Role of the Microbiome in Interstitial Lung Diseases

Abstract

There are trillions of microorganisms in the human body, consisting of bacteria, viruses, fungi, and archaea; these collectively make up the microbiome. Recent studies suggest that the microbiome may serve as a biomarker for disease, a therapeutic target, or provide an explanation for pathophysiology in lung diseases. Studies describing the impact of the microorganisms found in the respiratory tract on lung health have been published and are discussed here in the context of interstitial lung diseases. Additionally, epidemiological and experimental evidence highlights the importance of cross-talk between the gut microbiota and the lungs, called the gut-lung axis. The gut-lung axis postulates that alterations in gut microbial communities may have a profound effect on lung disease. Dysbiosis in the microbial community of the gut is linked with changes in immune responses, homeostasis in the airways, and inflammatory conditions in the gastrointestinal tract itself. In this review, we summarize studies describing the role of the microbiome in interstitial lung disease and discuss the implications of these findings on the diagnosis and treatment of these diseases. This paper describes the impact of the microbial communities on the pathogenesis of lung diseases by assessing recent original research and identifying remaining gaps in knowledge.

Keywords: fibrosis; gut microbiome; idiopathic pulmonary fibrosis; infection; interstitial lung disease (ILD); lung microbiome; sarcoidosis.

Figure 1

Graphical representation of the role of gut microbiome in regulating lung pathogenesis. The gut microbiome profoundly impacts human physiology and nutrition, and is essential for human life. (A) The healthy gut aids the clearance of pathogens by enhancing the innate immune responses to bacteria in the lungs, promotes immunity following vaccination, and can stimulate TLRs for effective adaptive immune responses to influenza. (B) Microbial imbalance or dysbiosis in the gut microbiome is influenced by drugs, diet and diseases, and can be associated with illness and disorders, including interstitial lung diseases. Gut bacteria, bacterial components, and metabolites such as LPS, PAMPs, cell wall components, and flagellin contribute lead to changes in lung immunity. Dysbiosis contributes to pulmonary infections and inflammatory conditions, aberrant TH17 responses and intestinal damage, altered microbiota (decrease in microbial diversity and pathogen multiplication), tissue damage, and changes in immune responses [i.e., activation of innate immune system, due to secretion of pathogen-associated molecular patterns (PAMPs)]. TLR, Toll-like receptors; LPS, Lipopolysaccharide; PAMPs, pathogen-associated molecular patterns; SCFA, short-chain fatty acids; NLR, Nod-like receptor.