At the Roots: Natural Healing for Cystic Fibrosis
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Carbohydrate Malabsorption, Gut Flora, and Leaky Gut

PictureThe human digestive system.
The human lower intestine is inhabited by over 400 species of bacteria that help us break down food and allow us to absorb nutrients we can't on our own. Our gut bacteria provide us with innumerable services that scientists have only just begun to discover in the last several years. These services including the regulation of our immune systems, producing hormones and neurotransmitters (e.g. serotonin), and directly feeding the cells of our intestines with butyrate. There are trillions of bacteria down there and in a healthy colon and distal ileum they are all living in harmony, keeping each other in check and preventing overgrowth or dominance by one species or another. The collective community of microorganisms living in the gastrointestinal tract is what is referted to as our gut microbiota. The microbiota's collective genome is called the microbiome (though many people use these two words interchangeably). Microorganisms also inhabit many other parts of our bodies including the skin, respiratory tract, and genitals, each of which has its own unique microbiota.

However, fewer and fewer people have healthy gut microbiomes nowadays due to our unhealthy modern diets and lifestyles. CFers are especially likely to have an unhealthy gut microbiome (also called dysbiosis) because we are constantly on and off antibiotics, have functional malabsorption issues, and are often given poor dietary advice from mainstream doctors. Thus, it is a good idea for CFers to be aware of microbiome science and take good care of our precious bacteria. We may not be able to avoid taking antibiotics, but we can choose to take probiotic supplements (which I discuss here), eat fermented foods (e.g. sauerkraut, kombucha, and yogurt/keifer if you tolerate dairy), and eat foods high in prebiotic fibers. In addition, we should consider removing foods from our diets that contribute to harmful bacterial overgrowth. This past piece is the focus of this page.

The Standard American/Westernized Diet contains significant amounts of refined carbohydrates (especially sugar), rancid vegetable oils, factory-farmed animal foods, and very few fruits and vegetables. The resulting gastrointestinal and systemic inflammation contributes to the development of increases intestinal permeability, commonly referred to as leaky gut syndrome, which in turn can lead to the develop of other diseases and imbalances including allergies, autoimmunity, mental imbalances, blood sugar irregularities, obesity... and the list goes on. By eating too many inflammatory foods and too few anti-inflammatory foods (i.e. berries, vegetables, and wild or pastured animal foods) our bodies' systems of self-healing and self-regulation can be stressed and fall into dysfunction. This process is mediated through the gut via the GALT (mentioned in the previous section). Several important aspects of the diet, including quality of the carbohydrates we eat, have a profound impact on the microbiome for good or ill.

Gut Dysbiosis, Carbohydrate Malabsorption, and Leaky Gut Syndrome
Several factors can disrupt the balance of bacterial, fungal, viral, and parasitic species which make up the human gut microbiota. These may include: inheritance of a parent's imbalanced microbiota (via the birth canal, breast feeding, and touch), frequent antibiotic or other pharmaceutical use, chronic physical and/or psychological stress, unhealthy diet, pollution, etc. In situations such as these, the populations of beneficial bacteria which protect the health of our digestive systems diminish, and the populations of pathogenic bacteria and fungi (including fungi like Candida albicans) are flourishing.

More specifically, a common dietary cause of dysbiosis is the over-consumption of refined carbohydrates such as sugar, soda, pastries, bread, pasta, etc. These are the preferred foods for many pathogenic bacterial and fungal species, especially those who wish to creep higher into the upper intestines where they are not supposed to be. Complex carbohydrates with significant amounts of fiber (from whole root vegetables, grains, fruits) preferentially feed the beneficial gut flora lower down in the distal ileum and colon. By eating too many refined carbohydrates and not enough fiber, we feed the opportunistic bacteria, favoring the proliferation of pathogenic species while starving the beneficial species. If this style of eating is maintained for a longer period of time, gut dysbiosis will result. Unfortunately, since the post-WWII era, modern low-nutrient "foods", especially refined carbohydrates and industrial seed oils, have become a staple of the Western diet. Since microbiomes are inherited from the parents and we are now moving into the fourth generation of modern industrialized dietary habits since that era, the Western microbiome is shrinking in diversity and causing a growing number of diseases never before seen, as evidenced by the epidemic of autoimmune diseases [1].

Antibiotics also have a profound effect on the microbiome. Antibiotics are broad-spectrum killers of gut microbes, whether the species are helpful or harmful. Beneficial gut bugs often have a harder time bouncing back from an assault by antibiotics compared to pathogenic flora, which can recover more quickly. Every use of antibiotics must be accompanied by probiotic foods and/or supplements plus prebiotic fiber supplementation or else dysbiosis may occur. Dozens of clinical studies have demonstrated the benefit of taking probiotic supplementation with or after antibiotic therapy to reduce negative gastrointestinal side effects of antibiotics and to reverse the long-term health of our microbiomes [2, 3].

Many Americans, CFers included, are prescribed long-term courses of antacids or proton-pump inhibitors (PPIs). These drugs lower stomach acid, a secretion critically necessary for protein digestion, killing pathogens in our food, absorbing nutrients, and triggering a cascade of important digestive secretions lower down in the GI tract such as sodium bicarbonate, bile, and pancreatic enzymes. Adequate levels of stomach acid help prevent gut infections and prevent flora in the lower intestines from traveling upward and colonizing the upper intestines. Bacterial colonization of the upper intestine is called small intestine bacterial overgrowth (SIBO). PPIs were not designed for long term use, and yet they are often improperly prescribed this way, leading to many serious side effects. I discuss PPIs at length in this article.  

When pathogenic bacteria dominate the microbiota, our gut tissue can become inflamed by the exotoxins that they produce and by the undigested proteins in the gut lumen. Undigested proteins can act as antigens (i.e. compounds that stimulate an immune response) and when detected by the GALT lead to an inflammatory response. Inflammatory compounds such as cytokines can cause the enterocytes (intestinal cells) to separate, allowing pathogens, undigested proteins (food antigens), and bacterial toxins to enter the blood stream. When this happens, the body's immune response gets even more ramped up in order to attack and neutralize those antigens which should not be in the blood stream. At this point a wide range of symptoms can present, such as fever, body pain, mood swings, cognitive issues, fatigue, skin eruptions, hormone imbalances, and much more [4, 5]. In some cases, an antigen from an invading pathogen or undigested food protein may look very similar to the structure of a human tissue. This is called molecular mimicry, and can lead to the body creating antibodies against itself, which is called autoimmunity. Dr. Alessio Fasano, head of the Maryland Center for Celiac Research and world leader in the field of autoimmunity, believes that leaky gut is a necessary precursor to the development of many autoimmune diseases [6]. The food antigens that are the most common culprits of molecular mimicry are gluten (the protein in wheat and several other grains) and casein (the protein in dairy). Unfortunately, an antibody created against gluten can have cross-reactivity with casein, meaning that if you're sensitized to gluten (as are people with Celiac disease or gluten sensitivity) dairy can cause a similar immune reaction. 

If this gut inflammation lasts long enough, the process of digestion begins to degrade and we may see diarrhea, constipation, gas, bloating, undigested food in the stools, malabsorption, clay-colored stools, mucus in the stools, or even bloody stools. In situations of more serious dysbiosis and digestive disease, the villi on the enterocytes can be destroyed, and the enzymes that are produced by those villi (e.g. lactase, sucrase, and maltase) disappear. This means that the ability to break down lactose (milk sugar), sucrose (table sugar), and maltose (sugar in beer and other malted foods) declines and digestive upset can result. Thus, it is common to see lactose intolerance develop in those with chronic gut inflammation, and this is one reason why I recommend that CFers avoid dairy unless their digestive capacity is excellent and have no associated digestive symptoms. Without these brush-border enzymes doing their jobs, carbohydrates like lactose and sucrose are no longer absorbed across the intestinal membrane so they are flushed down to the lower intestines where they can feed pathogenic bacterial fermentation further causing gas, bloating, and other uncomfortable symptoms. 

Carbs and Evolution
Evolutionarily, a diet high in simple or refined carbs is very new, less than 200 years old. Archaeological and anthropological evidence shows us that the diets we have evolved to eat over 1.3 million years of hominid evolution were generally low in concentrated sugars (wild honey being one of the few exceptions) and lower in all carbohydrates compared to modern peoples. The carbohydrates that our hunter-gatherer ancestors ate were always high in fiber, nutrients, and medicinal phytochemicals. Depending on our ethnic backgrounds, our ancestors may not have been practicing intensive agriculture or eating grains for very long. Many peoples throughout the world still do not practice agriculture, and others have only been practicing intensive farming for a few hundred years or less. This is certainly not a long enough time for our digestive systems to adapt to well to heavy reliance on carbs from grains and refined sugars. Such adaptation takes hundreds of generations to occur, which would increase the prevalence of genes that code for increased insulin secretion and the production of certain digestive enzymes. Furthermore, we must remember that all of our foods were wild or lightly cultivated (i.e. not heavily bred or hybridized) until the Neolithic period less than 10,000 years ago. Wild foods are much higher in nutrients than modern hybridized crops, incuding vitamins, minerals, antioxidants, medicinal phytochemicals, and prebiotic fibers. Although modern fruits and vegetables (which have been heavily bred to increase their size and sugar content) are "healthy" compared to processed foods, they are nowhere near as nutritious as wild foods [7]. Our modern diets of the Western world are extremely heavy in carbohydrates, specifically sugars and simple starches, which are very difficult for our digestive systems to handle in large quantities. Given the long length of time evolution takes, the human body still operates as if it is in the Paleolithic era when we were all hunter-gatherers. Some human populations (such as those in the Middle East and East Asia) have been relying on intensive agriculture the longest, thus have had a longer time to adapt to carb-heavy diets than other populations such as the Indigineous peoples of the Americas and many populations in Africa. When we are poorly adapted to these high-carb modern diets the refined carbohydrates we eat can feed pathogenic bacteria and fungi and overwhelm the pancreas's ability to produce insulin, causing diabetes (which I discuss in the next article). Incidence of diabetes is significantly higher in populations with shorter historical exposure to carb-heavy diets.

Yet not all carbohydrates are harmful for those with gut dysbiosis or leaky gut. Depending on the type of infection (i.e. where it is located and what species are overgrown) certain carbohydrates are preferable to others. In some cases of SIBO where bacteria from the lower intestines has invaded too high up, any type of carbohydrate including monosaccharides, disaccharides, and complex carbohydrates can feed bacterial fermentation and cause distress. In other types of SIBO, monosaccharides are tolerated but not complex carbohydrates, especially FODMAPs (fermentable oligo-, di-, monosaccharides, and polyols). In dysbiosis lower down in the colon, simple sugars like mono- and disaccharides and simple starches can be tolerated but not any fibers that may be fermented upon by colonic pathogens. So each case of dysbiosis needs to be assessed based on the individual case, thus it's important to consult a qualified health care practitioner (i.e. herbalist, naturopath, functional medicine practitioner, etc.) on how to proceed. Often times the client may require some combination of antimicrobial therapy (preferably herbal) alongside a dietary protocol with multiple stages. In addition, some fibers and phytochemicals in whole foods as well as food additives can be irritating to certain people's guts if they have significant inflammation or tissue damage. This may include lectins in grains; phytic acid in grains, legumes, and some nuts; oxalic acid in certain vegetables like spinach and rhubarb; histamines; compounds in the nightshade family (tomatoes, potatoes, bell peppers, etc.); sulfites in wine; nitrites in cured meats; and other food preservatives and additives. Once the dysbiosis is addressed and the tissue begins to heal, often these things no longer produce irritation for the individual.


PictureLactose, a disaccharide.
Carbohydrate Digestion
In order to be absorbed into the blood, all sugars and complex carbs that we ingest must be broken down into their single-sugar elements, called monosaccharides, which include glucose, fructose, and galactose. Monosaccharides are used by our cells for energy or can be turned into glycogen or fat by the liver to store for use at a later time. There are a number of ways healthy bodies break down sugars into monosaccharides. In the saliva and in the pancreatic juices, amylase is secreted, an enzyme that breaks down certain carbs into monosaccharides. Because CFers with pancreatic insufficiency secrete little to no digestive enzymes at all, you'll see that our supplemental enzyme lists three classes of enzymes: lipase to break down fats, protease to break down proteins, and amylase to break down carbs. 

But amylases only breaks down certain carbs, such as starches. There are other enzymes needed to break down other types of carbs and sugars in the small intestine, and not all of them are secreted by the pancreas. Lactase breaks down the milk sugar lactose and is secreted by the microvilli on small intestinal cells. However, you must be genetically predisposed to produce lactase in your gut past childhood (called "lactase persistence"), yet only about 35% of the world's population has this trait. In other words, 65% of the world is lactose intolerant [8]. You had no idea, huh? Neither did I! Many people of European, Middle Eastern, and South Asian descent have lactase persistence and therefore can tolerate and breakdown lactose to some extent because their ancestral diets have included dairy. However, even if we do have lactase persistence, we depend on the microvilli in our guts to be healthy enough to produce lactase, but the microvilli can be damaged due to inflammation and gut dysbiosis. Thus, it is my belief that the ability of CFers to tolerate lactose is very often compromised because our microvilli may not be healthy enough to produce lactase. This may explain the dairy sensitivities I commonly see in CFers, including myself. Have you ever heard someone suggest not to eat dairy when you've got a cold? This is why. A cold creates excess mucus production in all of your epithelial tissues (since they're all connected via the vagus nerve) including your intestines, which is inhibiting the production of lactase and the ability to break down lactose. In conclusion, most CFers have trouble digesting lactose-containing dairy (e.g. milk, store-bought yogurt, soft cheeses) and they exacerbate our mucus problems and gut inflammation. The microvilli produce other disaccharidases such as sucrase and maltase, so digestion of sugar (sucrose) and foods containing maltose may be compromised in people with significant gut inflammation. 

Humans can only digest and absorb a narrow scope of carbohydrates, while other animals can digest a wider variety. For example, beavers can digest tree bark and horses can digest grass, but humans can do neither. There are other types of carbohydrates that humans digest only partially, giving beneficial gut bacteria the opportunity to use them for their own fermentation inside the human gut. These complex carbohydrates are called prebiotic fibers because they preferentially feed our beneficial gut bacteria in the colon. These symbiotic bacteria ferment upon the prebiotic fibers in certain plants, producing short-chain fatty acids to feed our enterocytes and secreting compounds that calm the immune system. In a healthy gut, prbiotic fibers in plants are very important for mainting a healthy gut ecosystem. These fibers include oligosaccharides, soluble and insoluble fibers, and resistant starches. Eating enough fiber is a good way to prevent dysbiosis. The best way to obtain these prebiotic fibers is to eat fibrous vegetables and fruits like cabbage, garlic, onions, leaks, dark-colored potatoes, sweet potatoes, sunchokes, root vegetables in general (especially wild ones like burdock), leafy greens, celery, apples, berries, and many more. You can even use prebiotic fiber powders (e.g. burdock root, dandelion root, ground flax seed, or raw potato starch) to add to smoothies, drinks, herbal formulas, or foods. The modern Western diet is very low in fiber, essentially starving the microbiota and setting up long-term problems.

If the diet has been deficient in prebiotic fibers for long enough (several years to several generations) a person may become susceptible to infection by gut pathogens leading to leaky gut, colitis, IBS, and more. When pathogenic species have taken hold they can sometimes use certain plant fibers for their own nefarious purposes, and their fermetation produces compounds that irritate and inflame the gut. Some persons with dysbiosis find that eating certain plant fibers (especially FODMAPS) causes GI upset. These individuals may find using a low-FODMAP diet or a specific carbohydrate diet like the GAPS protocol [9] alongside an herbal protocol may help to re-regulate the microbiome. The best way to do this is to work with a health care practitioner who knows a lot about the gut, the microbiome, and holisitic herbal inteventions. Ultimately, the goal is to correct the dysbiosis, improve microbiota diversity, and add prebiotic fibers back into the diet for long-term gut health. It is a common mistake for people to stay on a low-FODMAPS or low-fiber diet for too long without thinking about the end-game of eventually eating a high-fiber diet. This can keep the micrbiota in a low-diversity state and may not allow the body to come back into balance.

In a healthy gut, enzymes secreted by the pancreas and upper digestive tract break down certain carbohydrates like starches and disaccharides into monosaccharides for absorption through the walls of the small intestine. But if these enzymes are not secreted in proper amounts corresponding to the kinds of foods eaten (i.e. sucrase production for sucrose, lactase production for lactose, etc.) then sugars, starches, and fibers can pass into the colon to feed bacteria lower down. These bacteria often produce methane and hydrogen in the process of their fermentaiton causing gas and flatulence. Excessive gas production may be a sign of carb malabsorption and dysbiosis. If the fermentation is significant enough to stimulate an immune response, this may eventually lead to leaky gut syndrome. It is very important for people with gas and bloating or dysbiosis generally to minimize their consumption of sugars and refined carbohydrates! For those with healthy guts, simple sugars can be eaten as an occasional treat, but never as a daily staple for eventually this would select for bacterial and fungal species that could do long-term harm.

Yeast Infections
Another problem associated with carb malabsorption is Candida overgrowth. This most often takes the shape of vaginal yeast infections or oral thrush, though in severely immunocompromised individuals (e.g. those on chemotherapy, long-term immunosuppresive drugs, or those with AIDS) a systemic Candida infection may occur, though rarely. One of the most effective ways to control Candida overgrowth is to strictly restrict intake of simple sugars. Having an imbalance of the bacteria and fungi in the gut allows certain opportunistic pathogens to dominate, including the common yeast Candida albicans. Candida is a normal commensal fungus in the human gut, but only if it is overgrown does it cause trouble. Yeasts are a kind of fungus, and they LOVE to eat simple sugars. Eating a significant amount of sugars, especially sugars you may not be breaking down or absorbing entirely like sucrose, lactose, or fructose,  may feed an overgrowth of Candida in the gut and the tissues at the "in" and "out" ends of the tube: the mouth and genitals. Transient dysbiosis caused by antibiotics and other antimicrobial pharmaceuticals may trigger a sudden yeast infection of the mouth or genitals causing painful white patches in the mouth, white discharge of the vagina, itching, and pain. Pharmaceutical antibiotics kill beneficial flora in the gut (especially the good ones like Lactobacillus species that dominate in the vagina) but do not kill fungi, thus yeast are left untouched and the ecosystem is cleared of the competitors which usually keep them in check. I have gotten oral thrush many times in my life when taking IV antibiotics.

Mainstream modern docs treat oral thrush or vaginitis with a prescription for antifungal medications, but disregard the importance of reducing sugar intake. Some antifungal medications have troublesome side effects and are hard on the liver. I prefer to address the root cause by reducing sugar intake, increasing probiotic foods and supplements, and using certain antifungal herbs. Many antimicrobial and vulnerary herbs can be used in mouth washes (for thrush) and creams (for vaginitis), including calendula, goldenseal (or other less-endangered berberine-containing plants like barberry or oregon grape), thyme, yarrow, and more. To treat oral thrush I have compared the use of a nystatin oral rinse (NOT swallowed) and a tea of calendula flowers with a little goldenseal powder mixed in. Both were effective at clearing up the thrush within 3-4 days, but the calendula tea was a bit quicker and didn't taste as bad. In addition, I recommend rinsing or douching with probiotic yogurts to rebalance a healthy oral or genital flora. An added perk is that cold yogurt feels nice and soothing to inflamed nether-regions. 

For certain individuals, fructose can also be a factor in feeding yeast and bacterial infections. Fructose is not as well absorbed in the small intestine as glucose, so foods and food-like-substances (e.g. sodas and candy) with high amounts of fructose can directly feed bacterial and yeast overgrowth. High-fructose corn syrup, agave syrup, dried fruit, and fresh tropical fruits with a high ratio of frustose to glucose should be avoided by people who have trouble with fructose absorption. A great tool to assess the fructose content of foods is this database [10]. I highly suggest reading up on fructose malabsorption [11] if you experience chronic yeast infections or excessive gas or bloating when eating fruit. 

CF and Leaky Gut Syndrome
Leaky gut syndrome, also called "increased intestinal permeability", is not a common term in the CF lexicon. Yet it should be, since more research is elucidating the importance of a healthy gut flora in CF and the hidden prevalence of leaky gut syndrome in the CF population. Research has shown that "the intestinal microflora of [CF] children is often abnormal due to massive exposure to antibiotics, and in addition their intestinal permeability is increased suggesting disruption of intestinal barrier function". Furthermore, "the disruption of the intestinal epithelial barrier is central to the pathogenesis of several inflammatory diseases. Interestingly, an increase in intestinal permeability has been reported in atopic dermatitis and IDDM (insulin-dependent diabetes mellitus), as well as in CF. These findings suggest that probiotics may contribute in several ways to the first line host defence to environmental challenges" [12]. In addition, research is finding that gut inflammation is very common in CF: "intestinal inflammation is another typical feature of CF and is much more common than previously thought. Recently, we reported that fecal calprotectin concentration and rectal nitric oxide production are increased in virtually all children with CF, suggesting that intestine is a target organ in CF and is constantly in an inflammatory state" [12].

As I have written in previous articles, gut inflammation is a central part of the pathogenesis of leaky gut syndrome, and maintaining a healthy gut microbiota via good diet and probiotic supplementation is essential to maintaining lung health. As one study reported: "our findings suggest that nutritional factors and gut colonization patterns are determinants of microbial development in the respiratory tract in infancy and present opportunities for early intervention in CF" [13]. From my communication with other CFers around the world, I've found that many of us are presenting typical symptoms of leaky gut syndrome which include low secretory IgA, high systemic inflammatory markers, comorbidity with IBS, Celiac's, and Crohn's disease, chronic bloating and gas, achy joints and bones, food sensitivities, and more. However I have found it quite rare for CF docs to discuss the importance of healthy microbiota with their patients, let alone suggest dietary interventions. I believe leaky gut and dysbiosis is more common the CF population than not. In the future, I hope mainstream docs will be treating CF with much more attention paid to the maintenance of healthy intestinal and lung microbiomes. We should expect this transition to take decades, so in the meantime it's up to us to take charge of our microbial health in this way. I discuss herbal and dietary interventions in the rest of the literature on this website.

 
Next section: CF-Related Diabetes and Impaired Glucose Tolerance

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[1] Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019 Jul 16;11(7):1613. doi: 10.3390/nu11071613. PMID: 31315227; PMCID: PMC6682904.
[2] Engelbrektson, Anna, et al. "Probiotics to minimize the disruption of faecal microbiota in healthy subjects undergoing antibiotic therapy." Journal of medical microbiology 58.5 (2009): 663-670.
[3] Hempel, Susanne, et al. "Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis." Jama 307.18 (2012): 1959-1969.
[4] Arrieta, Marie-Claire, Lana Bistritz, and J. B. Meddings. "Alterations in intestinal permeability." Gut 55.10 (2006): 1512-1520.
[5] Leech, Bradley, Janet Schloss, and Amie Steel. "Association between increased intestinal permeability and disease: a systematic review." Advances in integrative Medicine 6.1 (2019): 23-34.
[6] Rich, et al. “Alessio Fasano M.D. on Gluten, Autoimmunity and Leaky Gut: RHR.” Chris Kresser, 8 Aug. 2012, www.chriskresser.com/pioneering-researcher-alessio-fasano-m-d-on-gluten-autoimmunity-leaky-gut/.
[7] Robinson, J. (2014). Eating on the wild side: The missing link to optimum health. New York, NY: Little, Brown and Company.
[8] Itan, Yuval, et al. "A worldwide correlation of lactase persistence phenotype and genotypes." BMC evolutionary biology 10.1 (2010): 1-11.
[9] Campbell-McBride, N. (2017). Gut and psychology syndrome: Natural treatment for autism, dyspraxia, A.D.D., dyslexia, A.D.H.D., depression, schizophrenia. Cambridge, UK: Medinform Pubslishing.
[10] Food Standards Australia/ New Zealand (2019). Australian Food Composition Database. Retrieved February 16, 2021, from https://www.foodstandards.gov.au/science/monitoringnutrients/afcd/Pages/foodsearch.aspx
[11] Gibson, Peter Raymond, et al. "Fructose malabsorption and the bigger picture." Alimentary pharmacology & therapeutics 25.4 (2007): 349-363.
[12] 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.
[13] 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 3.4 (2012).

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