A MAJOR multinational investigation has identified a unique gut microbial signature linked to the presence and severity of interstitial lung disease (ILD) in systemic sclerosis (SSc), offering new insights into how intestinal bacteria may influence lung involvement in autoimmune disease. The findings represent the first large-scale, international exploration of the gut–lung axis in SSc-ILD.
Gut microbiota linked to ILD extent
Researchers analysed data from 285 patients across seven systemic sclerosis centres on five continents, with a mean disease duration of 9.8 years. Among participants, 62.5% had ILD, as confirmed by quantitative image analysis of high-resolution computed tomography (HRCT) scans.
Using shotgun metagenomic sequencing of stool samples, investigators compared intestinal microbiota between patients with and without ILD. Multivariate analysis revealed that those with ILD had a distinct microbial composition, characterised by an increased abundance of potential pathobiont species—microorganisms capable of contributing to inflammation under certain conditions.
Further analysis of a subgroup of 103 patients with SSc-ILD identified specific bacterial species and metabolic pathways that correlated with the radiological extent of lung disease (QILD), suggesting that microbial alterations may contribute to pulmonary fibrosis progression.
A step toward microbiome-based therapies
Lead author Kristofer Andréasson and colleagues propose that these intestinal species, or their metabolic by-products, could influence immune regulation and fibrotic mechanisms in systemic sclerosis.
This study provides the strongest evidence to date linking gut dysbiosis with lung disease progression in systemic sclerosis, supporting future research into microbiome modulation as a component of treatment strategies.
Reference
Andreasson K et al. International Investigation of the Gut-Lung Axis in Systemic Sclerosis-Interstitial Lung Disease. ACR. 2025;DOI:10.1002/acr.25623.
