Asthma Education Empowers

Current Research into Asthma and the Gut Microbiome

Asthma is a chronic lung condition that causes respiratory symptoms such as wheezing, shortness of breath, chest tightness and a cough _[1]. These symptoms are associated with bronchoconstriction, increased mucus production and the thickening of airway walls _[2]. Asthma affects an estimated 300 million people worldwide _[2,3]. The aims of asthma treatments are to manage symptoms; to allow patients to exercise without limitation, have good quality sleep, prevent exacerbations and to achieve as normal lung function as possible _[2]. There are currently two classifications of asthma based on the immunopathogenesis, Type 2 (T2)-High Endotype and T2- Low Endotype. The T2- High classification is driven by the Type 2 immune response: a myriad of immune pathways including T helper 2 cell recruitment, the release of pro-inflammatory cytokines, eosinophil degranulation and mast cell activation. T2- Low endotype is based on physiological and lifestyle factors that include smoking, obesity, and old age. There is now emerging evidence of a gut-lung axis and may play a role in the aetiology of asthma.

Previous studies have shown that obesity and asthma are closely related conditions and obesity is a risk factor for asthma in adults and children, with asthma-related exercise intolerance further contributing to obesity risk _[3]. Alterations in the gut microbiome composition can alter gut permeability, digestion, metabolism, and immune responses. Huang et al (2024) recently reviewed current research into the implications of the gut-lung axis in obesity related asthma. Gut microbiome dysbiosis and reduced diversity leads to impaired gut barrier function and changes in immune responses _[3]. A reduction in short chain fatty acid (SCFA) production can affect histone deacetylase inhibitor (HDAC) mediated pathways, that repair damaged epithelial cells, including within the lungs _[3]. The research group claimed that several studies have shown that a higher fibre diet with SCFA supplementation can alleviate allergic lung inflammation through the SCFA receptor Gpr41 pathway _[3]. Furthermore, dysbiosis and inflammation related to obesity causes elevated intestinal mucosal permeability, which can activate the release of pro-inflammatory cytokines such as TNF-α and IL-6 and in turn worsen asthma symptoms _[3]. Lastly, obesity induced gut dysbiosis creates changes in cholesterol metabolism, which mediates the secretion of IL-1b via macrophages, and induces a bronchoconstriction response that is a classic characteristic in asthma _[3].

It has also been well documented that the infant gut microbiome is crucial for development, plus reductions in certain groups of bacteria can predict the onset of asthma/associated allergies through an imbalance of Th2/Th1 responses _[3]. Fujimura et al (2016) found that that a low relative abundance of species from the genera Akkermansia, Bifidobacterium, and Faecalibacterium at 1 month of age can be associated with a higher risk of developing asthma by 4 years of age _[4]. Additionally, an increased relative abundance of the fungal strains Candida and Rhodotorula, along with a lower relative abundance of Malassezia at 1 month of age was associated with increased asthma risk at 4 years of age _[4]. Kahhaleh et al (2024) have more recently reported on the role of the lymphatic system as a route of communication between the gut microbiome and the lungs: bacterial fragments and their metabolites can be transferred across the intestinal barrier and modulate the lung immune response _[5]. The presence of regulatory T cells during infancy appears to be important in suppressing Th2 immune responses such as asthma in later life _[5]. The significant organisms involved in this pathway are Bacteroides fragilis, Clostridium leptum and other SCFA producing bacteria _[5].                                                                                                                                                                                                                                                                                                                                         

 Written by DWS microbiologist Charlotte Austin

References

1. Asthma and lungs UK (2022) Symptoms of asthma. https://www.asthmaandlung.org.uk/conditions/asthma/symptoms-asthma
2. GINA (July 2023) Asthma management and prevention. https://ginasthma.org/wp-content/uploads/2023/07/GINA-2023-Pocket-Guide-WMS.pdf 
3. Huang, J., Zhou, X., Dong, B., Tan, H., Li, Q., Zhang, J., Su, H., & Sun, X. (2024). Obesity-related asthma and its relationship with microbiota. Frontiers in cellular and infection microbiology, 13, 1303899.
4. Fujimura, K. E., Sitarik, A. R., Havstad, S., Lin, D. L., Levan, S., Fadrosh, D., Panzer, A. R., LaMere, B., Rackaityte, E., Lukacs, N. W., Wegienka, G., Boushey, H. A., Ownby, D. R., Zoratti, E. M., Levin, A. M., Johnson, C. C., & Lynch, S. V. (2016). Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nature medicine, 22(10), 1187–1191
5. Kahhaleh, F. G., Barrientos, G., & Conrad, M. L. (2024). The gut‐lung axis and asthma susceptibility in early life. Acta Physiologica, e14092.