Gut bacteria may affect respiratory infection severity

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The composition of microbiota found in the gut influences how susceptible mice are to respiratory virus infections and the severity of these infections, according to new research.

The findings in the journal Cell Host & Microbe show that segmented filamentous bacteria, a bacterial species found in the intestines, protected mice against influenza virus infection when these bacteria were either naturally acquired or administered.

This protection against infection also applied to respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. To maintain this protection, the study notes that segmented filamentous bacteria required immune cells in the lungs called basally resident alveolar macrophages.

In this study, the researchers investigated how differences in specific microbial species can affect outcomes of respiratory virus infections and how they might do so, which hasn’t been well defined previously. They studied mice with discrete microbiome differences and mice differing in only the presence or absence of segmented filamentous bacteria. Viral titers in the lung were measured several days after infection and varied significantly depending on the nature of the microbiome of the different animal groups.

“These findings uncover complex interactions that mechanistically link the intestinal microbiota with the functionality of basally resident alveolar macrophages and severity of respiratory virus infection,” says Andrew Gewirtz, co-senior author of the study and a professor in the Institute for Biomedical Sciences at Georgia State University.

The study found that in segmented filamentous bacteria-negative mice, basally resident alveolar macrophages were quickly depleted as respiratory virus infection progressed. However, in segmented filamentous bacteria-colonized mice, basally resident alveolar macrophages were altered to resist influenza virus infection depletion and inflammatory signaling.

The basally resident alveolar macrophages disabled influenza virus, in large part by activating a component of the immune system referred to as the complement system.

“We find it remarkable that the presence of a single common commensal bacterial species, amidst the thousands of different microbial species that inhabit the mouse gut, had such strong impacts in respiratory virus infection models and that such impacts were largely attributable to reprogramming of basally resident alveolar macrophages,” says Richard Plemper, co-senior author of the study and director of the Center for Translational Antiviral Research. “If applicable to human infections, these findings will have major implications for the future risk assessment of a patient to advance to severe disease.”

“We find it highly unlikely that segmented filamentous bacteria is the only gut microbe capable of impacting the phenotype of alveolar macrophages, and consequently, proneness to respiratory virus infection,” Gewirtz says.

“Rather, we hypothesize that gut microbiota composition broadly influences proneness to respiratory virus infection. Microbiota mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory virus infection, but may also be a long-term post-respiratory virus infection health determinant.”

Additional study authors are from the Center for Translational Antiviral Research and the Institute for Biomedical Sciences at Georgia State, and the University of Georgia.

Funding for the study came from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases.

Source: Georgia State University