The Gut-Lung Axis in Health and Respiratory Diseases: A Place for Inter-Organ and Inter-Kingdom Crosstalks

Abstract

The gut and lungs are anatomically distinct, but potential anatomic communications and complex pathways involving their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Compared to the better-studied gut microbiota, the lung microbiota, only considered in recent years, represents a more discreet part of the whole microbiota associated to human hosts. While the vast majority of studies focused on the bacterial component of the microbiota in healthy and pathological conditions, recent works have highlighted the contribution of fungal and viral kingdoms at both digestive and respiratory levels. Moreover, growing evidence indicates the key role of inter-kingdom crosstalks in maintaining host homeostasis and in disease evolution. In fact, the recently emerged GLA concept involves host-microbe as well as microbe-microbe interactions, based both on localized and long-reaching effects. GLA can shape immune responses and interfere with the course of respiratory diseases. In this review, we aim to analyze how the lung and gut microbiota influence each other and may impact on respiratory diseases. Due to the limited knowledge on the human virobiota, we focused on gut and lung bacteriobiota and mycobiota, with a specific attention on inter-kingdom microbial crosstalks which are able to shape local or long-reached host responses within the GLA.

Keywords: Dysbiosis; Gut-Lung Axis; Microbiome; Mycobiota; Respiratory disease.

Figure 1

Inter-kingdom and inter-compartment crosstalks within the gut–lung axis. Bacteriobiota, mycobiota, and virobiota are closely interacting within each organ by either direct or indirect mechanisms shaping each other. Gut microbiota influences both the gut immune system and the lung immune system via local or long-reaching interactions, which involve either CD8+ T cell, Th17, IL-25, IL-13, prostaglandin E2, and/or NF-κB–dependent pathways. The lung microbiota impacts the mucosal immunity and contributes to immune tolerance, through neutrophil recruitment, production of pro-inflammatory cytokines mediated by receptor 2 (TLR2), and the release of antimicrobial peptides, such as β-defensin 2 stimulated by T helper 17 (Th17) cells. On the other hand, the lung microbiota also influences the gut immune system, but precise mechanisms remain to be deciphered, even if an intestinal microbial disruption has been associated with Th17 cell mediation after influenza virus lung infection. Several factors are well-known to influence the composition of the intestinal and/or lung microbiota, such as diet, drugs, and probiotics. *Of note, the virobiota is not covered in this review.