Gut microbiome-metabolome dysregulation in systemic sclerosis: a multi-omics study

Area of Science:

• Microbiome research
• Metabolomics
• Systemic Sclerosis (SSc)

Background:

• The gut microbiome (GM) and plasma metabolites' roles in systemic sclerosis (SSc) are not well understood.
• A disrupted GM-metabolome interface may contribute to SSc pathogenesis.

Purpose of the Study:

• To investigate gut microbiome composition and plasma metabolite profiles in SSc patients.
• To explore the interplay between the GM, plasma metabolites, and SSc.

Main Methods:

• Deep shotgun metagenomic sequencing of fecal samples from 15 SSc patients and 33 controls.
• Untargeted Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) metabolomic profiling of plasma from 14 SSc patients and 30 controls.

Main Results:

• Significant alterations in 11 microbial species and 266 metabolites were observed in SSc patients.
• Elevated Escherichia coli, Lactobacillus mucosae, and Parabacteroides distasonis in SSc; reduced amino acid and lipid-like molecules.
• 168 significant microbiota-metabolite correlations identified, linking disease-enriched species to metabolic dysregulation.

Conclusions:

• This study comprehensively characterizes the disrupted GM-metabolite interface in SSc.
• Findings provide novel perspectives on SSc pathogenesis.
• Identified disruptions may represent potential therapeutic targets for SSc.