Health in Diagrams I — Gut Flora and Diet

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

Health in Diagrams II -- Curing Autoimmunity and Allergies

Health in Diagrams III -- Inflammation from Cell to Tissue

Everyone Leaves Out Gut Flora

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

Health Requires a Match between Diet and Gut Flora

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

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

Antibiotics and Autoimmunity

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

Food is just Protein, Fat and Soluble Fiber

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

Phytochemicals, Natural Antibiotics and Antioxidants

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

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

Antimicrobial Heparin-binding Domains

Fats are Dissolved by Bile, Digested by Lipase and Absorbed

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

Heparin-binding Domains

Plant Polysaccharides are Soluble Fiber and Food for Gut Flora

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

Resistant Starch as a Panacea

Food Intolerance/“Allergy” Indicates Missing Bacteria

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

Paleo Gut Flora Repair

Immune Cells Develop in Response to Gut Bacteria

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

Free the Animal: A Resistant Starch Primer for Newbies

Gut Biofilms Release Vitamins as Quorum Sensing Signals

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

Dr. Oz, Vitamins, Biofilms

Volume of Stools Reflects Gut Flora Fermenting Soluble Fiber

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

Milk, Kefir and Gut Flora

Paleo Gut Flora Repair

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

Paleo is not Paleo

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

Gut Flora/Microbiota are Friends

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

Paleo Diet without Prebiotic Fiber is Hard on Gut Flora

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

Changing Diet Does Not Repair Gut Flora

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

Dairy Probiotics Do Not Repair Gut Flora Destroyed by Antibiotics

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

Health in a Crock

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

Fermented Vegetables Repair Gut Flora

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

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

Major Points of a Healthy Paleo Diet

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

Dr. Oz on Gut Flora Repair

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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.