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

Silicosis patients exhibited significantly altered beta diversity in gut microbiota compared with healthy controls.

• Study included 78 silicosis patients (27 stage I, 24 stage II, 27 stage III) and 30 matched healthy controls (HCs)
• 16S ribosomal RNA gene sequencing was performed on fecal samples
• Beta diversity differences were significant between silicosis patients and HCs

Progressive changes in gut microbiota composition at the phylum level were observed across silicosis stages.

• A progressive increase in Proteobacteria was observed across silicosis stages
• A progressive decline in Bacteroidota was observed across silicosis stages
• These phylum-level changes tracked with disease stage progression

Stage I silicosis represents a critical turning point for gut microbiome dysbiosis, with specific taxa significantly enriched at this stage.

• Pantoea, Kluyvera, and unclassified Pasteurellaceae were significantly enriched in stage I patients
• These alterations persisted across later stages (stage II and stage III)
• Stage I was identified as the key turning point of microbial dysbiosis based on untargeted fecal metabolomics profiling conducted specifically in stage I patients
• Metabolomic profiling was further conducted in stage I patients as the critical point for microbial dysbiosis

Fecal metabolomic profiles of stage I silicosis patients were distinct from healthy controls, with enrichment in specific metabolic pathways.

• Untargeted fecal metabolomics profiling was conducted in stage I silicosis patients and healthy controls
• Distinct metabolic profiles were enriched in tyrosine metabolism, histidine metabolism, purine metabolism, and arginine biosynthesis pathways
• Metabolomic analysis revealed profiles distinguishing stage I patients from HCs

Strong associations were identified between specific gut microbial taxa and fecal metabolites in early-stage silicosis.

• Correlation analysis identified strong associations between specific taxa and metabolites
• The combined microbial-metabolite signature of Lactobacillus with N-succinyl-2-amino-6-ketopimelate (N-Succinyl-AKP) was among the associations identified
• These microbe-metabolite associations were used to develop diagnostic signatures

Combined microbial-metabolite signatures demonstrated diagnostic potential for distinguishing stage I silicosis patients from healthy controls.

• The combination of Lactobacillus with N-succinyl-2-amino-6-ketopimelate (N-Succinyl-AKP) achieved an area under the curve (AUC) of 0.84
• This AUC was achieved in distinguishing stage I patients from HCs
• The findings highlight the gut microbiome-metabolome combination as a promising source of non-invasive biomarkers for early detection of silicosis