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.

Peanut Allergy Cause and Cure

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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.

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 

Can Apple’s HealthKit Avoid Health-Exploitation?

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More healthcare begets more health costs and less health.  Tests detect symptoms that trigger treatment, but more often than not fail to contribute to health.  Apple’s newly announced HealthKit promises to facilitate increased surveillance of personal health statistics and to integrate the data with the health industry.  If recent history is a guide, more data will simply mean more inappropriate interventions, greater expense and further deterioration of public health.  More public interaction and scrutiny is needed to keep the public safe from the health industry and to hold doctors to their pledge to do no harm.

Breast, Prostate and Pelvic Exams Lead to Costly, Harmful, Unnecessary Interventions

In the last two years, major studies have found that frequent breast exams, prostate tests and pelvic exams cause more harm than good.  The surgery, followup procedures and treatments that the screening tests trigger are worse than the cancers that went unnoticed under more relaxed scrutiny.  The bottom line is that the information gathered from screening was not sufficient to produce appropriate, measured treatment.  Patients were harmed without benefit and the health industry was compromised by increased profits from inappropriate tests and treatments.  Doctors routinely convinced themselves of the value of routine exams that they performed to yield excessive false positives that resulted in unnecessary biopsies or disfiguring surgery.  Those flawed exams, tests and procedures also contributed substantially to the profitability of their practices.  Patients may have inadvertently been harmed, but the doctors knew that they benefited.

The Health Industry Pursues Profitable Tests and Treatment, not Causes and Cures

I was astounded a few years ago to read an article in the biomedical literature by a researcher who bemoaned the lack of interest in understanding the causes of diseases and the pursuit of cures.  Public and private funds were only spent on patent-protected tests and treatments.  I watched as the development and testing of fecal transplants demonstrated a safe and effective treatment for numerous diseases, and yet this approach was tracked down and caged by the health industry.  I think broad use of this approach could save billions of health dollars, but there is no patent protection and minimal profit, so the approach was stiffled.  The efficacy of fecal transplants also points directly at damaged gut flora (and antibiotics) as the cause of many diseases.  Where is the public forum to discuss the use of public funds to promote approaches that are safe, effective, cheap, but without potential for proprietary exploitation?  What will happen to simple cures, such as resistant starch and probiotics with Clostridium butyricum?

Is HealthKit Personal Data for Personal or Corporate Gain?

Will there be mechanisms for individuals to contribute their HealthKit data to large scale public health experiments to determine simple lifestyle, dietary and exercise approaches that can replace expensive and destructive pharmaceutical-based health industry approaches?  HealthKit provides the potential to wrest health from the health industry.  We will see if there is an app for that.

Health Diagrams II — Curing Autoimmunity and Allergies

---All 200 posts here---

In this second in a series of posts explaining the concepts that I think are central, but misunderstood, about health, I am focusing on how diet and gut flora impact the immune system and cause autoimmunity and allergies.  This cause also suggests a simple cure.

Health in Diagrams I -- Gut Flora and Diet
Health in Diagrams III -- Inflammation from Cell to Tissue

Gut Flora to Tregs to Suppression of Autoimmunity

It is important to understand at the outset that autoimmunity and allergies are caused by a damaged immune system, and repairing the damage cures the diseases.  Damage to the immune system typically represents a break in the continual development of immune cells in the lining of the intestines.  Immune cell development in the gut is dependent on bacteria, the gut flora.  Damage to the gut flora, e.g. by antibiotics, processed foods that lack flora feeding fiber or extreme diets, disrupts development of immune cells.  Typically, loss of the immune cells that keep the aggressiveness of the immune system in check, regulatory T cells or Tregs, results in autoimmunity.  Fix the gut flora and autoimmunity recedes.  

Health Requires Suppression of the Aggressive Immune System

For simplicity, I am focusing on the T cells of the immune system that develop in the intestines and either kill other human cells that are dangerous, e.g. virus-infected or cancer cells, or provide protection by regulating the aggression, Tregs.  Normal functioning of the immune cells permits elimination of damaged or dangerous human cells, while at the same time avoiding rampages of lethally armed T killers.  Examples of untamed T killers in action are degenerative autoimmune diseases, such as arthritis, asthma, prostatitis, celiac, Hashimoto’s thyroiditis, type I diabetes, inflammatory bowel diseases and atherosclerosis. 

Milk Births Baby Immune System

It should not be surprising that the focus of immune system development is the gut.  We start as babies with explicit links between nourishment and immunological protection.  Milk connects the immune systems of mother to baby.  Immune cells from the mother are transferred in milk and colonize the respiratory and digestive system of the baby — the mother’s immune system coats and buffers the baby’s exposure to the world.  Milk hormones close the baby’s gut and milk bacteria are the first probiotics that exploit the milk prebiotics (bifidus factor, human milk oligosaccharides) to produce a gut flora.  [Also note that most commercial probiotics are adapted to grow on cow’s milk and hence these dairy probiotics do not survive in adults.]  The lymphatic system of the breast terminates at the nipple and samples antigens/pathogens from the baby’s mouth, resulting in baby-specific secretory antibodies that return in the milk.  Milk supports a starter set of gut flora, essentially dairy probiotics, that stimulates development of the baby immune system, but inhibits adult gut flora that would digest the protective components of milk.  Formula, on the other hand, is inflammatory to the baby gut, because it supports adult gut flora before the immune system is ready.  Inflammation and stimulation of innate immunity is sufficient, if supported with high levels of sanitation, to permit survival of babies fed formula.  Milk of any type is incompatible with adult gut flora, so breast milk will attack adult gut flora and adult gut flora will digest and inactivate the otherwise beneficial components of the milk.

Milk, Kefir and Gut Flora

Aggressive and Suppressive Cells of Immune System Develop in Intestines

Gut bacteria are required for the development of immune T cells in the lining of the intestines.  Mice grown without gut flora do not have functional immune systems.  In humans, extensive antibiotic treatment produces defective immune systems that are either overly aggressive, i.e. autoimmune, or susceptible to infection and cancer.  They can’t be both.  Aggressive T killers are stimulated to develop by filamentous bacteria and Tregs develop in response to members of the Clostridium family.  In a healthy body, there is a balance between aggression and suppression; there are functional defenses against infection and cancer, while also avoiding autoimmune disease and allergies.

Suppressive Tregs are Deficient in Autoimmunity

Immune cells result from replicative divisions of stem cells.  Antibody producing B cells are produced through a million random rearrangements of antibody genes and those B cells producing antibodies against common self proteins are killed (clonal deletion).  Similarly, T cells are produced by rearrangements of receptors and those that would recognize self are eliminated.  The T cells then migrate to the intestines where they can develop into killer T cells or Tregs, in response to gut flora.  The Tregs act to suppress killer T cells that mistakenly recognize healthy self cells.  Thus, the initial elimination of self-attacking T cells or for B cells that produce antibodies that bind to normal cells, is not perfect and the Tregs are needed to avoid the mistakes.  Tregs are necessary to avoid the immune attack on healthy cells that is the basis of autoimmunity.

Autoimmunity Starts with Inflammation, but Requires Deficient Tregs

Bacterial or viral infections, or physical damage causing inflammation is the first step in autoimmunity.  It is the inflammation that initiates the interactions between proteins, autoantigens, of normal cells and cells of the immune system that bind, internalize, fragment and present the antigen fragments/peptides to activate B or T cells with corresponding receptors.  The activated B cells make antibodies specific for the antigen and the T cells will kill cells displaying the antigen.  It is interesting that most proteins are not autoantigens and are never involved immune reactions.  Only proteins with an unusual triplet of basic amino acids, similar to the quartet of basic amino acids used to transport proteins into the cell nucleus, are candidates to be autoantigens or allergens.  In fact, since nuclear proteins already have a quartet, i.e. the nuclear localization signal, they are common autoantigens.  The last requirement for autoimmunity is a deficiency in Tregs, because if the Tregs are functioning, they will block attack on healthy cells.  Treg deficiency usually results from loss of the type of gut bacteria that stimulate Treg production in the lining of the intestines, i.e. species of Clostridium.

Hospitals are Notorious for Clostridium difficile Infections

Fecal transplants are now recommended as a safe and efficacious treatment for C. diff hospital infections.  That makes sense, because hospitals are where antibiotics are routinely used and C. diff can only infect people missing their healthy species of Clostridium.  Thus, the hospitals wipe out the gut flora with antibiotics and then recolonize them with their own antibiotic resistant C. diff.  More antibiotics can’t fix it, but providing healthy gut flora (transplant) can.

Autoimmune Diseases are Treated/Exacerbated with Antibiotics

Both the aggressive and the suppressive immune cells require gut flora, so after initial antibiotic treatment wipes out bacteria required for suppression and results in autoimmunity, the remaining aggressive half of the immune system can be eliminated by blasting the remaining gut flora with more antibiotics.  Of course this will leave a highly compromised, incompetent immune system that will ultimately yield more extreme symptoms.  This is the typical medical progression for Crohn’s disease, for example.  The alternative is just fixing the gut flora to begin with and curing autoimmunity.

Cure Autoimmunity by Feeding Clostridium Resistant Starch

Autoimmune diseases, by their symptoms, show that sufficient gut flora to stimulate the aggressive half of the immune system is still present.  What is missing are the Clostridium species that convert soluble fiber, such as resistant starch, into short chain fatty acids, e.g. butyrate.  Patients treated with antibiotics usually walk away from the hospital with a suggestion to eat some yogurt to repopulate their missing gut flora.  Unfortunately, dairy probiotics don’t survive in the gut and cannot repair the gut flora and immune system.  The result, after the gut fails to repair and the immune system crashes, is autoimmunity.  There is a more appropriate possibility to avoid or fix autoimmunity.  Some people suffering from autoimmunity (and with remnants of their gut flora intact) have simply fed their gut flora on resistant starch and achieved complete recoveries.  Others fail to respond, because their gut flora is too severely damaged and necessary bacterial species are gone.  Those individuals need to eat the missing species of bacteria and some probiotics (more common in Asia) contain Clostridium species.  Consistent with this use of soluble fiber to feed gut bacteria that produce butyrate and stimulate the suppressive immune system are reports of healing by combining potato starch (RS) and probiotics with Clostridium butyricum (Probiotic-3).  Repair of the suppressive immune system by repair of gut flora (including fecal transplants) and feeding gut flora with appropriate soluble fiber, may be a general approach to the cure of most autoimmune diseases and allergies.

Paleo Gut Flora Repair

Health in Diagrams I — Gut Flora and Diet

---All 200 posts here---

This is the first of three posts to summarize my thoughts on diet, inflammation and disease mediated by gut flora.  I decided that I needed to make my points as explicit as possible by putting them down in diagrams and making references to my other posts.  By the time I finish, I will reach my 200th blog post at Cooling Inflammation.

Health in Diagrams II -- Curing Autoimmunity and Allergies

Health in Diagrams III -- Inflammation from Cell to Tissue

Everyone Leaves Out Gut Flora

I want to first explain and diagram my current understanding of the relationship between gut flora (the complex community of hundreds of different types of bacteria and fungi in the intestines) and diet.  My impression is that many people have health problems based on diet, but when they try to heal their health, they fix their diet and see only limited benefits.  Medicine provides only a temporary treatment using dairy probiotics.  The problem is that they failed to fix their gut flora, which was also damaged by their unhealthy diet.  

Health Requires a Match between Diet and Gut Flora

It is a myth that gut flora will just adjust to diet and a healthy diet leads to a healthy gut flora.  

A damaged gut flora lacks necessary species of bacteria.  Antibiotics, for example, can permanently delete dozens of particular bacterial species of gut flora that can only be replaced by reintroducing the missing bacteria by eating those bacteria again.  The missing bacteria may be needed to digest particular foods and the result is food intolerances, commonly mistaken for food allergies.  Antibiotic use frequently leads to autoimmune diseases, that are caused by deficient regulatory T cells of the immune system that develop in the lining of the intestines in response to particular gut bacteria.  The natural source of gut bacteria is eating the bacteria clinging to raw or fermented vegetables.

Antibiotics and Autoimmunity

Diagram Showing the Interaction of Food, Gut Flora and the Immune System

Food is just Protein, Fat and Soluble Fiber

The human body produces enzymes to fully digest proteins, fats and one polysaccharide, starch.  All other parts of plants and animals are edible (fermented by gut flora) soluble fiber polysaccharides or insoluble, undigestible fiber consisting of cellulose or lignin, which together also make up the undigested organic matter, humus, of soil.  Grains are problematical for health, because their starch is readily converted to sugar, i.e. high glycemic, and their fiber is insoluble (not fermented by gut flora) and high in phytate.  Phytochemicals, plant polyphenolics, are of questionable value as antioxidants and are of unexplored importance for their antimicrobial impact on gut flora.

Phytochemicals, Natural Antibiotics and Antioxidants

Polymers (Protein, Starch) are Hydrolyzed by Enzymes to Oligomers and then Monomers (Amino Acids, Glucose)

The stomach mixes protein digesting enzymes, proteases, and starch digesting amylase, with food protein and starch.  Proteases convert the long chains polypeptides, polymers of protein amino acids, into shorter fragments, oligopeptides.  The specific nature of the stomach proteases leaves groups of basic amino acids (lysine, arginine), heparin-binding domains, intact.  These peptides, similar to the defensins of the microvilli crypts, are anti-microbial and work with residual acidity to reduce bacterial growth in the first part of the small intestines.  Pancreatic enzymes then digest the peptides further and the small peptides are ultimately digested by enzymes on the surface of intestinal epithelial cells just prior to absorption.  Similarly, starch is degraded to oligosaccharide amylodextrins, which are then hydrolyzed to glucose at the intestinal surface prior to absorption.  Amino acids and glucose are not normally available to bacteria in the intestines.

Antimicrobial Heparin-binding Domains

Fats are Dissolved by Bile, Digested by Lipase and Absorbed

Fats are triglycerides, i.e. three fatty acids attached to the three hydroxyl groups of glycerol.  Fats are hard to digest, because they form oily droplets.  The droplets are dissolved in the intestines with bile, which is an acidic form of cholesterol, that is produced in the liver and stored in the gall bladder.  Fat in a meal triggers bile release from the gall bladder into the small intestines.  The bile represents a huge reservoir of the cholesterol that is synthesized by the body and dwarfs the cholesterol content of any meal.  Statins decrease body production of cholesterol, interfere with bile/fat digestion and lower lipid cholesterol levels.  (Unfortunately, lowering lipid cholesterol levels has minimal impact on heart disease and the only impact of statins on cardiovascular disease is through weak anti-inflammatory side effects.)  Pancreatic lipase removes two of the fatty acids from each triglyceride.  The fatty acids (a.k.a. soap) and monoglyceride are absorbed by the intestinal cells and reformed into triglycerides that make their way to lymphatic lacteals and are dumped into the blood, where they circulate as chylomicrons surrounded in lipoprotein.  Lipoprotein lipase binds to heparan sulfate on the surface of blood vessels and gradually removes fatty acids, until the diminished chylomicron is absorbed by the liver and exits as a VLDL.  (Note that this is another connection between lipid metabolism and inflammation, since inflammation decreases heparan sulfate on cell surfaces.  Heparan sulfate also mediates LDL binding to cells and amyloid stacking.)

Heparin-binding Domains

Plant Polysaccharides are Soluble Fiber and Food for Gut Flora

All that remains of food after the protein, fat and glycemic starch (glycogen) have been removed in the small intestines are plant cell wall polysaccharides, resistant starch, storage polysaccharides, e.g. inulin, plant beta-glucan, animal glycans, e.g. chondroitin sulfate and heparan sulfate, and insoluble fiber.  The insoluble fiber passes on to be a minor contributor to the bulk of stools and the rest of the polysaccharide is potentially fermentable by gut flora into short chain fatty acids (formic, acetic, propionic, butyric acids).  Some of the polysaccharides are simple repeating units of one or two sugars in long chains, but others are made of five to ten different sugars in complex branched structures.  Simple repeating polysaccharides require just a few different enzymes for their initial synthesis and a few for their digestion.  Thus, resistant starch can be digested by a couple of enzymes into glucose that can be used by most gut flora.  Arabinogalactan, on the other hand, requires a dozen enzymes for plant synthesis and an equal number of hydrolytic enzymes to produce arabinose and galactose, which require further enzymes for metabolism in a select few of species of gut flora bacteria.  

Resistant Starch as a Panacea

Food Intolerance/“Allergy” Indicates Missing Bacteria

Gut flora in general can produce several hundred different enzymes for digestion of diverse soluble fiber,  but most soluble fiber polysaccharides can only be digested by certain bacteria and those bacteria increase, if the complementary fiber is present in the diet.  If a fiber is absent from the diet, bacteria that specialize in digesting that polysaccharide will be eliminated.  People living on diets limited to just a few types of soluble fiber can only digest those fibers and a shift in diet to other types of soluble fiber will lead to symptoms of dietary upset, such as bloating, gas production and food intolerance.  Food intolerances reflect inadequate diversity in gut flora and a mismatch between bacteria and food.  Food intolerances can be eliminated by repairing gut flora and the typical repair solution is eating homegrown fermented vegetables that provide the missing species of bacteria.

Paleo Gut Flora Repair

Immune Cells Develop in Response to Gut Bacteria

Most of the body’s immune cells are in the intestines.  Cells of the immune system are constantly dividing in bones and the thymus gland, developing in the lining of the intestines and migrating to other tissues.  Filamentous bacteria of the gut flora stimulate the development of aggressive immune cells that kill other cells that are infected with pathogens or viruses or are cancerous.  Furrows perpendicular to the flow of food cultivate the growth of Clostridium species that ferment soluble fiber, e.g. resistant starch, and release butyric acid that stimulates the development of regulatory T cells, Tregs.  It is the Tregs that control the aggressive immune cells and prevent attack on self (autoimmunity) or innocuous antigens (allergy).  It appears that merely eating resistant starch, e.g. potato starch, with probiotics that contain butyric acid producing Clostridium bacteria may provide a cure for many autoimmune diseases.

Free the Animal: A Resistant Starch Primer for Newbies

Gut Biofilms Release Vitamins as Quorum Sensing Signals

 The gut flora lines the intestines in numerous biofilm communities, which form from dozens of different species of bacteria that communicate by exchanging molecules called quorum sensing signals.  These signals from the biofilms intimately attached to the lining of the intestines are vitamins.  Thus, healthy gut flora are the major source of vitamins and other sources, such as fruits and vegetables are only needed, if the gut flora is damaged, e.g. by antibiotics.

Dr. Oz, Vitamins, Biofilms

Volume of Stools Reflects Gut Flora Fermenting Soluble Fiber

The bulk of bowel movements, stools, is bacteria, the compressed gut flora that accumulated in the colon while fermenting soluble fiber.  We always hear that we need to eat fiber for regularity, but since insoluble fiber is only a minor contributor to stool volume and it is associated with anti-nutritive attributes, such as the binding and removal of zinc and iron by phytate, the fiber that counts for regularity is soluble fiber.  Regularity results from the fermentation of soluble fiber polysaccharides producing short chain fatty acids, such as butyrate, that are the major source of energy for colon cells.  And the growing bacteria in the colon provide most of the bulk of the hydrated stools.  Inadequate dietary soluble fiber or damaged gut flora, dysbiosis, leave only dehydrated insoluble fiber and compact stools of constipation.  Constipation can result from dehydration or excessive retention, but chronic constipation, even in the presence of adequate dietary soluble fiber, is an indication of damaged gut flora and an increased risk for diseases resulting from deficiencies of Treg production:  autoimmune diseases and allergies.  Constipation and associated autoimmune diseases can be cured by repairing gut flora and supplying adequate dietary soluble fiber.

Milk, Kefir and Gut Flora

Paleo Gut Flora Repair

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I was shocked to learn that there were some paleo (meat and veggie) eaters who were getting cured with resistant starch.  I didn’t know that some were sick and, as I said in a previous post, I would not have guessed that starch was good for anything, but spikes in blood sugar.  I was rudely awakened by the shouts of Richard Nikoley on Free the Animal, though I suspect the sanity behind the argument came from Tim and Dr. BG (though she has now modified her position)  He presented a kind of Second Coming of Paleo with resistant starch to feed the gut flora as soluble fiber.  How could I question food for flora?  (How could I question Nikoley without my karate gi?)

Paleo is not Paleo

It took me a while to realize that paleo is not the same for everyone.  I thought my Anti-Inflammatory Diet (meat/fish/eggs/dairy and veggies, without vegetable oils or sugars or grains) was paleo.  The way that I used this AID, it was high in saturated fat, low in polyunsaturated fat, high in protein, low in high glycemic carbs and ample in prebiotic, soluble fiber.  Some would say it is low carb.  Judging from comments on Free the Animal, I think I would be cast out by some of the more carnivorous (LC and VLC) in the paleo community for including prebiotic fiber.  Some people don’t want to feed their flora, microbiota.  It is a kind of “Let them eat meat,” mentality.

Gut Flora/Microbiota are Friends

I think of my gut flora as fellow travelers on my life journey and what’s good for them is good for me.  I don’t intentionally abuse them, but I also forget that they might not enjoy bourbon or the phytoalexins in herbs and spices.  I don’t begrudge them the soluble fiber that they need, and I think that they are a little happier with each apple (pectin) I feed them.  I simply forget that most people haven’t taught micro, DNA sequencing and the biochemistry of plant cell wall polysaccharides.  My wife starts to roll her eyes at any sentence containing “flora”, “antioxidant”, “inflam-“, “omega-“, “carb”, “paleo”, or even “microbiobiota.”  And the list gets longer.  I think that I'm out of touch, until I read Nikoley.

Paleo Diet without Prebiotic Fiber is Hard on Gut Flora

People get sick on paleo, because they don't feed their flora.  Gut flora are needed to supply vitamins, short chain fatty acids and immune system stimulants.  If you don’t feed your flora you get vitamin deficiencies, gut inflammation and autoimmune diseases (Treg deficiency).  It is very important to remember that feeding your flora means matching the soluble fiber with the existing flora.  Most people make the mistake of assuming that if they change their diet, then their flora will also change.  Their flora will adapt with each of their hundred different species of gut bacteria increasing or decreasing in numbers, but no new genes will be present to digest new soluble fiber.  Eating a meat diet will eventually eliminate gut bacteria needed to digest some plant materials and produce intolerances.  The missing bacteria will not be regained upon return to eating plants again.

Changing Diet Does Not Repair Gut Flora

Many people lose species of gut flora as they change from diet to diet, eat processed foods lacking soluble fiber or use antibiotics.  The loss may be permanent, but need not be.  Food intolerance and most “allergies” merely reflect missing species of bacteria, and introducing new bacteria fix the problem.  Lactose intolerance, for example, can be cured by eating live yogurt.  Similarly, many immunological problems, such as autoimmune diseases, result from species of gut bacteria that are needed for the development of the immune system, which takes place in the lining of the gut in response to gut bacteria.  New bacteria need to be introduced to fix the deficiency and diet alone is not enough.  Just to be clear;  meat-exclusive paleo can lead to autoimmune diseases, because of deficiencies in gut flora diversity/species and adding back soluble fiber can only cure the diseases, if the bacteria needed to digest the fiber polysaccharides are still present or are reintroduced.  Also note that there is soluble fiber polysaccharide sufficient in a carnivorous diet to support properly adapted gut flora.

Dairy Probiotics Do Not Repair Gut Flora Destroyed by Antibiotics

Don’t expect dairy probiotics to cure diseases caused by deficient gut flora.  Bacteria that grow on dairy cannot survive in the gut.  I know that physicians, including Dr. Oz, recommend that patients treated with antibiotics eat yogurt to repair their gut flora.  It ain’t  gonna happen.  That treatment is just for the doctor’s benefit (and provide some temporary functionality), to make her feel like she is addressing the problem responsibly.  I suggest that the antibiotic-damaged gut flora will screw up the immune system and bring the patient back to the doctor’s office even sicker.  Antibiotics are very good for business.

Health in a Crock

So, here comes the part that was missing from Nikolay’s Paleo plus RS.  He left out the missing gut flora.  RS is a panacea for those with some gut bacteria that can digest RS, but for those with profoundly crippled gut flora, e.g. some of those with autoimmune symptoms, RS is just inert fiber, not flora food.  

Fermented Vegetables Repair Gut Flora

New bacteria must be eaten, and I think that the cure, short of the real deal fecal transplant, is still available in the original, paleo form of naturally fermented, live foods.  The answer (and please forgive the fervor, because I think health can be this simple) is Fermented Vegetables, by Kirsten and Christopher Shockey.  Their book, right, is coming out in September, and I think that the most important part of this cure is that it looks and tastes fantastic.  This is not canned, dead sauerkraut.  These are culinary delights from simple recipes in which the natural bacteria do all the work.  Since they are long time friends of mine, I have coerced Kirsten into giving me some advance access to some of her recipes.  She has also tentatively agreed to share on my blog some of her personal fermentations on happy bellies.  So check back for future posts.

Pay close attention, because some of these recipes may cure what ails you.  They have the potential to repair your gut and are the healthful fix for a sickening faux “paleo” diet.  Note that homemade, live fermented veggies contain 1) fermenting bacteria responsible for acidifying the brined veggies for storage, 2) additional bacteria of the species missing from your gut flora and are just along for the ride, and 3) veggies that have their soluble fiber intact and ready to feed your gut flora.  Cooking, pasteurizing or otherwise harming the live, working bacteria in fermented vegetables destroys their benefit in contributing to your gut flora.  It only takes a few of the bacteria that do survive passage through your acid stomach to fix your gut flora.

Major Points of a Healthy Paleo Diet

• Meat/fish/eggs and veggies, without dairy, grains, vegetable oils and processed foods.
• Nikoley and others pointed out that a healthy paleo diet has soluble fiber, e.g. RS, to feed gut flora.
• Resistant starch is a unique category of soluble fiber with health benefits.  (Other types of soluble fiber may also be needed.)
• Diet alone is not enough for health, add gut flora.
• Diet and gut flora need to match.
• The natural paleo source of gut flora bacteria is homemade fermented vegetables.

Resistant Starch, Panacea, but Why?

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I am definitely not a bandwagon kind of guy (except maybe in the case of fecal transplants.)  So embracing evil, high-glycemic starch as a medicinal godsend was tough.  As a biochemist raised on structural analysis of carbohydrates, the idea of starch as a mixture of linear amylose and branched amylopectin, was straightforward.  Amylase in saliva and pancreatic solutions digests the linear alpha,1-4,glucan stretches and pullulanase (bacterial) degrades the alpha,1-6, glucan branch points.  But this suggests that starch should be digested before it gets to the colon and most of the gut flora.  This ignores the spirals of amylose that resist amylase digestion, i.e. resistant starch (RS), and that lead to the puzzling role of RS as a special food for gut flora and a health panacea.

Why is resistant starch, RS, difficult to digest and terrific for gut flora?  

There are several conceptual difficulties to understanding why RS is Real Special:

• Polysaccharides are not all simple linear chains of sugars, e.g. they branch (amylopectin) or form helices (RS, amylose).
• Sugars and polysaccharides have hydrophobic patches.  They are amphipathic like soap.
• Amylose (RS) forms a spiral with a hydrophobic surface of each sugar facing inward to make a hydrophobic core and hydrophobic patches on the outer surface that structures water to hold the spirals together.  The same principle holds together the double helices of DNA around a central hydrophobic core of stacked base pairs.
• Polysaccharides (soluble fiber) are made of many different sugars, e.g. glucans, mannans, xylans, galacturonans, etc.
• Starch is enzymatically hydrolyzed to glucose, which most gut flora can ferment.  Other sugars from other polysaccharides (e.g. pectin, polygalacturonan) must first be converted to glucose for fermentation.
• Soluble fiber polysaccharides made from multiple sugars, e.g. arabinogalactans or xyloglucans, require multiple bacterial enzymes for digestion by gut flora.
• Several hundred bacterial enzymes of the gut flora are required to digest the complex soluble fibers of food plants in a typical diet.  Resistant starch requires two.
• Food intolerances (also mistakenly called food allergies) result from missing bacteria and their enzymes to fully digest soluble fibers.
• Novel soluble fibers or sugars are used as laxatives, and they lose their loosening impact as your gut flora adapts to digest the new fiber.  Normal, softened stools are half bacteria.
• Amylose spirals are used as a storage form of glucose in seeds, potatoes, roots, etc., because enzymes can’t attack their glycosidic bonds to hydrolyze the starch into amylodextrins and glucose.
• Bacteria digest amylose by attaching the spirals to their cell walls and using wall-bound enzymes to tear the amylose apart.  It's like the different requirements of a wood chipper (pancreatic amylase) versus a man with a chain saw (bacterial amylase).
• The spirals of RS melt during cooking and become susceptible to gut amylase.  Melted amylose can sometimes slowly reform enzyme-resistant spirals, RS, when chilled.  Al dente or chilled pasta has more RS and raises blood sugar less than soft pasta.

Resistant Starch, a Unique Soluble Fiber  

Humans only produce enzymes (amylases) to degrade one of the hundreds of plant polysaccharides, linear starch.  RS is not degraded by human amylases and, as with other soluble fibers, it is degraded by bacterial enzymes in the colon and is fermented to short chain fatty acids.  The difference is that the glucose released from hydrolysis of RS is used directly by common gut bacteria, whereas the other sugars released from other soluble fibers require enzymes produced by particular species of bacteria to be converted first to glucose.  RS is a unique form of starch and a unique soluble fiber.

Short Chain Fatty Acids and Immune Cells Required for Health

Gut flora eat soluble fiber and produce short chain fatty acids, e.g. acetic, butyric, propionic acids, that feed the cells of the intestines and lower inflammation.  The development of both the aggressive and the suppressive (Tregs) halves of the immune system requires healthy gut bacteria.  The bacteria that digest RS, for example, are Clostridia (see EM right, note bacterium dissolving its way into the grain of RS), the type of gut flora that also stimulates Tregs and prevents autoimmunity.  Thus, the beneficial impact of dietary RS results from feeding gut flora.  Most people already support gut flora that can utilize RS, so most people benefit from RS in their diet.  Some people have severely damaged gut flora, dysbiosis and constipation, and they may need to eat live, fermented foods (not just dairy probiotics) to recruit enough new bacteria to benefit from RS.  Other healthy people may already have healthy gut flora that can exploit all of the soluble fiber in a compatible healthy diet, and need no further enhancement of their health by RS.  Health always requires gut flora complementary to diet and each change in diet requires accommodation by corresponding changes in gut flora.  Some changes in diet may require new species of gut bacteria.

Does Altered RS in Modern Bread Explain Gluten Intolerance?

The RS remaining in today’s superfine flour that is rapidly cooked into bread and other foods, may be very different from previous generations.  Traditional hydration and exposure to fermenting microorganisms may have produced breads with higher levels of RS that contributed to healthier gut flora.  Healthier gut flora would in turn produce less intestinal inflammation and a reduced response to gluten.