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Health

The surprising role of gut bacteria in fighting the flu and COVID-19

Research from Georgia State University shows that gut bacteria, particularly segmented filamentous bacteria, play a crucial role in protecting mice from respiratory viruses by influencing immune cells in the lungs. This study could have profound implications for the understanding and management of respiratory infections in humans.

Researchers at the Center for Translational Antiviral Research at the Institute of Biomedical Sciences at Georgia State University have discovered that the composition of the gut microbiota affects the vulnerability of mice to respiratory disease.

virus
A virus is a small infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made of lipids which surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They depend on host cells to replicate and multiply, hijacking the cellular machinery to copy themselves. This process can damage the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections.

” data-gt-translate-attributes=”({“attribute”:”data-cmtooltip”, “format”:”html”})” tabindex=”0″ role=”link”>virus infections and the severity of these infections.

The results, published in the journal Cellular host and microbereport that segmented filamentous bacteria, a bacterium

species
A species is a group of living organisms that share a common set of characteristics and are capable of reproducing and producing fertile offspring. The species concept is important in biology because it is used to classify and organize the diversity of life. There are different ways to define a species, but the most widely accepted is the biological species concept, which defines a species as a group of organisms capable of interbreeding and producing viable offspring in nature. This definition is widely used in evolutionary biology and ecology to identify and classify living organisms.

” data-gt-translate-attributes=”({“attribute”:”data-cmtooltip”, “format”:”html”})” tabindex=”0″ role=”link”>species found in the intestines, protected mice against influenza virus infection when these bacteria were either naturally acquired or administered.

Illustration of the intestinal microbiota and lungs

This image illustrates an example of gut microbiota composition dictating how resident pulmonary alveolar macrophages (AMs) respond to viral infection. The presence of segmented filamentous bacteria, a commensal microbe found in some mice, reprograms AM gene expression, thereby increasing complement expression and phagocytosis, thereby allowing AM to engulf and destroy viral pathogens without inflammatory signaling. Credit: Dr. Andrew Gewirtz

This protection against infection also applied to respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (

SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the official name for the viral strain that causes coronavirus disease (COVID-19). Before this name was adopted, it was commonly referred to as 2019 novel coronavirus (2019-nCoV), Wuhan coronavirus or Wuhan virus.

” data-gt-translate-attributes=”({“attribute”:”data-cmtooltip”, “format”:”html”})” tabindex=”0″ role=”link”>SARS-CoV-2), the virus that causes

COVID-19
First identified in 2019 in Wuhan, China, COVID-19, or coronavirus disease 2019 (originally called "2019 novel coronavirus" or 2019-nCoV) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It spread globally, resulting in the 2019–2022 coronavirus pandemic.

” data-gt-translate-attributes=”({“attribute”:”data-cmtooltip”, “format”:”html”})” tabindex=”0″ role=”link”>COVID-19. To maintain this protection, the study noted that the segmented filamentous bacteria needed immune cells in the lungs called basally resident alveolar macrophages.

Study results

Richard Plemper

Dr. Richard Plemper, co-senior author of the study, Regents Professor and director of the Center for Translational Antiviral Research at Georgia State University. Credit: Georgia State University

In this study, researchers investigated how and how differences between specific microbial species can impact the outcomes of respiratory viral infections, which has not been well defined before. They studied mice with discrete differences in the microbiome and mice differing only in the presence or absence of segmented filamentous bacteria. Viral titers in the lungs were measured several days after infection and varied significantly depending on the nature of the microbiome of different groups of animals.

“These results reveal complex interactions that mechanistically link the gut microbiota to the functionality of basally resident alveolar macrophages and the severity of respiratory virus infection,” said Dr. Andrew Gewirtz, co-senior author of the study. and Regents Professor at the Institute for Biomedical. Science at Georgia State.

The study found that in segmented filamentous bacteria-negative mice, basally resident alveolar macrophages were rapidly depleted as respiratory virus infection progressed. However, in mice colonized with segmented filamentous bacteria, basal resident alveolar macrophages were modified to resist exhaustion from influenza virus infection and inflammatory signaling.

Basally resident alveolar macrophages deactivated the influenza virus, largely by activating a component of the immune system called the complement system.

Implications and future directions

“We find it remarkable that the presence of a single common commensal bacterial species, among the thousands of different microbial species that inhabit the mouse gut, had such significant impacts on patterns of infection by respiratory viruses and that these impacts are largely attributable to the reprogramming of basal resident systems. alveolar macrophages,” said study co-senior author Dr. Richard Plemper, Regents Professor and director of the Center for Translational Antiviral Research at Georgia State. “If applicable to human infections, these results will have major implications for future assessment of a patient’s risk of progression to severe disease.”

“We find it very unlikely that segmented filamentous bacteria are the only gut microbe capable of impacting alveolar macrophage phenotype and, therefore, predisposition to respiratory viral infections,” Gewirtz said. “Rather, we hypothesize that the composition of the intestinal microbiota largely influences the predisposition to infections by respiratory viruses. Microbiota-mediated programming of basally resident alveolar macrophages may not only influence the severity of acute respiratory viral infection but may also be a determinant of long-term health after respiratory viral infection.

Reference: “Gut microbiota programming of alveolar macrophages influences the severity of respiratory viral infection” by Vu L. Ngo, Carolin M. Lieber, Hae-ji Kang, Kaori Sakamoto, Michal Kuczma, Richard K. Plemper and Andrew T . Gewirtz, January 30, 2024, Cellular host and microbe.
DOI: 10.1016/j.chom.2024.01.002

The study’s lead authors were virologist Carolin M. Lieber of the Antiviral Translational Research Center and immunologist Vu L. Ngo of the Georgia State Institute of Biomedical Sciences. Other contributing authors were Hae-ji Kang and Michal Kuczma of the Georgia State Institute of Biomedical Sciences and Kaori Sakamoto of the University of Georgia.

The study is funded by the

National Institutes of Health
The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides significant biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of this knowledge to improve health, prolong life, and reduce disease and disability.

” data-gt-translate-attributes=”({“attribute”:”data-cmtooltip”, “format”:”html”})” tabindex=”0″ role=”link”>National Institutes of HealthNational Institute of Allergy and Infectious Diseases.

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