Khadka Veda D, Markey Laura, Boucher Magalie, Lieberman Tami D
Institute for Medical Engineering & Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Civil and Environmental Engineering, School of Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
The Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
J Invest Dermatol. 2024 Nov;144(11):2541-2552.e10. doi: 10.1016/j.jid.2024.03.033. Epub 2024 Apr 10.
The skin microbiome can both trigger beneficial immune stimulation and pose a potential infection threat. Previous studies have shown that colonization of mouse skin with the model human skin commensal Staphylococcus epidermidis is protective against subsequent excisional wound or pathogen challenge. However, less is known about concurrent skin damage and exposure to commensal microbes, despite growing interest in interventional probiotic therapy. In this study, we address this open question by applying commensal skin bacteria at a high dose to abraded skin. Although depletion of the skin microbiome through antibiotics delayed repair from damage, probiotic-like application of commensals-including the mouse commensal Staphylococcus xylosus, 3 distinct isolates of S. epidermidis, and all other tested human skin commensals-also significantly delayed barrier repair. Increased inflammation was observed within 4 hours of S. epidermidis exposure and persisted through day 4, at which point the skin displayed a chronic wound-like inflammatory state with increased neutrophil infiltration, increased fibroblast activity, and decreased monocyte differentiation. Transcriptomic analysis suggested that the prolonged upregulation of early canonical proliferative pathways inhibited the progression of barrier repair. These results highlight the nuanced role of members of the skin microbiome in modulating barrier integrity and indicate the need for caution in their development as probiotics.
皮肤微生物群既能引发有益的免疫刺激，也会构成潜在的感染威胁。先前的研究表明，用典型的人类皮肤共生菌表皮葡萄球菌定殖小鼠皮肤，可保护其免受后续切除伤口或病原体攻击。然而，尽管人们对介入性益生菌疗法的兴趣与日俱增，但对于同时存在的皮肤损伤和共生微生物暴露情况，我们了解得还比较少。在本研究中，我们通过将高剂量的共生皮肤细菌应用于磨损皮肤来解决这个悬而未决的问题。虽然通过抗生素消耗皮肤微生物群会延迟损伤修复，但类似益生菌的共生菌应用——包括小鼠共生菌木糖葡萄球菌、表皮葡萄球菌的3种不同分离株以及所有其他测试的人类皮肤共生菌——也会显著延迟屏障修复。在暴露于表皮葡萄球菌后的4小时内观察到炎症增加，并持续到第4天，此时皮肤呈现出慢性伤口样的炎症状态，中性粒细胞浸润增加、成纤维细胞活性增加且单核细胞分化减少。转录组分析表明，早期典型增殖途径的长期上调抑制了屏障修复的进程。这些结果突出了皮肤微生物群成员在调节屏障完整性方面的细微作用，并表明在将它们开发为益生菌时需要谨慎。
