| High-altitude skin diseases,including acne,chronic actinic dermatitis,actinic keratosis,and skin cancer,are prevalent in regions with strong ultraviolet radiation and high altitudes.These conditions have an insidious onset and recurrent course,with limited treatment options and unsatisfactory efficacy.Melanoma,in particular,lacks effective early diagnostic tools,making surgery the only cure for a limited population.Given the current diagnostic and treatment difficulties,there is an urgent need to implement tertiary prevention and early diagnosis,develop novel therapeutic approaches,promote multi-tiered and diverse transformation of existing treatment plans,and find solutions to this issue.The balance of the skin microbiome is crucial to maintaining skin health.Numerous studies have shown that the skin microbiome participates in the development of various chronic inflammatory skin diseases,and some bacterial strains have anti-inflammatory and anti-tumor activity.A comprehensive understanding of the skin microbiome characteristics of healthy individuals is crucial to understanding microbiome communities associated with disease states and is the basis for targeted microbiome intervention for high-altitude skin disease prevention and treatment.However,current research mainly focuses on disease cohorts,European and American populations,and residents of low-altitude regions,leaving the species composition,functional potential,and adaptation mechanisms of skin microbiomes in healthy populations in high-altitude areas largely unknown.To address this knowledge gap,this project utilizes metagenomic sequencing technology to analyze the skin microbiome distribution characteristics and potential functions of 430 healthy volunteers from three ethnic groups residing in Lasa and Shenzhen,China.The volunteers are excluded if they have undergone systemic or local application of antibiotics or corticosteroids in the past six months,and have no history of digestive system diseases,cardiovascular diseases,psychological disorders,acute or chronic skin diseases,or related family history.The skin microbiomes of four anatomical sites(forehead,nose,inner forearm,and periumbilical area)and two physiological environments are analyzed to describe the skin microbiome characteristics of Chinese adults living in high-altitude areas,search for biomarkers for the auxiliary diagnosis of high-altitude skin diseases,and explore new treatment directions.Additionally,the project aims to gather existing global skin microbiome data to promote the construction of a baseline of skin microbiome structure and composition in healthy adult populations.The research methods of this project include metagenomic sequencing technology,bioinformatics analysis,and statistical methods,with a focus on species composition,functional potential,and adaptation mechanisms.The research results of this project can provide important scientific evidence for the prevention and treatment of high-altitude skin diseases and valuable references for related clinical diagnostic and treatment work.Additionally,this research can provide important data support for the construction of a global skin microbiome baseline,providing a broader perspective and richer data resources for skin microbiome research.The primary research contents and results are as follows:1.Systematically reviewed the relationship between the skin microbiome and various skin diseases,as well as the intrinsic and extrinsic factors that affect the skin microbiome,while also delving into the historical development of research strategies used in the field of skin microbiome research.2.To further elucidate the complexity of the skin microbiome,we comprehensively integrated skin microbiome sequencing data from healthy populations across diverse regions,resulting in the construction of the largest intercontinental catalog of prokaryotic genes present in the skin to date.This groundbreaking catalog has effectively challenged the existing phylogenetic tree structure and led to the discovery of a staggering 985 new species,accounting for 49.18% of the total catalog,that have yet to be classified.Moreover,21.84 million genes,comprising a substantial 56% of the total,have yet to be annotated with a functional description,providing an avenue for further exploration into the enigmatic workings of the skin microbiome.3.With bioinformatics techniques,the skin microbiomes of volunteers residing at various altitudes were subjected to analysis to discern the differences in species and functional metabolic pathway.This investigation exposed noteworthy heterogeneity in the microbiome structure and composition of populations at different altitudes,particularly in high-altitude regions,where microbial diversity was lower,and the community was more susceptible to environmental stress.Furthermore,a considerable boost in the function of tetrahydrofolate biosynthesis was observed in the high-altitude microbiome,indicating that related bacterial strains could act as photoprotective agents for the prevention and treatment of high-altitude skin diseases.4.The skin microbiomes of volunteers living in different areas of high-altitude environments were subject to analysis to determine the variations in species and functional metabolic pathway at various taxonomic levels.The findings revealed that Stenotrophomonas maltophilia,Sphingomonas paucimobilis,Corynebacterium accolens,Corynebacterium senegalense,and Staphylococcus epidermidis exhibited uniformity in UV exposure environments.These bacterial species may serve as biological targets for studying the biological effects of UV radiation and as auxiliary diagnostic tools for skin cancer.5.Through an analysis of the correlation between the skin microbiome and host phenotypes,we assessed the relative contributions of different host phenotypes in various anatomical sites.Our results revealed that Bifidobacterium and Corynebacterium may serve as potential biomarkers for different ethnic groups and genders.Based on these findings,we aim to further develop targeted microbiome-derived products tailored to the unique needs of diverse populations in China.6.Predictive analysis of the assembly of microbiota communities in high-altitude and low-altitude environments and different anatomical sites deepened the understanding of the formation process of skin microbiota communities,laying a theoretical foundation for the artificial regulation of microbiota balance.Despite the limitations of small sample sizes and the challenge of low microbial biomass in skin,this study has demonstrated the effectiveness of skin microbiome analysis through metagenomic sequencing.While many findings require validation in larger population cohorts,this study significantly contributes to the understanding of the species diversity,structural composition,and functional differences of skin microbiota in healthy Chinese individuals,particularly those residing in extreme high-altitude environments.As such,it fills a crucial gap in our knowledge of the skin microbiota of humans residing in such locales.Additionally,the valuable dataset resource constructed in this study serves as a critical tool for advancing research in the burgeoning field of skin microbiota. |
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