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Review
. 2021 Mar;14(2):296-304.
doi: 10.1038/s41385-020-00361-8. Epub 2021 Jan 26.

The lung-gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

Valentin Sencio  1   2   3   4   5 , Marina Gomes Machado  1   2   3   4   5 , François Trottein  6   7   8   9   10
Affiliations
Review

The lung-gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

Valentin Sencio et al. Mucosal Immunol. 2021 Mar.

Abstract

Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host's defense against viral respiratory infections. The gut microbiota's composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota's composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung-gut axis in coronavirus disease 2019.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The role of the gut microbiota in viral respiratory infections.
Factors released by a healthy gut microbiota arm the lungs against viral respiratory infections. In contrast, antibiotic treatment disturbs the ecological equilibrium in the gut and alters the lung’s defenses. Aging and co-morbidities are also associated with altered gut microbiota function and enhanced susceptibility to respiratory infections.
Fig. 2
Fig. 2. The gut–lung axis during viral respiratory infections.
Viral respiratory infections, such as influenza, alter the functions of pulmonary immune and stromal (epithelial) cells, thus leading to secondary bacterial infections. Meanwhile, systemic inflammatory cytokines, inappetence (less fiber), change in oxygen levels, and altered epithelial metabolism disrupt the composition and function of intestinal microbiota. These alterations contribute to intestinal inflammation, epithelial barrier disruption, and decreased production of antimicrobial peptides (AMPs). Secondary enteric infections then develop. Epithelial leakage may enhance bacterial translocation and trigger systemic inflammation and organe dysfunction. Dysbiosis due to viral respiratory infection also results in diminished production of microbial-associated molecular patterns including Toll-like receptor (TLR) and nucleotide oligomerization domain (NOD)-like agonists and microbial metabolites such as SCFAs, thus reducing antibacterial pulmonary immunity. Hence, by altering the gut homeostasis, respiratory viral infections lead to bacterial superinfection. The interconnectedness of the lung and the gut might be particularly relevant during SARS-CoV-2 infection.
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