More Evidence Connecting Microbiome-Related Issues to COVID-19 Patients
A large, prominent team of researchers represented by corresponding authors Jonas Schluter and Ken Cadwell, both affiliated with New York University Grossman School of Medicine, recently offered more confirmation as to the importance of the microbiome with conditions such as SARS-CoV-2, the virus behind COVID-19. As this media has tracked investigators from Malibu, California (Progenabiome) to Chinese University of Hong Kong (CUHK) have detected a connection between the gut microbiome and SARS-CoV-2 infection. Based on this latest study result based on experimentation with mice as well as 96 COVID-19 patients at two different trial site locations revealing substantial gut microbiome dysbiosis, or a disruption to the microbiome resulting in an imbalance in the microbiota, change in functional composition and metabolic activities for example. In this study, the scientists found blooms of opportunistic pathogenic bacterial genera called antimicrobial-resistant species. The team also tested for secondary microbial bloodstream infections, analyzing blood culture results with paired microbiome data suggesting that bacteria may translocate from the gut into the “systemic circulation of COVID-19.” Schluter, Cadwell, et al share, “These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19.”
The team summarizes that their results suggest “an unappreciated link between SARS-CoV-2 infection, gut microbiome dysbiosis, and a severe complication of COVID-19, BSIs.” What’s more, the study authors verified a disturbing loss of diversity and immune-supportive Faecalibacterium in patients with BSIs to a comparable loss of diversity in the sickest mice deliberately infected with SARS-CoV-2 verifying other labs and reports.
What are some of these supportive studies?
According to the authors, one recent study reproduced comparable changes in the microbiome in an antibiotics naïve cohort, indicating that viral infection causes gut dysbiosis, for example. This may occur either via gastrointestinal infection or a systemic inflammatory response.
The authors also observed a boost in Akkermansiaceae in mice can also be seen in patient samples as well as previously in patients and in K18h-ACE2 mice. But it would appear the dysbiosis is worse in patients than mice—in humans, the microbiome can be dominated by single taxa, which isn’t observed in the mice samples. Although there are several factors that may impact these outcomes associated with mouse model limitation.
Does SARS-CoV-2 infection lead to alteration of intestinal epithelial cells with established roles in intestinal homeostasis and gastrointestinal disease?
Yes. They are likely the result of microbiome ecosystem shifts associated with these epithelial cell alterations.
Does the study data here suggest that dynamics in COVID-19 patients in this context compared to those observed in cancer patients?
Yes.
So, in summary, the research group showcased evidence that microorganisms from the dysbiosis gut microbiome translocate into the blood of COVID-19 patients, plausibly due to a combination of the immunocompromising effects of the viral infection and antibiotic-driven depletion of commensal gut microbes?
Yes.
What’s their summary statement?
This prominent study team’s finding back a hypothesis that gut-to-blood translocation of microorganisms following microbiome dysbiosis suggests a path to dangerous BSIs during COVID-19, a complication seen in other immunocompromised patients, including patients with cancer, acute respiratory distress syndrome, and in ICU patients receiving probiotics.
What are the limitations of this research?
A series of limitations impact this work. They include:
Many patients infected with SARS-CoV- are exposed to other possible sources predisposing them to bacteremia, including immunosuppressive drugs, lengthy hospital stays, and catheters—the study couldn’t differentiate these factors
Few available whole genome sequences of blood isolates are available because of discarded blood cultures associated with several BSIs, and the temporal ordering of samples—this impacts access to data
Occasionally, stool samples were collected after observation of BSI, and this mismatch in temporal ordering is counterintuitive for gut-to-blood translocation and a causal interpretation of our associations
Importantly the authors note that contrary to above, blood infections can populate and transform gut communities, and this is not likely the organisms identified in the blood, and the authors point out if the associations in this study write-up were not causal, they would expect no match between BSI organisms and compositions.
Lead Research/investigator
Jonas Schluter, Ph.D. Institute for Systems Genetics, Assistant Professor, Department of Microbiology, New York University Grossman School of Medicine, Corresponding Author
Ken Cadwell, Ph.D. Professor, Department of Medicine, Recant Family Professor of Microbiology, Department of Microbiology, Corresponding Author
Call to Action: The study team thinks future investigation into the underlying mechanism behind their current observations could inform the judicious application of antibiotics and immunosuppressives in patients with respiratory viral infections and increase our resilience to pandemics.