Disease Genes in the Gut Microbiota

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Species of Gut Microbiota

 

Summary:  Doctors take medical histories and enquire about family diseases.  It seems like they think there are human genes behind human diseases, but when we say, “It runs in the family,” what we actually mean is our gut bacteria, microbiota, are shared with relatives along with our eating habits.  Diseases result from problems with gut bacteria and not from problems with our genes.

Genetic Diseases are Rare

Not too many years ago, the technology for massive projects to thoroughly identify the genes behind the most prevalent human diseases became available.  The results were clear and shocking.  Genes were not a major contributor (less than 10%) to disease.  And yet, the families studied clearly had a major predisposition to each of the diseases studied.  Something was causing the disease in those families, but it just wasn’t any of the 23,000 genes identified in the human genome project.  People all have essentially the same physiology determined by very similar genes.  Health differences are predominantly due to gut bacteria.

A Decade Later, Genetic Map Yields Few New Cures

Genes are not Destiny

Commercial analysis of personal gene sequences was recently prohibited as a method of determining risk of disease, because the link between gene sequences and risk could not be substantiated.  The reality is that, aside from a few obvious molecular diseases, most genetic variations in gene sequences do not matter in an otherwise healthy person.  There aren’t  Alzheimer’s or obesity or heart disease genes.  Diet, gut microbiota, sleep and exercise are far more (>90%) important.  Most genetic risk factors can be overcome by an Anti-Inflammatory Diet with fermented vegetables, and a robust gut microbiota protected from medicine/antibiotics.

Gut Bacteria are Family

So if it is not human genes that run in families to make relatives share similar diseases, what is making them sick?  Relatives share their eating habits and gut bacteria.  This makes sense.  Diet and gut microbiota are the major determinants of disease and relatives pass their bacteria around the table with their food.  There are eating habits and particular patterns of gut microbiota that lead to common diseases.  Unbeknownst to us, most of the diseases of modern life, e.g. heart disease, obesity, diabetes, cancer, autoimmune disease, mental illness, are transmissible by gut bacteria.

The Hygiene Hypothesis is Right and Wrong

For decades it has been obvious that early exposure to a farm environment, meaning an abundance of microbes, a diverse microbiota, eliminates allergies and many autoimmunities.  The Hygiene Hypothesis explained how early exposure to abundant microorganisms could eliminate allergies, as an early exposure to antigens that trained the immune system.  Early training of the immune system was later discounted, but the Hygiene Hypothesis then morphed into the current explanation, that early development of a diverse gut microbiota is needed to produce a healthy immune system.

Fix Your Diet, Fix Your Gut Microbiota and Fix Your Diseases

The good news is that all of the chronic diseases that threaten your future can be cured by just fixing your diet and repairing the complex bacterial communities in your gut.  Your immune system is critical to your health and damage to your immune system is the typical beginning to most diseases.  Damage to the immune system starts in the gut, where the aggressive and suppressive halves of the immune system develop in response to particular species of bacteria.  Those essential bacteria grow on the food in your diet that is not digested in the stomach and absorbed as nutrients in the small intestines, i.e. prebiotic fiber.  Thus, you eat to feed yourself and your gut bacteria.  Without the gut bacteria, you would be deficient in vitamins, your immune system would cease to function and you would be constipated.  Fixing your diet and gut microbiota will cure your diseases.

Posts that discuss repair of gut microbiota 

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.

Essential Oils, Phytoalexins, Drugs Are All Antibiotics

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Superbug multidrug resistant plasmid

A recent, informative article by Tori Rodriguez for The Atlantic suggests that,

Essential Oils Might Be the New Antibiotics.

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

The logic for using essential oils in place of medical antibiotics is compelling: 

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

Obesity is a Symptom of Antibiotic Damage to Gut Microbiome

Antibiotics make meat fatter

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

As It Is with Cattle, so It Is with Middle Americans

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

But Essential Oils Are Just Natural Antibiotics

Essential oils are natural antibiotics

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

Resistance to Essential Oils as Antibiotics

Antibiotic resistance develops in sewage

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

Essential Oils Are just Mixtures of Natural Antibiotics

Statins from fungal antibiotics

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

Common Medicines Are the Source of Superbugs

Common meds are antibiotics

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

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 

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

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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.