Gut Dysbiosis and Leakage in the Plasma are Indicators of Severe COVID-19

A new pre-print article has revealed that the presence of gut bacteria in the plasma may be an indicator of progressive disease. The current study, based in Birmingham, Alabama, in the USA, aimed to capture the presence of plasma biomarkers that indicate breaches of the gut epithelial barrier, and the presence of gut microbes in the plasma.

Of the 30 patients enrolled in the study with confirmed SARS-CoV-2 infection, all had diarrhea and nausea along with fever and shortness of breath. The median age was 63 years. Only two patients had a critical disease. The 14 plasma samples sent for evaluation for the presence of bacteria yielded over 150,000 sequencing reads, with the signal indicating the strong bacterial presence in two-thirds of the samples. The total microbial population was comparable between patients with COVID-19. Using polymerase chain reaction, a dysbiosis index was arrived at to measure the abundance of bacterial groups in each sample.

All the nine samples which indicated the presence of bacteria showed the same three major phyla, Proteobacteria, Firmicutes, and Actinobacteria, with one patient showing unknown bacteria in more significant numbers among all 14. These are the same that have been found in healthy plasma, as well. The most enriched phylum was Proteobacteria, while Bacteroides were present in very limited numbers.

Among the two patients with a fatal COVID-19 outcome, the number of Firmicutes was low. Perhaps the abundance of this phylum may be a biomarker for the severity of the disease. Both Gram-negative bacteria and lipopolysaccharides (LPS), which is a major endotoxin originating from the cell wall of these bacteria, are higher in the plasma samples from COVID-19 patients. The presence of gut microbes in plasma may suggest defects in the gut epithelial barrier, allowing bacteria to migrate through the epithelial cells into the systemic blood vessels. This is an important component in systemic inflammation and underlies the progression of COVID-19 in these patients.

As a marker of gut permeability, fatty acid-binding protein-2 (FABP2) levels were measured, as this is a protein found within intestinal epithelial cells to bind free fatty acids, cholesterol, and retinoids. As such, its elevation in plasma indicates mucosal damage in the gut. As expected, FABP2 levels were high in the plasma of COVID-19 patients relative to healthy individuals. Gut microbial peptides in plasma are toxic in that they trigger inflammatory pathways and lead to systemic damage. As a measure of this phenomenon, the researchers observed higher levels of peptidoglycan (PGN) and LPS in COVID-19 plasma, at almost double the levels in healthy controls.

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