The Role of Gut Microbiota on Idiopathic Pulmonary Fibrosis Mediated by Circulating Inflammatory Proteins: A Two-Step, Two-Sample Mendelian Randomization Study

Background

Persistent inflammation is a crucial characteristic of idiopathic pulmonary fibrosis (IPF). Gut microbiota (GM) contribute to the occurrence and development of several pulmonary diseases through the “gut–lung axis.” The genetic role of GM in IPF and the mediating effect of circulating inflammatory proteins.

Methods

A single nucleotide polymorphism (SNP) was used as an instrumental variable (IV) for exposure to evaluate the causal relationship between exposure and outcome. A two-step, two-sample Mendelian randomization study mainly based on an “inverse variance weighted (IVW)” approach was performed to explore the causal relationship between GM and IPF mediated by circulating inflammatory proteins.

Results

The IVW way illustrated 12 taxa (Bacillales, Gastranaerophilales, Selenomonadales, Family XIII, Bacteroidaceae, Bacteroides, and Actinomyces, Bifidobacterium, Oscillibacter, Ruminococcus gnavus, Subdoligranulum, Veillonella) of GM and 8 circulating inflammatory proteins (CCL11, CXCL6, CXCL9, CCL8, CCL7, NRTN, STAMPB, and TGFa) had suggestive evidence of causality on IPF. The mediation MR demonstrated the causal pathway from Actinomyces to IPF was partly mediated by CCL11 (the mediation effect: 0.063, 95% CI [1.016–1.126]; p = 0.004) with a mediation proportion of 13.035%.

Conclusions

These findings may suggest a genetically predicted association between GM and IPF mediated by circulating inflammatory proteins.