The role of respiratory microbiota in the protection against viral diseases: respiratory commensal bacteria as next-generation probiotics for COVID-19

Abstract

On March 11, 2020, the World Health Organization declared a pandemic of coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and imposed the biggest public health challenge for our civilization, with unforeseen impacts in the subsequent years. Similar to other respiratory infections, COVID-19 is associated with significant changes in the composition of the upper respiratory tract microbiome. Studies have pointed to a significant reduction of diversity and richness of the respiratory microbiota in COVID-19 patients. Furthermore, it has been suggested that Prevotella, Staphylococcus, and Streptococcus are associated with severe COVID-19 cases, while Dolosigranulum and Corynebacterium are significantly more abundant in asymptomatic subjects or with mild disease. These results have stimulated the search for new microorganisms from the respiratory microbiota with probiotic properties that could alleviate symptoms and even help in the fight against COVID-19. To date, the potential positive effects of probiotics in the context of SARS-CoV-2 infection and COVID-19 pandemics have been extrapolated from studies carried out with other viral pathogens, such as influenza virus and respiratory syncytial virus. However, scientific evidence has started to emerge demonstrating the capacity of immunomodulatory bacteria to beneficially influence the resistance against SARS-CoV-2 infection. Here we review the scientific knowledge regarding the role of the respiratory microbiota in viral infections in general and in the infection caused by SARS-CoV-2 in particular. In addition, the scientific work that supports the use of immunomodulatory probiotic microorganisms as beneficial tools to reduce the severity of respiratory viral infections is also reviewed. In particular, our recent studies that evaluated the role of immunomodulatory Dolosigranulum pigrum strains in the context of SARS-CoV-2 infection are highlighted.

Keywords: Dolosigranulum pigrum; coronavirus infectious disease 2019 (COVID-19); probiotics; respiratory microbiota; respiratory viral infections; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Fig. 1.

Members of the respiratory microbiota with beneficial or detrimental effects on the infection risk. The composition of the nasal cavity and nasopharynx microbial populations influence the susceptibility to respiratory tract infections. A higher burden of opportunistic pathogens, including Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, Haemophilus influenzae, and Prevotella spp., is positively correlated with an increased risk of respiratory tract infections. On the other hand, the respiratory tract commensal bacteria that are predominant in healthy non-infected hosts include Dolosigranulum pigrum, Staphylococcus epidermidis, Corynebacterium spp., Rothia spp., and Lactobacillus spp. The abundances of these bacteria in the upper respiratory tract are negatively correlated with lower risks of respiratory tract infections [11, 12, 13].

Fig. 2.

Immune mechanisms used by beneficial microorganisms to improve protection against respiratory viral infections. When administered nasally, the immunomodulatory microorganisms Lactiplantibacillus plantarum MPL16, L. plantarum CRL1506, and Dolosigranulum pigrum 040417 reach the pulmonary alveoli by inhalation or mucosal dispersion. The beneficial microbes interact with alveolar macrophages and respiratory epithelial cells, increasing their ability to produce type I IFNs (IFN-β) in response to viral challenges. Type I IFNs also favor the activation of Th1 lymphocytes that produce IFN-γ, enhancing the respiratory antiviral immunity. In addition, alveolar macrophages stimulated by beneficial microbes are capable of producing IL-6 and IL-27, which stimulate regulatory T cells, enhancing their production of IL-10. Through these mechanisms, the MPL16, CRL1506, and 040417 strains enhance the protection against inflammatory damage during the course of viral infections.