skin microbiome

皮肤微生物组
  • 文章类型: Journal Article
    背景:皮肤微生物群对于维持健康至关重要。光老化是影响皮肤稳态的主要环境因素,但它是否会影响皮肤微生物群仍不清楚。
    目的:本研究的目的是研究光老化与皮肤微生物组之间的关系。
    方法:一组高级公交车司机被认为是长期单侧紫外线(UV)照射的人群。进行16SrRNA扩增子测序以评估其面部不同侧的皮肤微生物组成变化。通过光老化豚鼠模型进一步检查了光老化群体的微生物组特征,通过高通量测序和逆转录聚合酶链反应分析微生物代谢产物与衰老相关细胞因子之间的相关性。
    结果:光老化降低了人类皮肤中包括Georgenia和Thermobifida在内的微生物的相对丰度,并下调了皮肤微生物来源的抗氧化代谢产物如外泌素的产生。在动物模型中,紫外线照射后,表皮和真皮中的乳酸菌和链球菌丰度下降,导致皮肤抗氧化分子水平较低,导致胶原蛋白降解因子基质金属蛋白酶(MMP)-1和MMP-2以及白细胞介素(IL)-1β和IL-6等炎症因子的表达升高。
    结论:皮肤微生物特征影响光老化,微生物来源的抗氧化代谢产物的损失损害皮肤细胞并加速老化过程。因此,基于微生物组的疗法可能具有延缓皮肤老化的潜力。
    BACKGROUND: Skin microbiota is essential for health maintenance. Photoaging is the primary environmental factor that affects skin homeostasis, but whether it influences the skin microbiota remains unclear.
    OBJECTIVE: The objective of this study is to investigate the relationship between photoaging and skin microbiome.
    METHODS: A cohort of senior bus drivers was considered as a long-term unilateral ultraviolet (UV) irradiated population. 16S rRNA amplicon sequencing was conducted to assess skin microbial composition variations on different sides of their faces. The microbiome characteristics of the photoaged population were further examined by photoaging guinea pig models, and the correlations between microbial metabolites and aging-related cytokines were analyzed by high-throughput sequencing and reverse transcription polymerase chain reaction.
    RESULTS: Photoaging decreased the relative abundance of microorganisms including Georgenia and Thermobifida in human skin and downregulated the generation of skin microbe-derived antioxidative metabolites such as ectoin. In animal models, Lactobacillus and Streptobacillus abundance in both the epidermis and dermis dropped after UV irradiation, resulting in low levels of skin antioxidative molecules and leading to elevated expressions of the collagen degradation factors matrix metalloproteinase (MMP)-1 and MMP-2 and inflammatory factors such as interleukin (IL)-1β and IL-6.
    CONCLUSIONS: Skin microbial characteristics have an impact in photoaging and the loss of microbe-derived antioxidative metabolites impairs skin cells and accelerates the aging process. Therefore, microbiome-based therapeutics may have potential in delaying skin aging.
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  • 文章类型: Journal Article
    皮肤微生物组代表了当今高度关注的话题。多项研究表明皮肤微生物组在不同皮肤病学中的重要性,强调皮肤微生物在皮肤疾病的发病机理或预后中的可能意义。牛皮癣是一种常见的炎症性皮肤病,在全球人口中患病率很高。皮肤微生物组在牛皮癣中的作用可以解释这种无法治愈的皮肤病的许多致病理论和治疗目标。我们对皮肤微生物组的特征感兴趣,尤其是在Galati的三级皮肤病中心就诊的银屑病患者,罗马尼亚,反映在我们目前的研究中,本文对其初步结果进行了讨论。使用三种类型的皮肤取样技术(拭子,胶带,和穿刺活检),我们试图描述牛皮癣患者和健康个体皮肤中的微生物特征。这项研究是使用基于培养的探针进行的,使用MALDI-TOF质谱仪设备进行分析。我们的初步结果表明,在银屑病患者的周围区域观察到最大的多样性。最低的皮肤多样性是通过对银屑病斑块进行采样获得的。这些结果与牛皮癣中皮肤微生物组的其他研究相似。在所有研究组中发现的最常见的微生物是葡萄球菌:表皮葡萄球菌,人葡萄球菌,和金黄色葡萄球菌。从这项研究中分析了每个人的生活环境,我们的初步结果表明与其他研究不同的结果,因为在城市环境中观察到比在农村生活地区更高的多样性和异质性。关于性别差异,我们的初步结果显示,男性参与者的皮肤微生物组比女性参与者有更高的数量和质量变化,与其他牛皮癣皮肤微生物组研究的结果相反。鉴于这些初步结果,我们可以得出结论,通过研究银屑病患者和健康对照人群的皮肤微生物组,我们发现了重要的差异,根据我们的知识,还没有从这个角度进行研究。我们的结果显示了东欧人群皮肤微生物组的重要特征,文化和环境生活习惯会影响皮肤微生物组。
    The cutaneous microbiome represents a topic of high interest nowadays. Multiple studies have suggested the importance of the skin microbiome in different dermatological pathologies, highlighting the possible implications of cutaneous microorganisms in either the pathogenesis or prognosis of skin maladies. Psoriasis represents a common inflammatory skin disease, with a high prevalence in the worldwide population. The role of the cutaneous microbiome in psoriasis could explain a number of pathogenic theories and treatment objectives of this incurable skin disease. Our interest in the characteristics of the cutaneous microbiome, especially in psoriatic patients who attended a tertiary dermatological centre in Galati, Romania, is reflected in our current study, of which the preliminary results are discussed in this article. Using three types of skin sampling techniques (swabs, adhesive tape, and punch biopsies), we tried to characterise the microorganisms harboured in the skin of psoriatic patients and healthy individuals. This study was performed using culture-based probes, which were analysed using MALDI-TOF mass spectrometer equipment. Our preliminary results suggested that the greatest diversity was observed in the perilesional areas of psoriatic patients. The lowest cutaneous diversity was obtained from sampling psoriatic plaques. These results are similar to other studies of the cutaneous microbiome in psoriasis. The most frequent microorganisms found in all groups studied were of the Staphylococcus species: Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus aureus. Analysing the living environment of each individual from this study, our preliminary results suggested different results from other studies, as higher diversity and heterogenicity was observed in urban environments than in rural living areas. Regarding the differences between sexes, our preliminary results showed higher quantitative and qualitative changes in the skin microbiome of male participants than female participants, opposite to the results found in other studies of the cutaneous microbiome in psoriasis. Given these preliminary results, we can conclude that we have found important differences by studying the cutaneous microbiome of psoriatic patients and healthy control individuals from a population that, to our knowledge, has not been yet studied from this point of view. Our results showed important characteristics of the skin microbiome in an Eastern European population, where cultural and environmental living habits could influence the cutaneous microbiome.
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  • 文章类型: Journal Article
    皮肤微生物组随着个体年龄的变化仅部分已知。为了更好地了解衰老的影响,对100名健康女性白种人志愿者的面部皮肤拭子进行了全基因组测序分析,这些志愿者按年龄和皱纹等级分组.通过问卷调查和非侵入性生物物理测量收集志愿者的元数据。使用简单模型和生物学统计模型来显示两个年龄组之间皮肤微生物群组成的差异。分类和非度量多维尺度分析表明,老年人组(≥55岁)的皮肤微生物组更加多样化。放线菌也显著减少,即在痤疮切杆菌中,和棒杆菌的增加。属于Firmicutes门的某些链球菌和葡萄球菌物种以及属于Proteobacteria门的物种增加。在18-35岁的年轻人组中,微生物组的特征是痤疮杆菌和乳酸杆菌的比例明显更高,最引人注目的是,卷曲乳杆菌。使用GO术语的功能分析显示,年轻群体具有参与生物和代谢过程以及先天皮肤微生物组保护的基因的更高的显著表达。对观察到的与年龄相关的影响的更好理解将支持对皮肤微生物组在抗衰老保护中的影响的研究。
    The change in the skin microbiome as individuals age is only partially known. To provide a better understanding of the impact of aging, whole-genome sequencing analysis was performed on facial skin swabs of 100 healthy female Caucasian volunteers grouped by age and wrinkle grade. Volunteers\' metadata were collected through questionnaires and non-invasive biophysical measurements. A simple model and a biological statistical model were used to show the difference in skin microbiota composition between the two age groups. Taxonomic and non-metric multidimensional scaling analysis showed that the skin microbiome was more diverse in the older group (≥55 yo). There was also a significant decrease in Actinobacteria, namely in Cutibacterium acnes, and an increase in Corynebacterium kroppenstedtii. Some Streptococcus and Staphylococcus species belonging to the Firmicutes phylum and species belonging to the Proteobacteria phylum increased. In the 18-35 yo younger group, the microbiome was characterized by a significantly higher proportion of Cutibacterium acnes and Lactobacillus, most strikingly, Lactobacillus crispatus. The functional analysis using GO terms revealed that the young group has a higher significant expression of genes involved in biological and metabolic processes and in innate skin microbiome protection. The better comprehension of age-related impacts observed will later support the investigation of skin microbiome implications in antiaging protection.
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  • 文章类型: Journal Article
    特应性皮炎(AD)中皮肤微生物组被破坏。现有的研究集中在中度到重度,未用药的疾病。
    我们试图调查基于宏基因组和培养的细菌菌株水平差异,药物AD及其对人角质形成细胞(HKs)的影响。
    从20名儿科参与者(11名AD患者在病变和非病变部位取样,9名年龄和性别匹配的对照)收集前臂前臂的皮肤拭子。参与者主要患有轻度至中度AD并维持药物使用。处理样品用于微生物宏基因组测序和细菌分离。测试鉴定为金黄色葡萄球菌的分离株的肠毒素产生。用来自代表性葡萄球菌物种的无细胞条件培养基处理HK培养物以测量屏障效应。
    宏基因组测序确定了AD组和对照组之间微生物组组成的显着差异。在葡萄球菌的物种和菌株水平上观察到差异,仅在AD参与者中发现金黄色葡萄球菌,对照和AD拭子之间的表皮葡萄球菌菌株存在差异。这些菌株显示出毒素基因存在的差异,这在体外证实了金黄色葡萄球菌肠毒素。来自患有最严重AD的参与者的菌株产生的肠毒素B水平比其他菌株高100倍以上(P<.001)。菌株对HK代谢和屏障功能也表现出不同的影响。
    来自葡萄球菌菌株的毒素基因的菌株水平差异可能解释了对HK的不同影响,金黄色葡萄球菌和非金黄色葡萄球菌菌株对生存力和屏障功能产生负面影响。这些差异可能在AD发病机理中很重要。
    UNASSIGNED: The skin microbiome is disrupted in atopic dermatitis (AD). Existing research focuses on moderate to severe, unmedicated disease.
    UNASSIGNED: We sought to investigate metagenomic- and culture-based bacterial strain-level differences in mild, medicated AD and the effects these have on human keratinocytes (HKs).
    UNASSIGNED: Skin swabs from anterior forearms were collected from 20 pediatric participants (11 participants with AD sampled at lesional and nonlesional sites and 9 age- and sex-matched controls). Participants had primarily mild to moderate AD and maintained medication use. Samples were processed for microbial metagenomic sequencing and bacterial isolation. Isolates identified as Staphylococcus aureus were tested for enterotoxin production. HK cultures were treated with cell-free conditioned media from representative Staphylococcus species to measure barrier effects.
    UNASSIGNED: Metagenomic sequencing identified significant differences in microbiome composition between AD and control groups. Differences were seen at the species and strain levels for Staphylococci, with S aureus found only in participants with AD and differences in Staphylococcus epidermidis strains between control and AD swabs. These strains showed differences in toxin gene presence, which was confirmed in vitro for S aureus enterotoxins. The strain from the participant with the most severe AD produced enterotoxin B levels more than 100-fold higher than the other strains (P < .001). Strains also displayed differential effects on HK metabolism and barrier function.
    UNASSIGNED: Strain-level differences in toxin genes from Staphylococcus strains may explain varying effects on HK, with S aureus and non-aureus strains negatively affecting viability and barrier function. These differences are likely important in AD pathogenesis.
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  • 文章类型: Journal Article
    皮肤微生物组不断暴露于太阳辐射(SR),对健康的影响有据可查。然而,了解SR对宿主相关皮肤共生的影响仍然是新生的。这篇综述调查了关于SR对皮肤微生物组影响的现有知识,并提出了保护皮肤完整性和微生物组平衡的创新防晒方法。一组皮肤光损伤专家对来自PubMed和ResearchGateway的122篇文章进行了全面审查。关键术语包括皮肤微生物组,光保护,光损伤,皮肤癌,紫外线辐射,太阳辐射,皮肤共生,皮肤保护,和前/益生菌。专家提供了对新型防晒产品的见解,这些产品不仅旨在保护皮肤,还旨在减轻SR对皮肤微生物组的影响。关于SR对皮肤微生物组的影响的现有文献是有限的。SR暴露可以改变微生物组组成,可能导致菌群失调,受损的皮肤屏障功能,和免疫系统激活。目前的防晒方法通常忽视微生物组的考虑。同时优先考虑皮肤和微生物组健康的量身定制的防晒产品可能会增强对SR引起的皮肤状况的防御。通过保护皮肤和微生物群,这些专业产品可以减轻与SR暴露相关的菌群失调风险,增强皮肤防御机制并降低SR介导的皮肤问题的可能性。
    The skin microbiome undergoes constant exposure to solar radiation (SR), with its effects on health well-documented. However, understanding SR\'s influence on host-associated skin commensals remains nascent. This review surveys existing knowledge on SR\'s impact on the skin microbiome and proposes innovative sun protection methods that safeguard both skin integrity and microbiome balance. A team of skin photodamage specialists conducted a comprehensive review of 122 articles sourced from PubMed and Research Gateway. Key terms included skin microbiome, photoprotection, photodamage, skin cancer, ultraviolet radiation, solar radiation, skin commensals, skin protection, and pre/probiotics. Experts offered insights into novel sun protection products designed not only to shield the skin but also to mitigate SR\'s effects on the skin microbiome. Existing literature on SR\'s influence on the skin microbiome is limited. SR exposure can alter microbiome composition, potentially leading to dysbiosis, compromised skin barrier function, and immune system activation. Current sun protection methods generally overlook microbiome considerations. Tailored sun protection products that prioritize both skin and microbiome health may offer enhanced defense against SR-induced skin conditions. By safeguarding both skin and microbiota, these specialized products could mitigate dysbiosis risks associated with SR exposure, bolstering skin defense mechanisms and reducing the likelihood of SR-mediated skin issues.
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  • 文章类型: Journal Article
    炎症性皮肤病,像特应性湿疹(特应性皮炎,AD),影响全球儿童和成人。在AD中,皮肤屏障在多个层面上受损。潜在因素包括遗传,化学,免疫学,和微生物成分。AD中增加的皮肤pH是改变的微生物微环境的一部分,该微生物微环境促进了金黄色葡萄球菌的皮肤微生物组的过度生长(S.金黄色葡萄球菌)。毒力因子的分泌,比如毒素和蛋白酶,金黄色葡萄球菌进一步加剧了皮肤屏障的缺乏,并且使已经扭曲的免疫应答失衡。皮肤共生细菌,然而,可以通过群体感应系统抑制金黄色葡萄球菌的生长和致病性。因此,恢复健康的皮肤微生物组可能有助于AD的缓解诱导。这篇综述讨论了通过调节皮肤pH来靶向皮肤微生物组的直接和间接方法,UV处理,和前,pro-,和postbiotics。此外,探索性技术,如皮肤微生物组移植,臭氧疗法,讨论了噬菌体疗法。最后,我们总结了通过靶向免疫调节改变疾病和微生物组的最新发现,全身治疗和生物制剂。我们认为,靶向皮肤微生物组应被认为是未来成功治疗AD的关键组成部分。
    Inflammatory skin diseases such as atopic eczema (atopic dermatitis [AD]) affect children and adults globally. In AD, the skin barrier is impaired on multiple levels. Underlying factors include genetic, chemical, immunologic, and microbial components. Increased skin pH in AD is part of the altered microbial microenvironment that promotes overgrowth of the skin microbiome with Staphylococcus aureus. The secretion of virulence factors, such as toxins and proteases, by S aureus further aggravates the skin barrier deficiency and additionally disrupts the balance of an already skewed immune response. Skin commensal bacteria, however, can inhibit the growth and pathogenicity of S aureus through quorum sensing. Therefore, restoring a healthy skin microbiome could contribute to remission induction in AD. This review discusses direct and indirect approaches to targeting the skin microbiome through modulation of the skin pH; UV treatment; and use of prebiotics, probiotics, and postbiotics. Furthermore, exploratory techniques such as skin microbiome transplantation, ozone therapy, and phage therapy are discussed. Finally, we summarize the latest findings on disease and microbiome modification through targeted immunomodulatory systemic treatments and biologics. We believe that targeting the skin microbiome should be considered a crucial component of successful AD treatment in the future.
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  • 文章类型: Journal Article
    金黄色葡萄球菌由于其致病性和产生抗生素抗性的能力而经常被强调为新药研究的优先事项。凝固酶阴性葡萄球菌(CoNS)是皮肤和鼻孔的常驻菌群。先前的研究已经证实了它们通过产生生物活性物质来杀死和防止金黄色葡萄球菌定植的能力。这项研究筛选了一组37种CoNS抑制耐甲氧西林金黄色葡萄球菌(MRSA)生长的能力。延迟拮抗试验,生长曲线,和使用过夜CoNS培养物的无细胞上清液进行的抗生物膜测试表明抗微生物和抗生物膜对MRSA指标的作用。对11种CoNS分离株的全基因组测序和BAGEL4分析入围了它们对MRSA的抑制作用,从而鉴定出两种具有完全推定的细菌素操纵子的菌株。预测操纵子编码努卡星变体和新的结语变体。从这一点来看,菌株人葡萄球菌C14和表皮葡萄球菌C33成为调查的重点。通过HPLC,分别从C14和C33的培养物中分离出与先前表征的努卡星KQU-131相同的肽和新的epilancin变体。质谱证实了活性部分中每种肽的存在。草坪上斑点试验表明,两种细菌素都可以抑制MRSA指示剂的生长。鉴定具有临床相关活性的天然产物在当今抗生素耐药性不断升级和抗生素管道枯竭的气候中很重要。这些发现还强调了CoNS可能作为具有抗关键病原体活性的生物活性物质来源的预期作用。
    Staphylococcus aureus is frequently highlighted as a priority for novel drug research due to its pathogenicity and ability to develop antibiotic resistance. Coagulase-negative staphylococci (CoNS) are resident flora of the skin and nares. Previous studies have confirmed their ability to kill and prevent colonization by S. aureus through the production of bioactive substances. This study screened a bank of 37 CoNS for their ability to inhibit the growth of methicillin-resistant S. aureus (MRSA). Deferred antagonism assays, growth curves, and antibiofilm testing performed with the cell-free supernatant derived from overnight CoNS cultures indicated antimicrobial and antibiofilm effects against MRSA indicators. Whole genome sequencing and BAGEL4 analysis of 11 CoNS isolates shortlisted for the inhibitory effects they displayed against MRSA led to the identification of two strains possessing complete putative bacteriocin operons. The operons were predicted to encode a nukacin variant and a novel epilancin variant. From this point, strains Staphylococcus hominis C14 and Staphylococcus epidermidis C33 became the focus of the investigation. Through HPLC, a peptide identical to previously characterized nukacin KQU-131 and a novel epilancin variant were isolated from cultures of C14 and C33, respectively. Mass spectrometry confirmed the presence of each peptide in the active fractions. Spot-on-lawn assays demonstrated both bacteriocins could inhibit the growth of an MRSA indicator. The identification of natural products with clinically relevant activity is important in today\'s climate of escalating antimicrobial resistance and a depleting antibiotic pipeline. These findings also highlight the prospective role CoNS may play as a source of bioactive substances with activity against critical pathogens.
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  • 文章类型: Journal Article
    人体皮肤作为身体和外部环境之间的保护屏障。角质层(SC)中的皮肤微生物组和细胞间脂质对于维持皮肤屏障功能至关重要。然而,皮肤细菌和脂质之间的相互作用尚未完全了解。在这项研究中,我们在57名健康参与者的队列中,对前臂和面部的皮肤微生物组和SC血脂谱进行了表征.16SrRNA基因测序显示皮肤微生物组成在体位和性别之间存在显著差异。女性前臂样本具有最高的微生物多样性。人葡萄球菌的相对丰度,黄体微球菌,结核杆菌,Finegoldiamagna,和Moraxellaceaesp.前臂明显高于面部。通过系统发育对16SrRNA基因测序的预测功能分析通过不受保护状态的重建(PICRUSt2)和ANCOM-BC进行的群落调查显示,身体位置或性别之间的细菌代谢途径谱不同,并确定了271种不同的途径,包括精氨酸和多胺生物合成,分支酸盐生物合成途径,在女性前臂中更丰富,和硫氧化途径,在男性脸上更丰富。SC脂质分布在身体位置之间也不同。总游离脂肪酸(FFA),胆固醇硫酸盐和鞘氨醇在脸上更丰富。二氢-/6-羟基/植物神经酰胺在前臂中更丰富。16SrRNA基因测序和脂质的相关性分析揭示了细菌和皮肤脂质之间的新相互作用。香农熵和人源与FFA呈负相关,胆固醇硫酸盐和鞘氨醇;同时与二氢-/6-羟基/植物神经酰胺呈正相关。预测途径谱和脂质识别的参与氨基酸代谢途径的相关性,碳水化合物降解,芳香族化合物代谢和脂肪酸降解代谢与二氢-/6-羟基/植物-神经酰胺呈正相关,与FFA呈负相关,胆固醇硫酸盐和鞘氨醇。这项研究提供了有关皮肤微生物组和脂质之间潜在相关性的见解。
    Human skin acts as a protective barrier between the body and the external environment. Skin microbiome and intercellular lipids in the stratum corneum (SC) are essential for maintaining skin barrier function. However, the interplay between skin bacteria and the lipids is not fully understood. In this study, we characterized the skin microbiome and SC lipid profiles from the forearm and face in a cohort of 57 healthy participants. 16S rRNA gene sequencing showed the skin microbial composition is significantly different between body locations and genders. Female forearm samples have the highest microbial diversity. The relative abundance of Staphylococcus hominis, Micrococcus luteus, Corynebacterium tuberculostearicum, Finegoldia magna, and Moraxellaceae sp. are significantly higher in the forearm than the face. The predictive functional analysis of 16S rRNA gene sequencing by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) and ANCOM-BC showed different bacterial metabolic pathway profiles between body locations or genders, and identified 271 differential pathways, including arginine and polyamine biosynthesis, chorismate biosynthesis pathways, which are more abundant in the female forearm, and sulfur oxidation pathway, which is more abundant in the male face. The SC lipid profiles differ between the body locations as well. Total free fatty acids (FFA), cholesterol sulfate and sphingosine are more abundant in the face. Dihydro-/6-hydroxy/phyto-ceramides are more abundant in the forearm. The correlation analysis of 16S rRNA gene sequencing and lipids revealed novel interplay between the bacteria and skin lipids. Shannon entropy and S. hominis negatively correlated with FFA, cholesterol sulfate and sphingosine; while positively correlated with dihydro-/6-hydroxy/phyto-ceramides. The correlation of predictive pathway profiles and lipids identified pathways involved in amino acids metabolism, carbohydrates degradation, aromatic compounds metabolism and fatty acid degradation metabolism are positively correlated with dihydro-/6-hydroxy/phyto-ceramides and negatively correlated with FFA, cholesterol sulfate and sphingosine. This study provides insights on the potential correlation between skin microbiome and lipids.
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  • 文章类型: Journal Article
    皮肤T细胞淋巴瘤(CTCL)是一组引起慢性炎症的皮肤归巢T细胞的淋巴增殖性疾病。这些疾病会导致免疫环境受损,这导致严重的感染和/或败血症由于菌群失调。在这项研究中,我们阐明了光疗治疗方案期间CTCL中发生的宿主-微生物相互作用,并确定了皮肤微生物群的调节是否可以有益地影响CTCL的病程.将EL4T细胞淋巴瘤细胞皮内移植到C57BL/6小鼠的背部。在存在或不存在局部抗生素治疗(新霉素,杆菌肽,和硫酸多粘菌素B)作为佐剂。评估皮肤的微生物定植与疾病严重程度和肿瘤生长相关。三联抗生素治疗显着延迟肿瘤发生(p=0.026),这延长了小鼠的存活时间(p=0.033)。分配给光疗剂PUVA,UVB,或者这些都没有,随着抗生素干预,显著降低肿瘤生长(p=0.0327,p≤0.0001,p≤0.0001)。使用Bray-Curtis模型计算的β多样性指数表明,抗生素处理后微生物种群显着差异(p=0.001)。通过抗生素治疗调节皮肤微生物组后,我们看到共生梭菌物种的增加,例如,落叶松科sp.(p=0.0008),反刍动物科。(p=0.0001)。,Blautiasp.(p=0.007),兼性病原体棒状杆菌的显着减少。(p=0.0009),Pelomonassp.(p=0.0306),链球菌。(p≥0.0001),假单胞菌。(p=0.0358),和Cutubacteriumsp.(p=0.0237)。有趣的是,我们观察到金黄色葡萄球菌的频率显着下降(p=0.0001),但葡萄球菌属的整体检测频率增加,表明抗生素治疗有助于恢复微生物平衡并增加非致病性葡萄球菌种群的数量。这些研究结果表明,通过局部抗生素治疗来调节微生物群有助于通过减少病原微生物的数量来恢复微生物平衡,which,反过来,减少慢性炎症,延迟肿瘤生长,并提高CTCL模型的生存率。这些发现支持在CTCL的疾病过程中调节微生物环境的基本原理,并表明其治疗潜力。
    Cutaneous T-cell lymphomas (CTCL) are a group of lymphoproliferative disorders of skin-homing T cells causing chronic inflammation. These disorders cause impairment of the immune environment, which leads to severe infections and/or sepsis due to dysbiosis. In this study, we elucidated the host-microbial interaction in CTCL that occurs during the phototherapeutic treatment regime and determined whether modulation of the skin microbiota could beneficially affect the course of CTCL. EL4 T-cell lymphoma cells were intradermally grafted on the back of C57BL/6 mice. Animals were treated with conventional therapeutics such as psoralen + UVA (PUVA) or UVB in the presence or absence of topical antibiotic treatment (neomycin, bacitracin, and polymyxin B sulphate) as an adjuvant. Microbial colonisation of the skin was assessed to correlate with disease severity and tumour growth. Triple antibiotic treatment significantly delayed tumour occurrence (p = 0.026), which prolonged the survival of the mice (p = 0.033). Allocation to phototherapeutic agents PUVA, UVB, or none of these, along with antibiotic intervention, reduced the tumour growth significantly (p = 0.0327, p ≤ 0.0001, p ≤ 0.0001 respectively). The beta diversity indices calculated using the Bray-Curtis model showed that the microbial population significantly differed after antibiotic treatment (p = 0.001). Upon modulating the skin microbiome by antibiotic treatment, we saw an increase in commensal Clostridium species, e.g., Lachnospiraceae sp. (p = 0.0008), Ruminococcaceae sp. (p = 0.0001)., Blautia sp. (p = 0.007) and a significant reduction in facultative pathogens Corynebacterium sp. (p = 0.0009), Pelomonas sp. (p = 0.0306), Streptococcus sp. (p ≥ 0.0001), Pseudomonas sp. (p = 0.0358), and Cutibacterium sp. (p = 0.0237). Intriguingly, we observed a significant decrease in Staphylococcus aureus frequency (p = 0.0001) but an increase in the overall detection frequency of the Staphylococcus genus, indicating that antibiotic treatment helped regain the microbial balance and increased the number of non-pathogenic Staphylococcus populations. These study findings show that modulating microbiota by topical antibiotic treatment helps to restore microbial balance by diminishing the numbers of pathogenic microbes, which, in turn, reduces chronic inflammation, delays tumour growth, and increases survival rates in our CTCL model. These findings support the rationale to modulate the microbial milieu during the disease course of CTCL and indicate its therapeutic potential.
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  • 文章类型: Journal Article
    特应性皮炎(AD)是最常见的炎症性皮肤病之一。皮肤微生态失衡是AD发病的重要因素,但其与人类相互作用的潜在机制尚不清楚。
    进行16SrRNA基因测序以揭示皮肤微生物群动态。通过LC-MS代谢组学追踪皮肤代谢物的变化。然后,我们通过分析相应皮肤相关样品中皮肤细菌群落和代谢物之间的相关性来探索相互作用的潜在机制。
    对来自18名AD患者和18名健康志愿者(HVs)的样品进行16SrRNA基因测序和LC-MS代谢组学。AD患者皮肤细菌群落的菌群失调,物种丰富度和均匀度降低。葡萄球菌属的相对丰度在AD中显著增加,而丙酸杆菌属和Brevundimonas属的丰度显着下降。健康女性葡萄球菌属的相对丰度明显高于健康男性,而在有或没有病变的AD患者中没有差异。AD状态的影响,性别和皮疹的存在或不存在对人均代谢产物数量差异的影响依次减少。在AD患者中,嘌呤代谢和苯丙氨酸代谢途径中涉及的多种代谢物(例如黄嘌呤/黄嘌呤和L-苯丙氨酸/反式肉桂酸酯)增加。这些趋势在女性AD患者和女性HV之间更为明显。Spearman相关分析表明,葡萄球菌属与苯丙氨酸代谢和嘌呤代谢途径中的各种化合物呈正相关。Brevundimonas和乳酸杆菌与参与嘌呤代谢的各种化合物呈负相关,苯丙氨酸代谢和鞘脂信号通路。
    我们认为嘌呤代谢和苯丙氨酸代谢途径紊乱可能在金黄色葡萄球菌在AD的致病机制中起一定作用。我们还发现,女性比男性更容易被葡萄球菌属定植。参与嘌呤代谢和苯丙氨酸代谢途径的代谢物含量差异在女性中更为明显。然而,我们应该注意到我们检测到的代谢物不一定来自微生物,它们也可能来自宿主。
    UNASSIGNED: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. Skin microecological imbalance is an important factor in the pathogenesis of AD, but the underlying mechanism of its interaction with humans remains unclear.
    UNASSIGNED: 16S rRNA gene sequencing was conducted to reveal the skin microbiota dynamics. Changes in skin metabolites were tracked by LC-MS metabolomics. We then explored the potential mechanism of interaction by analyzing the correlation between skin bacterial communities and metabolites in corresponding skin-associated samples.
    UNASSIGNED: Samples from 18 AD patients and 18 healthy volunteers (HVs) were subjected to 16S rRNA gene sequencing and LC-MS metabolomics. AD patients had dysbiosis of the skin bacterial community with decreased species richness and evenness. The relative abundance of the genus Staphylococcus increased significantly in AD, while the abundances of the genera Propionibacterium and Brevundimonas decreased significantly. The relative abundance of the genera Staphylococcus in healthy females was significantly higher than those in healthy males, while it showed no difference in AD patients with or without lesions. The effects of AD status, sex and the presence or absence of rashes on the number of differentially abundant metabolites per capita were successively reduced. Multiple metabolites involved in purine metabolism and phenylalanine metabolism pathways (such as xanthosine/xanthine and L-phenylalanine/trans-cinnamate) were increased in AD patients. These trends were much more obvious between female AD patients and female HVs. Spearman correlation analysis revealed that the genus Staphylococcus was positively correlated with various compounds involved in phenylalanine metabolism and purine metabolic pathways. The genera Brevundimonas and Lactobacillus were negatively correlated with various compounds involved in purine metabolism, phenylalanine metabolism and sphingolipid signaling pathways.
    UNASSIGNED: We suggest that purine metabolism and phenylalanine metabolism pathway disorders may play a certain role in the pathogenic mechanism of Staphylococcus aureus in AD. We also found that females are more likely to be colonized by the genus Staphylococcus than males. Differentially abundant metabolites involved in purine metabolism and phenylalanine metabolism pathways were more obvious in female. However, we should notice that the metabolites we detected do not necessarily derived from microbes, they may also origin from the host.
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