Microbial and metabolic multi-omic correlations in systemic sclerosis patients

Area of Science:

• Microbiology
• Immunology
• Metabolomics

Background:

• Intestinal microbiota alterations are linked to systemic autoimmune diseases, but their functional impact remains unclear.
• Systemic sclerosis (SSc) is an autoimmune disease with poorly understood contributing factors.
• Understanding the gut microbiome's role in SSc pathogenesis is crucial.

Purpose of the Study:

• To characterize fecal microbiota and plasma metabolome in SSc patients and healthy controls (HCs).
• To identify microbial and metabolic signatures associated with SSc.
• To investigate the interplay between gut dysbiosis and metabolic alterations in SSc.

Main Methods:

• Fecal microbiota analysis using 16S rRNA gene sequencing.
• Plasma metabolome profiling via high-performance liquid chromatography-mass spectrometry.
• Cross-correlation and data mining of microbial and metabolic datasets.

Main Results:

• A nine-bacteria model distinguished SSc patients from HCs.
• SSc patients exhibited reduced butyrate-producing bacteria and increased proinflammatory genera, notably Desulfovibrio.
• A 17-metabolite model differentiated SSc cases from controls, with key alterations in glycerophospholipid and benzene derivative metabolites.
• Significant interactions were observed between Desulfovibrio and specific metabolites (alpha-N-phenylacetyl-l-glutamine, 2,4-dinitrobenzenesulfonic acid).

Conclusions:

• Intestinal microbiota in SSc is characterized by proinflammatory alterations intertwined with the metabolic state.
• Desulfovibrio plays a significant role in SSc-associated gut dysbiosis, potentially driving intestinal damage and influencing amino acid metabolism.
• These findings highlight the gut microbiome as a potential therapeutic target in SSc.