The Gut Microbiome and Asthma

May is Asthma and Allergy Awareness Month!

In light of this event, we are highlighting exciting news about the gut-lung-axis. Yes, you read that correctly – the health of your gut can affect the health of your lungs!

Emerging experimental and epidemiological evidence confirms there is crucial cross-talk between the gut microbiome and the lungs. When the gut microbiome changes due to diet, antibiotics, or other factors, the airways in the lungs may also be affected. Fortunately, there are healthy steps you can take to support the optimal function of both the gut microbiome and the lungs.

It is estimated that asthma currently affects over 300 million people worldwide. Some of the risk factors that can contribute to the development of asthma during childhood or adulthood include prenatal and early-life stress, delivery by cesarean section, genetics, use of antibiotics during the neonatal period, a maternal diet low in fiber, milk formula feeding, gender, ethnicity, monthly household income, higher BMI, smoking status, exposure to air pollution, and the diversity of microbes in the microbiome.^1-3 Asthma is a chronic inflammatory disease characterized by symptoms that include wheezing, cough, shortness of breath,  and chest tightness.⁴ Since asthma is caused by inflammation, treatment options focus on reducing inflammation or minimizing the effects of inflammation. While those with asthma must have at least one emergency medication on hand at all times, there are natural treatment options that could reduce inflammation and the symptoms of asthma. For example, consuming more fruits and vegetables is associated with fewer asthma symptoms.⁵ And, research shows the gut microbiome has a profound effect on the lungs, so nourishing the microbiome could also reduce inflammation to improve the health of the lungs.¹

What is the gut microbiome?

The typical healthy person has trillions of microorganisms distributed throughout the entire gastrointestinal tract, and they are collectively referred to as the gut microbiome. Several large research studies, including the Human Gut Microbiome Project and the Human Microbiome Project, have provided insight into the composition of the gut microbiome. Ongoing investigations continue to reveal the numerous beneficial effects a healthy gut microbiome exerts on human health.⁶

Does the gut microbiome really affect the lungs?

Yes!

The bacteria and other organisms present in our gut do affect our lungs! This phenomenon is known as the “gut-lung-axis.”¹ While we know a healthy gut microbiome provides health benefits, an unhealthy or imbalanced gut microbiome can contribute to disease. When the organisms present in the gut are not in optimal balance, it is known as dysbiosis. Dysbiosis has been associated with the development of several chronic diseases, including allergies and asthma.¹ Several studies confirm dysbiosis of the gut microbiome early in life leads to an enhanced risk for asthma development, although the mechanisms by which the gut microbiome influences the lungs are not yet fully understood.^6,7 But, inflammation or imbalance in the gut does appear to contribute to lung inflammation based on the latest research.⁶

How do the bacteria in my gut affect my lungs?

Believe it or not, there are hundreds of metabolites produced by gut bacteria that circulate systemically to distant organs, including the lungs.⁸ The metabolites produced by the gut microbiome are called postbiotics, a relatively new area of study. Postbiotics were only recently defined in 2021 by the International Scientific Association of Probiotics and Prebiotics (ISAPP).⁹ Even though postbiotics as a whole are a relatively new research topic, the results of the studies are quite exciting so far! Postbiotic substances include enzymes, bioactive peptides, short-chain fatty acids, antimicrobial peptides, polysaccharides, cell surface proteins, vitamins, plasmalogens, organic acids, and other compounds. Several studies demonstrate that short-chain fatty acids (SCFAs), in particular, positively affect inflammation and the function of the lungs in numerous ways.⁸

SCFAs include acetate, propionate, and butyrate; and are produced primarily from dietary fiber by microbial fermentation.^8,10 SCFAs play a role in many physiological processes, including the production of satiety hormones, energy expenditure, regulation of immune function, gut cell proliferation, and gut barrier function.^8,11 There is even a growing body of evidence demonstrating that SCFAs protect the lungs from infections by inhibiting the growth and virulence of infectious pathogens and modulating the immune response.¹² We will not dive too deeply into how profoundly SCFAs affect immune function and reduce inflammation, but research shows SCFAs impact many, many different types of immune cells, including T regulatory cells, neutrophils, macrophages, dendritic cells, mast cells, effector CD4+ T cells, and B cells!^10,13

How do I increase my postbiotic levels to reduce inflammation?

The good news is there are several ways to increase postbiotic and specifically SCFA levels in the body. Since SCFAs are produced from the fermentation of dietary fiber, increasing the intake of dietary fiber could increase the production of SCFAs. Many researchers hypothesize the insufficient consumption of fiber-rich fruits and vegetables in Western countries may contribute to an increased prevalence of chronic disease due to the development of dysbiosis. Animal studies confirm a high-fiber diet increases circulating levels of SCFAs, decreases circulating levels of IgA, IgG, and IgE antibodies, reduces airway mucous production, alters gene expression, and provides protection against allergic inflammation in the lungs.^8,12,13 Since the good bacteria in the gut microbiome ferment or transmute the dietary fiber into SCFAs, consuming more probiotics could also increase the production of SCFAs.¹⁴ The third option is taking supplemental SCFAs. Yes! Postbiotics, including SCFAs, are now available as supplements! In animal studies, treatment with SCFAs replicated the protective effects of a high-fiber diet against allergic airway inflammation and inhibited the development of general airway hyper-reactivity.⁸ In additional animal studies, those treated with butyrate, a postbiotic SCFA, had lower levels of the inflammatory immune cells known as eosinophils, fewer inflammatory infiltrates, and less mucus production in the lungs.¹⁵

Overall, current research data suggest the gut-lung-axis is characterized by a significant interplay between the gut microbiome and airway inflammation through the production of SCFAs and other postbiotic compounds. Future research will determine if changes in the gut microbiome and/or supplementation with postbiotics could reduce the symptoms of chronic asthma in humans.¹²

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References:

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2. Jeyagurunathan A, Abdin E, Shafie S, et al. Asthma Prevalence and its Risk Factors Among a Multi-Ethnic Adult Population. Yale J Biol Med. 2021;94(3):417-427.

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9. Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics [published correction appears in Nat Rev Gastroenterol Hepatol. 2021 Jun 15;:]. Nat Rev Gastroenterol Hepatol. 2021;18(9):649-667. doi:10.1038/s41575-021-00440-6

10. Föh B, Buhre JS, Lunding HB, et al. Microbial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells. PLoS One. 2022;17(3):e0266071. doi:10.1371/journal.pone.0266071

11. Salameh M, Burney Z, Mhaimeed N, et al. The role of gut microbiota in atopic asthma and allergy, implications in the understanding of disease pathogenesis. Scand J Immunol. 2020;91(3):e12855. doi: 10.1111/sji.12855

12. Kim YJ, Womble JT, Gunsch CK, et al. The Gut/Lung Microbiome Axis in Obesity, Asthma, and Bariatric Surgery: A Literature Review. Obesity (Silver Spring). 2021;29(4):636-644. doi:10.1002/oby.23107

13. Yip W, Hughes MR, Li Y, et al. Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma. Front Immunol. 2021;12:628453. doi:10.3389/fimmu.2021.628453

14. Machado MG, Sencio V, Trottein F. Short-Chain Fatty Acids as a Potential Treatment for Infections: a Closer Look at the Lungs. Infect Immun. 2021;89(9):e0018821. doi:10.1128/IAI.00188-21

15. Vieira RS, Castoldi A, Basso PJ, et al. Butyrate Attenuates Lung Inflammation by Negatively Modulating Th9 Cells. Front Immunol. 2019;10:67. doi:10.3389/fimmu.2019.00067