Making Monsters, Renegade C. butyricum and E. coli

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Clostridium

It is common knowledge that our gut is teeming with good bacteria that we feed with prebiotic fiber to keep us healthy.  But a sick gut, caused by antibiotics or fiber deficient processed food, can make us susceptible to infection with pathogens, such as the notorious, toxin-producing strains of E. coli that cause food poisoning or Clostridium difficile, a.k.a. C. diff. of hospital infections.  What prompted me to write this post, was reading that premature babies in neonatal intensive care units are dying from gut infections caused by a pathogenic strain of C. butyricum, known as a probiotic that provides protection from C. diff.

Healthy Gut Microbiota

New Toxin-Producing, Antibiotic Superbugs are Manmade

Closer examination of the report revealed that the new strain of C. butyricum is a toxin producer.  This made a lot of sense to me.  When I started working with E. coli in the early 70’s, it was known as the safe ubiquitous lab bacterium that everyone cultivated in their colons.  Similarly, C. butyricum is present in commercial probiotics and is a hero for producing butyric acid from resistant starch, promoting immune system development and reducing inflammation.  How did these beneficial gut bacteria become converted into pathogens?

Source of Antibiotic Resistant Superbugs

Antibiotic and Drug Use in Hospitals and Farms Select for Antibiotic Resistance

C. butyricum and E. coli have been converted into toxin-producing, antibiotic resistant pathogens by common procedures of meat production and hospital treatments.  These bacteria do not normally produce toxins nor are they resistant to antibiotics.  They have been systematically selected for those pathogenic properties.

Formula Contributes to NEC

Common Practices in Neonatal Intensive Care Units Lead to NEC

Chronic inflammation is one of the common contributing factors to premature births, because labor is stimulated by a spike of inflammation, normally occurring at 40 weeks of gestation.  Chronic inflammation from autoimmune disease, infection, or obesity, can cause labor to be early and a newborn to be unprepared for life without some special care.  Unfortunately, there is not uniform enlightenment about the development of newborn gut flora, and immature newborns are exposed to antibiotics and formula, which prevent normal gut flora development.  C. butyricum is not present in low birth weight babies exclusively fed breast milk, but the combination of antibiotics and formula select for colonization by antibiotic resistant hospital strains of C. butyricum.  This sets the stage for necrotizing enterocolitis, NEC, which is as nasty and lethal as the name suggests.

Toxin Producing E. Coli are Manmade

Antibiotics Used to Make Fat Cattle Select for Toxin Production

The development of toxin producing E. coli in cattle suggests how pathogenic C. butyricum was produced in the hospital environment.  E. coli was a healthy component of the digestive system of cattle, until the gut flora community was reengineered by antibiotics, so that short chain fatty acids that were normally converted into more gut bacteria and more steer manure, were instead absorbed by the gut to produce a fatter steak.  Unfortunately, this newly designed gut flora community left no place for E. coli.  Some of the E. coli spontaneously mutated to antibiotic resistance and/or picked up multi-drug resistant plasmids from other bacteria, but that still didn’t provide a niche in the new community.  Picking up a toxin-producing gene solved that problem, because the toxin releases needed nutrients from host cells.  Thus, antibiotic use in cattle directly selected for the evolution of toxin-producing, antibiotic resistant E. coli.

Antibiotics and Formula Use Lead to NEC Bacteria

Toxin-producing C. butyricum would be expected to develop in the hospital environment, because high antibiotic use will select for multiple drug resistant C. butyricum, and the disrupted gut flora produced in the presence of antibiotics will also favor toxin producing strains.  Thus, the hospital environment selects for toxin-producing, multiple drug resistant C. butyricum.  The gut flora of newborns in a neonatal intensive care unit are acquired from the staff and relatives that handle the babies.  Since the babies are routinely treated with antibiotics and drugs, multiple drug resistant bacteria, including C. butyricum, are common in fecal samples of neonates and persist for at least two years. 

Breastmilk Prevents NEC in Newborns

Breastfeeding or Donor Bank Milk Avoids NEC Caused by Formula

Exclusive use of breastmilk from mothers, donor banks or breastmilk products, eliminates NEC.   Some hospitals respond to the scientific evidence and use only breastmilk for newborns.  Other hospitals simply stick to old practices until law suits force them to change.  They continue to use formula and cow’s milk products,  even though breastmilk is available, and as a consequence NEC is still a problem. Prejudice against breastmilk persists and there is intense promotion of commercial alternatives that contribute to NEC.  None of the alternatives containing probiotics and prebiotics have been found to be adequate.   Hospitals are slow to change, because patients are uninformed and low birthweight babies continue to die.

Healthy Gut Microbiota Means: No Supplements, No Cleanses, No Drugs, No Processed Foods

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A healthy, functional gut microbiota (bacteria and fungi) supplies all of the vitamins needed, stimulates the development of a balanced immune system and promotes vitality.  If you feed and maintain the diversity of the pounds of bacteria in your gut, you will be healthy.  If you listen to the medical and food industries, you will be sick, i.e. a good patient/consumer.

Supplements Compensate for Deficiencies/Sickness

The key to this discussion is the functions of the healthy communities of bacteria and fungi called the gut microbiota.  These pounds of bacteria produce all of the vitamins that your body needs, and spiking your diet with multivitamins may disrupt your microbiota, because vitamins are actually the chemical signals used for communications between bacteria in biofilms.  Numerous studies have shown that daily multivitamins are not beneficial, so if you see extra vitamins on the ingredients label, try some whole foods instead.  If, however, you have been exposed to antibiotics or other medications, since most have potent antibiotic activities, then your gut bacteria may not be producing vitamins normally, and you may need to supplement.  Vitamin deficiencies are a symptom of gut dysbiosis, damaged gut microbiota.

Vitamin D is a Steroid Hormone Produced from Cholesterol in Skin by Sunlight

Most people know that sunlight striking skin produces vitamin D, but they still think that they can get a significant amount of vitamin D from their diet.  The confusion comes from the fact that vitamin D is a major hormone that influences many body systems including bone production and immunity.  So in the absence of skin production of vitamin D, the low amounts added to milk are sufficient to prevent deficiency/rickets.  However, chronic inflammation can block solar production of vitamin D, so that even individuals near the equator and basking daily still remain deficient.  Vitamin D deficiency may also, insidiously, be a major source of chronic inflammation.  Thus, most individuals treated for deficiency with supplemental vitamin D3, do not reach high enough levels to suppress chronic inflammation and restart solar production, so they remain deficient.  Chronic inflammation is a symptom of vitamin D deficiency.

Bowel Cleanses Damage Gut Microbiota

The bowels are a long tubelike conveyance and it takes food about a day to travel from table to toilet.  In the colon, all of the plant polysaccharide fibers remaining after removal of sugar, starch, fat and protein, are digested by enzymes of the microbiota and converted into more bacteria and short chain fatty acids that feed the colon tissue. There is nothing toxic left behind in the colon. Protein from meat is readily digested in the stomach and the first part of the small intestines.  Plant materials cannot be digested without the help of a complex array of hundreds of enzymes produced by gut bacteria.  Food intolerances are caused by the loss of particular bacterial species needed for complete digestion of one type of plant fiber.  The bacteria form the stools, and insufficient healthy bowel bacteria, normally fed by the fiber, is the cause of constipation.  Clearly, flushing out bacteria with a "cleanse" is unhealthy and counterproductive.  There is nothing in the colon but gut bacteria and fiber to feed the bacteria. Those bacteria are needed for vitamin production, normal development of the immune system and normal stools.  A cleanse merely removes healthy gut bacteria and leads to constipation or replacement by pathogens. 

Processing Removes Prebiotic Fiber from Food and Starves Gut Microbiota

Diverse and complex plant polysaccharides, e.g. pectin, arabinogalactan, various glucans and fructans, are systematically digested by hundreds of different bacterial enzymes of the healthy gut microbiota.  The sugars that result are eventually converted into short chain fatty acids, such as butyrate, that feed the cells lining the colon.  The plant polysaccharides that feed gut bacteria are called prebiotics.  Unfortunately, prebiotics are removed during food processing to enhance ease of preparation and palatability.  The result of decreased dietary prebiotics is selective starvation and removal of bacterial species needed for the development of the immune system, and autoimmune diseases.

Most Medicines Have Substantial Antibiotic Activity and Damage Gut Microbiota

It is not surprising that antibiotics damage the bacteria in the gut.  What most people don’t realize is that most pharmaceuticals/medicines are developed from the natural antibiotics of plants, phytoalexins.  Numerous recent studies have demonstrated most common medicines, e.g. statins, NSAID, antidepressants, etc. have substantial antibiotic activity and damage gut bacteria.  Surgeons commonly suggest that patients eat yogurt to help repair their gut micro biomes after operations and antibiotics, but they don’t tell them how to fix their gut and immune system as they take medications for the rest of their lives.  The permanently damaged gut just causes further deterioration of the immune system and health.

Damaged Gut Microbiotas/Immune Systems Can Be Fixed

I have several other posts on repair of gut microbiota.

Examination of antimicrobial activity of selected non-antibiotic medicinal preparations.

Kruszewska H1, Zareba T, Tyski S.   Acta Pol Pharm. 2012.  69(6):1368-71.

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

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

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

Health Diagram I    — Gut Flora and Diet, 

Health Diagram II   — Curing Autoimmunity and Allergies,

Health Diagram III  — Inflammation from Cell to Tissue  

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

Antibiotics Contribute to Autoimmune Diseases

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

Feed the Gut Microbiome for a Healthy Immune System

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

Repairing the Gut Microbiome by Eating the Missing Bacteria

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

Phytochemicals Are First and Foremost Antibiotics

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

I Missed the Antibiotic Activity of Common Medicines

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

Unlabelled Antibiotic Drugs Cause the Rise of Superbugs

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

Fermented Vegetables Repair Gut Flora

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

Old Friends Become Fermentista

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

Fermented Vegetables are a Source of Gut Flora

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

The Guide to Fermentation

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

Fermented Vegetables is Available Now (bottom)

All of the Answers to Fermenting Vegetables

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

Health Diagrams II -- Curing Autoimmunity and Allergies

The Cure for Damaged Gut Flora and Inflammatory Diseases

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

Celiac, Gluten and Trypsin Inhibitor

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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.

Health Diagrams II — Curing Autoimmunity and Allergies

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.

Dr. Oz Five Food Felons

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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?"

Gut Flora, Disease and Obesity

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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.

ref.

Gut microbiota composition correlates with changes in body fat content due to weightloss 

Health Diagrams III — Inflammation from Cell to Tissue

---All 200 Posts---

I have explained my perspective in diagrams of the relationship between diet, gut flora and disease:

Health Diagrams I — Gut Flora and Diet

and of the interaction between gut flora, the immune system and autoimmunity:

Health Diagrams II — Curing Autoimmunity and Allergies

Now I am discussing how inflammation, the foundation of most chronic diseases, begins at the cellular level and results in the classic symptoms of tissue inflammation: redness, heat, swelling and pain.

NF-kB is the Transcription Factor that Controls Inflammation Genes

Of the 23,000 human genes, about 1,000 on each of 23 chromosomes, five dozen, e.g. enzymes involved in nitric oxide (vasodilation and erection hormone), synthesis of heparin sulfate and prostaglandin synthesis from omega-6 fatty acids or cytokines (IL-1, IL-6, TNFa), are associated with inflammation.  These inflammatory genes are turned on or expressed in individual cells, when the inflammation transcription factor, NF-kB, is activated by any of numerous external signals, including inflammatory cytokines, bacterial or fungal cell wall materials (LPS or beta-glucan), advanced glycation end products (AGE, e.g. HgA1C, resulting from high blood sugar) or reactive oxygen species (ROS, e.g. super oxide, from insulin resistance).

NF-kB and Inflammation
Superoxid Causes Insulin Resistance

Inflammation is the Foundation of Growth, Birth, Cancer and Pain

We think of inflammation as the sum of physical symptoms, and our purpose in responding to inflammation is typically to limit its impact.  We try to stop swelling by applying cold or hot, and we take aspirin to lower fevers and stop pain.  We fail to realize that inflammation is essential to the growth and development of many different tissues, and that inflammation is a cycle that leads back to normal function.  

Body tissues, such as the lining of the intestines or the uterus, continually produce new cells to replace the old that are sloughed off.  NF-kB must be turned on for these growth and attrition cycles.  Taking aspirin blocks NF-kB in the gut and stops local development of the lining, resulting in weak areas that bleed.  That is why doctors encourage patients to drink a half glass of water before and after swallowing aspirin tablets. 

Another more dramatic example of control of inflammation is conception, gestation and birth.  Conception and gestation require inhibition of inflammation, to permit growth of a foreign organism (a fetus is half sperm genes) in the uterus.  Chronic inflammation limits the ability of the uterus to suppress immune attack and can produce infertility, which is treated by aspirin and heparin, which suppress chronic inflammation.  The return of inflammation at the end of gestation precipitates labor and birth.  Excess Inflammation produces high levels of circulating inflammatory cytokines, which causes postpartum depression.  Depression and chronic inflammation have the same cytokine profiles, i.e. depression is a symptom of chronic inflammation.

Birth and Inflammation

Proliferation, or enhanced cell division, is another aspect of inflammation and is also the foundation for cancer.  That is the reason that some doctors recommend low dose aspirin to reduce colon cancer.  Similarly, since inflammation is the basis for coronary artery disease, doctors sometimes recommend low dose aspirin, although this is controversial.  Doctors also use aspirin as a so called blood thinner, since it blocks inflammatory signaling in platelets and discourages clotting.  Inflammation of nerve cells is experienced by the brain as pain.  

When it is understood that inflammation is an essential feature of many normal, healthy cell and tissue functions, then “inflammation," with its negative connotations, becomes a misnomer.

NSAIDs Inhibit Inflammatory Prostaglandin Production

Aspirin directly inhibits NF-kB activation inside the cell, but it also chemically modifies COX, the enzyme that converts omega-6 polyunsaturated fatty acids (common in polyunsaturated vegetable oils) into inflammatory prostaglandins.  Other NSAIDS (Non-Steroidal Anti-Inflammatory Drugs) just inhibit COX, but Aspirin transfers its acetyl group to make acetyl-COX, which has a new activity that converts omega-6 fatty acids into anti-inflammatory prostaglandins.  The high omega-6 fatty acid content of vegetable/seed oils, such as corn, soy, canola, etc. is why these oils, in contrast to olive oil or butter, are inflammatory.  Omega-3 fish oil is anti-inflammatory, because it is converted to anti-inflammatory prostaglandins.  Plant omega-3 fatty acids are shorter and are not converted to prostaglandins, but inhibit omega-6 conversion.

Aspirin

Nitric Oxide, Vasodilation and Viagra

Swelling is caused by vasodilation, the relaxation of blood vessels, and accumulation of serum in the tissue.  This vasodilation also makes the tissue red and warm from the increased amount of warm blood in the capillaries.  Vasodilation is caused by nitric oxide, NO, that is produced by an enzyme under the control of NF-kB, which takes the nitrogen from arginine (or nitroglycerine).  The NO diffuses easily and binds to receptors that produce an amplified signal, cyclic GMP, that relaxes the muscle cells surrounding blood vessels.  [Viagra is potentially dangerous, because it just exaggerates the amplified signal and obscures the underlying vascular damage, e.g. hypertension, that causes erectile dysfunction by blocking normal vasodilation.]

Nitric Oxide and Erectile Dysfunction

Hot/Cold and Endorphins

The dilemma of whether to use hot or cold therapy to block inflammation is based on a misunderstanding of what the temperature changes are actually doing.  Changing the temperature of the skin alters the structure of sensory proteins in nerves of the skin and triggers signals to the brain that register as hot or cold.  Chemicals, e.g. capsaicin or menthol, can have the same effect without changing skin temperature.  The important response for inflammation control, is return signals from the brain that release neurohormones, e.g. endorphins, from different nerves that reach not only some of the skin that was hot or cold, but also deeper tissue.  The endorphins block inflammation and all of its symptoms.  That is why chemically treated pads are more effective than icing or changing from hot to cold, because "hot" and "cold" signaling chemicals can be applied simultaneously.  None of the treatments is more than skin deep.  Actually chilling or heating tissue below the skin is damaging and causes more inflammation.  Low dose Naltrexone may be effective in some cases of chronic inflammation, by stimulating systemic rebound endorphin production.

Dr. Oz, Pain, Hot/Cold Receptors

Lymphocyte Offloading, Mast Cells, Heparin

Rosacea is a group of diseases that involve inflammation of the face in an exaggerated blush.  Any of the signals that would lead to blushing cause intense vasodilation.  A blush is fleeting, but rosacea is made chronic by another aspect of inflammation, offloading of lymphocytes.  Large numbers of lymphocytes accumulating in response to a local infection would produce pus.  In the case of rosacea, the distributed leucocytes, including neutrophils, respond to the blushing signals by producing inflammatory signals, such as P protein.  The result is cycles of inflammation, autoinflammation.

Mast cells can also be offloaded from blood vessels and provide a link between the immune system and inflammation.  Mast cells display IgE receptors on their surfaces, which bind antigens and trigger release of histamine, heparin and protease.  Histamine is a neurotransmitter that binds to receptors on blood vessels and nerve cells.  In the gut, histamine mediates many digestive processes.  Heparin released along with  histamine, coats the gut and prevents attachment of pathogens by competing for binding to the heparan sulfate proteoglycans (HSPGs) that form the surface of cells that line the gut.  [Heparin is the most common drug used in hospitals and is produced from intestines of cattle and hogs in the meat industry.]  Heparin also binds and inactivates the proteases released from mast cells.  Upon release, the now active proteases attack and activate receptors on nerves and immune cells.

Mast Cells and Heparin

Heparin is Anti-Inflammatory

Heparin is the most negatively charged polysaccharide, mediates most of the receptor/hormone interactions at cell surfaces; facilitates amyloid plaque formation, e.g. in Alzheimer's, atherosclerosis, diabetes, dementia; and controls numerous protease reactions in the complement system and clotting, etc.  There are hundreds of heparin-binding proteins.  Heparin is produced in secretory granules of mast cells by the action of heparanase on heparan sulfate proteoglycans. Heparin is a mixture of small fragments, oligosaccharides of heparan sulfate polysaccharides.  Heparin is anti-inflammatory and is administered to facilitate conception and gestation.  Inflammation also inhibits the genes involved in heparan sulfate proteoglycan production and since HSPGs are a major component of basement membranes of tissues and provide the barrier function of blood vessels in kidneys and brain, inflammation leads to proteinuria and loss of the blood brain barrier.  Since HSPGs have a short half life of six hours and are rapidly recycled, heparin added to the blood is rapidly absorbed by vessels, and heparin taken orally is absorbed by intestinal cells, but does not reach the blood.  HSPGs and heparin are central components of immunity and inflammation.

Heparin and Inflammation

Inflammation Blocks Skin Synthesis of Vitamin D from Cholesterol

Inflammation blocks solar synthesis of vitamin D in the skin and is more important than skin pigmentation, use of sunblock or latitude in producing vitamin D deficiency.  The vitamin D content of food is negligible compared to solar production in the skin.  It is not surprising that rising chronic inflammation is also accompanied by rising vitamin D deficiency.  Vitamin D supplementation is usually ineffective in curing vitamin D deficiency, because the supplements are too low and very high levels of supplemental vitamin D are required to reverse underlying chronic inflammation.  Statins are very effective at blocking cholesterol synthesis and although reducing cholesterol has minimal impact on the target, cardiovascular disease, it dramatically reduces vitamin D causing muscle pain, etc.

Most vitamins are enzyme cofactors synthesized by gut bacteria and used as quorum sensing signals during formation of biofilms.  Vitamin D, in contrast, is a steroid hormone and receptors for vitamin D are inside cells.  The receptor/vitamin D complex is transported into the nucleus where it acts as a transcription factor to control the expression of genes.  Vitamin D controls the expression of defensins in the crypts of the villi of the small intestines.  The antimicrobial activity of defensins is based on the basic amino acids (arginine and lysine) of its heparin binding domains.  Vitamin D also interacts with NF-kB in the nucleus and modulates inflammation.

Inflammation and Vitamin D

Bacteria and LPS

Lipopolysaccharide is a wall component that is indicative of bacteria, just as beta-glucan is indicative of fungi, and both are intense activators of NF-kB and inflammation.  LPS is released from damaged bacteria, e.g. by antibiotic treatment, binds to receptors on the surface of intestines and stimulates inflammation with release of NO, which produces diarrhea.  Food intolerances, which are based on incomplete digestion of food components, because of an incomplete gut flora (immunological responses/food allergies are rare) are probably also the result of LPS release from gut flora and inflammation.

Innate Immunity is also Triggered by LPS

The basic defenses of humans against microorganisms are mediated at the cellular level by triggering molecules common to all microorganisms, e.g. LPS for bacteria.  The responses are equally general: lysozyme to digest bacterial wall peptidylglycan, lactoferrin that binds iron and yields antibacterial peptides.  LPS (and inflammatory cytokines) also stimulates the liver to produce CRP (C Reactive Protein) that binds to choline on bacteria as the first step in phagocytosis and DNAse I that digests NETs (neutrophil extracellular traps) that are the DNA and histones released by triggered neutrophil cells that enmesh bacteria for engulfment by phagocytic cells.  [NETS plug peripheral catheters and can be cleared with probiotics that stimulate DNAse I release from the liver.]  NETs are also present at sites of inflammation and the accompanying nuclear proteins have the basic triplets that stimulate immune presentation and act as autoantigens, i. e. produce anti-nuclear antibodies, in the absence of adequate Tregs.

Diet and Inflammation

The diagram outlines the interactions that produce the tissue symptoms of inflammation.  Many components of modern diet can trigger inflammation:

Sugars and high glycemic starches raise blood sugar and enhance AGE/HgA1C.

Vegetable oils high in omega-6 oils are converted into inflammatory prostaglandins.

Wheat and other grains have high glycemic starch and insoluble fiber that is inflammatory.  Gluten is inflammatory.

Antibiotics damage the gut flora and produce vitamin deficiencies, autoimmunity and allergies.

Food intolerances result from damaged gut flora and produce gut inflammation.

Fish high in omega-3 EPA and DHA are anti-inflammatory.

The Anti-Inflammatory Diet

Health Results from a Balance of:

Diet (meat, fish, eggs, dairy, vegetables), containing macronutrients of protein, starch 30-100 g/d and fat (low omega 6/3 and saturated fat for most calories), and micronutrients

Soluble Fiber, e.g. resistant starch (consult Free the Animal), inulin, pectin, (plant polysaccharides, animal GAGs)

Gut Flora, diverse and adapted to dietary soluble fiber,

Exercise

Resistant Starch, Panacea, but Why?

Mark’s Daily Apple provides an authoritative diet guide (except for the gut flora).