The Microbiome: Your Gut and Immunity
The gut microbiome.
The gastrointestinal tract is a central part of the immune system. The digestive system is linked either directly or indirectly to every organ system in the body, and part of its role is to kill pathogens we swallow with stomach acid, produce protective mucus, or trigger an evacuation response upon exposure to harmful substances. The gut's lymphatic tissue (called peyer's patches) trap and kills pathogens as well. 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 led 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that what you eat has little bearing on your overall health--and even this belief is being disproven and rejected as outdated and myopic. It is a leftover of the harmful and false belief that the human body is a machine, a machine that runs on "fuel". Many doctors still in practice today were educated in this belief system, yet fortunately the new generations of practitioners are coming to realize the truths that traditional medical systems have always known: that food is medicine. As Hippocrates (the father of Western medicine) once said, "Let thy food be thy medicine and medicine be thy food". The mechanical model of modern medicine has adopted the delusion that the organ systems are isolated from one another, but neither good science nor clinical observation backs up this belief. Everything is connected, and the gut is that center.
So gut health is connected to everything else in the body. But how? In several ways. Firstly, 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 linked to each other via the central nervous system. When you eat a really spicy food have you ever wondered why your eyes start to water, your nose starts to run, you cough and start to sweat? You surely didn't get any spice in your eyes, up your nose, or on your skin. Many of our epithelial tissues are connected through central nervous system via the vagus nerve, including the lungs and GI tract. When we eat something very irritating, our tongue or stomach or small intestine detects that something is not right (it thinks: "this spicy chemical could be dangerous!") and so the small intestine starts secreting 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 (your mouth, the air, your nose, etc.) so it produces mucus in all the hollow tubes that could have imbibed the irritant, just to be safe. These tubes include the bronchi and the sinus chambers. This is why eating irritating foods, toxins, or allergens can cause or exacerbate lung infections or post-nasal drip: because secretion of gut mucus can trigger secretion of respiratory mucus. 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, the human stomach environment 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 (this is, by the way, the opposite of what antacid commercials tell you), gas, constipation, diarrhea, carbohydrate malabsorption, bacterial overgrowth of the upper GI tract, increased risk of developing GI infections like Clostridium dificile, gastroparesis (delayed gastric emptying), bone fractures, vitamin B12 deficiency, asthma, vocal chord dysfunction, 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 and poor diet choice, so we should pay close attention to this issue. Low stomach acid is corrected by lowering the stomach pH through supplementation with betaine HCL, apple cider vinegar, or 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 primary ways (or a combination of both):
CFers naturally have problems with number 2, but due to the toxic diets that Americans in general eat, plus the harmful nutritional advice that many 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, chronic infections, and inflammation but also as a result of our doctors telling us to eat less healthy foods (as in vegetables naturally high in antioxidants and anti-inflammatory nutrients) in favor of higher calorie foods such as junk food and dairy. Many low-quality, 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, how they were raised or harvested, and our individual 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. The bacteria in our guts (microbiota) are responsible for educating these T and B cells about which incoming antigens are safe, and which ones are enemies to the body [3]. When the gut microbiota is disrupted and the ecosystem becomes unhealthy (which can be 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. pollen or food allergies) and over-reactions that target our own tissues (i.e. autoimmunity).
The human 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, we have more bacterial cells in and on our bodies than we 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 includes 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]. This role that beneficial bacteria play in the gut microbiome is very similar to the role that native plant species play in a forest. When human disruption (clear-cutting, pesticide use, etc.) or natural disaster reduce the natural biodiversity in the forest, invasive species have an easier time taking over, crowding out native species and imbalancing the ecosystem. But if there is a healthy population of native species, this invasion is less likely. As above, so below.
As a result of the modern obsession with germ theory (the idea that all disease is caused by catching germs), the public and medical institutions alike have become obsessed with sanitation. While germ theory is a valid idea and has very useful in controlling communicable diseases by preventing and treating infections, it has been taken to the extreme in some situations. Over-treating for infectins or over-sanitizing our modern lives has led to two major problems: 1) declining diversity of the human microbiome, and 2) drug-resistant infections. Regarding the former, in a traditional lifestyle connected with Nature our ancestors spent much of the day outdoors and in contact with wild or domesticated animals. By being in constant contact with Nature we carry the bacteria, fungi, viruses, and parasites in the world around us, which when balanced, protect and educate our immune systems. We are now finding that people who live hyper-sanitized modern lives have the lowest microbiome diversity and the highest incidence of modern diseases such as autoimmune diseases, allergies, obesity, and so on [5]. Secondly, when antimicrobial drugs and cleaners are mis-prescribed and over-used, pathogens can develop resistance to those drugs and chemicals, leading to an arms race between pathogens and modern science [6]. Because Nature is far more intelligent and far more creative than modern science can keep up with, pathogens will always win that race. Better to avoid that contest whenever possible!
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" [7]. 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. Healthy lungs host far fewer bacteria than the guts, and the healthy respiratory microbiome is not particularity diverse. However, in CF low diversity in the lung microbiome corresponds to increased disease severity and lower lung function. We could also say that since the microbiome of the lungs are connected to the guts, a less-diverse gut microbiome could mean a less-diverse lung microbiome. 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 microbiota diversity is associated with antibiotic use, therefore overuse of antibiotics may set up a vicious cycle of declining diversity and dependence on antibiotics: "[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" [7].
Thus, it's 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 balance our immune systems. So what are the implications for CFers who often have to rely on regular courses of high-dose antibiotics their whole lives? It will of course disrupt the intestinal ecosystem and increase the risk of developing problems associated with dysbiosis (e.g. leaky gut syndrome). However, refusing to use antibiotics for the sake of preserving protecting gut health may have its own negative consequences as I have personally experienced. Avoiding taking antibiotics when I needed them may have caused me unnecessary lung damage. So it is a fine balance. Inhaled antibiotics (e.g. tobramycin or colistin) have far less impact on intestinal flora, and certain IV antibiotics like vancomycin also have minimal impact. All oral antibiotics impact the gut flora, and most IV antibiotics do as well (e.g. tobramycin, meropenum, ceftazadime, linezolid, etc.). Unfortunately, most CF docs are not educated on the importance of a healthy gut microbiome for overall health. Most CF docs are pulmonologists by training, and modern Western medicine generally sees organ systems as separate and independent from one another. Both the latest research and traditional medicinal paradigms blow this belief apart. Don't be surprised if you have to remind your doctors of this point!
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 children's 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 direct action against Pseudomonas and have a systemic anti-inflammatory effect [8]. Thus, taking oral probiotics is very 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] McCarthy, Denis M Adverse effects of proton pump inhibitor drugs: clues and conclusions, Current Opinion in Gastroenterology: November 2010 - Volume 26 - Issue 6 - p 624-631
doi: 10.1097/MOG.0b013e32833ea9d9
[2] Back, Evelyn I., et al. "Antioxidant deficiency in cystic fibrosis: when is the right time to take action?." The American journal of clinical nutrition 80.2 (2004): 374-384.
[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.
[4] Buffie, Charlie G., and Eric G. Pamer. "Microbiota-mediated colonization resistance against intestinal pathogens." Nature Reviews Immunology 13.11 (2013): 790-801.
[5] Dominguez-Bello, Maria Gloria, Rob Knight, et al. "Role of the microbiome in human development." Gut 68.6 (2019): 1108-1114.
[6] English, B. Keith, and Aditya H. Gaur. "The use and abuse of antibiotics and the development of antibiotic resistance." Hot topics in infection and immunity in children VI (2010): 73-82.
[7] Madan, J C et al. “Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures.” mBio vol. 3,4 e00251-12. 21 Aug. 2012, doi:10.1128/mBio.00251-12
[8] Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G, Maiuri L, Guarino A. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007 Jun;26(3):322-8. doi: 10.1016/j.clnu.2007.01.004. Epub 2007 Mar 13. PMID: 17360077.
Much of this has to do with eliminating toxins, irritants, allergens, and inflammatory foods from our diets. My experimentation in this realm has led 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 overall health--and even this belief is being disproven and rejected as outdated and myopic. It is a leftover of the harmful and false belief that the human body is a machine, a machine that runs on "fuel". Many doctors still in practice today were educated in this belief system, yet fortunately the new generations of practitioners are coming to realize the truths that traditional medical systems have always known: that food is medicine. As Hippocrates (the father of Western medicine) once said, "Let thy food be thy medicine and medicine be thy food". The mechanical model of modern medicine has adopted the delusion that the organ systems are isolated from one another, but neither good science nor clinical observation backs up this belief. Everything is connected, and the gut is that center.
So gut health is connected to everything else in the body. But how? In several ways. Firstly, 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 linked to each other via the central nervous system. When you eat a really spicy food have you ever wondered why your eyes start to water, your nose starts to run, you cough and start to sweat? You surely didn't get any spice in your eyes, up your nose, or on your skin. Many of our epithelial tissues are connected through central nervous system via the vagus nerve, including the lungs and GI tract. When we eat something very irritating, our tongue or stomach or small intestine detects that something is not right (it thinks: "this spicy chemical could be dangerous!") and so the small intestine starts secreting 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 (your mouth, the air, your nose, etc.) so it produces mucus in all the hollow tubes that could have imbibed the irritant, just to be safe. These tubes include the bronchi and the sinus chambers. This is why eating irritating foods, toxins, or allergens can cause or exacerbate lung infections or post-nasal drip: because secretion of gut mucus can trigger secretion of respiratory mucus. 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, the human stomach environment 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 (this is, by the way, the opposite of what antacid commercials tell you), gas, constipation, diarrhea, carbohydrate malabsorption, bacterial overgrowth of the upper GI tract, increased risk of developing GI infections like Clostridium dificile, gastroparesis (delayed gastric emptying), bone fractures, vitamin B12 deficiency, asthma, vocal chord dysfunction, 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 and poor diet choice, so we should pay close attention to this issue. Low stomach acid is corrected by lowering the stomach pH through supplementation with betaine HCL, apple cider vinegar, or 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 primary ways (or a combination of both):
- Not eating enough nutrient-rich foods, either by:
- (a) simply not eating enough (as in 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);
- (c) by orthorexia, that is following a popular diet in attempts to lose weight or "get healthy" but which is actually is harmful;
- (d) by eating too many foods with negative nutritional value (food-like-substances/toxins that bind to nutrients, flush them out of our bodies, or store them in inaccessible places. These include refined sugars, phytic acid, and transfats).
- Not being able to adequately break down, digest, or absorb the nutrients consumed.
CFers naturally have problems with number 2, but due to the toxic diets that Americans in general eat, plus the harmful nutritional advice that many 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, chronic infections, and inflammation but also as a result of our doctors telling us to eat less healthy foods (as in vegetables naturally high in antioxidants and anti-inflammatory nutrients) in favor of higher calorie foods such as junk food and dairy. Many low-quality, 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, how they were raised or harvested, and our individual 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. The bacteria in our guts (microbiota) are responsible for educating these T and B cells about which incoming antigens are safe, and which ones are enemies to the body [3]. When the gut microbiota is disrupted and the ecosystem becomes unhealthy (which can be 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. pollen or food allergies) and over-reactions that target our own tissues (i.e. autoimmunity).
The human 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, we have more bacterial cells in and on our bodies than we 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 includes 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]. This role that beneficial bacteria play in the gut microbiome is very similar to the role that native plant species play in a forest. When human disruption (clear-cutting, pesticide use, etc.) or natural disaster reduce the natural biodiversity in the forest, invasive species have an easier time taking over, crowding out native species and imbalancing the ecosystem. But if there is a healthy population of native species, this invasion is less likely. As above, so below.
As a result of the modern obsession with germ theory (the idea that all disease is caused by catching germs), the public and medical institutions alike have become obsessed with sanitation. While germ theory is a valid idea and has very useful in controlling communicable diseases by preventing and treating infections, it has been taken to the extreme in some situations. Over-treating for infectins or over-sanitizing our modern lives has led to two major problems: 1) declining diversity of the human microbiome, and 2) drug-resistant infections. Regarding the former, in a traditional lifestyle connected with Nature our ancestors spent much of the day outdoors and in contact with wild or domesticated animals. By being in constant contact with Nature we carry the bacteria, fungi, viruses, and parasites in the world around us, which when balanced, protect and educate our immune systems. We are now finding that people who live hyper-sanitized modern lives have the lowest microbiome diversity and the highest incidence of modern diseases such as autoimmune diseases, allergies, obesity, and so on [5]. Secondly, when antimicrobial drugs and cleaners are mis-prescribed and over-used, pathogens can develop resistance to those drugs and chemicals, leading to an arms race between pathogens and modern science [6]. Because Nature is far more intelligent and far more creative than modern science can keep up with, pathogens will always win that race. Better to avoid that contest whenever possible!
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" [7]. 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. Healthy lungs host far fewer bacteria than the guts, and the healthy respiratory microbiome is not particularity diverse. However, in CF low diversity in the lung microbiome corresponds to increased disease severity and lower lung function. We could also say that since the microbiome of the lungs are connected to the guts, a less-diverse gut microbiome could mean a less-diverse lung microbiome. 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 microbiota diversity is associated with antibiotic use, therefore overuse of antibiotics may set up a vicious cycle of declining diversity and dependence on antibiotics: "[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" [7].
Thus, it's 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 balance our immune systems. So what are the implications for CFers who often have to rely on regular courses of high-dose antibiotics their whole lives? It will of course disrupt the intestinal ecosystem and increase the risk of developing problems associated with dysbiosis (e.g. leaky gut syndrome). However, refusing to use antibiotics for the sake of preserving protecting gut health may have its own negative consequences as I have personally experienced. Avoiding taking antibiotics when I needed them may have caused me unnecessary lung damage. So it is a fine balance. Inhaled antibiotics (e.g. tobramycin or colistin) have far less impact on intestinal flora, and certain IV antibiotics like vancomycin also have minimal impact. All oral antibiotics impact the gut flora, and most IV antibiotics do as well (e.g. tobramycin, meropenum, ceftazadime, linezolid, etc.). Unfortunately, most CF docs are not educated on the importance of a healthy gut microbiome for overall health. Most CF docs are pulmonologists by training, and modern Western medicine generally sees organ systems as separate and independent from one another. Both the latest research and traditional medicinal paradigms blow this belief apart. Don't be surprised if you have to remind your doctors of this point!
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 children's 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 direct action against Pseudomonas and have a systemic anti-inflammatory effect [8]. Thus, taking oral probiotics is very 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] McCarthy, Denis M Adverse effects of proton pump inhibitor drugs: clues and conclusions, Current Opinion in Gastroenterology: November 2010 - Volume 26 - Issue 6 - p 624-631
doi: 10.1097/MOG.0b013e32833ea9d9
[2] Back, Evelyn I., et al. "Antioxidant deficiency in cystic fibrosis: when is the right time to take action?." The American journal of clinical nutrition 80.2 (2004): 374-384.
[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.
[4] Buffie, Charlie G., and Eric G. Pamer. "Microbiota-mediated colonization resistance against intestinal pathogens." Nature Reviews Immunology 13.11 (2013): 790-801.
[5] Dominguez-Bello, Maria Gloria, Rob Knight, et al. "Role of the microbiome in human development." Gut 68.6 (2019): 1108-1114.
[6] English, B. Keith, and Aditya H. Gaur. "The use and abuse of antibiotics and the development of antibiotic resistance." Hot topics in infection and immunity in children VI (2010): 73-82.
[7] Madan, J C et al. “Serial analysis of the gut and respiratory microbiome in cystic fibrosis in infancy: interaction between intestinal and respiratory tracts and impact of nutritional exposures.” mBio vol. 3,4 e00251-12. 21 Aug. 2012, doi:10.1128/mBio.00251-12
[8] Bruzzese E, Raia V, Spagnuolo MI, Volpicelli M, De Marco G, Maiuri L, Guarino A. Effect of Lactobacillus GG supplementation on pulmonary exacerbations in patients with cystic fibrosis: a pilot study. Clin Nutr. 2007 Jun;26(3):322-8. doi: 10.1016/j.clnu.2007.01.004. Epub 2007 Mar 13. PMID: 17360077.
