Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation

Abstract

The microbial populations in the gut microbiome have recently been associated with COVID-19 disease severity. However, a causal impact of the gut microbiome on COVID-19 patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. Antibiotics and other treatments during COVID-19 can potentially confound microbiome associations. We therefore first demonstrate that the gut microbiome is directly affected by SARS-CoV-2 infection in a dose-dependent manner in a mouse model, causally linking viral infection and gut microbiome dysbiosis. Comparison with stool samples collected from 101 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, paralleling our observations in the animal model. Specifically, we observed blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species in hospitalized COVID-19 patients. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data obtained from these patients suggest that bacteria translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.

Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice

“…A recent study reported that COVID-19 patients present higher levels of markers associated with gut leakage than healthy individuals, and the levels of these markers are higher in patients with a more severe form of COVID-19 compared with patients with less severe forms of this infection [ 59 ]. In addition, the dysbiotic microbiota of COVID-19 patients has been associated with the development of secondary bloodstream infections [ 24 ]. It is worth mentioning that Abx treatment reduces the gut bacterial load, thus diminishing the amount of microorganisms that interact with the epithelium and may cross this barrier.…”

“…Moreover, a recent study found an association between COVID-19 gut dysbiosis, particularly depletion of Faecalibacterium and Roseburia genera, and an increased inflammatory profile, as observed in severe or critical COVID-19 patients [ 23 ]. A recent study found an association between dysbiotic microbiota and the translocation of bacteria into the blood of COVID-19 patients, thus contributing to the increased inflammatory profile observed in these patients and the development of secondary infections [ 24 ]. Intestinal dysbiosis has also been reported in mice, hamsters and nonhuman primates infected with SARS-CoV-2 [ 25 , 26 , 27 ], indicating that the gut microbiome profile is involved in this disease and strategies to alter the intestinal microbiota might change the disease outcome.…”

Recent Advances in Understanding the Structure and Function of the Human Microbiome

“…The researchers observed an abundance of opportunistic pathogenic bacteria in hospitalized COVID-19 including antimicrobial-resistant species (Lau et al, 2021;Venzon et al, 2021). Leakage of bacteria into the bloodstream following dysbiosis is critical to control and can drive detrimental effects.…”

Distal Consequences of Mucosal Infections in Intestinal and Lung Inflammation

“…Several works have postulated that gut dysbiosis may lead to bacterial translocation into the blood and contribute to COVID-19 severity. K18-hACE2 mice infected with a high dose SARS-CoV-2 also exhibit alterations in gut permeability and defective Paneth cell function associated an increase in Akkermansiaceae ( 108 ). Similarly, blood culture analysis of COVID-19 patients revealed bloodstream infection, which matched with bacterial species found in the stool from the same patients, supporting the idea that gut bacteria can translocate into the blood during SARS-CoV-2 infection.…”

“…Similarly, blood culture analysis of COVID-19 patients revealed bloodstream infection, which matched with bacterial species found in the stool from the same patients, supporting the idea that gut bacteria can translocate into the blood during SARS-CoV-2 infection. In addition, Faecalibacterium was negatively associated with bloodstream infection, suggesting that their decrease during disease may favor bacterial translocation ( 108 ). Furthermore, increased levels of markers of bacterial and fungal translocation together with increased levels of markers of tight junction permeability have been reported in patients with severe COVID-19, indicating that altered gut permeability may allow bacterial translocation into the blood and contribute to disease severity ( 109 ).…”