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Published on: April 14, 2011
Signals from intestinal microbiota mediate the crosstalk between the lung-gut axis in an influenza infection mouse
Yijia Zhang1, Youdi Wan1, Xin Xin1
1Laboratory of Animal Neurobiology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
Introduction:
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.
Methods:
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.
Results:
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 Toll-like receptor 7 (TLR7) and Interferon-b (IFN-b) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased Enterobacteriaceae and decreased Lactobacillaceae. Conversely, antibiotic treatment reduced microbial diversity, notably affecting Firmicutes, Proteobacteria, and Bacteroidetes. 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 Lactobacillus showed reduced lung and intestinal damage, decreased Enterobacteriaceae levels in the intestine, and decreased IDO1 activity.
Discussion:
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 Lactobacillus improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.
Insights
Influenza infection damages lungs and intestines, altering gut bacteria and metabolites. Supplementing with tryptophan and Lactobacillus alleviates this damage, revealing a crucial lung-intestine connection in disease.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Influenza virus primarily affects the respiratory system, but causes damage to both respiratory and intestinal tracts.
- The precise link between lung and intestinal damage during influenza infection is not well understood.
Purpose of the Study:
- To investigate the impact of influenza virus infection on intestinal microbiota and metabolites.
- To elucidate the mechanisms underlying influenza-induced intestinal damage and the lung-intestine axis.
Main Methods:
- 16S rRNA sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) for microbial and metabolic profiling.
- Histopathology (HE staining), Western blot, Q-PCR, and flow cytometry to assess intestinal damage and immune responses.
- In vivo mouse model of influenza infection with and without antibiotic treatment or supplementation.
Main Results:
- Influenza infection caused significant lung and intestinal damage, with the virus localized to the lungs.
- Antibiotic treatment exacerbated both lung and intestinal damage, reduced microbial diversity, and altered metabolite profiles.
- Influenza infection disrupted intestinal microbiota (increased Enterobacteriaceae, decreased Lactobacillaceae) and amino acid metabolism, leading to an imbalance in T helper 17 (Th17) and regulatory T cells (Treg cells) via indoleamine 2,3-dioxygenase 1 (IDO1) pathway.
- Supplementation with tryptophan and Lactobacillus ameliorated lung and intestinal damage, reduced Enterobacteriaceae, and restored Th17/Treg balance.
Conclusions:
- Influenza infection induces significant lung and intestinal pathology, mediated by gut dysbiosis and metabolic alterations.
- Antibiotics worsen influenza-induced damage, underscoring the importance of a balanced gut microbiota.
- Tryptophan and Lactobacillus supplementation represent a potential therapeutic strategy for mitigating influenza-induced intestinal disease by restoring gut homeostasis and immune balance.
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