Minh Ho, Huynh-Nga Nguyen, Minh Van Hoang, Tien Thuy Thi Bui, Bao-Quoc Vu, Truc Huong Thi Dinh, Hoa Thi My Vo, Diana C. Blaydon, Sherif A. Eldirany, Christopher G. Bunick, Chi-Bao Bui
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Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. This case–control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. 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引用次数: 0
摘要
先天性鱼鳞病(CI)是一组罕见的遗传性皮肤病。患者表现为表皮脱屑、裂开、慢性炎症和更易感染。近来,人们对皮肤微生物组的兴趣日益浓厚;因此,我们推测,CI 患者很可能因为各种潜在的皮肤屏障缺陷而表现出表皮微生物异常。在招募的东南亚人种中,我们进行了皮肤元基因组学研究(即全外显子组测序,以捕捉包括真菌、原生生物、古生菌、细菌和病毒在内的整个多基因组图谱),将 36 名 CI 患者(代表 7 个亚型)与 15 名无 CI 家族史的年龄和性别匹配的对照者进行了比较。这项病例对照研究发现了 20 种新型致病变异和 31 种复发性致病变异。微生物组元分析表明,与 CI 相关的微生物种群不同、共生微生物群减少、病原体定植率升高;这些与外周血单核细胞中炎症细胞因子和 Th17- 及 JAK/STAT 信号通路的产生增加有关。在 CI 患者的伤口中,我们发现了微生物群的特定变化和炎症通路的改变,这可能是导致伤口愈合受损的原因。总之,这项研究加深了我们对 CI 微生物、免疫学和分子特性的了解,并为改善 CI 患者的治疗管理提供了重要信息。
Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients
Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. This case–control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.
期刊介绍:
Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics.
Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.