Heritable Tissue-Specific Gene Expression Associates With Chronic Wound Microbial Species

Area of Science:

• Genomics
• Microbiology
• Wound Healing Research

Background:

• Interpatient variability in chronic wound microbiome composition is poorly understood.
• The influence of host genetics on wound microbiome is an emerging area of research.

Purpose of the Study:

• To investigate how genetically regulated tissue expression influences chronic wound bacterial composition.
• To identify specific genes and pathways linking host genetics to microbial presence in wounds.

Main Methods:

• A microbiome-transcriptome-wide association study was conducted on 509 patients.
• Tissue-specific gene expression was estimated from DNA genotypes.
• Gene expression was associated with relative abundances of bacterial species detected in chronic wounds.

Main Results:

• 251 transcriptional differences at 109 genes significantly explained the abundances of 39 bacterial species found in approximately 63% of wounds.
• Genes were associated with species across multiple tissue types (artery, blood, fibroblast, skeletal muscle, skin, subcutaneous fat, nerve).
• Explained variance in species relative abundance ranged from 5%-36%, with enriched pathways related to collagen, cell signaling, and extracellular matrix interactions.

Conclusions:

• Host genetics may partially determine microbial colonization and infection in chronic wounds.
• This study provides a new perspective on the interplay between host genetics and the wound microbiome.
• Findings suggest potential for personalized approaches in chronic wound management based on genetic profiles.