Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia

Abstract

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on 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. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may 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.

Marginal notes, November 2022. From crisis to crisis

“…Interestingly, this study demonstrated that the shortest treatment (3 days) produced longer lasting microbiome effects in some bacterial taxa for several weeks. The convergence of COVID-19, antimicrobial treatment and the gut microbiome adds more complexity, which another group investigated [5]. They demonstrated structural changes and reduced antimicrobial factors in the intestinal mucosa of SARS-CoV-2-infected mice, and observed signs of barrier permeability.…”

Pathogenic Mechanisms of the Severe Acute Respiratory Syndrome Coronavirus 2 and Potential Direct and Indirect Counteractions by Intermittent Fasting

“…The gut microbiome, including the appendix that is now recognized as a non-vestigial well that maintains the microbiome [ 72 ], is recognized today for substantial influences on human health [ 30 , 31 , 32 , 73 , 74 , 75 , 76 ]. The microbiome impacts human health, both in the prevention of or acceleration of chronic diseases and in limiting or enhancing infectious diseases [ 16 , 30 , 31 , 32 , 73 , 74 , 75 , 76 ]. This includes the potential for acute infections in the intestine or in the appendix to radically alter organ-level health [ 73 , 74 , 75 , 76 ].…”

“…This includes the potential for acute infections in the intestine or in the appendix to radically alter organ-level health [ 73 , 74 , 75 , 76 ]. SARS-CoV-2 may be one of such infections, inducing gut microbiome dysbiosis that leads to enhanced proliferation of pathogenic microbial species, including anti-microbial resistant strains, and to the movement of harmful secondary pathogens into the bloodstream from the gut [ 30 , 73 ]. In a study of a murine model and, in parallel, of patients with COVID-19, substantial loss of microbiome diversity was observed with many of the human cases having a single taxa that accounted for >50% of the bacteria in their gut and the loss of diversity was associated with the presence of blood stream infections [ 30 ].…”

“…SARS-CoV-2 may be one of such infections, inducing gut microbiome dysbiosis that leads to enhanced proliferation of pathogenic microbial species, including anti-microbial resistant strains, and to the movement of harmful secondary pathogens into the bloodstream from the gut [ 30 , 73 ]. In a study of a murine model and, in parallel, of patients with COVID-19, substantial loss of microbiome diversity was observed with many of the human cases having a single taxa that accounted for >50% of the bacteria in their gut and the loss of diversity was associated with the presence of blood stream infections [ 30 ]. Further, one member of Firmicutes (i.e., Faecalbacterium ) that is present in abundance in the healthy human gut (see Figure 1 for an overview of the common composition of the human microbiome) was found to be substantially reduced in prevalence in patients infected by SARS-CoV-2 [ 30 ].…”

“…For example, during a fasting period while energy intake is restricted, fasting may boost physiological mechanisms of human immunity specifically related to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 15 , 16 ], activate other mechanisms related to general human immune responses [ 17 , 18 , 19 , 20 ], reduce the hyperinflammatory response to SARS-CoV-2 infection [ 21 , 22 , 23 , 24 , 25 , 26 ], and strongly induce the cellular “housecleaning” of autophagy [ 19 , 27 , 28 , 29 ]. The diet and gut-microbiota play an important role in health generally [ 13 , 18 ], and SARS-CoV-2 can cause major adverse effects on the microbiome [ 30 ], but fasting may support a healthy microbiome and increase resistance to gut dysbiosis [ 16 , 31 , 32 ]. In the long-term, fasting may improve basal levels of factors related to the response to infectious disease and to inflammation modulation [ 17 , 23 , 33 , 34 , 35 ], and generally reduce the risk and the prevalence of morbidities that are associated with worse prognosis after COVID-19 diagnosis, such as coronary artery disease, myocardial infarction, heart failure, and diabetes [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 14 , 20 , 36 , 37 , 38 , 39 , 40 ].…”