugs to people.
  • Plants/essential oils contain natural antibiotics that kill gut flora and increase livestock productivity.
  • Resistance to essential oil antibiotic activity is slower, because of simultaneous use of multiple antibiotics.

Obesity is a Symptom of Antibiotic Damage to Gut Microbiome
Antibiotics make meat fatter
We may enjoy a fat marbled steak, but the corn and antibiotics used to produce that mouth-watering plate of satiety, is not so healthy.  Corn and antibiotics make that meat on the hoof fit for human consumption, but the cattle are quickly dying and the fat marbling is a symptom of cattle metabolic syndrome.  The corn and antibiotics disrupt the bovine gut microbiome and alter energy flow.  The result is prime beef. 

As It Is with Cattle, so It Is with Middle Americans
General descriptions of Americans with metabolic syndrome and steers ready for the abattoir are similar.  That should not be surprising, because both are caused by damaged gut microbiomes and consequences of metabolic syndrome.  Americans routinely damage their gut microbiomes with antibiotics (processed food, etc.) and the major symptoms of the resulting gut dysbiosis are chronic inflammation, depression, autoimmune diseases, obesity and metabolic syndrome.  Repairing gut microbiomes reverses all of these symptoms. 

But Essential Oils Are Just Natural Antibiotics
Essential oils are natural antibiotics
Is it better to use essential oils than medical antibiotics to fatten cattle or treat Lyme disease or hospital infections such as C. diff.?  Most pharmaceuticals were derived from plants or fungi and were originally used to kill microorganisms, i.e. they were natural antibiotics.  We call these phytochemicals by a variety of names, e.g. antioxidants or essential oils, but they are more appropriately called phytoalexins, all natural, all plant, all toxic antibiotics.  It is entertaining that essential oils have had so many different traditional and pharmaceutical uses, and yet they have always been experienced by microorganisms (and our livers) as simply toxic.  Essential oils do have the significant advantage of being a mixture of antibiotics and might be very useful where pharmaceutical antibiotics have problems.  The toxicity of essential oils, especially toward gut bacteria, should not be ignored.

Resistance to Essential Oils as Antibiotics
Antibiotic resistance develops in sewage
I previously kept track of laboratory strains of bacteria by simply exposing large numbers of the bacteria to an antibiotic and selecting for the rare individual that had already spontaneous mutated (DNA replication error of one in a million).  We could then use the new drug resistant strain in experiments and identify it by its resistance.  The same thing happens to your gut bacteria with an overnight exposure to an antibiotic.  And of course it also occurs immediately in livestock exposed to antibiotics or in sewage plants where tons of antibiotics and gut bacteria are mixed.  Resistance to each of the chemicals in an essential oil also would rapidly occur, if bacteria were exposed to each alone and in a  toxic concentration.  This is repeatedly observed, since commonly used drugs are just individual components of essential oils that have been produced in large amounts in pills and marketed based on their predominant physiological activity, rather than just another antibiotic.  Thus, resistance to a statin or Metformin, as antibiotics, could be easily observed (even on multiple drug resistance plasmids), but is just ignored.

Essential Oils Are just Mixtures of Natural Antibiotics
Statins from fungal antibiotics
The impact of essential oils on gut microbiomes is unpredictable, because the composition of essential oils is highly dynamic and so are gut microbiomes.  Each component of an essential oil has a different spectrum of toxicities to hundreds of different target proteins to each of the hundreds of different species of bacteria in the human gut.  Ingested essential oils are modified by the detox enzymes of the intestine and liver.  The modified phytochemicals have different toxicities and act as additional antibiotics.  Mixtures of antibiotics, as in essential oils, less likely to select for resistance than individual antibiotics, but an antibiotic is still just an antibiotic, regardless of whether it is straight from the plant or via a pharmaceutical salesman. 

Common Medicines Are the Source of Superbugs

Common meds are antibiotics
Doctors with prescription pads and steers eating antibiotics are blamed, I think unjustly, for the crisis of antibiotic resistance.  The real culprit is you taking NSAIDs, statins, proton pump inhibitors, antidepressants and other common medicines.  Since they are all developed from plant antibiotics, they are still antibiotics, and they still select for antibiotic resistance.  It is important to remember that pharmaceuticals are repurposed natural antibiotics from plants.  The answer to the superbugs that are resistant to all of the common antibiotics is to dramatically reduce the use of all pharmaceuticals.  The initial goal should be a 90% reduction.  Costly pharmaceutical chemicals could be replaced with preventive diets and less disruptive manipulations of gut microbiomes, e.g. ingestion of capsules containing freeze-dried gut flora.  This more gentle approach to health care would also provide huge cost savings, as well as vastly improving health.

Monday, January 19, 2015

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

The year 2014 began with my posts on damage to the gut microbiome 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 II   — Curing Autoimmunity and Allergies,



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 microbiome 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 microbiome 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 microbiome 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 microbiome is clearly a major factor in health and sickness.  Antibiotics that kill bacteria, damage the gut microbiome.  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 microbiome, 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.

Friday, January 2, 2015

Frankincense and Myrrh, Terpenoids

 --- the other 200 posts ---
Frankencense Resin
 'Tis the season to discuss phytochemicals.  Plants produce a vast array of organic chemicals starting from molecules produced by all organisms, including humans.  Essentially all of these phytochemicals are potent adaptations to kill.  Phytochemicals kill plant pathogens, bacteria and fungi, as well as insects.  Thus, the natural, plant extracts that humans use for flavor enhancers (herbs, spices, and teas), fragrances, recreational/medicinal mind and attitude modifiers (alkaloids, psychopharmaceuticals, etc.), herbal medicines, etc. are present in plants, first and foremost, as antibiotics and insecticides.  Humans have evolved to taste (bitter) and smell phytochemicals to avoid their toxicity, and have adapted culturally to exploit the impact of phytochemicals on body and mind.  In this seasonal post, I focus on the terpenoids in Frankincense and Myrrh, to explore how plant biochemistry contributed to the gifts of the Magi.

It All Starts with Central Metabolism
Phytochemicals are complicated plant chemicals that are produced by a series of enzyme-controlled reactions (Central Metabolism) from the array of chemicals used by plants to convert photosynthetic carbohydrates (fructose and glucose) into the molecules (sugars, amino acids, fatty acids, nucleic acids) used to make the macromolecules of cells (polysaccharides, proteins, fats, DNA/RNA).  Alkaloids and phenolics, e.g. phytoalexins, are made from amino acids (phenylalanine) and terpenoids are made from fatty acids (acetyl CoA/Mevalonate) or other intermediates in glycolysis.  Thus, central metabolism that converts glucose/fructose into pyruvate and the acetyl CoA (see mevalonate pathway left) of mitochondrial fatty acid metabolism, is further converted into amino acids and plant secondary compounds, phytochemicals.  I am going to talk mainly about terpenoids in Frankincense (triterpenoid Boswellic acids) and Myrrh, and many related molecules (steroids) also produced by humans.  

The major thesis here is that carbon dioxide is converted by photosynthesis into either sugars used to build the cell wall polysaccharides (soluble fiber) or larger toxic defensive chemicals, e.g. phytoalexins, resins, essential oils or lignin.  Phytoalexins, e.g. the natural antibiotic resveratrol in wine, are made from phenylalanine along the same biochemical pathway used to produce lignin.  Glyphosate, the herbicide, kills by blocking this unique plant pathway.  Essential oils and resins are another group of natural antibiotics produced by converting acetyl CoA into a five carbon unit, IPP, which is then linked into larger and larger (10, 15, 20 carbons) molecules, terpenoids, that can rearrange into multiple ring structures.  Only the smallest chemicals in the series evaporate to provide identifiable smells, e.g. Frankincense and Myrrh, while larger forms, e.g. cholesterol or testosterone in animals, are odorless solids.

Acetyl CoA to IPP
IPP
For those who enjoy the beauty of biochemistry:  The most abundant enzyme on earth is RibisCo (ribulose bisphosphate carboxylase), the plant enzyme that combines carbon dioxide from air with a five-carbon phosphorylated sugar, ribulose bisphosphate, to produce two, three-carbon intermediates of glycolysis that can be converted into glucose or into acetyl CoA, the starting chemical for fatty acids, the mitochondrial TCA cycle, or via mevalonic acid to isopentanyl pyrophosphate (IPP), the building block for terpenoid synthesis.

In brief:  Photosynthesis uses the energy from sunlight to convert carbon dioxide into sugars (glucose and fructose).  Those sugars can be converted into a five-carbon, molecular building block for terpenoids, IPP.  IPP molecules can then be linked together to make increasingly longer chains and those chains can be ultimately twisted into rings to make resins in plants and steroids in humans.

Five, Ten, Fifteen, Thirty; IPP (5), GPP (10), Sesquiterpenoids (15), Triterpenoids (30)
Terpenoid Polymerization
Terpenoid synthesis begins with IPP, which has five carbons in a branched chain and has a pair of phosphates, pyrophosphate that provide the energy to form chains of 5, 10, 15, etc.  In plants, molecules of each of the incremental lengths are produced together and additional enzymes in different species of plants result in mixtures of molecules with different rings and functional groups.  The smaller molecules evaporate more readily, so that mixtures are extruded from damaged trees as oils and gradually form resins as the remaining larger molecules predominate and solidify.

Shark Livers and the Horn of Africa
IPP with five carbons, an isoprene, is used to make GPP with ten, a monoterpene.  Common monoterpenes are geranol and limonene that make the characteristic odors of geraniums and lemons. Sesquiterpenoids (15 carbons made from three IPPs) include the fragrance of patchouli. Diterpenes, such as sweet steviol, have twenty carbons, which can be chemically twisted into the chemicals that predominate in Myrrh resin, the Balm of Gileade.  The triterpenes with 30 carbons can be rearranged with five rings to form steroids, such as cholesterol in animals or Frankincense.  Linear squalene, is the major component in shark liver oil and provides the same function as a swim bladder in a boney fish.

Essential Oils Are Mixtures of Distilled Terpenoid and Phenylpropanoid Phytoalexins
Boswellic Acid
Phytoalexins and terpenoids have evolved as plant defenses against bacteria, fungi and insects, and they are toxic, because they interact aggressively with proteins through their chemical ring structures that are hydrophobic.  These ring structures make the smaller versions volatile and soluble in organic solvents.  Many of these chemicals have properties similar to petroleum products and may be used as solvents themselves, e.g. paint strippers or thinner.  Steam distillation of plants produces mixtures of phytoalexins and terpenoids commonly called essential oils, which contain the volatile components “essential” for the odor identity of a plant.


Statins Block Cholesterol Synthesis

Statins were identified among a group of fungal antibiotics for their ability to block an early enzyme (marked in the mevalonate pathway above) in the production of cholesterol.  The toxic side effects of statins derive from wholesale disruption of all of the essential pathways (everything below the inhibited enzyme) that are related to cholesterol, such as blood heme A found in hemoglobin, and ubiquinone (CoQ) found in mitochondrial electron transport and needed to reduce oxidative stress and glucose intolerance.  Thus, for these examples, statins would contribute to anemia and type II diabetes/metabolic syndrome.  The side effects are not surprising, since statins are fungal antibiotics that target pathways common to bacteria and human mitochondria.  It is also not surprising that statins have unpredictable impacts on gut flora and the immune system.

Wednesday, October 22, 2014

Fermented Vegetables Repair Gut Flora

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.

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.

Sunday, October 5, 2014

Celiac, Gluten and Trypsin Inhibitor

Wheat

Summary
Forget the gluten.  Celiac is caused by trypsin inhibitors (ATI) that were increased in wheat fifty years ago to combat pests.  Immune response to ATI spreads to include gluten and transglutaminase that perpetuates the disease.  Celiac is an unexpected consequence of traditional plant breeding that could be fixed with GMO approaches.

Plants Protect Themselves with Antibiotics, Pesticides and Trypsin Inhibitors.
Plants respond to pathogens and pests by making themselves toxic.  Thus, plants produce natural antibiotics, phytoalexins, a.k.a. phytochemicals, polyphenolics or antioxidants, to kill bacteria and fungi.  They also produce chemical pesticides and proteins, e.g. trypsin inhibitor, that block the digestion and utilization of plant proteins by insects.  One of these trypsin inhibitors makes ground soybeans inedible until it is removed in water rinses during the production of tofu.  Another of these trypsin inhibitors, in wheat, is the cause of celiac.

Plants Target the Nerves, Immune Cells and Intestines
Plants have evolved chemicals and proteins that attack and punish plant-eating animals.  A single molecule of caster bean toxin protein, for example, can kill a human cell.  Plants produce some of the most toxic molecules on earth.  The nervous system of insects and other herbivores is typically targeted by plants.  Many recreational drugs, e.g. opioids, THC, nicotine, caffeine, etc., for example, are made by plants in self defense.  Human nerves respond to these natural pesticides and the bitter taste and the vomit reflex help us to detect and avoid toxic phytochemicals.  Gluten proteins contain polyglutamine stretches of amino acids that resist digestion and bind to intestinal cells.  Seed lectins bind to the glycoproteins on the surface of the intestines and inhibit digestion.  Wheat seeds also contain an inhibitor of starch and protein digestion, the amylase/trypsin inhibitor, ATI.  ATI binds to the receptors on immune cells that trigger general inflammatory responses to pathogens, e.g. TLR4.  It is the ATI in wheat that starts an immune response to gluten and celiac.
Wheat trypsin inhibitor causes celiac and autoimmunity

ATI Increased to Make Wheat Resistant to Pests
More than fifty years ago, plant breeders began to screen wheat varieties for resistance to pests.  Breeding ultimately resulted in enhanced pest resistance that resulted from increased production of ATI in wheat kernels.  Modern wheat flour contains modest changes in gluten and other components over the last century with the singular exception of ATI, which has increased about 50 fold.  It is also interesting that ATI is a major wheat allergen.  This suggests that celiac starts as an allergy to ATI present in wheat flour.

Celiac Results from Superfine Milling of High-ATI Wheat
Wheat has been milled more and more finely to improve the shelf-life of bread flour.  The inedible bran and the germ are first removed from the wheat kernels and then the endosperm is ground so finely that the starch granules are broken.  Even "whole wheat flour" is ground in the same way and the bran and germ are simply added back to make it “whole.”  The important point here is that superfine milling results in starch that is readily digested by amylase in the small intestines, instead of acting as soluble fiber to feed gut flora.  The result of eating bread from superfine flour is that gut flora are starved for soluble fiber and the immune system is depleted of Tregs that would otherwise suppress allergy and autoimmunity.  Superfine milling of high-ATI wheat presents ATI to an immune system that is primed for allergy.

ATI is a Good Immunogen
Allergy development requires 1) inflammation, 2) an appropriate immunogen and 3) lack of Tregs (immune system cells that develop in the lining of the intestines and block allergies and autoimmunity.)  The modern milling of wheat flour eliminates a major source of soluble fiber, starves gut flora and reduces Tregs, but allergy development still requires inflammation and an appropriate immunogen.  An immunogen is a protein that will interact with cells of the immune system to produce antibodies and activate aggressive attacks.  I have found that all proteins of food or the environment, i.e. allergens, or of the body, i.e. autoantigens, that act as immunogens to initiate allergies or autoimmunity have the same sequence of three amino acids, a "basic triplet."  ATI has a characteristic basic triplet in its protein amino acid sequence and that is why it is a good immunogen to initiate allergies.

Allergy to ATI is Aggrevated by TLR Recognition of ATI
ATI enriched, superfine flour Is a powerful initiator of allergies, because it starves gut flora to block Treg production and is a good immunogen, but the immune system will still ignore ATI in the gut, unless inflammation is also activated.  Unfortunately, ATI actively stimulates inflammation of the intestines by specifically binding to TLR4, which is the receptor that also binds/recognizes the LPS of bacteria.  Thus, ATI is a way for the wheat plant to defend its seeds by triggering excessive Intestinal inflammation.  Inflammation, immunogen and Treg insufficiency is the ATI allergy trifecta.

Wheat ATI Allergy Leads to Celiac
First exposure to ATI and development of an allergy will make subsequent expose to wheat proteins more immunologically intense.  I discussed the response of the intestinal lining to gluten in previous posts.  Wheat gluten proteins are adapted to provide nutrients for growing wheat embryos and to provide defense against pathogens and herbivores.  Gluten proteins contain long stretches of amino acid glutamine, which is poorly digested by gut enzymes.  The glutamine is also converted into glutamate by the gut enzyme, transglutaminase, tTG.  Unfortunately, during the process, the enzyme is covalently connected to the undigested gluten fragments.  The allergic ATI reaction combined with gluten/tTG conjugates, leads to presentation of the gluten/tTG to the immune system and antibody production agains both gluten and tTG.  Subsequent exposure to gluten results in the autoimmune disease of celiac.

Celiac is Self-Perpetuating
The aggressive immune attack on the intestines in response to eating gluten-containing grains, is bad in itself, but it also causes a series of related autoimmune diseases.  Attack on the intestines also disrupts the development of the lining of the intestines, which in turn disrupts the community of bacteria and fungi, gut flora, that are essential for digestion of plant polysaccharides, soluble fiber, and the development of the immune system.  Gut flora dysfunction results in vitamin deficiencies, food intolerances and autoimmunity.  Thus, celiac is self-perpetuating, because it causes inflammation, immunogen presentation and Treg deficiency.

Celiac Causes Numerous Autoimmune Diseases
Celiac is often associated with other autoimmune diseases, because it causes them.  Antibodies to tTG are diagnostic for celiac and the autoimmune attack on the intestines is mediated by anti-tTG antibodies.  But anti-tTG antibodies of celiac don’t just attack the intestines, they attack any other tissues that have tTG, such as the thyroid gland and hair follicles.  Thus, it should not be a surprise that celiacs are at high risk for autoimmune disease, e.g. Hashimoto’s thyroiditis, of the thyroid gland, including both hypothyroid and hyperthyroid diseases, depending on which region of the thyroid is attacked.  Some forms of hair loss, alopecia, are also initiated by autoimmune attack on the tTG in hair follicles.  Persistent exposure of celiacs to gluten will result in a cascade of autoimmune diseases as other body antigens are presented to the immune system and tissues with those antigens are targeted and attacked to produce arthritis, vitiligo, etc.

Pest Resistance, Plant Breeding and GMO Solutions
Genetic modification of plants occurs every time seeds are planted.  Traditional plant breeding by selecting desirable individual plants grown from crosses of selected parents is one form of genetic modification.  Specifically introducing desired genes using recombinant DNA techniques is another, more controlled method.  Traditional plant breeding has systematically destroyed the diversity of crop plants by loss of genes that are not selected, but even the traits, such as pest resistance, that provide benefit, have also brought unintended consequences.  We now have grains with many desirable features of high yield and disease resistance, but they also provide increased risk of celiac, gluten intolerance and associated autoimmune diseases.  Maybe it is time to consider GM techniques as a safer alternative to fix modern wheat and to examine milling approaches to save our gut flora.

Cure for Celiac and Autoimmunity

Celiac and other autoimmune diseases are perpetuated by the presence of the corresponding autoantigen/allergen, in this case tTG and gluten proteins, and a deficiency of Tregs.  Oddly enough, some pathogens (Helicobacter pylori) and parasites (Helminth worms) stimulate Treg development in the lining of the intestines, in addition to normal gut flora, Clostridium spp.  It may be the relative absence of pathogens and parasites in affluent societies that reduces Tregs and enhances the incidence of allergies and autoimmunity.  Antibiotics and the antibiotic activity of pharmaceuticals in general may also contribute to Treg deficiencies by damage to gut flora.  Clearly, the repair of gut flora and reestablishment of the associated immune system will go a long way toward curing autoimmune diseases such as celiac.  Celiac, however, provides the added complexity that it damages the ability of the intestines to maintain a functional gut flora.  Thus, the cure for celiac would require simultaneous repair of both the gut and its flora, e.g. by a  fecal transplant and supportive diet containing numerous soluble fibers to which the donor flora have been previously adapted, i.e. lacking antigenic triggers.

Thursday, September 11, 2014

Peanut Allergy Cause and Cure

Summary:  The cure for peanut allergy should follow naturally from knowledge of the cause.  Since most allergies and autoimmune diseases result from the combination of 1) inflammation, 2) breakdown of immunological tolerance and 3) presentation of a primary immunogen, it follows that some types of peanut allergy are based on a continued problem with immune tolerance and fixing that defect should eliminate an allergic response to peanuts.  The current cure to resurrect immune tolerance is by enhancing regulatory T cells (Tregs) in the gut using resistant starch to improve the growth of Clostridia in the gut.

Peanut allergies are dangerous and this post does not advocate any medical treatments, but rather attempts to explain the cause and cures of allergies.

Just Treat the Immunological Tolerance Problem Instead of Mast Cells
Most people in fear of anaphylaxis from peanut dust, just try desperately to avoid peanuts in any guise.  That avoids the problem, but why not cure the allergy?  Recent research shows that peanut allergens can be prevented from establishing an allergic response in mice by addition of Clostridium species of bacteria in the gut flora.  It was shown that the Clostridia increased Tregs (regulatory T cells responsible for immune tolerance) in the lining of the intestines via interleukin 22 production.  So the cure to some peanut allergies may be increasing Tregs and fixing tolerance.

I Said It All Before
It is not a large step to combine my previous posts covering potato resistant starch for treatment of deficiencies of immunological tolerance with my explanation of the cause of allergies and autoimmunity to provide a simple explanation of the cause and cure for some peanut allergies.

Peanut Allergen is a Typical Bean Storage Protein Except for the Basic Triplet
It is not difficult to find out why peanuts are allergenic.  I just went to the National Center for Biotechnology Information (NCBI) web site and queried the protein sequence databases for “peanut allergen.”  Here is the complete amino acid sequence (each of the 20 amino acids of the protein is assigned a letter) of the major peanut [Arachis hypogaea] allergen:

MMVKLSILVALLGALLVVASATRWDPDRGSRGSRWDAPSRGDDQCQRQLQRANLRPCEEHMRRRVEQEQEQEQDEYPYSRRGSRGRQPGESDENQEQRCCNELNRFQNNQRCMCQALQQILQNQSFWVPAGQEPVASDGEGAQELAPELRVQVTKPLRPL

The triplet of basic amino acids (R=arginine, K=lysine), RRR in this case, which is found in all allergens and autoantigens, is highlighted in red.  If you eat peanuts with an inflamed gut and you have wiped out your Clostridia and associated Tegs with antibiotics, you have a good chance of developing autoimmunity, as well as a peanut allergy.  The cause of allergies is that simple and the cure is equally simple.

Shellfish Allergy Shows the Relationship between Allergy and Autoimmunity
I ran across a list of other food allergens when I was checking up on peanuts.  Shellfish was listed as another of the big allergies.  I looked up “shellfish allergen” and ran into thousands of entries.  The first couple of dozen proteins lacked the characteristic basic triplet, so I had to step back and try to guess the most typical shellfish for first exposure, i.e. the primary immunogen.  All of the other shellfish allergens were various versions of the muscle protein, tropomyosin, so I looked up “shrimp allergen.”

MDAIKKKMQAMKLEKDNAMDRADTLEQQNKEANNRAEKSEEEVHNLQKRMQQLENDLDQVQESLLKANIQLVEKDKALSNAEGEVAALNRRIQLLEEDLERSEERLNTATTKLAEASQAADESERMRKVLENRSLSDEERMDALENQLKEARFLAEEADRKYDEVARKLAMVEADLERAEERAETGESKIVELEEELRVVGNNLKSLEVSEEKANQREEAYKEQIKTLTNKLKAAEARAEFAERSVQKLQKEVDRLEDELVNEKEKYKSITDELDQTFSELSGY

Note the predicted basic triplet in red.  Since I was on a roll, I also checked out related tropomyosin sequences in humans:

MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEDRSKQLEDELVSLQKKLKGTEDELDKYSEALKDAQEKLELAEKKATDAEADVASLNRRIQLVEEELDRAQERLATALQKLEEAEKAADESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAEERAELSEGKCAELEEELKTVTNNLKSLEAQAEKYSQKEDRYEEEIKVLSDKLKEAETRAEFAERSVTKLEKSIDDLEDELYAQKLKYKAISEELDHALNDMTSM

Once again the basic triplet indicated that there was a related human tropomyosin that could interact with antibodies to the shellfish allergen or could be an autoantigen participating in autoimmune diseases.  So I checked PubMed for “tropomyosin autoantigen” and quickly found that antibodies to tropomyosin are important in ulcerative colitis (UC).  Thus, shellfish allergy may be an indication of an underlying predisposition to UC.  And, the traditional cure for allergy by injection with small amounts of the allergen to convert from IgE to IgG, would convert a shellfish allergy into UC.

Avoiding Allergens Makes No More Sense Than Trying to Avoid Autoantigens
To fix allergies, it is necessary to eliminate the cause and block perpetuation of the condition.  The cause is based on 1)inflammation, 2) broken immune tolerance and 3) primary immunogen.  Peanuts are the primary immunogen, but that is unimportant if the causing conditions are eliminated and tolerance is reestablished.  Clearly, if immunological tolerance is reestablished, then it's just a matter of time before peanuts are no longer a problem, because increasing Tregs will silence the dramatic immunological response to peanuts.  Tolerance is based on Tregs and Tregs develop in the intestines in response to Clostridia feeding on soluble fiber/resistant starch.

Curing Peanut Allergies is Based on Repairing Gut Flora

There are a couple of hundred different species in the pounds of bacteria in the healthy human gut.  Most of those bacteria require soluble fiber that is systematically removed during food processing.  For most people, the cure for peanut allergies will be resistant starch/Clostridium therapy, followed by further repair with fermented foods that provide the typical lactic acid bacteria and soluble fiber along with companion bacteria that can recolonize the gut.  The cure for many allergies and autoimmune diseases is just to eat a couple of tablespoons of resistant starch each day and if needed, supplement with probiotics containing Clostridium butyricum.  If there is severe dysbiosis, as indicated by constipation, then fixing the gut flora is a little more difficult, but for most people cures are much cheaper and effective than just treating symptoms.

A guide for the use of resistant starch is provided by Richard Nikoley, et al. at Free the Animal.

Friday, July 25, 2014

Dr. Oz Five Food Felons

Biofilms on intestine microvilli
The medical industry is slowly pulling away from diet advice that has contributed significantly to disease in America.  It promoted or at least tolerated, the shift from butter to margarine and polyunsaturated vegetable oils, and from saturated fats in meats to starches and grains.  The medical emissary, Dr. Oz, still supports medical advice that is not based on medical research.

Dr. Oz's Five Food Felons and Why His Choices Are Unhealthy:

"1) Trans fats raise lousy LDL cholesterol and triglyceride levels, lower your healthy HDL cholesterol level and fuel disease-triggering inflammation."  Trans fats are inflammatory and should not be eaten.  New labeling has permitted substantial amounts of trans fats to be added to processed foods and still be labelled "No trans fats."  LDL blood levels reflect inflammation, but artificially lowering the LDL with statins has no impact on heart disease.  Lowering LDL, by lowering inflammation with fish oil and/or repair of gut flora, diet and exercise is effective.

"2) Saturated fat in red meats, poultry skin, full-fat dairy products and palm and coconut oils fuels cancer risk, coronary artery disease, dementia, obesity and diabetes."  Linking saturated fats with heart disease, etc. was never supported by medical research.  Elimination of red meat, removing skin from chicken, avoiding egg yolks, etc. and replacing them with omega-6 polyunsatured vegetable oils has been a major contributor to inflammation and disease.  Full fat milk is the healthful choice, especially for children.  The change was dangerous and is being reversed with new emphasis placed on omega-3 fish oils.

"3) Added sugars and 4) sugar syrups cause the proteins in your body to be less functional and age your immune and cardiovascular systems and your joints. Plus, they disrupt your metabolism and contribute to almost every lifestyle-related malady, including some cancers."  Oz got this right even though they initially promoted high fructose corn syrup (half glucose/oligos) and its evil and even higher fructose sister agave nectar (all fructose/oligos.)  Equally bad, however, are the hyperglycemic starch in breads (including whole grain!) and over cooked pasta.


Gut flora
"5) Refined and processed grains don't contain the fiber or nutrients (contained in 100 percent whole grains) that you need to keep the bacteria in your guts happy, glucose levels regulated, immune system strong and digestion running smoothly."  Dr. Oz and company fail to understand the basics of vitamins, soluble fiber and gut flora.  Grains are not healthy for most people, because of the toxicity of gluten and hyperglycemic starch.  Ultra fine milling and fast commercial bread making eliminate the resistant starch.  "Whole grain" processed foods just add back the insoluble fiber that is considered toxic, because of its phytic acid content.  Grains should just be replaced with whole foods, such as vegetables that contain the soluble fiber that feeds the gut flora that provide all of the needed vitamins and are required for immune system development.

Why Does Dr. Oz Make Health Mistakes?

Dr. Oz has been criticized for promoting foods, supplements, medical treatments, etc. that are not supported by medical research.  While that is true, I think that he is just following the general views of the medical industry and simply doesn't know any better.  Sadly, most doctors don't have the background to read scientific research papers, let alone their own biomedical literature that is rife with scandals of nonreproducibility and inappropriate industry influence.  Doctors find it hard to give valid dietary advice, because nutritionists have false information and celebrity doctors, and their research teams, don't do their homework.  The result is the mix of ancient orthodoxy, industry promotion, alternative medicine and unscientific fads that appears in the media.  Doctors need a scientific background sufficient to answer the essential question posed to health claims, "Does it make sense?"

Friday, July 18, 2014

Bacteria Migrating to Breast May Cause Cancer

—-The other 200 posts—-
The readers of this blog are probably aware of my interest in the causes and related cures of diseases.  Juxtaposition of recent research findings has made me reconsider the role of bacteria in breast cancer.

The Findings
  • Lactation/breastfeeding lowers risk of breast cancer (improves path of normal mammary duct micro biome from nipple.)
  • Tubal ligation lowers risk of ovarian cancer (eliminates path for bacteria from vagina.)
  • Aspirin reduces pancreatic cancer (by reducing inflammation involved in the transition from bacterial infection to cancer.)
  • Pancreatic and breast cancer risks are both dramatically increased by BRCA (tumor suppressor genes involved in 5% of breast cancer.)
  • Bacteria are transported from gut to blood to breast to milk to infants.  (Google entero-mammary bacterial circulation involving intestinal M cells and dendrocytes.)

Bacteria Have Access to Organs with Common Cancers
Serum or fluid flows from organs outward; liver to gall bladder to intestines, pancreas to intestines, prostate to urethra, ovary to fallopian tube to uterus to vagina.  In each case there is also an related infection and inflammation associated with the backward path to the organ.  Urinary tract infections can lead to prostatitis.  Vaginitis can lead to pelvic inflammation, gastritis to stomach cancer, and intestinal infection/inflammation can result in pancreatitis.  The theme seems to be that bacterial infections can cause inflammation that leads to cancer.

Bacterial Path to the Breast
Lactating women occasionally have bacteria that migrate back up milk ducts to cause mastitis, but this is not quite parallel to my other examples of bacterial movement, because women are not continually producing milk.  There is, however, another path of bacteria to mammary tissue.  Prior to birth, bacteria move from the maternal gut, through the blood (presumably in lymphocytes) and into mammary tissue.  Subsequent nursing transports the bacteria to the infant to initiate the milk controlled gut flora unique to exclusively breastfed infants.

Monthly Transport of Bacteria to Breast
The menstrual cycle is an abbreviated ovulation, conception, gestation and birth, which suggests that just as in the normal prelude to lactation, there may also be monthly transport of gut bacteria to mammary tissue.  These bacteria may also cause infection and inflammation, though they may not be sufficient to cause more than transient breast tenderness.

Healthy Gut Flora Means Healthy Breasts
I expect that many diseases in infants may be associated with the wrong bacteria being transported from maternal gut to breast to infant.  Clearly, if the mother suffers from dysbiosis, which is very common, it may be difficult for the correct Lactobacilli and Bifidobacteria to be transported to mammary tissue.  Transport of other bacteria may cause problems.  Those problems may be severe as a consequence of menstrual cycles that don’t end in pregnancy, but rather end in infection, inflammation and breast cancer.  It may all come down to gut flora.  The difference between women who develop breast cancer and those that remain healthy may be the health of their gut flora.  Breastfeeding, of course, reduces the risk of breast cancer, as well as improving infant gut flora.  Formula is always a risk factor for infant health, because it attacks normal infant gut flora and promotes inflammation. Since many breast cancers naturally resolve, it may also be the case that a healthy immune system can reverse breast cancer and the health of the immune system is determined by the gut flora.

Tuesday, July 15, 2014

Gut Flora, Disease and Obesity


The health of your gut flora (the interacting trillions of bacteria of a couple of hundred different species that make up the pound of bacteria that you carry primarily in your large intestines) is more important than your genetics to your overall health.  Thus, your health is a result of diet, gut flora adapted to your diet and exercise.  Everything else, your genetic risks, environmental toxins, etc. are of only minor impact.

I am trying to paint the big picture of how the food that you eat and your gut flora interact to determine your health, by which I mean whether you get sick, become obese and/or bloat with gas.

Health Depends on Gut Flora
If you are healthy, you have a couple of hundred different species of bacteria that help you to digest the protein, fats and carbs that you eat in meat and vegetables.  Your body easily digests protein and fats in meat, fish, eggs and dairy, because enzymes to digest them are present in your stomach and small intestines.  The only carbs that your body can digest are some simple sugars and starch.  The rest of the polysaccharides present in plants cannot be digested without the help of bacteria.  The polysaccharides that your gut flora can digest are fermentable, soluble fiber, e.g. resistant starch, pectin, inulin, arabinogalactan, xylans, beta-glucan, etc.  If you can’t digest soluble fiber, because you have damaged gut flora, dysbiosis, and are missing essential bacterial species normally found in a healthy gut, then the soluble fiber just passes through as insoluble fiber and readily dehydrates into hard, constipated stools.  Partial digestion due to just a few missing bacterial species produces the symptoms of food intolerances.  

Constipation Results from Dysbiosis
The bottom line is that the volume of healthy, soft, firm stools is made up of gut flora that digested dietary soluble fiber and converted it into more bacteria.  If you eat more soluble fiber, this food for your gut flora, will produce proportionately more bowel movements.

Gut Flora Guide Immune System Development
Most of cells of your immune system are in the lining of your gut and there are particular species of gut bacteria directly involved in the development of immune cells that have different functions as they spread throughout your body.  Some of these cells are aggressive and attack pathogens, while others make sure that the aggression doesn’t get out of control and cause autoimmune diseases or allergies.

Gut Flora Divided into Groups to Show Involvement in Disease
Recent studies have demonstrated the role of gut bacteria in producing nutrients, vitamins and neurotransmitters.  To highlight the essential role of gut flora in disease, I have divided the hundreds of species of gut bacteria into groups to illustrate their direct involvement in development of the immune system and regulation of the flow of dietary nutrients involved in obesity.  A recent study shows that an infection can produce a change in gut flora associated with marshaling additional fatty acid nutrients for the host instead of just producing more gut flora.  Chronic change of gut flora in this way leads to obesity.  Other types of dysbiosis contribute to infections, cancer, autoimmune disease, allergies, food intolerances, gas and bloating.

Group A Bacteria  Provide Aggressive Immunity
There are several dozen species of bacteria in healthy gut flora, including the filamentous bacteria, that trigger the development of the aggressive part of your immune system that attacks pathogens, and kills cells of your body that are infected with viruses or are cancerous.  Most antibiotics don’t permanently damage this group of bacteria, so after a course of antibiotics you can usually still stop infections.  Excessive suppression of aggressive immunity contributes to cancer.

Group B Bacteria Provide Suppressive Immunity
There are dozens of other species of bacteria, including Clostridia, that control the development of the suppressive half of your immune system that produces immune cells, such as regulatory T cells, Tregs, that stop the aggressive cells of your immune system from attacking your own cells and innocuous things such as food and pollen.  Many common antibiotics damage these species of bacteria and are thought to contribute to the development of autoimmune diseases and allergies.  Inflammatory bowel disease is characterized by a simplified gut flora with only half the healthy number of bacterial species.  Resistant starch preferentially feeds these bacteria to enhance suppressive immunity and in some individuals cure autoimmune disease.

Group C Bacteria Convert Soluble Fiber to Short Chain Fatty Acids (SCFA)
The fermentable soluble fiber in your diet is typically from vegetables and it is converted by the largest and most diverse group of bacterial species into short chain fatty acids.  Each different plant polysaccharide, and there are hundreds, requires many enzymes for complete digestion to the simple molecules used by the bacteria to make its own proteins, fats and polysaccharides.  Absence of bacteria that are specialized for the digestion of particular polysaccharides or other dietary components can disrupt gut flora and cause digestive disturbances that are experienced as food intolerances (also confused with food allergies that are rare.)  Some of the bacterial species convert polysaccharides into butyric acid and other short chain fatty acids that are the major source of energy for cells that form the lining of the intestines.  These SCFAs are also a major food source for other gut bacteria.

Group D Bacteria Convert SCFAs to Fecal Bacteria to Produce Bulk of Bowel Movements
In healthy people, the SCFAs produced by gut flora feed the intestines and the remainder produced in the large bowel is converted into more gut bacteria, which forms soft stools.  Antibiotics typically damage these bacteria and result in constipation.  These bacteria are typically more sensitive to antibiotics than those that digest the soluble fiber and produce SCFAs, so the excess SCFAs pass into the blood stream and contribute to obesity instead of stools.  Lean mice with gut flora exchanged from obese mice, become obese.  Cattle are fed antibiotics to enhance the conversion of corn polysaccharides into SCFAs and body fat prior to slaughter.

Group E Bacteria convert Soluble Fiber to Methane and Hydrogen, Bloat
Increased volume of the intestines, bloating, results from conversion of soluble fiber into methane, hydrogen and carbon dioxide gases.  Some of this gas is absorbed into the blood and can pass from the large intestines, through the blood, and back to the stomach and small intestines.  Helicobacter pylori, the cause of stomach ulcers and gastric cancer, can utilize hydrogen from the blood as an energy source.

In Summary:
A+B+C+D = healthy, normal weight
A+C+D = normal weight, autoimmunity and allergies
B+C+D = normal weight, susceptibility to cancer, chronic Lyme disease, food poisoning
A+B = normal weight, constipated
A+B+C = obese, constipated
A+B+D = normal weight, food intolerances
A+B+C+E = obese, constipated, bloated

Cure for Dysbiosis and Associated Diseases is Repair of Gut Flora
The excitement about the use of resistant starch (RS) and probiotics with Clostridia and other soil bacteria to reverse the symptoms of autoimmune diseases is based on the ability to repair gut flora damaged by poor nutrition and antibiotics.  Low carbohydrate diets that do not provide soluble fiber to feed gut flora lead to dysbiosis and chronic diseases.  Resistant starch, as the name suggests, passes on to the colon by avoiding digestion with amylases in the small intestines and acts as a soluble fiber to feed gut flora in the colon.  Clostridia convert the RS to sugars and SCFAs usable by other gut flora.  Note that some species of Clostridia produce toxins and it is these pathogens that take over in hospitals after the healthy species are killed off with antibiotics.  Fecal transplants are the best treatment for these hospital acquired infections. 

 I have discussed the role of hygiene, muddy veggies, fermented foods, etc. in several other posts on repair of gut flora.  

Complete repair of gut dysbiosis is possible, but it requires more than just changes in diet and dairy probiotics, as typically recommended erroneously by the medical industry.

Health is dependent on:
  1. an Anti-Inflammatory Diet,
  2. gut flora adapted to your diet
  3. exercise and
  4. adequate sleep
The rest (genetics, vegan vs. paleo, environmental toxins, organic veggies, GMOs, etc.) are minor contributors, less than 10% in aggregate, to overall health.