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Review
. 2024 Apr 5;25(7):4051.
doi: 10.3390/ijms25074051.

Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair

Veronica Marrella  1   2 , Federico Nicchiotti  3 , Barbara Cassani  2   3
Affiliations
Review

Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair

Veronica Marrella et al. Int J Mol Sci. .

Abstract

Bacterial and viral respiratory tract infections are the most common infectious diseases, leading to worldwide morbidity and mortality. In the past 10 years, the importance of lung microbiota emerged in the context of pulmonary diseases, although the mechanisms by which it impacts the intestinal environment have not yet been fully identified. On the contrary, gut microbial dysbiosis is associated with disease etiology or/and development in the lung. In this review, we present an overview of the lung microbiome modifications occurring during respiratory infections, namely, reduced community diversity and increased microbial burden, and of the downstream consequences on host-pathogen interaction, inflammatory signals, and cytokines production, in turn affecting the disease progression and outcome. Particularly, we focus on the role of the gut-lung bidirectional communication in shaping inflammation and immunity in this context, resuming both animal and human studies. Moreover, we discuss the challenges and possibilities related to novel microbial-based (probiotics and dietary supplementation) and microbial-targeted therapies (antibacterial monoclonal antibodies and bacteriophages), aimed to remodel the composition of resident microbial communities and restore health. Finally, we propose an outlook of some relevant questions in the field to be answered with future research, which may have translational relevance for the prevention and control of respiratory infections.

Keywords: bacteria; dysbiosis; gut–lung axis; host–microbe interactions; microbial therapies; microbiota; mucosal immunity; virus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic overview of the lung microbiota and immunity in health and during respiratory infections. The lung microbiota plays a critical role in lung homeostasis. In eubiotic condition, Proteobacteria, Firmicutes, Fusobacteria, Bacteroidetes, and Actinobacteria phyla mainly colonize the human lungs. Lung microbiota can promote the polarization of naïve T cells and the differentiation of alveolar macrophages to protect against pathogens. Moreover, mucociliary clearance and barrier protection are fundamental mechanisms together with host defenses. On the other hand, dysbiosis of the lung microbiome leads to immune cells activation. Immune cells then migrate into the tissue, produce proinflammatory cytokines, and finally contribute to local inflammatory response. Moreover, alterations in cytokines milieu promote pathologic fibrotic remodeling, NETosis, and apoptosis. Arrows indicate changes in relative abundance of immune cell subsets and bacterial species. Credit: BioRender.com.
Figure 2
Figure 2
Schematic representation of the main interactions underlying the gut–lung axis. The interactions between the gut and the lung are mediated by the microbiota and its products as well as by the immune cells. A bidirectional communication is recognized: SFB, a commensal gut microbiota, and microbial metabolites, such as SCFAs, stimulate and promote the differentiation of Th-17 cells, which have immunomodulatory functions in the lungs. Moreover, the gut microbes enter the intestinal mucosa and may be phagocytosed by antigen presenting cells (APCs), DCs, and macrophages. Travelling to the lung, APCs stimulate T cells and lung immune responses. On the other hand, the lung microbiota exhibits similar effects influencing the immune system and homeostasis of the gut. Several factors are well known to influence the composition of the intestinal and/or lung microbiota, such as diet, drugs, etc. Credit: BioRender.com.
Figure 3
Figure 3
Summary of the main topics and mechanisms addressed in the present review. Respiratory infections directly affect lung epithelial barrier integrity (bold arrow), while their effects on gut permeability are indirect, except for SARS-CoV-2 which has been demonstrated to infect intestinal epithelial cells (thin arrow). This results in a cascade of events ending with pathological manifestations. The different therapy attempts are designed to inhibit gut dysbiosis (bold inhibitory arrow) with the consequent immune modulation and host protection. Only a minority of these therapies target directly the lung microbiota (thin inhibitory arrow). Credit: BioRender.com.
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