January 2022 Issue
The Gut-Lung Axis
By Carrie Dennett, MPH, RDN, CD
Today’s Dietitian
Vol. 24, No. 1, P. 28
Today’s Dietitian explores foods that promote a healthy gut to maintain healthy lungs.
Say that the human gut microbiota plays a role in gastrointestinal (GI) disease, and that likely wouldn’t come as a surprise. But what about lung disease? A growing body of research suggests that the gut microbiota impacts pulmonary health and disease through cross-talk between the gut microbiota and the lungs. Perhaps Hippocrates was right more than 2,000 years ago when he said “all disease begins in the gut.”
The American Lung Association estimates that asthma affects 24.8 million Americans and COPD affects 16.4 million, each accounting for millions of emergency department visits and billions of dollars in health care costs each year. Lung cancer has been the leading cause of cancer deaths among men since the 1950s, and for women since 1987—the year it surpassed breast cancer deaths.1
Long-term impairment (dysbiosis) of the gut microbiota can aggravate or increase susceptibility to a diverse array of inflammatory diseases.2 This includes both acute and chronic lung diseases, such as pneumonia, asthma, tuberculosis, and lung cancer. It appears that the precise composition of the gut microbiota may be associated with different lung diseases.3 This is because the GI tract and the respiratory tract, while composed of separate organs, are both parts of a shared mucosal immune system known as the gut-lung axis, which may serve as a new target for lung disease treatment.3-5
Pathophysiology
The gut microbiota plays a key role in the development and maturation of the mucosal and systemic immune systems, as well as in the maintenance of epithelial barrier function.6 It’s also an important moderator of immune responses, including inflammation. While the exact mechanisms by which the gut microbiota affects lung health aren’t fully understood, researchers do know that immune cells travel from gut to lung through the mucosal immune system, so disturbances to immune function at the gut level due to dysbiosis may affect immune responses at the lung level.5
More specifically, it appears that commensal bacteria—bacteria that trigger protective responses from the immune system that prevent colonization and invasion by pathogens—can activate a signaling pathway that modulates memory B cells in the lungs.3 Memory B cells are part of the adaptive immune system, remembering infectious agents encountered by their parent B cells. If antibodies to a pathogen aren’t present or are at insufficient levels to block infection by the pathogen, memory cells help mount an immune response that’s quicker than the first time the pathogen was encountered.7 This plays a role in responses to COVID-19, but it also affects the response to lung autoimmune diseases.3,7 Moreover, metabolites of gut bacteria fermentation, including short-chain fatty acids (SCFAs), can stimulate and promote differentiation of T cells, which support anti-inflammatory and immune-modulating activity in the lungs.3
Although the gut microbiota gets the most attention, microbes are present in all mucosal sites in the body. While the lungs were long considered to be a sterile environment, research in the last several years has discovered a range of diverse microbial species in lung samples.8 The gut microbiota and the lung microbiota are similar at the higher phylum level—Bacteroidetes and Firmicutes predominate in the gut, and Bacteroidetes, Firmicutes, and Proteobacteria predominate in the lungs—but differ at the species level.2 The composition of the gut and lung microbiotas is closely correlated across the lifespan, further suggesting a hostwide network. Modifying a newborn’s diet influences the composition of its lung microbiota, and rat studies have found that fecal transplantation leads to changes in the lung microbiota.9
Researchers now know that the microbiotas of the upper and lower respiratory tracts—with the vocal cords being the dividing line between the two—act as gatekeepers to respiratory health, even though more research is needed to fully understand how these microbiotas are shaped and how they function.8 The GI and respiratory mucosal tracts share the same developmental origins and both have direct contact with the mouth and pharynx (the part of the throat behind the mouth and nasal cavity). And both have projections—microvilli in the gut and cilia in the respiratory tract—that play a role in local immune function.10
The epithelial surfaces of the GI tract and the lungs also are exposed to a variety of microorganisms. Not only can the microorganisms that humans ingest access both the gut and lungs, but microorganisms from the oral cavity and GI tract can enter the lungs through inhalation and microaspiration, the aspiration of small droplets of gastric contents into the lungs.4,11
The gut-lung axis is a two-way street, and the lung microbiota similarly can influence the immune system and gut homeostasis.3 Inflammation in the lungs also can cause changes in gut microbiota via migrating lymphocytes (a type of white blood cell) and inflammatory cytokines.5,10
Alterations in both the gut and lung microbiotas have been observed in many respiratory diseases.2 For example, chronic lung diseases, including asthma and COPD, often co-occur with chronic GI diseases, such as inflammatory bowel disease (IBD) and irritable bowel syndrome.4 In addition, animal studies have found that pneumonia caused by multidrug-resistant bacteria can induce intestinal injury, such as lower-than-normal growth of epithelial cells.12
Linking the Gut to Lung Function
Despite these inroads, understanding of the gut-lung axis is still somewhat limited, and research on the lung microbiota itself is in its infancy. But here’s an overview of what’s understood about some of the major lung diseases.
• Asthma. Asthma is the most common chronic lower respiratory tract condition in childhood. Animal studies and clinical trials have suggested that the gut microbiota plays a crucial role in the development of asthma. The initial infant gut microbiota comes from the mother and is influenced by the mode of childbirth, breast-feeding, and antibiotic use, eventually developing long-term stability around age 2 or 3.3 While the overall composition of the gut microbiota isn’t altered in infants who are at high risk of developing asthma, researchers have detected subtle temporary changes in certain types of bacteria in the first few months of life in high-risk infants.4 Intestinal colonization with Clostridium difficile at 1 month of age has been linked to wheezing and eczema throughout the first six to seven years of life as well as childhood asthma.13
• COPD. Recent evidence suggests the composition of the gut microbiota changes with age and may affect the lungs’ immune response.3 Patients with COPD are two to three times more likely to be diagnosed with IBD and typically have increased intestinal permeability, which promotes chronic inflammation. Smoking is also the primary risk factor for COPD and increases the risk of developing Crohn’s disease (one type of IBD) three-fold.9 However, it’s unclear whether observed changes in the gut and respiratory microbiota cause, or are caused by, COPD.4
• COVID-19. Infection with the SARS-CoV-2 virus responsible for COVID-19 has been shown to disrupt the homeostasis of the gut-lung axis, and COVID-19 patients presenting with GI symptoms were more likely to also have acute respiratory distress syndrome.14
• Cystic fibrosis (CF). While CF is different from other lung diseases in that it has direct manifestations in multiple organs, research has demonstrated that children who have had a respiratory exacerbation of CF have a significantly different gut microbiota than children with CF who haven’t had an exacerbation in the first six to 12 months of life. Research also suggests that the gut microbiota may play a larger role in predicting lung health outcomes in CF than do airway microbes, especially in early life.15
• Lung cancer. Several studies have found that the composition of the gut microbiota in patients with lung cancer is significantly different from that of healthy control subjects. Lung cancer patients also have been found to have a less functional gut microbiota with lower levels of various metabolites. However, the direction of causality between lung cancer and gut microbiota dysbiosis is unclear.3
• Tuberculosis. Chronic infections by the bacterium Mycobacterium tuberculosis can be asymptomatic for years or even for a lifetime without causing disease. But this latent tuberculosis infection can progress to active tuberculosis disease, especially in people with a weakened immune system.16 Research has observed that gut microbiota diversity is altered in tuberculosis patients and that this may correlate with disease progression.2 Patients with type 2 diabetes are more susceptible to tuberculosis infection and have a three-fold increased risk of developing active tuberculosis compared with people without diabetes. They also tend to have altered gut microbiota composition and altered SCFA levels, which research suggests result in alterations of pro- and anti-inflammatory cytokines that may impair the immune system’s ability to mount a defense against M tuberculosis.17
Dietary Interventions
Therapies focused on the gut microbiota for prevention and treatment of GI disorders are far more established than therapies targeting the gut-lung axis.4 However, improving the health of the gut microbiota through dietary interventions does have the potential to help protect against lung diseases.3 The assimilation of dietary nutrients by gut microbes produces metabolites that play significant roles in human health, influencing the health of other organs through the lymphatic and circulatory systems.12
For example, a fiber-rich diet can modify the composition of the gut microbiota and increase circulating levels of SCFAs and has specifically been observed to reduce airway inflammation in asthma and COPD.10 Results published in 2020 from a 10-year prospective cohort study of 35,339 Swedish women found that high fiber intake from grains and fruit (but not vegetable sources) was associated with a 30% lower risk of COPD.18
Mary Purdy, MS, RDN, a Seattle-based adjunct faculty member at Bastyr University and author of The Microbiome Diet Reset, says dietary fiber is a critical food source for the gut microbiota, primarily because the resulting SCFAs play a key role in protecting the intestinal lining as well as supporting metabolic health, immune function, and mental well-being. “With close to 7 g of fiber per 1/2 cup, introducing clients to a wide range of beans and lentils and how to prepare those foods in creative and tantalizing ways can be an easy way to up the fiber intake without a huge change.” She also calls out inulin and fructooligosaccharides, two types of prebiotic fiber found in foods such as onions, garlic, leeks, maple syrup, bananas, and asparagus for their demonstrated benefits in supporting a healthy gut microbiota.
Andrea Hardy, RD, owner of Ignite Nutrition in Calgary, Alberta, Canada, says her top food recommendation is simply to eat more plants, including fruits and vegetables, pulses, nuts, seeds, whole grains, and plant proteins such as tofu and edamame. “There are so many gut-healthy benefits to including more plants in your diet, including increasing your fiber and phytochemical intake and increasing the diversity of fibers you have in your diet,” she says, adding that consuming more plants often displaces less nutritious and less gut-healthy foods in the diet.
Purdy says phytochemicals, carotenoids, and anthocyanins in particular—which are found in bright-colored fruits and vegetables—are good for the gut. “Higher intake of these has been shown to both stimulate beneficial bacteria while inhibiting the growth of more pathogenic bacteria,” she says.19,20
Hardy recommends including fermented foods, especially because of recent research suggesting that increasing intake of fermented foods not only improves the diversity of the gut microbiota but also is associated with a reduction in inflammatory markers.21,22 “I like to tell my patients to ‘eat something living every day,’ including foods like yogurt, kefir, kimchi, and sauerkraut, to name a few.”
It’s one thing for patients who are already eating a balanced, nutritious diet to make a few tweaks, but what about dietitians working with clients who have been eating a gut-unfriendly diet? Hardy and Purdy suggest a few strategies for moving the needle in a more healthful direction.
“It’s really all about getting back to basics,” Hardy says. “Swapping out your refined carbohydrates for whole grains, cooking with pulses (beans, peas, lentils) at least once a week—for example doing a ‘meatless Monday,’ and ensuring your main meals are including lots of vegetables—aiming for that half a plate is a simple target.”
Purdy says many patients don’t fully understand or appreciate the significant role their gut microbiome has in influencing many aspects of their health, so education can be a great first step. “As always, it’s important to meet patients where they’re at,” she says. “It’s usually easier to begin with adding in some of the gut-supportive foods before advising around foods to take out. Most individuals are low in fiber and fruits and vegetables, so even just adding in an extra serving each day (or whatever that patient is able to take on) can be a great starting point.”
Dietary changes have been shown to alter the gut microbiota at the species and family level within 24 to 48 hours,23 but Purdy says this doesn’t mean larger systemic imbalances in the body will be resolved in that amount of time. “Dietary changes that are sustainable are essential,” she says. “It’s about a consistent intake of microbiome-supportive foods that’s going to make a long-lasting difference in gut health.”
When suggesting gut-friendly dietary changes to clients, Hardy suggests choosing a “Goldilocks” habit change—one that’s not too hard, but not too easy. “Start with one thing your patient can work towards building into their everyday lives. From there, you can build on more and more habits over time,” she says. “It’s all about small, meaningful changes and ensuring what we’re suggesting to patients is doable and can fit into their lives, otherwise we know it won’t be sustainable.”
Of course, diet isn’t the only lifestyle factor that can affect gut health and possibly our lung health. Purdy says stress is a big factor when considering gut health. “Chronically high levels of cortisol can negatively affect the makeup of the gut microbiome by reducing the production of short-chain fatty acids and negatively affecting the tight junctions, leading to a higher risk of intestinal permeability, which can have numerous health implications.” She also says that getting enough quality sleep is associated with a more diverse gut population, and that physical activity has been shown to favorably alter the gut microbial composition independent of dietary habits. “Diving into stress management, sleep hygiene, and exercise with a patient is a key part of the gut microbiome conversation. In fact, this may be a super realistic place to start.”
— Carrie Dennett, MPH, RDN, CD, is the nutrition columnist for The Seattle Times, owner of Nutrition by Carrie, and author of Healthy for Your Life: A Holistic Guide to Optimal Wellness.
References
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