AUTHOR=Zhang Yijia , Wan Youdi , Xin Xin , Qiao Yixuan , Qiao Wenna , Ping Jihui , Su Juan 

TITLE=Signals from intestinal microbiota mediate the crosstalk between the lung-gut axis in an influenza infection mouse model

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1435180

DOI=10.3389/fimmu.2024.1435180

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Introduction: The influenza virus primarily targets the respiratory tract, yet both the respiratory and intestinal systems suffer damage during infection. The connection between lung and intestinal damage remains unclear.</p></sec><sec><title>Methods</title><p>Our experiment employs 16S rRNA technology and Liquid Chromatography-Mass Spectrometry (LC-MS) to detect the impact of influenza virus infection on the fecal content and metabolites in mice. Additionally, it investigates the effect of influenza virus infection on intestinal damage and its underlying mechanisms through HE staining, Western blot, Q-PCR, and flow cytometry.</p></sec><sec><title>Results</title><p>Our study found that influenza virus infection caused significant damage to both the lungs and intestines, with the virus detected exclusively in the lungs. Antibiotic treatment worsened the severity of lung and intestinal damage. Moreover, mRNA levels of <italic>Toll-like receptor 7</italic> (<italic>TLR7</italic>) and <italic>Interferon-b</italic> (<italic>IFN-b</italic>) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased <italic>Enterobacteriaceae</italic> and decreased <italic>Lactobacillaceae</italic>. Conversely, antibiotic treatment reduced microbial diversity, notably affecting <italic>Firmicutes</italic>, <italic>Proteobacteria</italic>, and <italic>Bacteroidetes</italic>. Metabolomics showed altered amino acid metabolism pathways due to influenza infection and antibiotics. Abnormal expression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon disrupted the balance between helper T17 cells (Th17) and regulatory T cells (Treg cells) in the intestine. Mice infected with the influenza virus and supplemented with tryptophan and <italic>Lactobacillus</italic> showed reduced lung and intestinal damage, decreased <italic>Enterobacteriaceae</italic> levels in the intestine, and decreased IDO1 activity.</p></sec><sec><title>Discussion</title><p>Overall, influenza infection caused damage to lung and intestinal tissues, disrupted intestinal microbiota and metabolites, and affected Th17/Treg balance. Antibiotic treatment exacerbated these effects. Supplementation with tryptophan and <italic>Lactobacillus</italic> improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.</p></sec>