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

---  My other 200 posts here  ---

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

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

Health Diagram I    — Gut Flora and Diet, 

Health Diagram II   — Curing Autoimmunity and Allergies,

Health Diagram III  — Inflammation from Cell to Tissue  

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

Antibiotics Contribute to Autoimmune Diseases

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

Feed the Gut Microbiome for a Healthy Immune System

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

Repairing the Gut Microbiome by Eating the Missing Bacteria

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

Phytochemicals Are First and Foremost Antibiotics

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

I Missed the Antibiotic Activity of Common Medicines

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

Unlabelled Antibiotic Drugs Cause the Rise of Superbugs

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

Transglutaminase, Gluten, Celiac, Inflammation, Autoimmunity

The point of this post is that the intestines produce an enzyme, transglutaminase (TG) that normally protects the gut from toxic plant proteins, such as grain gluten, but modern food processing and antibiotics corrupt digestion of gluten to produce intestinal inflammation and a series of related autoimmune diseases including celiac, thyroiditis, diabetes, baldness and atherosclerosis. 

Transglutaminase Links Proteins Enzymatically

Transglutaminase is a ubiquitous enzyme produced in the intestines, thyroid, heart, skin, hair follicles, etc.  This enzyme attaches to a protein (TG + ProA ~~> TG-ProA) via amino groups extending from some of the protein's amino acids, e.g. lysine or glutamine, and then the enzyme replaces itself by another protein leaving the two proteins crosslinked (TG-ProA + ProB ~~> TG + ProA-ProB).  Another alternative reaction is to leave the original glutamine without its amino group to yield glutamic acid residues.

Linking Proteins Makes Connective Tissue Tough

Transglutaminase is useful to crosslink the proteins in connective tissue.  Proteins in basement membranes form a matrix by binding to the heparan sulfate sidechains of another basement protein, perlecan.  The heparin-binding domains consist of basic amino acids that TG can react with to crosslink the proteins.

Linking Pathogen Proteins

Transglutaminase is also produced to crosslink the DNA/heparin/matrix polysaccharide-binding domains of pathogenic bacteria leading to aggregation, localization and death of the bacteria.  Inflammation resulting from activation of the inflammatory transcription factor, NFkB, stimulates production of TG.

Gluten is a Plant's Way of Saying "Don't Eat Me!"

Gliadin is a protein component of gluten that contains long stretches of glutamine residues, i.e. it is a polyglutamine protein similar to the protein that causes Huntington's disease.  Gliadin is an advantage as a storage protein for grain, because it is aggregated by the TG that protects the lining of the intestines of herbivores, such as humans, makes the animal sick and thereby discourages eating the grain.  Aggregation of gliadin/gluten inhibits digestion of the grain protein and can leave TG bound to gliadin.  Conversion of the polyglutamine stretches to polyglutamic acid stretches that are negatively charged, produces proteins that will bind to the positively charged heparan sulfates that circulate along the surface of intestinal cells leading to damage and inflammation.

Basic Triplet Leads to Antibody Production

Transglutaminase is also transported into cells, because it contains a region with a triplet of basic amino acids (...EPKQKRKLVA...).  This internalization probably contributes to enhanced presentation of TG to the immune system for subsequent antibody production.

Transglutaminase is Inflammatory

Transglutaminase interaction on the surface of cells also activates, NFkB, the transcription factor responsible for inflammation. Thus, TG turns on inflammation and part of inflammation is the activation of the innate immune system that includes production of TG.  This circular activation may produce autoinflammation that is associated with various forms of inflammatory bowel diseases.

Gluten Sensitivity is Normally Controlled By Gut Flora

Gluten sensitivity expressed by most people, is the intestinal response to the toxicity of gluten as it interacts with TG and causes inflammation.  This inflammation will also result in immune presentation of both gliadin and TG, and production of antibodies to both. Antibody production will normally be controlled by regulatory T cells of the immune system, unless spreading inflammation in the gut and/or antibiotics destabilizes the gut flora and compromises regulatory T cell development in the intestines.  

Anti-Glutaminase Antibodies Attack the Gut

Celiac results from uncontrolled production of antibodies to gliadin and TG with attack by the immune system on the aggregated gliadin/TG on the surface of the intestinal epithelium.  Celiac flare ups in response to eating even small quantities of gluten lead to further inflammation of the gut and further disruption and simplification of gut flora.

Celiac Leads to Thyroiditis and Much More

Transglutaminase is also produced by the thyroid and celiac will develop into a more generalized autoimmune disease that results in Hashimoto's thyroiditis.   TG production in the skin can result in skin rashes and may contribute to rosacea.  The base of hair follicles contains TG involved in hair production, and may contribute to some forms of hair loss.  Another substantial worry about the sequelae of celiac and gluten intolerance is the presence of TG in coronary arteries.

Antibiotics are Part of the Gluten Problem

Celiac and gluten sensitivity seem to be increasing with modern processing of grains and increased use of antibiotics.  Wheat has been gradually changed by traditional breeding, but genetic engineering has not yet been developed for wheat.  So, at least in this case, GM wheat cannot be part of the problem.  Many recent studies show that antibiotics profoundly and permanently alter gut flora.  As a result, the immune system, which is dependent on gut flora diversity is compromised, and various forms of autoimmunity and allergies develop.

Super Fine Flour Damages Gut Flora

Germ and bran are removed from all wheat before it is ground.  This is true even for whole grain flours, which have some of the germ and bran added back after milling.  Modern milling may be part of the gluten problem, because the flour is ground so fine that the grains of starch are broken.  Broken starch grains are digested by pancreatic amylases in the upper intestines, whereas some of the starch from intact grains is digested by gut flora in the colon.  Thus, modern wheat flour fails to feed gut flora like soluble fiber to produce short chain fatty acids, e.g. proprionic acid that supports Treg development; modern superfine flour supports autoimmune diseases and allergies.

Cultural Practices Make Gluten Safe

Wheat has been bred to produce bread as fast as possible from superfine flour.  This rapid bread production eliminates the exposure of gluten to enzymes from both germinating wheat seed and fermenting bacteria, which are part of traditional bread making.  Coarsely milled, traditional flour responds to soaking in water by activating enzymes that partially digest gluten, since gluten is a storage form of amino acids destined for the seedling.  Sour dough starter, a mixture of bacteria that can ferment the starch and gluten into short chain fatty acids and bubbles of carbon dioxide, has been used traditionally to provide leavening and flavor to bread.  Both flour and bacterial enzymes modify the structure of gluten to render it less toxic to the intestines.  Cultural traditions insured that gluten would be systematically detoxified by enzymes during hydration and fermentation of dough prior to baking.  Modern processing leaves wheat gluten in bread unmodified and toxic.

Prevention and Cure:  Eliminate or Detoxify Wheat and Add Bacteria

Preventing and curing diseases associated with gluten and transglutaminase is simple.  Eliminating wheat would do the trick.  Unfortunately, wheat is the mainstay in many parts of the world.  Fortunately, gluten intolerance is not uniformly observed where wheat is eaten.  This indicates that there are potentially safe ways to eat wheat and bread.  I gained insight into how to eat wheat safely from two books that were recently published:  Cooked by Michael Pollan and Artisan Bread in Five Minutes a Day by Jeff Hertzberg, MD and Zoë François.

Michael Pollan has recently become interested in gut flora and his book revealed how he built up a healthy gut flora eating homemade fermented food and compromised his work with antibiotics.  The major breakthrough that I made by reading Cooked was based on his experiments in baking whole wheat bread.  He hydrated the flour first and then used sour dough starter for lengthy fermentation.  This was the same process that I had used to make great loaves of bread (photo above) using Jeff Hertzberg’s directions in Artizan Bread in Five Minutes a Day.

The answer to gluten intolerance and most autoimmune diseases amounts to eliminating wheat or treating wheat in a safe, traditional process that inactivates the toxic properties of gluten; and maintaining a healthy gut flora (probiotics are not enough) with hundreds of different species of bacteria that promote the development of the suppressive immune system mediated by regulatory T cells:

Safe Traditional Bread 

• Remove bran and discard as toxic insoluble fiber.
• Grind wheat to retain starch grain structure.
• Soak flour to hydrate and activate wheat enzymes to start digestion/detox of gluten.
• Ferment dough with bacteria (sour dough starter) to continue digestion/detox of gluten.
• Bake.

Develop Healthy Gut Flora and Suppressive Immune System

• Avoid antibiotics that kill bacteria.
• Avoid hygiene practices, e.g. antibacterial soaps, bleaching surfaces, closing toilet covers, etc. that eliminate sources of healthy bacteria.
• Kiss your loved ones and pets, and encourage everyone to garden/play in the soil (an excellent source of thousands of different species of bacteria.)
• Recruit healthy gut bacteria by eating a variety of homemade fermented vegetables. My most highly recommended source is my friends at: http://www.fermentista.us
• Remember that cooked or pasteurized foods do not contain useful bacteria.
• Remember that dairy probiotic bacteria cannot live in the human gut and can only provide a temporary help to the immune system.
• Limit the variety of foods that are consumed and gradually change with the seasons to avoid rapid changes in nutrients to which gut flora cannot adapt.  Food intolerances indicate maladapted gut flora.
• Constipation indicates dysfunctional gut flora and a compromised immune system.

Vitamin C, Guinea Pigs, Limeys and Gut Worms

Scurvy and the Need for Vitamin C

Old timey sailors got the symptoms of scurvy, defective collagen and connective tissue, presumably because they stopped eating leafy greens that contained the needed vitamin C, aka ascorbic acid.  Primates/humans and guinea pigs are among the few animals that lack the ability to make their own ascorbic acid and therefore must eat a diet with a minimum amount of the vitamin to avoid a deficiency disease.  This is the conventional wisdom partially based on observation and experiment, but also founded on conjecture.

Parasitic Gut Worms Were the Natural Source of Vitamin C

I don't believe that vitamins are essential ingredients of a healthy diet, but rather I contend that all of the necessary nutritional chemicals are produced by the microorganisms of the gut.  I have previously discussed the gut flora (bacteria and fungi) as the source of most vitamins.  I wish to expand vitamin production to include gut fauna (animals).  I think that it is likely that intestinal worms are the historically natural source of human vitamin C.

Gut Bacteria Control the Development of the Immune System

The human gut actively communicates with the biofilms of bacteria and fungi that form a lining for the healthy gut.  The aggressive cells of the immune system that attack invading pathogens, develop in response to chemical signals from filamentous gut bacteria, and the suppressive cells of the other half of the immune system, which prevents attack on innocuous food antigens (to avoid allergies) or the human body itself (autoimmunity), develop in response to Clostridium ssp.  Thus, the immune system can be highly compromised, if the gut flora bacteria are damaged, e.g. by antibiotics.

Vitamins are Signaling Chemicals of Gut Biofilms

The communities of bacteria in gut biofilms are self-regulating by exchanging chemicals called quorum sensing signaling molecules.  Different species of bacteria and fungi in the biofilms produce and detect different chemical signals.  Since the biofilms are in intimate contact with the cells that line the gut and absorb dietary nutrients, it is not surprising that the biofilm signaling molecules are also absorbed by intestine cells.  Many of these biofilm signal molecules are vitamins, e.g. the B vitamins.  Gut bacteria are the natural source of most vitamins and healthy gut flora eliminates the need for eating vitamins in food or supplements.  Vitamin deficiencies are a symptom of a damaged gut flora.  Antibiotics and vitamin supplements can damage healthy gut biofilms.

Dietary Soluble Fiber Feeds Gut Flora

The human gut flora consists of a couple of hundred different species of bacteria in each person.  Those bacteria in aggregate can produce about a hundred thousand different proteins that focus on the digestion of food molecules that the upper gut cannot digest and absorb.  Since the upper gut can only digest proteins, fats and starch/sugars, that means that the gut flora eat the rest, undigested plant/animal polysaccharides.  Soluble fiber is the plant polysaccharides, e.g. inulin and pectin, that are digested and feed the gut flora.  The undigested polysaccharides include cellulose.  Lignin and some other plant polymers also pass through the gut and are eliminated.  The undigested stuff is called insoluble fiber and it also has bound phytate, which drags some metals such as zinc out with it.  That is why insoluble fiber, such as wheat bran, is not nutritious or healthy.  Insoluble fiber is also a minor contributor to the bulk of stools, which are made up predominately of the gut bacteria that have grown on soluble fiber.

Sea Voyages Damage Gut Organisms

The hundred of different species of bacteria in the gut change in proportions to adapt to different foods in each meal.  If the diet is fairly constant, then the diversity of the population gradually increases, just as the diversity of species in a tropical rain forest is greater than in a temperate forest.  This also explains why gut flora diversity is far less in the USA than in other parts of the world.  Americans are encouraged to eat diverse diets in the search for vitamins and superfoods.  Each dramatic change in diet makes it hard for the gut flora to adapt and the remaining bacteria are those that are generalists.  It might also be expected that early sailors who changed their diets dramatically when they went to sea, ended up with a highly compromised ship-board gut flora (and fauna.)

The Perils of Hygiene

I have a fascination for stories involving the potential of rampaging tigers.  Images of a tiger attempting to drag a hunter from his seat on an elephant or the need of a colleague to employ an armed bodyguard when capturing crabs from Malaysian Mangrove roots at night, linger in my imagination.  I still think about the report of Wallace guarding his derrière while collecting beetles in Bukit Timah, Singapore, in “The Malay Archipelago.”  Humans tend to be incompatible with lions and tigers and bears, and we wipe them out.  We do the same with bacteria, fungi and worms.  We wash our hands, flush the toilet, use hand sanitizers, kill weeds, spray pesticides, grow meticulous lawns/crops, dose ourselves with antibiotics and cleanse.  We are free of the threat of tigers, but we failed to see what else was lost during their extermination.

Probiotics Don’t Fix the Damage of Antibiotics

Antibiotics ravage gut flora.  It is no surprise that a course of antibiotics frequently leads to diarrhea or constipation, since normal stools require normal gut flora.  What is surprising is that physicians, e.g. Dr. Oz, seem to think that antibiotic decimated gut flora can be fixed with probiotics.  Sure, probiotics can provide a temporary bandaid, since Lactobacilli that would normally live on milk in the gut of newborns, are able to provide most of the functions of an adult gut flora.  But probiotics don’t survive in the adult gut and probiotics to not repair damaged gut flora.

Changes to Gut Flora are Permanent, Unless....

Gut bacteria are like wolves in Idaho.  If you don’t bring in new wolves and stop hunting them, you never again have wolves in the wilderness.  If you don’t bring in new bacteria and feed them, damaged gut flora does not repair.  Antibiotic treatment that wipes out the bacteria needed for development of the suppressive immune system will lead to autoimmune disease.  However, repairing the gut flora by flushing in new bacteria (fecal transplant) or gradually reintroducing new diverse bacteria with fermented foods, can also reverse autoimmune diseases as the immune system is repaired.

Parasitic Worms Were Lost at Sea

We think that vitamin C is only provided by plants that we eat, because we didn’t notice what was lost when we cleaned out the worms that typically inhabit the human gut.  Who would have thought that those inconvenient creatures were there for our own good?  We unknowingly compensated for the lost vitamin C production of the worms by incorporating foods rich in vitamin C in our diets.  Shipboard diets that eliminated bowel worms were augmented with limes rich in ascorbic acid.

Guinea Pigs Also Need Worms

It is interesting to note that the experimental animal used to replicate human nutritional requirements for vitamin C is the guinea pig, which is one of the few animals (in addition to bats and primates) that doesn’t make its own.  It is also interesting that guinea pigs (and bats?) commonly have intestinal worms that have to be purged from their bowels before they are used in the lab. 

Gut Flora and Fauna Provide Vitamins

My bottom line is that a normal, healthy gut contains all of the bacteria, fungi and worms to supply all of the needed vitamins.  I do, however, think that dietary vitamin C is a good replacement for one function of intestinal worms, even though I will be watching for other benefits ( Helminth therapy?) that were lost with the removal of these parasites.

Some points:

•   Many vitamins are signal molecules for gut biofilm quorum sensing.
•   Intestinal worms are the typical source for human vitamin C.
•   Vitamin D is a hormone produced in the skin in response to sunlight.
•   Vitamin supplements are unnecessary (problem?), if gut flora and fauna are healthy.
•   Modern diets and hygiene eliminate gut parasites, so food needs to supply vitamin C.
•   Chronic inflammation consumes vitamin C and eliminates production of vitamin D.

New Antibiotics, Biofilm Inhibitors, Vitamin Deficiency

I was not expecting my recent reading of an article on femtosecond reaction kinetics to produce another discussion of quorum sensing, biofilms and vitamins. The idea behind the article was to identify new targets for drug design based on the ephemeral transition states that occur as enzymes bind substrates, stabilize transition states and yield product molecules. Drugs that mimic the transition states make good enzyme inhibitors. One of the target enzymes for the control of disease is an enzyme, MTAN, involved in the synthesis of quorum sensing molecules that orchestrate the construction of common biofilms. The idea is to inhibit MTAN and also avoid selection for antibiotic resistance. Unfortunately, targeting quorum sensing molecules also may produce vitamin deficiencies, since many of these molecules, in this case vitamin K, are also quorum sensing molecules.

Drugs have too many Side Effects
Specificity in the binding of molecules to the thousands of proteins that are coded by the ca. 20,000 human genes depends on a very tight fit between the molecular "key" and the binding site "lock" of the protein. Just as in physical world, a small key/drug molecule with limited surface detail is not as safe/specific as a larger key with many surface features, and a larger lock/enzyme active site that is harder to pick/has fewer interactions with random enzymes. Unfortunately, most drugs are small molecules with limited surface features that make them like molecular skeleton keys that produce many side effects by interacting with unintended proteins/enzymes.

Transition States are more Specific
A recent focus on drug research is to exploit molecular computation and modeling to design molecules that will bind to the part of an enzyme that actually participates in binding substrates and catalyzing chemical reactions. These designed molecules can interact with an expanded region of the enzyme and bind more strongly than the normal substrate. The designed molecules can be very effective inhibitors that will not react as nonspecifically as inhibitors identified by trial an error, e.g. statins.

Biofilm Inhibitors are Targets for Antibiotic Development
The enzymes involved in the synthetic pathways of biofilm quorum sensing signals have been identified and powerful inhibitors of some of these enzymes have now been designed and synthesized. These inhibitors are very effective in inhibiting biofilm formation by some common bacterial pathogens (and essential gut flora.)

Biofilm Inhibitors will also Block Vitamin Production in Gut Biofilms
The new biofilm inhibitor antibiotics may have enhanced specificity, but they target enzymes that also provide essential functions in biofilms that are needed for healthy gut and immune system function. Many of the vitamins that are produced by gut flora are also quorum sensing signal molecules in healthy gut biofilms. Thus, blocking MTAN to block biofilm formation of a pathogen, will also block gut synthesis of vitamin K, which is made in gut bacteria using the MTAN pathway. These inhibitors would be expected to be particularly damaging to the specialized gut flora of breastfed babies, since these gut bacteria are known producers of vitamin K.

Dr. Oz, Vitamins, Biofilms

Vitamins supplement enzyme action, but they are produced by gut flora for biofilm communication.

Dr. Oz and the general biomedical community promote the idea that vitamin supplements or in foods are needed or improve health. Of course, several research studies show that typical multivitamin supplements or the levels of vitamins in "enriched" foods do not provide improvements in health. Since gut flora produce all of the needed vitamins, this should be no surprise. But why do gut bacteria release vitamins needed for the normal functions of the human body?

Vitamins are Enzyme Cofactors

Vitamins are small molecules that bind to particular cellular enzymes and provide functions that can't be provided by proteins. Enzymes are linear strings, polymers, of about a thousand amino acids. The 23,000 human genes code for the sequence of amino acids in as many enzymes. The amino acid strings fold up systematically into three dimensional balls that bring together chemical groups of the amino acids that can catalyze biochemical reactions. The twenty different amino acids in proteins are limited in the scope of their reactions. Binding of some metabolic products, such as vitamins, expands the types of reactions possible. Vitamins are enzyme cofactors. Bacteria can synthesize all of the vitamins needed for metabolism, but humans can't.

Vitamin D is a Hormone

Vitamin D is not a typical vitamin.  It is not an enzyme cofactor, but rather it is a steroid hormone that is produced in the skin from cholesterol through the action of ultraviolet light. The production of antibacterial peptides in the small intestines, for example, is a response of intestinal cells to vitamin D. Exposing arms and legs to sunlight produces about 10,000 IU of vitamin D per minute. (Typical supplements contain only 1,000 IU.) Production of vitamin D is reduced by skin pigmentation, sunscreen and inflammation. People exposed to daily sunlight for hours in San Diego, for example, may still be deficient in vitamin D, if their production of vitamin D has been shut down by chronic inflammation, as indicated by typical inflammatory conditions, such as arthritis, allergies, inflammatory bowel diseases, obesity, dental/oral infections, prostatitis, thyroiditis and other autoimmune diseases.

Vitamins are Produced by Gut Biofilms

People with healthy, diet-adapted gut flora, can subsist on very limited diets without vitamin deficiency diseases, because all of the vitamins can be obtained from bacteria growing in films coating the lining of the gut. These biofilms are complex communities of dozens of different bacteria and fungi. The bacteria synthesize polysaccharides in which these and other bacteria and fungi become embedded. The biofilms release vitamins that are taken up by intestinal cells to provide the needs of the body.

Vitamins are Chemical Signals for Biofilm Assembly

Bacteria, such as E. coli, do not form biofilms, if they are just grown at low concentrations on laboratory nutrients. If the concentrations of bacteria become very high, however, the bacteria respond by activating genes that coordinate biofilm formation. Bacteria detect the presence of other bacteria by releasing and detecting chemical signals in a process called quorum sensing. The chemical signals used in quorum sensing and biofilm maintenance are vitamins. Thus, human intestines are adapted to exploit the presence of biofilms and vitamin secretion. Humans need not synthesize vitamins, because they are always produced by gut biofilms as an essential biofilm function.

Antibiotics and Multivitamin Supplements

Antibiotic use is known to disrupt gut flora and produce vitamin deficiencies. Killing off healthy gut biofilms with casual use of antibiotics should be anticipated. The medical industry is remiss, however, in not repairing gut flora after medically mandated antibiotic use. Probiotics can temporarily supply some of the functions of the hundreds of bacterial species in each healthy individual, but they do not replace complex biofilms.

 The vitamin production of some of the bacterial species eliminated from the gut by antibiotics can be replaced by vitamin supplements, but supplements may disrupt the normal vitamin/quorum sensing communication and further disrupt biofilms. Thus, vitamin supplements may be unhealthy, if they disrupt biofilms that are necessary for healthy function of the gut-based immune system, which is needed to avoid, for example, allergies and autoimmune diseases.

Major Points about Vitamins, Biofilms and Health

• Health requires gut biofilms to supply vitamins and control the immune system.
• Biofilms produce and use vitamins for maintenance of biofilms.
• Eating vitamins may disrupt normal biofilm formation.
• Antibiotics disrupt gut biofilms and cause vitamin deficiencies and immune system disfunction.
• Biofilm repair requires ingestion of missing bacterial species (150 total) and may be inhibited by excessive hygiene.