HELLP, Preeclampsia, Antiphospholipid Antibodies and Basic Triplets

—-the other 200 posts —-

Clotted RBCs in Capillary

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

HELLP, Cause and Cure Unknown?

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

Autoimmune Disease with Unknown Autoantigen 

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

Attack on P-Selectin Starts Immune Autoimmunity

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

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

......carboxy terminalGTLLALLRKRFRQKDDGKCPLNPHSHLGTYGVFTNAAFDPSP

Antibiotics and Liver Damage

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

HELLP from Cause to Cure

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

Fermented Vegetables Repair Gut Flora

---the other 200 posts---

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

Old Friends Become Fermentista

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

Fermented Vegetables are a Source of Gut Flora

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

The Guide to Fermentation

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

Fermented Vegetables is Available Now (bottom)

All of the Answers to Fermenting Vegetables

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

Health Diagrams II -- Curing Autoimmunity and Allergies

The Cure for Damaged Gut Flora and Inflammatory Diseases

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

Peanut Allergy Cause and Cure

--- the other 200 posts---

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.

200th Post — Diet, Inflammation, Disease & Gut Flora

— all 200 Posts —

I started posting to Cooling Inflammation on 21 Aug, 2008 with How Your Diet Makes You Sick or Healthy.  My impetus for writing was my growing awareness that diet was the major reason why people were sick, and that health myths were preventing people from being healthy.  Inflammation originated by diet-inflicted injury and people attributed their sickness to genetics, environmental toxins and pervasive pathogens. 

My Path to the Obvious

My research background started with plant biochemistry, including carbohydrate structural analysis and polyphenol chemistry.  At that stage I was interested in understanding how plants protected (phytoalexins) themselves from pathogens, and I expected to use this perspective to explore human innate immunity.  From there, I went on to enzymology and protein characterization, biofilm structure, plant genetic engineering and breeding, monoclonal antibody production, mycotoxin detection, stem cell analysis, passive immunity in neonates, computational modeling of collagen and heparin binding, and heparan sulfate proteoglycan inhibition by inflammation.  These were temporary foci and the research imperatives, in retrospect, prevented me from seeing the bigger pictures, although they did leave me with a broad skill set.

Perspective: Water and Surface Tension

When I finally decided to slow down, smell the flowers and start having kids, I switched from research to teaching, from university to small liberal arts college.  For the first time, I actually thought about what I was teaching and my first revelation was that after teaching biochemistry for twenty years, I didn’t understand water and surface tension.  I could provide the platitudes from the Molecular Biology of the Cell, but I couldn’t do it mechanistically with colliding, sticky, energetic water molecules in my mind or at the blackboard.  I had to develop functional explanations of hydrogen bonds, entropy and thermal energy, that translated into the structuring of a layer of water molecules responsible for hydrophobic interactions and surface tension.  I extended that to include an explanation of the two layers of water holding together cytoplasmic membranes, the tube of structured water that holds together the cylinder of stacked bases in DNA or the shrink wrapping water layer surrounding proteins.

Perspective: Heparin Binding and Amphipathy of Sugars and Basic Amino Acids

As the kids got older, I started to dabble in research again and my expertise in carbohydrate chemistry led me into cartilage (mostly the glycosaminoglycan, GAG, chondroitin sulfate) synthesis and ultimately another GAG, heparan sulfate proteoglycans (HSPGs).  I was attracted to the dynamic HSPGs, that recycled with a half-life of six hours and formed layers around chondrocytes that secreted cartilage as they burrowed/ate through living cartilage.  I learned that the heparin filled granules of mast cells could be stained with berberine, which similarly stained the heparin in basement membranes of tissues and amyloids of Alzheimer’s, atherosclerosis and diabetes.  I was led by protein modeling of collagens to the binding of heparin to proteins and the revelation that basic amino acids (heparin binding domains) and sugars (heparin) are amphipathic, i.e. they have both hydrophobic and hydrophilic regions.  This is also true of plant polyphenolics.  Thus, polyphenolics, “basic” amino acids, “hydrophobic” amino acids, and sugars will all stack together.

Amphipathic Interactions

• DNA bases stack.
• Heparin binding sites of proteins are basic amino acids (Arg, Lys).
• Sugar binding sites in enzymes and lectins are hydrophobic amino acids (Trp, Tyr, Phe).
• Nuclear translocation signals, quartets of basic amino acids, bind to receptors with tryptophans.
• Tryptophans are the most highly conserved amino acids in the same proteins across great evolutionary distances.
• Hydrophobic bonding between tryptophan and a sugar or basic amino acid is ten times greater than hydrogen or ionic bonds.
• Tryptophan/Arginine ladders zip regions of proteins together.
• Polyphenols can disrupt cellular protein interactions by binding to receptors for carbohydrates/heparin, steroid hormones, amyloids, etc.
• Heparin holds dozens of hormones to receptors and changes the shapes of proteins, e.g. clotting and complement.
• Most nucleic acid binding proteins will also bind to the more negatively charged heparin.
• Bacteria use a pair of lysines to mark proteins for export.
• Peptides containing the basic amino acids of heparin binding domains (also produced by the specificity of gastric proteases) are antimicrobial, e.g. defensins, and so are plant polyphenols.
• Many drugs are active because they are domesticated plant polyphenols.

From Heparin Binding to Antigen Presentation

As soon as I realized that basic amino acids were involved in heparin binding, I started to look for the basic amino acids (R for arginine and K for lysine in amino acid sequences) in proteins known to bind heparin.  After study of hundreds of structures, it became obvious that heparin binding domains were simply a pair of basic amino acids (RR or KK or RK) with another within a distance of six amino acids.  No particular structure was necessary, as I later deduced, since binding to the heparin provided the structure.  In fact, in many X-ray crystallographic structures, the heparin binding regions on the surface of the protein are missing, because they are not in a defined shape.  I suspected that protein antigens involved in autoimmunity and allergy might be brought into cells for presentation to the immune system by interacting with HSPGs on the surface and so started to check them out for heparin binding domains.  I was very skillful at picking out pairs of Ks or Rs within sequences of hundreds of amino acids by that time, so I was shocked to see that the first dozen antigens that I checked, all had a triplet of basic amino acids.  I had discovered that autoantigens and allergens utilize a basic triplet analogous to the basic quartet used in nuclear translocation!  This also explained why proteins that interact with nucleic acids and are transported into the nucleus with a basic quartet are also prominent autoantigens.

Gut Flora and Immunity

Twenty years ago I read a curious description of leprosy that said that the course of infection could be either innocuous or devastating depending on whether the aggressive or the suppressive part of the immune system dominated.  I remained perplexed until I realized that diet and gut flora were the major determinants.  I was aware of the importance of diet at the outset of this blog, because it was clear that diet trumped genetics.  I was also aware thirty years ago in my studies of passive immunity, that milk contained bifidus factor, now known to be milk oligosaccharides, that controlled the growth of Lactobacilli that in turn controlled the development of the neonate immune system.  It was also known that bacteria-free mice had impaired immune systems.  It still took me several years for the relationship between diet, gut flora and immunity to make sense.  I began searching the literature for connections between gut flora and development of the immune system and soon noted experiments that linked filamentous bacteria with aggressive components and Clostridium spp. with Tregs.  A further refinement was linking resistant starch, a soluble fiber, with Clostridium.

My Current Views are Summarized in Three Health Diagrams

Diet, Gut Flora, Inflammation, Antigen Presentation, Tregs and Autoimmunity

Protein from the body and from food don’t normally stimulate the immune system, because there in no inflammation, the proteins lack basic triplets that enhance presentation, and antibody production and aggressive T cells are suppressed by Tregs.  Diet can throw the balance toward autoimmunity and allergy, by producing inflammation, e.g. hyperglycemia/AGE or high omega-6 fatty acids/prostaglandins, and starving gut flora needed for Treg production by eating processed food lacking soluble fiber.  The combination of inflammation and Treg deficiency causes proteins, either self or potential allergens, which have basic triplets to be presented to the immune system and stimulates attack by the immune system.

The Cure is to Cool Inflammation and Stimulate Tregs with Diet and Bacteria

I have provided an outline with The Anti-Inflammatory Diet to avoid inflammation, to stimulate existing gut flora with soluble fiber and encourage Treg production.  Mark Sisson, on Mark’s Daily Apple has provided an excellent dietary guide that also provides starch guidelines.  If you already have symptoms of autoimmune disease or allergies, then Richard Nikoley provides gut flora repair advice on Free the Animal, and Dr. B G provides more details on Animal Pharm.

Autoimmunity and allergies are not genetic destiny and they can be cured with diet and bacteria.

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

Gut Flora Risk and Repair

….All 190 posts here….

The two most important contributors to health are diet and gut flora.  All of the other contributors, such as exercise, genetics, environmental toxins, hygiene, etc. are of minor importance.  A healthy diet, such as The Anti-Inflammatory Diet that I recommend on this blog, is simple and relatively easy to follow after weaning from the Standard American Diet.  One version of the healthy diet is just eating meat, fish, eggs, dairy and plenty of vegetables, but avoiding vegetable oils and grains.  Most people will be healthy with that general diet, but if and only if, they also have a healthy gut flora that is adapted to the food they eat.

Most people make themselves sick by not matching their gut bacteria to what they eat, so let me repeat the main point of this article:

You will get sick if the bacteria in your colon can’t digest your food.

And sick means allergies, autoimmunity, cancer, etc.

Read and Heed or Dead

What Killed American Gut Flora?

There are hundreds of different species of bacteria growing on partially digested food (soluble fiber) in your colon.  Americans are sick, not because they are too poor to buy food, but because they have the worst, i.e. least diverse, gut flora in the world.

Do:  We pick up, recruit, eat new bacteria and repair our gut flora by:

• touching surfaces, people, pets, etc. and putting our fingers near our mouths,
• eating live fermented food, or semi-clean vegetables,
• not cooking/killing/sanitizing all of the bacteria around us,
• eating probiotics and transferring some of their genes to our gut flora.

Don’t:  We wipe out or reduce the diversity of our gut flora by:

• using inappropriate hygiene that kills the bacteria we need for health,
• taking antibiotics that kill gut flora and compromise our immune system,
• trying to eat a wide variety of foods, which is counterproductive and only permits a few varieties of bacteria to survive.

Hygiene Kills Beneficial Bacteria

Nothing comes from nothing…  For bacteria to come out, bacteria must go in.  You have to eat bacteria to extrude them by the pound.  Each day a single bacterium growing and dividing in your gut once per hour will produce a million daughter bacteria (24 doublings, estimate that doubling two, ten times is about a thousand, and 1000X1000= million.)  So if you mixed a milligram (about the size of the period at the end of this sentence) of gut bacteria with ample food, you would have a kilogram (pounds) of bacteria by the end of the day.  Similarly, it takes about a day for a single bacterium applied to a petri dish of nutrient agar to produce a colony weighing about 10 milligrams.  The point here, is that a single bacterium that makes it through the acid bath of the stomach can be a major player in your colon in a couple of days.  This is a very good thing.  We want to kiss babies, because babies systematically vacuum up bacteria from the darkest  of corners and with shameless generosity present them in an irresistible pucker.  We need those bacteria, and so do the babies.  Hygiene, e.g. antibacterial hand soap, bleaching surfaces or closing toilet lids isolates people from potential sources of beneficial gut bacteria. 

Traditional Food is Fermented (with Live Bacteria)

Shockey

In most cultures, extra food is mixed with something like salt or spices to kill local problem microbes and then bacteria are permitted to grow.  The result is fermentation of the sugars available in the food with production of organic acids, e.g. vinegar, that stop the growth of other bacteria that might grow on protein and cause objectionable flavors.  Homemade fermented veggies contain a wide variety of happenstantial bacteria that can adapt to productive gut growth.

Cooking Kills

We cook to dissolve and soften foods.  Meat can be eaten whole and our stomach enzymes will easily digest the protein and fat to provide all of our nutritional needs.  The only plant material that can be digested by our enzymes is starch.  The rest of the plant requires cooking to make the protein available and the remaining carbohydrates, soluble fiber, require digestion by hundreds of different enzymes produced only by microorganisms.  Cooking will release soluble fiber to feed gut flora, but it also kills bacteria, so some raw foods must be eaten to make sure that the gut is always supplied with fresh bacterial recruits.  Cooked or pasteurized foods do not contain live bacteria and are not useful as sources to repair gut flora.

Probiotics are not Gut Flora

Commercial probiotics are made from bacteria used in dairy products (dairy probiotics) or bacteria used to make enzymes in other products, such as laundry detergents.  

These bacteria can be repackaged and sold as probiotics, because they have already been tested for toxicity.  These bacteria don’t normally grow in the gut and if you swallow them, they just pass through.  These “probiotics” can temporarily provide some of the functions of gut flora, because they are bacteria, but they don’t grow in the gut.

Gut Flora are Bacteria Created in the Gut

Gut bacteria produce chemical signals that coordinate the metabolism of food by hundreds of different species of bacteria.  We call these chemical signals vitamins, because humans extract the vitamins from the bacterial biofilms that always line the gut, so humans don’t need to produce their own vitamins.  Gut flora can produce all of the vitamins that we need, so it is not surprising that multivitamins do not provide any health benefit and concentrated vitamins my be harmful by disrupting normal metabolism of gut flora.  Biofilms also promote the exchange of genes between different species of bacteria, so the concept of species does not actually apply to gut flora, where new species are rapidly being created.  A common example of this process is the curing of lactose intolerance by simply eating small amounts of live yogurt for a couple of weeks.  The cure results from the transfer of a gene that produces an enzyme to digest lactose from the yogurt probiotic bacteria to the regular gut bacteria.  The new species, a natural GMO, continues to grow in the gut, digest lactose, and cure lactose intolerance.  The yogurt probiotics just get flushed away and that is why dairy probiotics must be eaten continuously to provide some of the benefits of healthy gut flora.

Antibiotics Kill Gut Flora, Compromise the Immune System and Cause Disease

Antibiotics are a huge benefit in curing and avoiding infectious disease.  Unfortunately, antibiotics can cause lasting damage by killing beneficial species of bacteria of the gut flora.  Loss of essential bacteria is commonly seen as food intolerances (true food allergies are rare) or constipation.  Since gut flora are needed for development of both the aggressive and suppressive parts of the immune system, which occurs in the lining of the gut, then antibiotics slowly lead to loss of function of the immune system that leads to autoimmunity or allergies.  Probiotics typically administered following antibiotic treatments do not repair the gut flora and leave the immune system damaged and prone to autoimmune diseases and allergies.

Variety in Foods Leads to Loss of Diversity in Gut Flora

It may be more entertaining to eat a new cuisine at each meal, but it confuses your gut flora.  Your gut is a river that endlessly moves food from mouth portal to pottie.  Bacteria divide and eddies cast some of the bacteria back to mix with food upstream before inevitably moving with the masses down and out.  Bacteria that don’t multiply as quickly as others eventually become extinct.  Bacteria that grow well on broccoli may wither with onions.  If you continue to eat some broccoli and some onions, then your gut flora will adapt, but if the type of polysaccharides, the soluble fiber, changes continuously, then you will end up with the stunted gut flora of Americans.  Diversity of gut flora is reduced by too much variety in food.

Matching Food to Gut Flora Takes Time

All of the gut problems that people complain about, gas, bloating, diarrhea, constipation, food intolerances/allergies (except gluten and a couple of others), etc. are due to a mismatch between food and the digestive enzymes of gut flora.  Modern food processing retains protein, fat and starch and removes the polysaccharides/soluble fiber that reaches the colon, feeds gut bacteria and produces short chain fatty acids (acetic acid, butyric acid, propionic acid) that feed the colon and reduce inflammation.  It takes time for gut bacteria to adapt to new soluble fiber in new foods by recruiting or creating new bacteria, and this is only possible, if inappropriate hygiene is avoided or if homemade fermented foods are eaten.

Dr. Oz Diet and Gut Flora Myths

….All 190 posts here….

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

The Big Truth about Diet and Gut Flora

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

Assorted Health Truths

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Summary Diet Truths

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

Antibiotics, Gluten, Hashimoto's Thyroiditis and Baldness

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

Antibiotics Compromise the Immune System

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

Antigens/Allergens Have Basic Amino Acid Triplets

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

Allergies / Autoimmune Diseases Are a Predictable Consequence of Antibiotics

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

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

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

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

Dr. Oz on Gut Flora Repair

---  the other 200 posts  ---

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

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

Generalizations about Gut Bacteria

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

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

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

Sources of Bacteria to Repair Damaged Gut Flora

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