Omeir Khalid, Ancira Jacob, Gabrilska Rebecca, Tipton Craig, Miller Clint, Noe Ashley, Subasinghe Kumudu, Rowe Megan, Phillips Nicole, Wolcott Joseph, Philips Caleb D
Department of Biological Sciences, Texas Tech University, Lubbock, Texas, USA.
RTL Genomics, MicroGenDX, Lubbock, Texas, USA.
Wound Repair Regen. 2025 Jul-Aug;33(4):e70055. doi: 10.1111/wrr.70055.
The reasons for interpatient variability in chronic wound microbiome composition are thought to be complex but are poorly known. To investigate how patients' genetically regulated tissue expression may influence chronic wound bacterial composition, we performed a microbiome-transcriptome-wide association study. This approach involved estimating for 509 patients their tissue-specific gene expression from DNA genotypes, followed by associating gene expression to the relative abundances of species detected in their wounds as provided on clinical reports to the physician. Comparisons to artery, blood, fibroblast, skeletal muscle, skin, subcutaneous fat, and nerve tissue resulted in 251 transcriptional differences at 109 genes significantly explaining abundances of 39 different species. Overall, these species were detected in ~63% of wounds. A similar number of associations per tissue was observed (range 31-39), and many genes were associated at multiple tissues in distinct ways. The cumulative variance across loci for species relative abundance explained ranged from ~5%-36%, depending on species. Although the same gene was almost never associated with more than one species, ~14% of enriched pathways were independently enriched for multiple species, which may reflect the diversity of ways microbes interact with partially overlapping attributes of the wound bed. Commonly enriched pathways pertained to collagen formation and modification, cell signalling, cytoskeletal dynamics, interactions with extracellular matrix, transmembrane proteins, amongst others. This work expands the new perspective that individual genetics may partially determine microbial colonisation and infection.
慢性伤口微生物群组成的患者间变异性原因被认为很复杂，但目前了解甚少。为了研究患者的基因调控组织表达如何影响慢性伤口细菌组成，我们进行了一项微生物组 - 转录组全关联研究。该方法包括根据DNA基因型估计509名患者的组织特异性基因表达，然后将基因表达与临床报告中提供给医生的伤口中检测到的物种相对丰度相关联。与动脉、血液、成纤维细胞、骨骼肌、皮肤、皮下脂肪和神经组织的比较导致109个基因出现251个转录差异，这些差异显著解释了39种不同物种的丰度。总体而言，这些物种在约63%的伤口中被检测到。每个组织观察到的关联数量相似（范围为31 - 39），并且许多基因以不同方式在多个组织中存在关联。物种相对丰度在各基因座上的累积方差解释范围约为5% - 36%，具体取决于物种。虽然同一个基因几乎从不与多个物种相关联，但约14%的富集途径独立富集了多种物种，这可能反映了微生物与伤口床部分重叠属性相互作用方式的多样性。常见的富集途径涉及胶原蛋白的形成和修饰、细胞信号传导、细胞骨架动力学、与细胞外基质的相互作用、跨膜蛋白等。这项工作拓展了新的观点，即个体遗传学可能部分决定微生物的定植和感染。
