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

## TL;DR

This study explores how gut microbes and metabolites change in early silicosis, identifying potential non-invasive biomarkers for early detection.

## Contribution

The integration of gut microbiome and fecal metabolome data in silicosis reveals novel microbial-metabolite signatures for early diagnosis.

## Key findings

- Silicosis patients show altered gut microbiome diversity compared to healthy controls.
- Stage I silicosis is marked by enriched Proteobacteria and reduced Bacteroidota, with specific taxa like Pantoea and Kluyvera.
- Microbe-metabolite signatures, such as Lactobacillus with N-Succinyl-AKP, show strong diagnostic potential with an AUC of 0.84.

## 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.

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.