The role of the gut microbiome in respiratory viral infections in general, and in COVID-19 patients, in particular, is only just beginning to be understood. Previous reports have shown that COVID-19 is often accompanied by gastrointestinal symptoms and that persistent microbiome changes are found in people with long-term COVID-19. Furthermore, investigations have shown that all COVID-19 patients manifest differences in gut bacterial populations when compared to healthy controls, and that infected patients treated with broad-spectrum antibiotics while in hospital have an increased risk of developing multi-drug resistant secondary infections and of dying from septic shock.
Despite these earlier findings, the causal direction of the relationship between disrupted gut microbiome and infection by coronavirus has remained unclear. Does coronavirus infection result in a disrupted gut microbiome, or does an already weakened or dysfunctional gut microbiome make the body more vulnerable to infection by the virus?
A recent study, led by researchers from NYU Grossman School of Medicine, has now set out to elucidate this relationship. Initially, the researchers tested the changes in gut microbes found in laboratory mice that had been infected with SARS-CoV-2, and found that the diversity of different bacterial species in the gut decreased dramatically within the first few days of infection. Some families of important bacteria disappeared from the gut, while other families proliferated. These results led the researchers to suspect that the virus would also disrupt the microbiome in human patients.
They then investigated changes to gut microbes in 96 men and women who were hospitalized with COVID-19 in 2020, in New York City and in New Haven, Conn. The researchers analyzed the microbe communities present in stool samples taken throughout each patient’s hospital stay.
The results, published in the journal Nature Communications, showed that the majority of patients had low gut microbiome diversity, as was found in the experimental mice, with around a quarter of the patients showing a microbiome 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 widespread antibiotic use early in the pandemic. Antibiotics kill off species that are susceptible to the drugs but leave, in their place, different species that are resistant to the drugs.
These antibiotic-resistant bacteria found in the gut were also observed to have migrated into the bloodstream in 20 percent of patients. In the bloodstream, they cause infections that can be life-threatening to patients. The study authors note that further research is needed to uncover why this group was at higher risk for a secondary infection while other patients 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 Dr. Ken Cadwell. “Now that we have uncovered the source of this bacterial imbalance, physicians can better identify those coronavirus patients most at risk of a secondary bloodstream infection.”
Under normal circumstances, microbes are not able to migrate between the gut and the bloodstream unless the intestinal barrier is damaged. In fact, the researchers found gut epithelial cell alterations in the mice infected with SARS-CoV-2, implying that the virus in some way also changes the permeability of the intestine lining. In previous research, the influenza virus was also shown to disrupt the intestinal barrier in mice by damaging the gut microbiota.
In the current study, the patients who were shown to have a microbiome dominated by one type of bacteria often suffered the migration of this drug-resistant species from the gut into the blood, indicating some compromise to the intestinal barrier. This caused a secondary infection in these patients that proved fatal, in some instances.
“Our results highlight how the gut microbiome and different parts of the body’s immune system are closely interconnected,” says study senior author Dr. Jonas Schluter. “An infection in one can lead to major disruptions in the other.” Schluter cautions that since the patients received different kinds of treatments for their illness, the investigation could not entirely account for all factors that may have contributed to the disruption of their microbiome and worsen their disease.
Taken together, these research findings support a scenario in which gut-to-blood migration of microorganisms occurs in COVID-19 patients due to the virus causing disruption to the normal gut microbiome. This migration leads to bloodstream infections that can be dangerous complications of the disease. According to Schluter, the study team next plans to examine why certain microbial species are more likely to escape 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.
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By Alison Bosman, Earth.com Staff Writer