Integrated analysis of gut microbiome and fecal metabolome reveals potential non-invasive biomarkers for early-stage silicosis

ABSTRACT Silicosis is an irreversible and progressive form of pulmonary fibrosis resulting from inhalation of silica particles, representing a persistent global health concern. Although the gut microbiota has been implicated in chronic lung diseases, its role in silicosis remains largely unexplored. Here, we performed 16S ribosomal RNA (rRNA) gene sequencing on fecal samples from 78 silicosis patients (27 stage I, 24 stage II, 27 stage III) and 30 matched healthy controls (HCs), and further conducted untargeted fecal metabolomics profiling in stage I patients, the critical point for microbial dysbiosis. Silicosis patients exhibited significantly altered beta diversity compared with HCs. At the phylum level, a progressive increase in Proteobacteria and a decline in Bacteroidota were observed. Notably, Pantoea, Kluyvera, and unclassified Pasteurellaceae were significantly enriched in stage I patients, with persistent alterations across later stages, suggesting stage I as a key turning point of microbial dysbiosis. Metabolomic analysis of stage I patients revealed distinct profiles enriched in tyrosine, histidine, purine metabolism, and arginine biosynthesis pathways. Correlation analysis identified strong associations between specific taxa and metabolites, and combined microbial–metabolite signatures such as Lactobacillus with N-succinyl-2-amino-6-ketopimelate (N-Succinyl-AKP) achieved an area under the curve (AUC) of 0.84 in distinguishing stage I patients from HCs. IMPORTANCE This study systematically characterizes gut microbial changes across different stages of silicosis and integrates microbiome–metabolome data specifically in early-stage patients. We demonstrate that stage I is a critical point for gut microbiome alterations and identify microbe–metabolite signatures with diagnostic potential. These findings highlight the gut microbiome–metabolome combination as a promising source of non-invasive biomarkers for the early detection of silicosis.