Antibiotics | Microbiome Analysis of Diabetic Foot Ulcers

This study systematically analyzed the microbiome composition of diabetic foot ulcers (DFU) under different clinical outcomes, revealing the enrichment of Gammaproteobacteria in chronic ulcers and the potential protective role of Corynebacterium in non-infected DFUs, providing new directions for clinical intervention biomarkers.

 

Literature Overview
This article, 'Exploring the Microbiome of Diabetic Foot Ulcers: A Focus on Cases with a Clinical Worse Outcome', published in the journal Antibiotics, reviews and summarizes microbiome composition changes in DFUs under different clinical conditions, focusing on microbial differences associated with ulcer duration, infection status, and bacterial load. The study emphasizes the complexity of DFU microbiomes and highlights that traditional culture-based methods may fail to comprehensively reflect the true microbial structure, whereas molecular techniques (e.g., 16S rRNA sequencing) offer more precise classification.

Background Knowledge
Diabetic foot ulcers (DFUs) are severe complications commonly observed in diabetic patients, often leading to infections, necrosis, and even amputation. The DFU microbiome consists of diverse commensal and pathogenic bacteria, and its dynamic shifts are closely linked to poor wound healing. Previous studies suggest that high bacterial load and enrichment of specific Gram-negative bacteria (e.g., Gammaproteobacteria) may be associated with DFU chronicity, while commensal bacteria (e.g., Corynebacteria) may exhibit pathogen-antagonizing potential. However, the association between DFU microbiome composition and clinical outcomes remains unclear, and studies on microbial interactions are lacking. This research fills the gap in understanding the microbiome-outcome relationship in DFUs by utilizing prospective multi-center cohort data, tissue biopsies, and high-throughput sequencing to explore correlations between microbiome profiles and clinical parameters (e.g., ulcer duration, infection status, bacterial load).

 

 

Research Methods and Experiments
The study included baseline tissue biopsy samples from 65 DFU patients, with 59 cases included in the final analysis. Genomic DNA was extracted from all samples using the QIAamp DNA Mini Kit and sequenced for the V3-V4 regions of the 16S rRNA gene on the Illumina MiSeq platform. High-resolution amplicon sequence variant (ASV) identification was performed using DADA2 and the SILVA database. Alpha and beta diversity analyses were conducted using the Phyloseq R package. Differentially enriched taxa were identified via LEfSE, and group comparisons were performed using Mann–Whitney–Wilcoxon and Kruskal–Wallis tests. The study primarily investigated the impact of DFU duration, infection status, and bacterial load (≥10⁶ CFU/mL) on microbiome composition.

Key Conclusions and Perspectives

• Long-term DFUs (≥4 weeks) showed significantly higher relative abundance of Gammaproteobacteria compared to short-term DFUs (p = 0.02), suggesting its potential association with ulcer chronicity.
• Non-infected DFUs exhibited higher relative abundance of the Actinobacteriota phylum and Corynebacterium genus, particularly in comparison with infected DFUs (0.063 ± 0.14 vs. 0.028 ± 0.13, p = 0.03), indicating that these commensal bacteria may play a protective role in maintaining microbial balance.
• Corynebacterium showed significantly higher relative abundance in DFUs with low Staphylococcus aureus load (<10⁶ CFU/mL) compared to those with high load (0.045 ± 0.08 vs. 0.003 ± 0.01, p = 0.01), suggesting potential inhibitory effects on S. aureus colonization through unknown mechanisms.
• DFUs with high bacterial load showed increased abundance of the Bacteroidota phylum (p = 0.004) and Porphyromonas genus (p = 0.001), while low-load DFUs were enriched with Proteobacteria and Alphaproteobacteria, reflecting niche shifts in low-load conditions.
• Microbiome diversity was significantly higher in high bacterial load groups (p = 0.015), indicating a positive correlation between diversity and load, which may influence ulcer healing potential.

Research Significance and Prospects
This study provides preliminary evidence for clinical applications of DFU microbiome analysis, demonstrating that shifts in specific microbial abundances could serve as potential biomarkers for impaired healing. Future research should explore the regulatory roles of these microbes in DFU treatment to develop microbiome-targeted interventions, such as probiotics or topical microbiota modulators. Additionally, the study supports integrating microbiome analysis into routine DFU management for personalized therapeutic strategies.

 

 

Conclusion
Through systematic microbiome analysis of DFU patients, this study identified associations between poor clinical outcomes and enrichment of specific pathogens (e.g., Gammaproteobacteria) or depletion of commensal genera (e.g., Corynebacterium). These findings suggest that microbiome composition may reflect ulcer healing potential, with certain commensals potentially inhibiting pathogens (e.g., S. aureus). Microbiome analysis may become a critical tool for guiding DFU treatment and enabling personalized interventions. Cyagen Biosciences offers comprehensive services from animal model construction to efficacy evaluation, spanning research areas such as metabolic diseases, neuroscience, and immunology, to advance translational medicine for DFU-related infections and chronic wounds.

 

Laura Soldevila-Boixader, Anna Carrera-Salinas, Isabel Mur, Sara Martí, and Oscar Murillo. Exploring the Microbiome of Diabetic Foot Ulcers: A Focus on Cases with a Clinical Worse Outcome. Antibiotics.