Wednesday, March 12, 2014
---All 200 posts here---
This is the first of three posts to summarize my thoughts on diet, inflammation and disease mediated by gut flora. I decided that I needed to make my points as explicit as possible by putting them down in diagrams and making references to my other posts. By the time I finish, I will reach my 200th blog post at Cooling Inflammation.
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.
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.
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.
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.)
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.
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.
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.
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.
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.