Summary Although microbial populations in the gut microbiome are associated with the severity of COVID-19, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with the translocation of bacteria into the blood during COVID-19, leading to life-threatening secondary infections . We first demonstrated that SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations in 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 for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may move from the gut to the systemic circulation of COVID-19 patients. These results are consistent with a direct role of gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19. |
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Infection with the pandemic virus, SARS-CoV-2, can reduce the number of bacterial species in a patient’s gut, and the lower diversity creates space for dangerous microbes to thrive, a new study finds.
The study is based on the understanding that the widespread use of antibiotics to combat infections with disease-causing bacteria in recent decades, by eliminating species most vulnerable to available drugs, has left more species resistant to antibiotics in their place. . Additionally, disruptions in gut bacteria ratios have previously been linked to more severe COVID-19.
However, researchers say, it was unclear until now which came first, whether the coronavirus infection disrupted the gut microbiome or an already weakened gut that made the body more vulnerable to the virus. The new study seems to favor the previous explanation. The new research also revealed that antibiotic-resistant species can escape into the bloodstream, putting patients at greater risk of life-threatening secondary infections.
Led by researchers at NYU Grossman School of Medicine, the research involved 96 men and women hospitalized with COVID-19 in 2020 in New York City and New Haven, Conn. The results showed that most patients had a low diversity of gut microbiomes , with a quarter dominated by a single type of bacteria. At the same time, populations of several microbes known to include antibiotic-resistant species increased, possibly due to the widespread use of antibiotics early in the pandemic.
These antibiotic-resistant bacteria found in the intestine were also observed to migrate into the bloodstream in 20% of patients . The study authors note that more research is needed to find out why this group was at higher risk of secondary infection while others remained protected.
“Our findings suggest that coronavirus infection directly interferes with the healthy balance of microbes in the gut, further endangering patients in the process,” says study co-senior author and microbiologist Ken Cadwell, PhD. “Now that we have discovered the source of this bacterial imbalance, doctors can better identify coronavirus patients at highest risk of secondary bloodstream infection,” adds Cadwell.
The new study is the first to show that coronavirus infection alone , and not the initial use of antibiotics to treat the disease as other experts had thought, damages the gut microbiome, says Cadwell, also a professor in the Departments of Microbiology and New York University Langone Health Medicine. He adds that the study also provides the first evidence that the same bacteria in the gut are also entering patients’ bloodstreams, causing dangerous infections.
The report is published in the journal Nature Communications.
For the research, the researchers first infected dozens of mice with the coronavirus and analyzed the bacterial species composition in their fecal samples. This step allowed them to unravel whether the coronavirus could directly alter the microbiome independent of hospitalization and treatment.
They then collected stool samples and blood tests from COVID-19 patients at NYU Langone Health and Yale University hospitals to assess the composition of gut microbes and the presence of secondary infection. If any group of bacteria made up the majority of bacteria living in the intestine, it was considered dominant.
"Our results highlight how the gut microbiome and different parts of the body’s immune system are closely interconnected," says the study’s senior author, Jonas Schluter, PhD, an assistant professor in the Department of Microbiology at NYU Langone and a member of its Institute of Microbiology. Systems Genetics. . “An infection in one can cause major disruptions in the other.” Schluter cautions that because the patients received different types of treatments for their disease, the research could not fully explain all the factors that may have contributed to the alteration of their microbiome and the worsening of their disease.
According to Schluter, the study team plans to next examine why certain microbial species are more likely to escape from the gut during COVID-19. The researchers say they also intend to explore how different microbes interact, which may contribute to this migration into the bloodstream.
