Colonization of nasal cavities by Staphylococcus epidermidis mitigates SARS‐CoV‐2 nucleocapsid phosphoprotein‐induced interleukin (IL)‐6 in the lung

Abstract

Summary Infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can trigger excessive interleukin (IL)‐6 signalling, leading to a myriad of biological effects including a cytokine storm that contributes to multiple organ failure in severe coronavirus disease 2019 (COVID‐19). Using a mouse model, we demonstrated that nasal inoculation of nucleocapsid phosphoprotein (NPP) of SARS‐CoV‐2 increased IL‐6 content in bronchoalveolar lavage fluid (BALF). Nasal administration of liquid coco‐caprylate/caprate (LCC) onto Staphylococcus epidermidis ( S. epidermidis )‐colonized mice significantly attenuated NPP‐induced IL‐6. Furthermore, S. epidermidis‐ mediated LCC fermentation to generate electricity and butyric acid that promoted bacterial colonization and activated free fatty acid receptor 2 (Ffar2) respectively. Inhibition of Ffar2 impeded the effect of S. epidermidis plus LCC on the reduction of NPP‐induced IL‐6. Collectively, these results suggest that nasal S. epidermidis is part of the first line of defence in ameliorating a cytokine storm induced by airway infection of SARS‐CoV‐2.

Lactobacillus plantarum Generate Electricity through Flavin Mononucleotide-Mediated Extracellular Electron Transfer to Upregulate Epithelial Type I Collagen Expression and Thereby Promote Microbial Adhesion to Intestine

“…Pretreatment with a riboflavin kinase inhibitor (i.e., roseoflavin) can reduce the electricity production in Gram-positive bacteria [29]. In this study, we showed that a 24 h pretreatment of L. plantarum MA with roseoflavin significantly reduced the concentration Pretreatment with a riboflavin kinase inhibitor (i.e., roseoflavin) can reduce the electricity production in Gram-positive bacteria [29].…”

“…Pretreatment with a riboflavin kinase inhibitor (i.e., roseoflavin) can reduce the electricity production in Gram-positive bacteria [ 29 ]. In this study, we showed that a 24 h pretreatment of L. plantarum MA with roseoflavin significantly reduced the concentration of FMN by approximately 12 folds ( Figure 3 b) while also decreasing electricity production ( Figure 3 c), suggesting that the bioelectrical activity of L. plantarum MA was mediated through the FMN-based EET system.…”

“…Pretreatment with a riboflavin kinase inhibitor (i.e., roseoflavin) can reduce the electricity production in Gram-positive bacteria [29]. In this study, we showed that a 24 h pretreatment of L. plantarum MA with roseoflavin significantly reduced the concentration Pretreatment with a riboflavin kinase inhibitor (i.e., roseoflavin) can reduce the electricity production in Gram-positive bacteria [29]. In this study, we showed that a 24 h pretreatment of L. plantarum MA with roseoflavin significantly reduced the concentration of FMN by approximately 12 folds (Figure 3b) while also decreasing electricity production (Figure 3c), suggesting that the bioelectrical activity of L. plantarum MA was mediated through the FMN-based EET system.…”

Environmental exposures, the oral–lung axis and respiratory health: The airway microbiome goes on stage for the personalized management of human lung function

“…Probiotic‐based experimental treatments for other nasal persistent conditions such as rhinitis are under investigation (Sarfraz et al., 2024 ), and the airway probiotic activity of other bacterial components of the human nasal microbiome is being explored. This is the case for nasal Staphylococcus epidermidis , whose protective role against influenza and SARS‐CoV‐2 viral infections has been shown, as it fermentates carbon‐rich molecules yielding short‐chain fatty acids and electricity, which have anti‐inflammatory properties and influence bacterial nasal colonization, respectively (Kao et al., 2022 ). In this context, direct topical probiotic use in the respiratory tract could also be considered as a targeted treatment option for chronic lung disease patients.…”

The role of SARS-CoV-2 nucleocapsid protein in antiviral immunity and vaccine development

“…SARS-CoV-2 N-protein also up-regulates the expression of tissue factor and intracellular adhesion molecule 1, markers involved in vascular coagulation and inflammation, and glucose transporter 4, a diabetic marker [ 27 ]. Lastly, complement activation and the activation of signaling pathways through Toll-like receptor 2 might be involved in increasing levels of IL-6 in the lungs of mice inoculated nasally with SARS-CoV-2 N-protein and inducing acute lung injury in mice administrated intratracheally with SARS-CoV-2 N-protein [ 26 , 28 ]. Indeed, the lung injury is associated with NF-κB p65 phosphorylation.…”