The Microbiome: Your Gut and Immunity
In most traditional medical systems, especially in Chinese Medicine, the gastrointestinal tracts is considered a central part of the immune system. Not only that, but in Chinese Medicine the spleen-pancreas (digestive) complex is understood to govern lung health. The digestive system is integrally linked to every organ system in your body, and part of its role is to kill pathogens we swallow with stomach acid, trap and kill pathogens through the lymphatic system, to trigger mucus production or an evacuatory responses or, when that's not enough, to cause the immune system to deal with infection on an intercellular level. By improving our gastrointestinal (G.I.) functions we can make significant progress in addressing our other disease symptoms in the lungs, immune system, liver, endocrine system, and other organ systems. Much of this has to do with eliminating toxins, irritants, allergens, and inflammatory foods from our diets. My experimentation in this realm has lead me to some incredible discoveries about my diet's effects on all my organ systems. Of all the thousands of medical systems in the world, it is only modern Western techno-medicine that believes that what you eat has little bearing on your disease symptoms or progression - and even this belief is quickly being disproved and rejected as arcane and idiotic.
But how exactly is our gut linked to everything else? In a number of ways. First, all of the epithelial cells in our body (cells in organ systems that have some kind of exposure to the "outside", i.e. G.I. tract, sinuses, pancreas ducts, certain reproductive organs, skin, lungs, etc.) are to linked to eachother via the central nervous system. Have you ever wondered why, when you eat some really spicy food, your eyes start to water, your nose starts to run, you cough and start to sweat, even though you didn't get any spice in your eyes, up your nose, or on your skin? It's because your brain can't necessarily tell where the irritation (the spice) is coming from - in your lungs, your nose, your mouth, your eyes, or on your skin - so it just starts a mucusy-evacuatory response in all your epithelial cells all at once! So everything really is connected! Many of our epithelial cells are connected through central nervous system via the vagus nerve, including the lungs and GI tract. When we eat something very irritating, when it reaches the small intestine (or sometimes even before that) our body starts to detect that something is not right, and so the small intestine starts to create mucus in order to flush the irritant away. But again, when your body detects the irritation, it doesn't necessarily know where it is coming from, so it starts to produce mucus in a whole bunch of places, just to be safe. These places include the lungs and sinuses. This is why eating irritating foods, toxins, or allergens can cause or exacerbate lung infections, and why for many people (including non-CFers) post-nasal drip is a common symptom of a food allergy, often wheat or dairy. I can tell you that whenever I eat something that upsets my digestion, one of the first symptoms I get is an increase in my lung mucus and more coughing.
Secondly, your stomach is highly acidic, with a healthy pH of under 3 (the lower the pH, the more acidic a substance). It is very important that we have a low stomach pH and enough acid to destroy any bacteria that may enter in our food, and to properly break down proteins and trigger the digestion of carbohydrates and fats in the small intestine. For a number of reasons, which I explain in this blog post, we can develop low stomach acid (i.e. develop a stomach pH of over 5). Having low stomach acid can cause many issues including heartburn/GERD/reflux (the opposite of what anti-acid commercials tell you), gas, constipation, diarrhea, carbohydrate malabsorption, bacterial overgrowth of the upper GI tract, increased risk of developing GI infections like Clostridium dificile ("C. diff"), gastroparesis (delayed gastric emptying), and further susceptibility to bacterial infections in other parts of the body, including the lungs [1]. I believe CFers are at higher risk for developing low stomach acid than our peers because of excessive pharmaceutical use, so we should pay close attention to this issue. Low stomach acid is corrected by lowering the stomach pH through supplementation with betaine HCL or use of a digestive bitters tincture before meals, and of course stopping use of all antacids and PPIs. I discuss all this in depth in the aforementioned blog post.
Another way your G.I. tract is linked to the rest of you is that it is responsible for absorbing nutrients and energy from what you ingest, which is used by all of your other organ systems to function properly. We are, quite literally, made up of what we eat. So if what you eat is lacking in essential nutrients and energy, your whole body will slowly cease to function properly. Malnutrition can be caused in two ways (and in combination): 1) not eating enough nutrient rich foods - either by (a) simply not eating enough (what happens primarily during starvation or famine), (b) by eating foods that lack nutritional value (what happens primarily in America, where junk food is a cultural staple. Modern society has invented a new phenomenon - simultaneous obesity and malnourishment), or (c) by eating too many foods with negative nutritional value (food-like-substances/toxins that bind to nutrients and flush them out of your body or store them in inaccessible places, e.g. sugars, phytic acid, and transfats); or 2) by not being able to adequately break down, digest, and absorb those nutrients you do consume. CFers naturally have problems with number 2, but due to the toxic diets that Americans in general eat, plus the bad nutritional advice that CF docs give us, we also end up having problems with number 1. CFers have higher than average levels of oxidative stress [2], due in part to our disease processes and chronic infection and inflammation, but also as a result of our doctors telling us to eat less foods that are naturally high in antioxidants and anti-inflammatory nutrients, such as vegetables, in favor of "higher calorie" foods such as junk food and dairy. Many low-quality animal-derived high calorie foods are inflammatory and can increase oxidative stress load, so we must choose them very wisely according to their nutrient density, their inflammatory or anti-inflammatory characteristics, other energetic characteristics, how they were raised or harvested, and our individual and unique reactions to these foods.
In addition, the entirety of the intestines is lined with lymphatic tissue that samples the lumen and sucks up pathogens and allergens into the lymph (the fluid that circulates through the lymphatic system, flows in special channels, and interacts with the blood). When in the lymph, pathogens or allergens are detected and neutralized by immune cells. The Gut Associated Lymphatic Tissue (GALT) also sends immune cells and inflammatory chemicals directly into the intestinal lumen to fight perceived infection. The GALT constitutes the largest amount of immune tissue in the body, and its ability to remove and kill pathogens before they get into the blood is critical to our health. The immune cells associated with the GALT, predominantly T and B cells, are responsible for telling our immune system to differentiate between organisms and antigens that are harmful, and those that are harmless. T and B cells are educated to know who to target as enemies and who to mark as friends by our gut flora [3]! When the gut microbiota is disrupted and the ecosystem becomes unhealthy (caused by poor diet, excessive pharmaceutical use, antibiotics, stress, lack of exposure to healthy environmental bacteria, etc.) the gut microbiome can no longer educate the immune system properly and we can develop a variety of immunological diseases including immunodeficiency, allergies, asthma, and autoimmunity. An improperly educated gut microbiota can result in inflammatory over-reactions to environmental challenges that are not dangerous (i.e. allergies) and over-reactions that target our own tissues (i.e. autoimmunity).
Your body is an ecosystem that harbors over 400 species of bacteria just in the intestines themselves. But the whole body is populated by bacteria; the skin, eyes, nose, mouth, ears, genitals, lungs, etc. In fact, you have more bacterial cells in and on your body than you do human cells! In reality we are more bacteria than human. We are walking, talking ecosystems, and our bacteria keep us happy and healthy... if we keep them happy and healthy. Beneficial bacteria in the gut help us break down and digest foods, particularly complex carbohydrates, and synthesize a number of nutrients that we cannot create ourselves including vitamin K2, folic acid, vitamins B1, B2, B3, B6, B12, and various amino acids. They also help us metabolize certain xenobiotic substances including plant constituents, pharmaceuticals, and toxins. But with our modern toxic lifestyles, it is becoming harder and harder to keep our beneficial bacteria healthy and our internal ecosystem balanced. It is very important to keep our friends happy by eating prebiotic fibers in plants. This can include fibers contained in roots, green vegetables, nuts/seeds, and whole grains. When beneficial bacteria in the colon ferment upon these fibers, they release short-chain fatty acids that directly feed our intestinal cells! These beneficial bacteria are competitive inhibitors of colonization by pathogenic species, and also have the ability to directly kill pathogenic species or stimulate our immune system to kill them [4].
The role of the gut microbiota in CF is getting more and more attention these days. Recent research has found that the bacteria that inhabit the gut early in life determines, in part, the bacteria that inhabit the lungs later in life. (As a side note, breast-feeding ensures an infant develops a healthy and diverse intestinal flora, so breastfeed your babe as long as possible!). The healthier the intestinal ecosystem is, the more resilient the lungs are to pathogenic bacterial infection. Thus, the guts and lungs are directly connected via their bacterial populations: "these findings are consistent with previous reports, with identification of bacteria in the respiratory tract in CF that are typically associated with the intestinal cavity and are theorized to contribute to the continuum of interactions between the host and microbial community in CF that relates to both the lung and gut microbiota" [5]. Although the biota of the guts and lungs are different, many species are shared between them, and this is especially true of pathogenic bacteria, like Staph. Furthermore, it has been found that respiratory bacterial populations are not particularly diverse in healthy lungs, however the less diverse the CF lung is, the more severe the respiratory disease and the lower the lung function. And the less diverse the intestinal flora, the less diverse the lung flora will be as a result. In other words, the more species you have in your lungs and guts, the better your lung functions will be. This is very similar to measuring the health of an ecosystem (like a rainforest) by its biodiversity, i.e. the number of species that inhabit it. A decline in CF lung microbiome diversity is associated with antibiotic use, therefore overuse of antibiotics may be partially responsible for declining lung function: "[research has] identified that diversity decreased over time in parallel with progressive disease and remained stable in patients with milder lung disease; however, they identified antibiotic use rather than lung function as the most significant driver of decreased microbial diversity in sputum samples. Additionally, based on sputum samples, Stressmann et al. corroborated similar findings for 14 patients with CF that antibiotic use was most associated with decreased microbial diversity and that overall decreased diversity was correlated to more-severe lung disease, as well as abundance of Pseudomonas aeruginosa" [5]. Thus, it is very important for us to use antibiotics sparingly and only when necessary, as they are particularly detrimental to the intestinal bacteria that keep us healthy and protect our lungs from further infection and domination by pathogenic species. Plus, emerging research is showing that even one short-term round of antibiotics can permanently impact the intestinal ecosystem and reduce its biodiversity. What does that mean for CFers who have been on regular courses of high-dose antibiotics their whole lives? An intensely disturbed intestinal ecosystem and a high risk for all of the problems that come along with it (especially leaky gut syndrome). Inhaled antibiotics do not impact intestinal flora directly, and certain IV antibiotics like vancomycin also have minimal impact. But all oral antibiotics impact gut flora, and most IV antibiotics do as well (tobramycin, meropenum, ceftazadime, linezolid, etc.). Unfortunately, most CF docs don't know about this problem so they go on prescribing us antibiotics in complete ignorance of what they are doing to our guts and our immune systems. They are pulmonologists by training, and modern Western medicine generally sees organ systems as separate and independent from one another. The latest research is blowing this belief apart. So don't be discouraged if your doc doesn't know any of this. They were not trained in it, so it is up to us to educate them.
Even more exciting is the research being done on treatment of the lungs through supplementation with oral probiotics. One study found that oral supplementation with only a single strain of Lactobacillus (GG) significantly increased CF childrens' FEV1, increased body weight, reduced the number and duration of hospitalizations, reduced the number of pulmonary exacerbations, and reduced the number of inflammatory markers (IgG). LGG and other Lactobacillus strains have a direct effect against Pseudomonas and have a systemic anti-inflammatory effect [6]. In conclusion, taking oral probiotics is extremely important for CFers, not only to restore intestinal microbial diversity, but to fight systemic inflammation and lung infections as well. But in order to restore ecological diversity in the intestines and the lungs, we should choose probiotics with as many strains of beneficial bacteria as possible. I discuss the use of probiotics more in my Supplements and Herbs section.
Next section: Carbohydrate Malabsorption and Gut Flora
******************************************
[1] Antioxidant deficiency in cystic fibrosis: when is the right time to take action? Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany. <http://www.ncbi.nlm.nih.gov/pubmed/15277158>[2] http://chriskresser.com/how-your-antacid-drug-is-making-you-sick-part-b
[2] http://mbio.asm.org/content/3/4/e00251-12.full
[3] Hooper, Lora V., Dan R. Littman, and Andrew J. Macpherson. "Interactions between the microbiota and the immune system." Science 336.6086 (2012): 1268-1273. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420145/
[4] Buffie, Charlie G., and Eric G. Pamer. "Microbiota-mediated colonization resistance against intestinal pathogens." Nature Reviews Immunology 13.11 (2013): 790-801. http://www.nature.com/nri/journal/v13/n11/abs/nri3535.html
[5] http://www.ncbi.nlm.nih.gov/pubmed/17360077
[6] Gut and Psychology Syndrome. Dr. Natasha Campbell-McBride.
But how exactly is our gut linked to everything else? In a number of ways. First, all of the epithelial cells in our body (cells in organ systems that have some kind of exposure to the "outside", i.e. G.I. tract, sinuses, pancreas ducts, certain reproductive organs, skin, lungs, etc.) are to linked to eachother via the central nervous system. Have you ever wondered why, when you eat some really spicy food, your eyes start to water, your nose starts to run, you cough and start to sweat, even though you didn't get any spice in your eyes, up your nose, or on your skin? It's because your brain can't necessarily tell where the irritation (the spice) is coming from - in your lungs, your nose, your mouth, your eyes, or on your skin - so it just starts a mucusy-evacuatory response in all your epithelial cells all at once! So everything really is connected! Many of our epithelial cells are connected through central nervous system via the vagus nerve, including the lungs and GI tract. When we eat something very irritating, when it reaches the small intestine (or sometimes even before that) our body starts to detect that something is not right, and so the small intestine starts to create mucus in order to flush the irritant away. But again, when your body detects the irritation, it doesn't necessarily know where it is coming from, so it starts to produce mucus in a whole bunch of places, just to be safe. These places include the lungs and sinuses. This is why eating irritating foods, toxins, or allergens can cause or exacerbate lung infections, and why for many people (including non-CFers) post-nasal drip is a common symptom of a food allergy, often wheat or dairy. I can tell you that whenever I eat something that upsets my digestion, one of the first symptoms I get is an increase in my lung mucus and more coughing.
Secondly, your stomach is highly acidic, with a healthy pH of under 3 (the lower the pH, the more acidic a substance). It is very important that we have a low stomach pH and enough acid to destroy any bacteria that may enter in our food, and to properly break down proteins and trigger the digestion of carbohydrates and fats in the small intestine. For a number of reasons, which I explain in this blog post, we can develop low stomach acid (i.e. develop a stomach pH of over 5). Having low stomach acid can cause many issues including heartburn/GERD/reflux (the opposite of what anti-acid commercials tell you), gas, constipation, diarrhea, carbohydrate malabsorption, bacterial overgrowth of the upper GI tract, increased risk of developing GI infections like Clostridium dificile ("C. diff"), gastroparesis (delayed gastric emptying), and further susceptibility to bacterial infections in other parts of the body, including the lungs [1]. I believe CFers are at higher risk for developing low stomach acid than our peers because of excessive pharmaceutical use, so we should pay close attention to this issue. Low stomach acid is corrected by lowering the stomach pH through supplementation with betaine HCL or use of a digestive bitters tincture before meals, and of course stopping use of all antacids and PPIs. I discuss all this in depth in the aforementioned blog post.
Another way your G.I. tract is linked to the rest of you is that it is responsible for absorbing nutrients and energy from what you ingest, which is used by all of your other organ systems to function properly. We are, quite literally, made up of what we eat. So if what you eat is lacking in essential nutrients and energy, your whole body will slowly cease to function properly. Malnutrition can be caused in two ways (and in combination): 1) not eating enough nutrient rich foods - either by (a) simply not eating enough (what happens primarily during starvation or famine), (b) by eating foods that lack nutritional value (what happens primarily in America, where junk food is a cultural staple. Modern society has invented a new phenomenon - simultaneous obesity and malnourishment), or (c) by eating too many foods with negative nutritional value (food-like-substances/toxins that bind to nutrients and flush them out of your body or store them in inaccessible places, e.g. sugars, phytic acid, and transfats); or 2) by not being able to adequately break down, digest, and absorb those nutrients you do consume. CFers naturally have problems with number 2, but due to the toxic diets that Americans in general eat, plus the bad nutritional advice that CF docs give us, we also end up having problems with number 1. CFers have higher than average levels of oxidative stress [2], due in part to our disease processes and chronic infection and inflammation, but also as a result of our doctors telling us to eat less foods that are naturally high in antioxidants and anti-inflammatory nutrients, such as vegetables, in favor of "higher calorie" foods such as junk food and dairy. Many low-quality animal-derived high calorie foods are inflammatory and can increase oxidative stress load, so we must choose them very wisely according to their nutrient density, their inflammatory or anti-inflammatory characteristics, other energetic characteristics, how they were raised or harvested, and our individual and unique reactions to these foods.
In addition, the entirety of the intestines is lined with lymphatic tissue that samples the lumen and sucks up pathogens and allergens into the lymph (the fluid that circulates through the lymphatic system, flows in special channels, and interacts with the blood). When in the lymph, pathogens or allergens are detected and neutralized by immune cells. The Gut Associated Lymphatic Tissue (GALT) also sends immune cells and inflammatory chemicals directly into the intestinal lumen to fight perceived infection. The GALT constitutes the largest amount of immune tissue in the body, and its ability to remove and kill pathogens before they get into the blood is critical to our health. The immune cells associated with the GALT, predominantly T and B cells, are responsible for telling our immune system to differentiate between organisms and antigens that are harmful, and those that are harmless. T and B cells are educated to know who to target as enemies and who to mark as friends by our gut flora [3]! When the gut microbiota is disrupted and the ecosystem becomes unhealthy (caused by poor diet, excessive pharmaceutical use, antibiotics, stress, lack of exposure to healthy environmental bacteria, etc.) the gut microbiome can no longer educate the immune system properly and we can develop a variety of immunological diseases including immunodeficiency, allergies, asthma, and autoimmunity. An improperly educated gut microbiota can result in inflammatory over-reactions to environmental challenges that are not dangerous (i.e. allergies) and over-reactions that target our own tissues (i.e. autoimmunity).
Your body is an ecosystem that harbors over 400 species of bacteria just in the intestines themselves. But the whole body is populated by bacteria; the skin, eyes, nose, mouth, ears, genitals, lungs, etc. In fact, you have more bacterial cells in and on your body than you do human cells! In reality we are more bacteria than human. We are walking, talking ecosystems, and our bacteria keep us happy and healthy... if we keep them happy and healthy. Beneficial bacteria in the gut help us break down and digest foods, particularly complex carbohydrates, and synthesize a number of nutrients that we cannot create ourselves including vitamin K2, folic acid, vitamins B1, B2, B3, B6, B12, and various amino acids. They also help us metabolize certain xenobiotic substances including plant constituents, pharmaceuticals, and toxins. But with our modern toxic lifestyles, it is becoming harder and harder to keep our beneficial bacteria healthy and our internal ecosystem balanced. It is very important to keep our friends happy by eating prebiotic fibers in plants. This can include fibers contained in roots, green vegetables, nuts/seeds, and whole grains. When beneficial bacteria in the colon ferment upon these fibers, they release short-chain fatty acids that directly feed our intestinal cells! These beneficial bacteria are competitive inhibitors of colonization by pathogenic species, and also have the ability to directly kill pathogenic species or stimulate our immune system to kill them [4].
The role of the gut microbiota in CF is getting more and more attention these days. Recent research has found that the bacteria that inhabit the gut early in life determines, in part, the bacteria that inhabit the lungs later in life. (As a side note, breast-feeding ensures an infant develops a healthy and diverse intestinal flora, so breastfeed your babe as long as possible!). The healthier the intestinal ecosystem is, the more resilient the lungs are to pathogenic bacterial infection. Thus, the guts and lungs are directly connected via their bacterial populations: "these findings are consistent with previous reports, with identification of bacteria in the respiratory tract in CF that are typically associated with the intestinal cavity and are theorized to contribute to the continuum of interactions between the host and microbial community in CF that relates to both the lung and gut microbiota" [5]. Although the biota of the guts and lungs are different, many species are shared between them, and this is especially true of pathogenic bacteria, like Staph. Furthermore, it has been found that respiratory bacterial populations are not particularly diverse in healthy lungs, however the less diverse the CF lung is, the more severe the respiratory disease and the lower the lung function. And the less diverse the intestinal flora, the less diverse the lung flora will be as a result. In other words, the more species you have in your lungs and guts, the better your lung functions will be. This is very similar to measuring the health of an ecosystem (like a rainforest) by its biodiversity, i.e. the number of species that inhabit it. A decline in CF lung microbiome diversity is associated with antibiotic use, therefore overuse of antibiotics may be partially responsible for declining lung function: "[research has] identified that diversity decreased over time in parallel with progressive disease and remained stable in patients with milder lung disease; however, they identified antibiotic use rather than lung function as the most significant driver of decreased microbial diversity in sputum samples. Additionally, based on sputum samples, Stressmann et al. corroborated similar findings for 14 patients with CF that antibiotic use was most associated with decreased microbial diversity and that overall decreased diversity was correlated to more-severe lung disease, as well as abundance of Pseudomonas aeruginosa" [5]. Thus, it is very important for us to use antibiotics sparingly and only when necessary, as they are particularly detrimental to the intestinal bacteria that keep us healthy and protect our lungs from further infection and domination by pathogenic species. Plus, emerging research is showing that even one short-term round of antibiotics can permanently impact the intestinal ecosystem and reduce its biodiversity. What does that mean for CFers who have been on regular courses of high-dose antibiotics their whole lives? An intensely disturbed intestinal ecosystem and a high risk for all of the problems that come along with it (especially leaky gut syndrome). Inhaled antibiotics do not impact intestinal flora directly, and certain IV antibiotics like vancomycin also have minimal impact. But all oral antibiotics impact gut flora, and most IV antibiotics do as well (tobramycin, meropenum, ceftazadime, linezolid, etc.). Unfortunately, most CF docs don't know about this problem so they go on prescribing us antibiotics in complete ignorance of what they are doing to our guts and our immune systems. They are pulmonologists by training, and modern Western medicine generally sees organ systems as separate and independent from one another. The latest research is blowing this belief apart. So don't be discouraged if your doc doesn't know any of this. They were not trained in it, so it is up to us to educate them.
Even more exciting is the research being done on treatment of the lungs through supplementation with oral probiotics. One study found that oral supplementation with only a single strain of Lactobacillus (GG) significantly increased CF childrens' FEV1, increased body weight, reduced the number and duration of hospitalizations, reduced the number of pulmonary exacerbations, and reduced the number of inflammatory markers (IgG). LGG and other Lactobacillus strains have a direct effect against Pseudomonas and have a systemic anti-inflammatory effect [6]. In conclusion, taking oral probiotics is extremely important for CFers, not only to restore intestinal microbial diversity, but to fight systemic inflammation and lung infections as well. But in order to restore ecological diversity in the intestines and the lungs, we should choose probiotics with as many strains of beneficial bacteria as possible. I discuss the use of probiotics more in my Supplements and Herbs section.
Next section: Carbohydrate Malabsorption and Gut Flora
******************************************
[1] Antioxidant deficiency in cystic fibrosis: when is the right time to take action? Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstrasse 30, 70593 Stuttgart, Germany. <http://www.ncbi.nlm.nih.gov/pubmed/15277158>[2] http://chriskresser.com/how-your-antacid-drug-is-making-you-sick-part-b
[2] http://mbio.asm.org/content/3/4/e00251-12.full
[3] Hooper, Lora V., Dan R. Littman, and Andrew J. Macpherson. "Interactions between the microbiota and the immune system." Science 336.6086 (2012): 1268-1273. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420145/
[4] Buffie, Charlie G., and Eric G. Pamer. "Microbiota-mediated colonization resistance against intestinal pathogens." Nature Reviews Immunology 13.11 (2013): 790-801. http://www.nature.com/nri/journal/v13/n11/abs/nri3535.html
[5] http://www.ncbi.nlm.nih.gov/pubmed/17360077
[6] Gut and Psychology Syndrome. Dr. Natasha Campbell-McBride.
