Maintaining a Healthy Upper Respiratory Tract Microbiome May Help Prevent Secondary Infections in Influenza A Patients

LA JOLLA, Calif., May 26, 2020 /PRNewswire/ -- Scientists from the J. Craig Venter Institute (JCVI), Icahn School of Medicine at Mount Sinai, and Pontificia Universidad Católica de Chile examined changes in the upper respiratory tract (URT) microbiome during an influenza A virus (IAV) infection.

The study examined the URT microbiome in both healthy and IAV-infected human and ferret cohorts. Humans and ferrets share similar lung physiology, and both are known to be susceptible to and transmit the same strains of IAVs, thus making ferrets an ideal model to study IAV infection in the URT.

Results suggest that microbiome disturbance and resilience dynamics may be critical to addressing bacterial co-infections associated with influenza-derived illnesses. "These secondary bacterial infections are a serious concern, exacerbating conditions caused by IAV, as well as many other disease conditions," noted Karen Nelson, Ph.D., JCVI president and a senior author on the study.

Uninfected human patients and ferret URT microbiomes have a stable and similar communities, both within and between individuals, representing a healthy microbiome. In contrast, infected patients and ferrets exhibit large changes in bacterial community composition over time and between individuals, with increased bacterial diversity present in the URT.

After viral infections clear, the microbiome of the individuals progress towards the healthy microbiome. However, there is a period where the virus is gone yet the microbiome is still disturbed. The disturbance of the healthy URT microbiome appears to create transient ecological niches for opportunistic bacterial pathogens, including changes in the relative abundance of Pseudomonas.

IAV does not directly infect the microbiome constituents, yet infection disturbs the healthy-state microbiome in both hosts in a statistically robust manner. Given the unequivocal association between viral and bacterial co-infection and influenza disease severity, there is a pressing need to better understand how changes in the host microbiome correlates with viral infections that facilitate opportunistic co-infections.

Adding to this, Chris Dupont, Ph.D. stated, "There is compelling rationale for the maintenance of a healthy URT microbiome as a potential therapeutic target to prevent IA-associated bacterial co-infections." Dr. Dupont is a senior author on the study and professor at JCVI.

Study results provide a clear approach for the design of future studies explicitly examining links between IAV and bacterial co-infection, along with the development of therapeutic treatments aimed at the microbiome as a community.

The complete results, Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection, are published in the journal Nature Communications.

Background

Influenza A virus is a highly infectious upper respiratory tract disease in humans and animals caused by a negative-sense segmented RNA virus. It is recognized as a major public health concern resulting yearly in significant disease and economic burden.

Frequent nucleotide substitutions lead to changes on the hemagglutinin and neuraminidase glycoproteins on the surface of IAV particles (also known as antigenic drift) that contribute to the need for continuous vaccine updates.

This evolutionary arms race between vaccine design and viral mutation contributes to annual influenza epidemics worldwide, which on average results in 3 to 5 million cases of severe illness and up to 291,000 to 646,000 deaths annually.

The modular architecture of the segmented IAV genome allows for genetic re-assortment (antigenic shift) with other divergent IAVs, resulting in the sporadic emergence of novel viruses capable of causing large epidemics or pandemics.

Circulation of a new IAV in the naïve human population has caused pandemics in the past resulting in significant morbidity and mortality, the most notable in 1918 and 1919, when the Spanish flu killed approximately 20 to 50 million people worldwide.

Retrospective analyses of autopsy specimens from the 1918 pandemic revealed the prevalence of secondary superinfection caused by URT bacteria. However, the role of bacterial co-infection in disease prognosis is not only confined to pandemics; bacterial and virus co-infection during seasonal influenza epidemics are commonly associated with increase hospital admissions, severe disease and deaths.

About J. Craig Venter Institute

The J. Craig Venter Institute (JCVI) is a not-for-profit research institute in Rockville, Maryland and La Jolla, California. dedicated to the advancement of the science of genomics; the understanding of its implications for society; and communication of those results to the scientific community, the public, and policymakers. Founded by J. Craig Venter, Ph.D., the JCVI is home to approximately 200 scientists and staff with expertise in human and evolutionary biology, genetics, bioinformatics/informatics, information technology, high-throughput DNA sequencing, genomic and environmental policy research, and public education in science and science policy. The JCVI is a 501(c)(3) organization. For additional information, please visit www.JCVI.org.

SOURCE J. Craig Venter Institute

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