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

Front Immunol. 2024 Jul 23:15:1435180. doi: 10.3389/fimmu.2024.1435180. eCollection 2024.

Abstract

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.

Keywords: Lactobacillus; gut-lung axis; influenza A virus; intestinal microbiota; tryptophan metabolism.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Disease Models, Animal*
  • Female
  • Gastrointestinal Microbiome*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Intestines / immunology
  • Intestines / microbiology
  • Intestines / virology
  • Lung* / immunology
  • Lung* / metabolism
  • Lung* / microbiology
  • Lung* / virology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections* / immunology
  • Orthomyxoviridae Infections* / metabolism
  • RNA, Ribosomal, 16S / genetics
  • Signal Transduction
  • Toll-Like Receptor 7 / metabolism

Substances

  • Toll-Like Receptor 7
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Tlr7 protein, mouse
  • IDO1 protein, mouse
  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Membrane Glycoproteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China: 32272992; the Xinjiang Animal Disease Prevention and Control Engineering Technology Research Center: GC2021003.