# Yinhua Pinggan Granules alleviate lung and intestinal damage in influenza virus-infected mice by modulating gut microbiota and its metabolites to activate the GPR43-MAVS-IRF3-IFN-β pathway

## TL;DR

This study shows that Yinhua Pinggan Granules help reduce lung and intestinal damage in mice infected with influenza by improving gut bacteria and activating a key immune pathway.

## Contribution

The study reveals a new mechanism by which YHPG alleviates influenza symptoms through gut microbiota modulation and activation of the GPR43-MAVS-IRF3-IFN-β pathway.

## Key findings

- YHPG restored gut microbiota diversity and increased SCFA-producing bacteria in influenza-infected mice.
- YHPG treatment activated the GPR43-MAVS-IRF3-IFN-β pathway, reducing lung and intestinal damage.
- Disrupted gut microbiota worsened colonic barrier damage in influenza-infected mice.

## Abstract

Derived from Ma Huang Decoction in the Shang Han Lun, Yinhua Pinggan Granules (YHPG) are used in traditional Chinese medicine for treating influenza. This study highlights the gut microbiota’s role in intestinal damage and acute lung injury from influenza virus infection, offering insights into influenza A virus prevention and treatment through the gut-lung axis.

Using a mouse model disrupted by a four-antibiotic regimen, we assessed survival, weight, lung, and spleen indices post-IAV infection. We evaluated lung and intestinal pathology, viral load, and protein expressions via H&E staining, RT-qPCR, and immunofluorescence. 16S rRNA sequencing and targeted metabolomics were utilized to uncover the impact of YHPG treatment on disrupted gut microbiota and its metabolites after H1N1 infection.

H&E staining showed severe lung and intestinal damage in IAV-infected mice with disrupted gut microbiota. Immunofluorescence results demonstrated that relative depletion of gut microbiota might exacerbate colonic barrier damage in IAV-infected mice. YHPG restored microbiota diversity, increasing SCFA-producing bacteria, aligning with metabolite changes. Western blot and RT-qPCR showed activation of the GPR43-MAVS-IRF3-IFN-I pathway, linked to SCFA regulation.

YHPG alleviate influenza symptoms, promoting SCFA-producing bacteria and maintaining gut homeostasis. They modulate the GPR43-MAVS-IRF3-IFN-β pathway, suggesting novel treatment avenues for influenza through gut microbiota modulation.