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 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=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.

Network Embedding Across Multiple Tissues and Data Modalities Elucidates the Context of Host Factors Important for COVID-19 Infection

“…Some genes that were identified over the serum and plasma patient data are involved in the cellular response to DNA damage and repair, namely, RAD51 recombinase (RAD51), mediator of DNA damage checkpoint 1 (MDC1), bloom syndrome RecQ-like helicase (BLM), and Erb-B2 receptor tyrosine kinase 2 (ERBB2). ERBB2, belonging to the epidermal growth factor receptor family of receptor tyrosine kinases, had also been previously linked to the cytokine release storm and thus severity of an infection with SARS-CoV-2 ( Khitan et al, 2022 ). This gene was especially of interest in combination with obesity and gut microbiome in COVID-19 patients ( Khitan et al, 2022 ).…”

“…ERBB2, belonging to the epidermal growth factor receptor family of receptor tyrosine kinases, had also been previously linked to the cytokine release storm and thus severity of an infection with SARS-CoV-2 ( Khitan et al, 2022 ). This gene was especially of interest in combination with obesity and gut microbiome in COVID-19 patients ( Khitan et al, 2022 ). Finally, we explored the tissue context of COVID-19–associated genes, identified in blood of mostly severe patients, independently if they were additionally associated to the genetic predisposition.…”

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

“…Obesity is a risk factor for poor outcomes of COVID-19. Using bioinformatics, Khitan et al found that oxidative stress due to deregulated Na + /K + -ATPase transporter signaling could lead to increased risk for more severe forms of the disease in obese individuals [ 50 ].…”