Linking Biofilm-Producing Bacteria to Inflammation and Tissue Destruction: The Role of MMP-13 and Pro-inflammatory Cytokines in Diabetic Foot Ulcers

Abstract

The present study sought to evaluate the relationship of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β), MMP-13, and biofilm-forming bacteria isolates with Wagner grading in diabetic foot ulcers. 

In this analytical cross-sectional study, a total of 100 participants were recruited, and patients were divided into four groups (DFU-strong biofilm-forming (S); DFU-weak/non-biofilm-forming (W); Type 2 diabetes mellitus control without foot ulcer (DC); healthy controls (HC)). Bacterial isolates were identified using standard microbiology methods and the VITEK-2 system. The Congo Red Agar and microtiter plate assays were used to evaluate biofilm formation. IL-6, TNF-α, IL-1β, and MMP-13 in serum were detected by ELISA kits. The ulcer severity condition was graded according to the Wagner grading system.

Pseudomonas aeruginosa and Staphylococcus aureus were the most frequently isolated among highly biofilm-forming isolates. The levels of IL-6, TNF-α, IL-1β, and MMP-13 were significantly higher in patients with strong biofilm-associated diabetic foot ulcers than those observed in the other groups (P < 0.001). Inflammatory cytokines, MMP-13, biofilm strength, and Wagner grade were all significantly positively correlated.

The presence of strong biofilm-forming bacteria isolates was associated with a higher inflammatory response, increased serum MMP-13 levels, and greater diabetic foot ulcer severity. Circulating pro-inflammatory cytokines and MMP-13 may serve as useful biomarkers for assessing ulcer severity and monitoring disease progression. However, further large-scale, multicenter studies are required to validate their potential value and clinical applications in risk stratification and therapeutic guidance.