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The Role of Gut Microbiota on Idiopathic Pulmonary Fibrosis Mediated by Circulating Inflammatory Proteins: A

Hongyu Zhu1, Caihua Chen1, Haixie Guo1

  • 1Department of Thoracic Surgery, Taizhou Hospital, Taizhou, Zhejiang, China.

The Clinical Respiratory Journal
|September 9, 2025
PubMed
Abstract

Insights

This study suggests gut microbiota influence idiopathic pulmonary fibrosis (IPF) through inflammatory proteins. Specific gut bacteria and proteins show a causal link to IPF, with Actinomyces and CCL11 partially mediating this relationship.

Area of Science:

  • Genetics
  • Microbiology
  • Pulmonology

Background:

  • Idiopathic pulmonary fibrosis (IPF) is characterized by persistent inflammation.
  • The gut-lung axis highlights the gut microbiota's (GM) role in pulmonary diseases.
  • Understanding GM's genetic influence on IPF is crucial.

Purpose of the Study:

  • To investigate the causal relationship between gut microbiota and IPF.
  • To explore the mediating role of circulating inflammatory proteins in this relationship.
  • To leverage Mendelian randomization for genetic insights.

Main Methods:

  • A two-sample Mendelian randomization study was conducted.
  • Single nucleotide polymorphisms (SNPs) served as instrumental variables for GM exposure.
  • The inverse variance weighted (IVW) method was primarily used.

Main Results:

  • Twelve gut microbial taxa and eight inflammatory proteins showed suggestive causal links to IPF.
  • A causal pathway from Actinomyces to IPF, mediated by CCL11, was identified.
  • The mediation effect of Actinomyces on IPF via CCL11 was statistically significant.

Conclusions:

  • A genetically predicted association exists between gut microbiota and IPF.
  • Circulating inflammatory proteins play a mediating role in the gut-lung axis concerning IPF.
  • These findings offer novel insights into IPF pathogenesis.
Keywords:
Mendelian randomizationcirculating inflammatory proteinsgut microbiotaidiopathic pulmonary fibrosis

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