Intestinal microenvironment dynamics and Sepsis-associated encephalopathy pathophysiology: insights from multi-omics...

Area of Science:

• Microbiology
• Genomics
• Neuroscience

Background:

• Sepsis-associated encephalopathy (SAE) is a severe sepsis complication with unclear gut-brain axis mechanisms.
• Gut dysbiosis is implicated in SAE, but the specific pathways remain elusive.

Purpose of the Study:

• To investigate the gut microenvironment in SAE using multiomics.
• To identify potential gut microbiota and miRNA biomarkers for SAE.

Main Methods:

• Integrated multiomics: 16S rDNA and fecal miRNA sequencing in SAE (n=10) and sepsis (SP, n=20) patients.
• Correlation network analysis to link gut microbiota and miRNAs.
• Machine learning (LASSO, elastic net) for biomarker identification.
• ceRNA network analysis for functional insights and experimental validation of IL-1β.

Main Results:

• Distinct gut microbiota compositional shifts in SAE patients (e.g., increased Neisseria, decreased Fusobacterium).
• 12 differentially expressed fecal miRNAs identified in SAE, with 11 upregulated.
• Significant interactions between fecal miRNAs and gut bacteria found, forming a complex network.
• MiR-30e-3p and miR-223-5p identified as promising diagnostic biomarkers (AUC=0.893).
• Functional analysis linked miRNAs to inflammation and immune regulation pathways, validated by elevated serum IL-1β in SAE patients.

Conclusions:

• This study reveals a novel fecal miRNA-gut microbiota interaction network in SAE pathogenesis.
• MiR-30e-3p and miR-223-5p are highlighted as key mediators and potential diagnostic/therapeutic targets for SAE.