Relationship between the gut microbiome and chronic lung diseases

The gut microbiome is important for health and disease, however, the significance of the microbiome on health has only recently been appreciated. As the gut is the largest reservoir for microbes in the human body, it is not surprising that studies have found the association of gut microbiome not only locally in the gut but also remotely in different organs, such as heart, brain, and lungs. For example, Bowerman et al. have shown that the gut microbiome in chronic obstructive pulmonary disease (COPD) is largely distinct from those of healthy subjects (1). Several studies implicate disturbances in the abundance or metabolism of gut bacteria in other respiratory diseases, such as asthma and allergic airway disease (2-4). In addition, the gut microbiome is associated with host immune responses to respiratory infection (5) and may, therefore, contribute to exacerbation frequency in COPD. COPD patients have a higher incidence of gastrointestinal disturbances than healthy individuals (6, 7), indicating potential roles for the gut microbiome in respiratory disease. However, the gastrointestinal microbiome of COPD patients has not yet been assessed extensively. The most extensive microbiome study of 8208 participants from a three-generational cohort was published in 2022 (8). In that study, a broad analysis was performed on a large group of diseases, including lung disease. However, the resolution and depth of the lung phenotypes were very limited in that paper as respiratory disease was not the primary focus of that manuscript. Moreover, the stratification into lung disease groups was heavily dependent on self-report, which was one of the major limitations. As the data collected in lifelines is more comprehensive, there is an unprecedented opportunity to perform microbiome analyses focusing on chronic respiratory diseases, such as asthma and COPD, and their clinical phenotypes. Furthermore, it is well-known that host genetics can influence gut microbiome (9, 10).Moreover, host genetics has shown interaction with microbiome to influence in inflammatory bowel disease (11). As many of the SNPs that have been associated with lung function have no known biological function, we propose that these SNPs may influence the gut microbiome to lead to a change in lung function. However, to the best of our knowledge, there has been no study on this avenue. Thus, we aim to explore the effects of host genetics and gut microbiome on the lung diseases with matching genetic data.