(WHS-L4.06) Detection of predictive human genetic markers of the wound microbiome
Thursday, May 16, 2024
10:30 AM – 11:30 AM East Coast USA Time
Background: Chronic wounds are a burden to millions of patients and healthcare providers worldwide. With rising incidence and prevalence, there is an urgent need to address these non-healing wounds with novel approaches. Impaired wound healing has been shown to be associated with the wound microbiota, as multiple bacterial species are known to contribute to infection and delays in closure. Whether these microbial communities are shaped by host genetics is less understood. Microbiome genome wide association studies (mbGWAS) can provide insight into host genetic factors that may influence bacterial community structure. Previous work reports that the alpha diversity of the chronic wound microbiome is significantly associated with specific human genomic loci and healing.
Methods: To compare wound microbiomes to human genomes, we performed a two-stage mbGWAS using a cohort of 458 patients. Briefly, patients with lower extremity, non-healing wounds were consented from the Southwest Regional Wound Care Center in Lubbock, TX. Buccal swabs and wound samples were collected then genotyped and sequenced for bacterial taxa, respectively. After quality control and genome imputation, mbGWAS was then performed to test association of the relative abundances of multiple wound-relevant bacteria with patient genotype.
Results: We identified bacterial taxa that are repeatedly significantly associated with single nucleotide polymorphisms (SNPs) in the host genome. The significance threshold was set at the Bonferroni adjusted p value of <0.05. Hundreds of unique SNPs across multiple unique bacterial species were repeatedly associated, and these species included both common and uncommon members of wound microbiomes.
Conclusions: Using an mbGWAS design, we reveal human genomic markers that significantly associate to specific bacterial taxa, suggesting a genetic predisposition to colonization or infection by members of the wound microbiome. Future studies will involve translating these mbGWAS findings to functionally validate likely causal SNPs. Identification of correlated biomarkers may provide new mechanistic insight into microbe-host interactions and may serve as predictive risk factors to guide personalized management for chronic wound patients.