Epidermolysis bullosa (EB) is a rare genetic disease characterized by fragile skin and mucous membranes. It can lead to infections, erosions, and chronic wounds. This study uses whole-genome sequencing to evaluate the functional pathway, microbial diversity, and potential impact on inflammation and wound healing. Oral complications are common in EB subtypes, specifically junctional and dystrophic EB, where dental cavities frequently occur. High sugar intake has been associated with reduced microbial diversity and loss of protective taxa. Targeted microbial analysis may therefore help to guide antimicrobial usage and support probiotic-based treatments to prevent infection and promote wound healing.
This study used saliva samples from 3 patients with oral lesions diagnosed with EB to evaluate the oral microbiome. The samples were collected at home and sent to the laboratory for testing. Total genomic DNA was isolated, quality checked, and processed into Illumina sequencing libraries. The samples were pooled and sequenced using Illumina NovaSeq analysis, which included down-sampling of sequencing reads and aligning against 30,000 bacterial reference genomes and the generation of individualized risk scores for human health and caries disease. The Bristle Comprehensive Oral Microbiome Test performed well, with an AUC of 0.88 for periodontal disease prediction and 0.81 for dental caries.
Whole-genome oral microbiome analysis of EB patients revealed shared species and significant inter-patient differences in microbial composition. Streptococcus mitis dominated sample BHE, while Sample BHU showed unusually high enrichment of Morococcus cerebrosus compared to healthy populations. Sample BHQ showed a more balanced microbial profile with Neisseria sicca as the top species, but with many other species present in moderate proportions, which reflects the greater diversity. Heatmap analysis emphasized that while some core species were common to all patients and others were uniquely abundant in only one individual, this illustrates both shared and individualized microbial signatures.
Alpha diversity was assessed by the Shannon Diversity Index, which confirmed these patterns. BHQ exhibited the highest diversity, reflecting an evenly distributed microbial community with multiple moderately abundant species. BHU showed intermediate diversity, and BHE had the lowest diversity because of the overwhelming predominance of S. mitis. These results highlight that EB patients carry both a core microbiota and individualized microbial imbalances. A balanced profile of BHQ may suggest a healthier state, while the skewed dominance in BHE and unusual enrichment in BHU may reflect dysbiosis linked to EB pathology.
Beta diversity analysis further confirmed these inter-patient differences. Principal Coordinate Analysis (PCoA) revealed that the three samples did not cluster together with BHU due to its unusual dominance of M. cerebrosus, appearing as a distinct outlier. High-percentile species analysis provided further insights, with BHQ harboring several unusual species at above 90th percentile abundance. BHE’s extreme profile centered on S. mitis and unclassified Streptococcus, and BHU was characterized by M. cerebrosus at the 100th percentile.
This result showed that EB patients exhibit distinct oral microbiome structures, which are caused by both core bacteria and unusual overgrowths of specific taxa. Such deviations from population norms may contribute to increased oral disease risk, supporting the need for individualized and microbiome-informed treatment in the management of EB.
Currently, preventive medications like fluoride and silver diamine fluoride help to reduce dental cavities in EB patients. However, this study shows that EB patients differ substantially from healthy controls in their oral microbiota. This suggests the necessity to investigate the pathogenic roles of Actinomyces naeslundii, Neisseria sicca, Streptococcus mitis, and Morococcus cerebrosus. Future studies should investigate the therapeutic methods specific to EB, like probiotics, xylitol, and antimicrobial peptides. It is critical to recognize these microbial patterns to create evidence-based and personalized dental care plans for individuals with EB.
Reference: Cannon M, Baghaie S, Guzman L, Cosantino A, Maurer B. Whole Genome Deep Sequencing of the Oral Microbiome in Epidermolysis Bullosa. Dermato. 2025; 5(3):17. doi:10.3390/dermato5030017
