Alterations in the Lower Respiratory Tract Microbiome During Influenza Infection: A Systematic Review

Abstract

Context: Influenza is a contagious respiratory disease that can cause mild to severe pneumonia in humans. For a long time, the lungs were believed to be sterile. However, advances in microbial diagnostic methods have revealed the presence of microbial communities in the lungs. This systematic review aimed to comprehensively synthesize scientific evidence on changes in the lower respiratory tract and/or oropharyngeal microbiomes in patients with influenza. Evidence Acquisition: We searched PubMed, Web of Science, Scopus, and Embase for studies published from January 2010 to April 2024 that compared the lung or lower respiratory tract (LRT) and/or oropharyngeal microbiomes of patients with influenza with those of healthy controls. Search terms included "Microbiota," "Microbiotas," or "Microbiome" and "lung," "influenza," or "flu." Two independent reviewers screened titles and abstracts according to the inclusion and exclusion criteria. Following full-text review, data extracted from eligible studies were assessed for completeness and accuracy. Results: We identified nine articles that met the PICOS (Population, Intervention, Comparison, Outcome, Study Design) criteria and were eligible for inclusion. The studies indicated that patients with influenza had increased levels of opportunistic pathogens, such as Acinetobacter and Staphylococcus, whereas beneficial bacteria, such as Veillonella, Streptococcus, Prevotella, and Rothia, were decreased compared with those in healthy individuals. Bacteria adhering to the oropharyngeal epithelium in patients with influenza may act as reservoirs for the lower respiratory tract microbiome. In murine models, increased levels of Enterococcus, Staphylococcus, Acinetobacter, Delftia, and Rubrobacter were observed in influenza-infected animals. Discussion: Overall, the included studies reported microbiome alterations and reduced diversity in the lower respiratory tract of patients with influenza. Decreased microbial diversity may increase susceptibility to opportunistic infections, leading to immune imbalance and more severe viral infections. These microbiome changes may also be associated with viral pneumonia, and microbiome replacement may represent a potential preventive strategy against viral infections.