Gut microbiome and diet in populations with obesity: Role of the Na+/K+-ATPase transporter signaling in severe COVID-19

Abstract

Objective: The triad of obesity, a high-protein diet from animal sources, and disturbed gut microbiota have been linked to poor clinical outcomes in patients with COVID-19. In this report, the effect of oxidative stress resulting from the Na⁺ /K⁺ -ATPase transporter signaling cascade is explored as a driver of this poor clinical outcome.

Methods: Protein-protein interactions with the SARS-CoV-2 proteome were identified from the interactome data for Na⁺ /K⁺ -transporting ATPase subunit α-1 (ATP1A1), epidermal growth factor receptor, and ERB-B2 receptor tyrosine kinase 2, using the curated data from the BioGRID Database of Protein Interactions. Data for the gene expression pattern of inflammatory response were from the Gene Expression Omnibus database for cardiomyocytes post SARS-CoV-2 infection (number GSE151879).

Results: The ATP1A1 subunit of the Na⁺ /K⁺ -ATPase transporter is targeted by multiple SARS-CoV-2 proteins. Furthermore, receptor proteins associated with inflammatory response, including epidermal growth factor receptor and ERB-B2 receptor tyrosine kinase 2 (which interact with ATP1A1), are also targeted by some SARS-CoV-2 proteins. This heightened interaction likely triggers a cytokine release that increases the severity of the viral infection in individuals with obesity.

Conclusions: The similarities between the effects of SARS-CoV-2 proteins and indoxyl sulphate on the Na⁺ /K⁺ -ATPase transporter signaling cascade suggest the possibility of an augmentation of gene changes seen with COVID-19 infection that can result in a hyperinduction of cytokine release in individuals with obesity.