Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis

• Published in: International journal of molecular sciences Vol. 23; no. 16; p. 9141
• Main Authors: Prasad, Ram, Patton, Michael John, Floyd, Jason Levi, Fortmann, Seth, DuPont, Mariana, Harbour, Angela, Wright, Justin, Lamendella, Regina, Stevens, Bruce R., Oudit, Gavin Y., Grant, Maria B.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.08.2022; MDPI
• Subjects: Actinobacteria - genetics; Bacteria; Bacteria - genetics; Bacterial infections; Blood; Coronaviruses; COVID-19; Diarrhea; Dysbiosis - microbiology; Feces - microbiology; Females; Firmicutes - genetics; Gastrointestinal Microbiome - genetics; Hospitalization; Humans; Infections; Laboratories; Lipopolysaccharides; Males; Microbiota; Mortality; Peptidoglycan; Permeability; Phylogenetics; Plasma; Pneumonia; Proteins; RNA, Ribosomal, 16S - genetics; SARS-CoV-2; Sepsis; Severe acute respiratory syndrome coronavirus 2; Taxonomy; United States > US; COVID-19; gut barrier permeability; circulating microbiome; dysbiosis
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23169141

The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n = 146) and healthy individuals (n = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. COVID-19 subjects exhibit significant dysbiosis (p = 0.001) of the plasma microbiome with increased abundance of Actinobacteria spp. (p = 0.0332), decreased abundance of Bacteroides spp. (p = 0.0003), and an increased Firmicutes:Bacteroidetes ratio (p = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (p = 0.0013) and the gut microbial antigens PGN (p < 0.0001) and LPS (p = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.