【《关于手足综合征与皮肤菌群的研究进展文献综述》5100字】

关于手足综合征与皮肤菌群的研究进展文献综述1.1手足综合征概述手足综合征（Hand-footSyndrome，HFS）是一种以手掌、足跖病变为特征，伴疼痛、感觉异常的化疗相关不良反应ADDINEN.CITE<EndNote><Cite><Author>Nagore</Author><Year>2000</Year><RecNum>136</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>136</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614254252">136</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nagore,E.</author><author>Insa,A.</author><author>Sanmartín,O.</author></authors></contributors><auth-address>InstitutoValencianodeOncología,Valencia,Spain.eduyame@meditex.es</auth-address><titles><title>Antineoplastictherapy-inducedpalmarplantarerythrodysesthesia('hand-foot')syndrome.Incidence,recognitionandmanagement</title><secondary-title>AmJClinDermatol</secondary-title><alt-title>Americanjournalofclinicaldermatology</alt-title></titles><periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></periodical><alt-periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></alt-periodical><pages>225-34</pages><volume>1</volume><number>4</number><edition>2001/11/13</edition><keywords><keyword>AntineoplasticAgents/*adverseeffects</keyword><keyword>Diagnosis,Differential</keyword><keyword>DrugEruptions/diagnosis/epidemiology/*etiology/therapy</keyword><keyword>FootDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>HandDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Syndrome</keyword></keywords><dates><year>2000</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1175-0561(Print) 1175-0561</isbn><accession-num>11702367</accession-num><urls></urls><electronic-resource-num>10.2165/00128071-200001040-00004</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。卡培他滨ADDINEN.CITEADDINEN.CITE.DATA[2]（Capecitabine，CAP）、5-氟尿嘧啶ADDINEN.CITEADDINEN.CITE.DATA[3]和多西他赛ADDINEN.CITEADDINEN.CITE.DATA[4]为常见导致HFS发生的化疗药物。此外肿瘤靶向药物索拉非尼等同样会引起HFS的发生ADDINEN.CITEADDINEN.CITE.DATA[5]。据文献报道，HFS的发病率在6%至64%之间，其中CAP致HFS发病率可高达50%以上ADDINEN.CITE<EndNote><Cite><Author>Nagore</Author><Year>2000</Year><RecNum>89</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>89</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614250716">89</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nagore,E.</author><author>Insa,A.</author><author>Sanmartín,O.</author></authors></contributors><auth-address>InstitutoValencianodeOncología,Valencia,Spain.eduyame@meditex.es</auth-address><titles><title>Antineoplastictherapy-inducedpalmarplantarerythrodysesthesia('hand-foot')syndrome.Incidence,recognitionandmanagement</title><secondary-title>AmJClinDermatol</secondary-title><alt-title>Americanjournalofclinicaldermatology</alt-title></titles><periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></periodical><alt-periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></alt-periodical><pages>225-34</pages><volume>1</volume><number>4</number><edition>2001/11/13</edition><keywords><keyword>AntineoplasticAgents/*adverseeffects</keyword><keyword>Diagnosis,Differential</keyword><keyword>DrugEruptions/diagnosis/epidemiology/*etiology/therapy</keyword><keyword>FootDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>HandDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Syndrome</keyword></keywords><dates><year>2000</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1175-0561(Print) 1175-0561</isbn><accession-num>11702367</accession-num><urls></urls><electronic-resource-num>10.2165/00128071-200001040-00004</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。此外，接受联合化疗方案患者HFS的发病率相对较高，如多柔比星联合5-氟尿嘧啶治疗患者HFS发病率高达89%ADDINEN.CITEADDINEN.CITE.DATA[5]。有研究报道，HFS发病率与化疗药物剂量、累计化疗时间相关ADDINEN.CITE<EndNote><Cite><Author>Nagore</Author><Year>2000</Year><RecNum>90</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>90</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614250817">90</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nagore,E.</author><author>Insa,A.</author><author>Sanmartín,O.</author></authors></contributors><auth-address>InstitutoValencianodeOncología,Valencia,Spain.eduyame@meditex.es</auth-address><titles><title>Antineoplastictherapy-inducedpalmarplantarerythrodysesthesia('hand-foot')syndrome.Incidence,recognitionandmanagement</title><secondary-title>AmJClinDermatol</secondary-title><alt-title>Americanjournalofclinicaldermatology</alt-title></titles><periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></periodical><alt-periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></alt-periodical><pages>225-34</pages><volume>1</volume><number>4</number><edition>2001/11/13</edition><keywords><keyword>AntineoplasticAgents/*adverseeffects</keyword><keyword>Diagnosis,Differential</keyword><keyword>DrugEruptions/diagnosis/epidemiology/*etiology/therapy</keyword><keyword>FootDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>HandDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Syndrome</keyword></keywords><dates><year>2000</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1175-0561(Print) 1175-0561</isbn><accession-num>11702367</accession-num><urls></urls><electronic-resource-num>10.2165/00128071-200001040-00004</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。Dranitsaris等ADDINEN.CITEADDINEN.CITE.DATA[6]研究发现，白细胞计数、性别及肝转移等患者自身因素与HFS也存在关系。以上研究表明HFS发生不仅取决于化疗药物，患者自身情况也是重要因素。1.1.1手足综合征的表现HFS发病持续时间个体之间差异较大，一部分长期接受化疗患者发病持续时间可长达10个月ADDINEN.CITEADDINEN.CITE.DATA[7,8]。HFS的临床特征较为显著，发病早期表现为手指局部刺痛感，随后发展至全手掌烧灼感ADDINEN.CITEADDINEN.CITE.DATA[9]。另外，由于手、足末端存在神经病变，使患者病灶部位的痛觉和温度觉减弱，但触觉等本体感觉不受影响ADDINEN.CITE<EndNote><Cite><Author>Stubblefield</Author><Year>2006</Year><RecNum>94</RecNum><DisplayText><styleface="superscript">[10]</style></DisplayText><record><rec-number>94</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614251030">94</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Stubblefield,M.D.</author><author>Custodio,C.M.</author><author>Kaufmann,P.</author><author>Dickler,M.N.</author></authors></contributors><auth-address>*DepartmentofNeurology,MemorialSloan-KetteringCancerCenter,RehabilitationMedicineServicedaggerDepartmentofNeurology,NewYork-PresbyterianHospital,NeurologicalInstitutedoubledaggerMemorialSloan-KetteringCancerCenter,BreastCancerMedicineService,NewYorkCity,NY.</auth-address><titles><title>Small-FiberNeuropathyAssociatedwithCapecitabine(Xeloda)-inducedHand-footSyndrome:ACaseReport</title><secondary-title>JClinNeuromusculDis</secondary-title><alt-title>Journalofclinicalneuromusculardisease</alt-title></titles><periodical><full-title>JClinNeuromusculDis</full-title><abbr-1>Journalofclinicalneuromusculardisease</abbr-1></periodical><alt-periodical><full-title>JClinNeuromusculDis</full-title><abbr-1>Journalofclinicalneuromusculardisease</abbr-1></alt-periodical><pages>128-32</pages><volume>7</volume><number>3</number><edition>2006/03/01</edition><dates><year>2006</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1522-0443</isbn><accession-num>19078798</accession-num><urls></urls><electronic-resource-num>10.1097/01.cnd.0000211401.19995.a2</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[10]。HFS的另外一个特征是患者手指或脚趾掌面以及远端指节病变最为明显，可能与手指脚趾等部位常受外力摩擦、挤压，皮肤易受损伤有关ADDINEN.CITEADDINEN.CITE.DATA[11]。因肿瘤患者接受化疗常导致骨髓抑制，HFS患者可出现紫癜、红斑，并可逐渐发展为水泡，随后出现脱皮、糜烂和溃疡等严重病变ADDINEN.CITEADDINEN.CITE.DATA[12]。部分HFS患者病变可侵及手足背侧面，主要表现为表皮营养不良及表皮坏死ADDINEN.CITE<EndNote><Cite><Author>Bolognia</Author><Year>2008</Year><RecNum>96</RecNum><DisplayText><styleface="superscript">[13]</style></DisplayText><record><rec-number>96</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614251123">96</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bolognia,J.L.</author><author>Cooper,D.L.</author><author>Glusac,E.J.</author></authors></contributors><titles><title>Toxicerythemaofchemotherapy:ausefulclinicalterm</title><secondary-title>JAmAcadDermatol</secondary-title><alt-title>JournaloftheAmericanAcademyofDermatology</alt-title></titles><periodical><full-title>JAmAcadDermatol</full-title></periodical><alt-periodical><full-title>JournaloftheAmericanAcademyofDermatology</full-title></alt-periodical><pages>524-9</pages><volume>59</volume><number>3</number><edition>2008/08/13</edition><keywords><keyword>Acrodermatitis/chemicallyinduced/pathology</keyword><keyword>AntineoplasticAgents/*adverseeffects</keyword><keyword>AntineoplasticCombinedChemotherapyProtocols/*adverseeffects</keyword><keyword>Diagnosis,Differential</keyword><keyword>DrugEruptions/*classification/etiology/pathology</keyword><keyword>EccrineGlands/pathology</keyword><keyword>Epidermis/pathology</keyword><keyword>Erythema/chemicallyinduced/*classification/pathology</keyword><keyword>Hidradenitis/chemicallyinduced/pathology</keyword><keyword>Humans</keyword><keyword>Paresthesia/*chemicallyinduced</keyword><keyword>Skin/pathology</keyword><keyword>*TerminologyasTopic</keyword></keywords><dates><year>2008</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>0190-9622</isbn><accession-num>18694683</accession-num><urls></urls><electronic-resource-num>10.1016/j.jaad.2008.05.018</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[13]。HFS患者的皮肤病理表现为角质细胞多发性坏死伴基底层空泡性改变，随症状加重发展为表皮坏死，血管周围炎性细胞浸润ADDINEN.CITEADDINEN.CITE.DATA[8,14]。美国国家癌症研究所（NationalCancerInstitute，NCI）依据临床表现严重程度将HFS分级为三个级别ADDINEN.CITE<EndNote><Cite><Author>Nagore</Author><Year>2000</Year><RecNum>99</RecNum><DisplayText><styleface="superscript">[1]</style></DisplayText><record><rec-number>99</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614252015">99</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Nagore,E.</author><author>Insa,A.</author><author>Sanmartín,O.</author></authors></contributors><auth-address>InstitutoValencianodeOncología,Valencia,Spain.eduyame@meditex.es</auth-address><titles><title>Antineoplastictherapy-inducedpalmarplantarerythrodysesthesia('hand-foot')syndrome.Incidence,recognitionandmanagement</title><secondary-title>AmJClinDermatol</secondary-title><alt-title>Americanjournalofclinicaldermatology</alt-title></titles><periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></periodical><alt-periodical><full-title>AmJClinDermatol</full-title><abbr-1>Americanjournalofclinicaldermatology</abbr-1></alt-periodical><pages>225-34</pages><volume>1</volume><number>4</number><edition>2001/11/13</edition><keywords><keyword>AntineoplasticAgents/*adverseeffects</keyword><keyword>Diagnosis,Differential</keyword><keyword>DrugEruptions/diagnosis/epidemiology/*etiology/therapy</keyword><keyword>FootDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>HandDermatoses/*chemicallyinduced/diagnosis/epidemiology/therapy</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Syndrome</keyword></keywords><dates><year>2000</year><pub-dates><date>Jul-Aug</date></pub-dates></dates><isbn>1175-0561(Print) 1175-0561</isbn><accession-num>11702367</accession-num><urls></urls><electronic-resource-num>10.2165/00128071-200001040-00004</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[1]。I级HFS患者主要表现为手掌、足底部位感觉异常如麻木烧灼感；II级HFS患者疼痛症状明显，显著影响患者生活质量；而III级HFS患者往往需要调整化疗方案甚至停止化疗来避免HFS病变进一步发展。HFS通常不会危及生命，其症状在停药后1个月内消失，但部分患者可能出现永久性伴随症状，如表皮损伤导致的指纹丢失、掌跖角化层增厚等ADDINEN.CITE<EndNote><Cite><Author>Wong</Author><Year>2009</Year><RecNum>101</RecNum><DisplayText><styleface="superscript">[15]</style></DisplayText><record><rec-number>101</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614252098">101</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Wong,M.</author><author>Choo,S.P.</author><author>Tan,E.H.</author></authors></contributors><titles><title>Travelwarningwithcapecitabine</title><secondary-title>AnnOncol</secondary-title><alt-title>Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology</alt-title></titles><periodical><full-title>AnnOncol</full-title></periodical><pages>1281</pages><volume>20</volume><number>7</number><edition>2009/05/28</edition><keywords><keyword>Antimetabolites,Antineoplastic/*adverseeffects</keyword><keyword>Capecitabine</keyword><keyword>Deoxycytidine/adverseeffects/*analogs&derivatives</keyword><keyword>Dermatoglyphics</keyword><keyword>EmigrationandImmigration</keyword><keyword>Fingers</keyword><keyword>Fluorouracil/adverseeffects/*analogs&derivatives</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>MiddleAged</keyword><keyword>NasopharyngealNeoplasms/*drugtherapy</keyword><keyword>Skin/drugeffects</keyword><keyword>*Travel</keyword><keyword>UnitedStates</keyword></keywords><dates><year>2009</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>0923-7534</isbn><accession-num>19470576</accession-num><urls></urls><electronic-resource-num>10.1093/annonc/mdp278</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[15]。1.1.2手足综合征的治疗HFS的治疗以控制症状为主，包括外用糖皮质激素以减少炎症；定期伤口护理以防止其发展为溃疡继发感染；外用抗角化剂以减少皮肤过度角化ADDINEN.CITEADDINEN.CITE.DATA[16]。但是，HFS最有效的治疗方法为调整化疗用药剂量，更换化疗方案或停止当前化疗，随后HFS症状通常在1个月内改善ADDINEN.CITE<EndNote><Cite><Author>Saif</Author><Year>2011</Year><RecNum>196</RecNum><DisplayText><styleface="superscript">[17]</style></DisplayText><record><rec-number>196</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1616154290">196</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Saif,M.W.</author></authors></contributors><titles><title>Capecitabineandhand-footsyndrome</title><secondary-title>ExpertOpinDrugSaf</secondary-title><alt-title>Expertopinionondrugsafety</alt-title></titles><periodical><full-title>ExpertOpinDrugSaf</full-title><abbr-1>Expertopinionondrugsafety</abbr-1></periodical><alt-periodical><full-title>ExpertOpinDrugSaf</full-title><abbr-1>Expertopinionondrugsafety</abbr-1></alt-periodical><pages>159-69</pages><volume>10</volume><number>2</number><edition>2010/12/23</edition><keywords><keyword>Administration,Oral</keyword><keyword>Animals</keyword><keyword>Antimetabolites,Antineoplastic/administration&dosage/adverseeffects/metabolism</keyword><keyword>Capecitabine</keyword><keyword>ContinentalPopulationGroups</keyword><keyword>Deoxycytidine/administration&dosage/adverseeffects/*analogs&</keyword><keyword>derivatives/metabolism</keyword><keyword>Diagnosis,Differential</keyword><keyword>Fluorouracil/administration&dosage/adverseeffects/*analogs&</keyword><keyword>derivatives/metabolism</keyword><keyword>FootDermatoses/*chemicallyinduced/diagnosis/physiopathology</keyword><keyword>HandDermatoses/*chemicallyinduced/diagnosis/physiopathology</keyword><keyword>Humans</keyword></keywords><dates><year>2011</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1474-0338</isbn><accession-num>21174613</accession-num><urls></urls><electronic-resource-num>10.1517/14740338.2011.546342</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[17]。研究表明，首次应用多重激酶抑制剂药物的患者，每天应用尿激酶乳膏2次可以有效预防HFS的发生ADDINEN.CITEADDINEN.CITE.DATA[18]。一项前瞻性队列研究发现，在Ⅰ/Ⅱ级HFS患者中，塞来昔布可以减轻HFS的严重程度ADDINEN.CITEADDINEN.CITE.DATA[19]。然而，有研究发现吡哆醇在预防CAP致HFS方面并无显著作用ADDINEN.CITEADDINEN.CITE.DATA[20]。激素类药物如地塞米松可降低脂质体阿霉素导致的HFS的发生率ADDINEN.CITEADDINEN.CITE.DATA[14]。研究发现，手足局部低温治疗也可有效预防HFS发生，其原因可能是局部皮肤温度降低会导致末端血管收缩、血流量减少，进而降低化疗药物在手足部位的浓度，减少药物对于局部皮肤的损伤作用ADDINEN.CITEADDINEN.CITE.DATA[21]。另有研究指出，应用多西他赛化疗的患者，手足局部应用冰冻手套和袜子可降低HFS的发生率ADDINEN.CITEADDINEN.CITE.DATA[22,23]。此外，常规护理方案，如避免热水淋浴、减少剧烈运动、避免在用药期间穿紧身衣服与鞋子亦可降低HFS的发生率ADDINEN.CITEADDINEN.CITE.DATA[24]。目前临床防治HFS的方法效果甚微，多采用综合对症等治疗措施，未来需要寻找新靶点来开发针对HFS的有效治疗手段。1.1.3导致手足综合征发生的可能机制有研究表明，化疗药物的直接毒性作用是HFS发生的主要原因ADDINEN.CITEADDINEN.CITE.DATA[25]。患者静脉滴注脂质体阿霉素后，由于手足部位皮肤具有丰富的汗腺且药物通过小汗腺管排泄，这使得药物易渗入手掌和脚底的角质层，这是HFS易发生在手足部位的原因之一ADDINEN.CITEADDINEN.CITE.DATA[25]。另外，手掌和脚底相对于其他部位角质层更厚，这会导致药物排泄延缓，化疗药物会诱导角质细胞分泌大量氧自由基，氧自由基大量蓄积和代谢迟缓会诱导局部组织发生氧化损伤导致HFSADDINEN.CITEADDINEN.CITE.DATA[26]。Yokomichi等ADDINEN.CITEADDINEN.CITE.DATA[27]研究发现，在HFS的小鼠模型中，阿霉素与铜离子相互作用产生活性氧，通过炎症信号加速角质细胞凋亡，并同时释放IL-1β、IL-1α和IL-6，从而导致炎症状态。这可能是未来治疗HFS的潜在靶点。此外，毛细血管在手、足、腋窝等部位易受到摩擦损伤，而多重激酶抑制剂有抑制血管修复的作用，导致药物更易渗入周围组织当中，进一步加重组织损伤，导致HFS的发生ADDINEN.CITEADDINEN.CITE.DATA[28]。在CAP致HFS中，局部角质细胞中胸腺嘧啶磷酸化酶的活性增高，使活化药物能力提高进而导致HFSADDINEN.CITEADDINEN.CITE.DATA[29,30]。总之，HFS的发生机制尚不明确，未来需更多研究来探索其发病机制。1.2皮肤菌群概述皮肤是人体重要的器官之一，是人体防御的第一道屏障。人体皮肤表面定植着大量的微生物，其中多数为细菌。机体皮肤表面的菌群构成了机体最庞大且最复杂的微生态系统ADDINEN.CITE<EndNote><Cite><Author>Kong</Author><Year>2012</Year><RecNum>116</RecNum><DisplayText><styleface="superscript">[31]</style></DisplayText><record><rec-number>116</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614253047">116</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kong,H.H.</author><author>Segre,J.A.</author></authors></contributors><auth-address>CenterforCancerResearch,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland20892,USA.konghe@maiI.</auth-address><titles><title>Skinmicrobiome:lookingbacktomoveforward</title><secondary-title>JInvestDermatol</secondary-title><alt-title>TheJournalofinvestigativedermatology</alt-title></titles><periodical><full-title>JInvestDermatol</full-title><abbr-1>TheJournalofinvestigativedermatology</abbr-1></periodical><alt-periodical><full-title>JInvestDermatol</full-title><abbr-1>TheJournalofinvestigativedermatology</abbr-1></alt-periodical><pages>933-9</pages><volume>132</volume><number>3Pt2</number><edition>2011/12/23</edition><keywords><keyword>Dermatitis,Atopic/*microbiology/*physiopathology</keyword><keyword>Dermatology/*trends</keyword><keyword>Humans</keyword><keyword>Metagenome/*physiology</keyword><keyword>*SkinPhysiologicalPhenomena</keyword></keywords><dates><year>2012</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>0022-202X(Print) 0022-202x</isbn><accession-num>22189793</accession-num><urls></urls><custom2>PMC3279608</custom2><custom6>NIHMS337954</custom6><electronic-resource-num>10.1038/jid.2011.417</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[31]，对机体的健康起到不可或缺的作用。人体皮肤菌群可分为常驻菌和暂驻菌。暂驻菌对皮肤健康所造成的影响相对较小。而常驻菌可长期寄居于人体皮肤表面，在皮肤疾病的发生发展中发挥着重要作用，被视为皮肤的核心菌群ADDINEN.CITEADDINEN.CITE.DATA[32,33]。既往研究报道，不同个体的皮肤菌群结构存在差异ADDINEN.CITEADDINEN.CITE.DATA[34]。人体皮肤根据不同部位可划分为油脂区、湿性区和干性区。已有文献报道，油脂区皮肤菌群多样性较低，而干性区皮肤菌群多样性较高ADDINEN.CITE<EndNote><Cite><Author>Sanford</Author><Year>2013</Year><RecNum>120</RecNum><DisplayText><styleface="superscript">[35]</style></DisplayText><record><rec-number>120</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614253201">120</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Sanford,J.A.</author><author>Gallo,R.L.</author></authors></contributors><auth-address>DivisionofDermatology,DepartmentofMedicine,UniversityofCalifornia,SanDiego,SanDiego,CA,USA.</auth-address><titles><title>Functionsoftheskinmicrobiotainhealthanddisease</title><secondary-title>SeminImmunol</secondary-title><alt-title>Seminarsinimmunology</alt-title></titles><periodical><full-title>SeminImmunol</full-title><abbr-1>Seminarsinimmunology</abbr-1></periodical><alt-periodical><full-title>SeminImmunol</full-title><abbr-1>Seminarsinimmunology</abbr-1></alt-periodical><pages>370-7</pages><volume>25</volume><number>5</number><edition>2013/11/26</edition><keywords><keyword>Animals</keyword><keyword>Dysbiosis</keyword><keyword>Humans</keyword><keyword>Microbiota/*immunology</keyword><keyword>Skin/*immunology/*microbiology</keyword><keyword>Antimicrobialpeptides</keyword><keyword>Keratinocyte</keyword><keyword>Propionibacteriumacnes</keyword><keyword>Staphylococcus</keyword></keywords><dates><year>2013</year><pub-dates><date>Nov30</date></pub-dates></dates><isbn>1044-5323(Print) 1044-5323</isbn><accession-num>24268438</accession-num><urls></urls><custom2>PMC4219649</custom2><custom6>NIHMS637404</custom6><electronic-resource-num>10.1016/j.smim.2013.09.005</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[35]。油脂区皮肤菌群中优势菌为丙酸杆菌（Propionibacterium），而湿性区皮肤菌群中优势菌多为葡萄球菌（Staphylococcus）和棒状杆菌（Corynebacterium）ADDINEN.CITEADDINEN.CITE.DATA[36]。不同部位的皮肤可呈现出不同的生理特征，如湿度、pH值和粗糙度等ADDINEN.CITEADDINEN.CITE.DATA[37]。既往研究发现不同解剖部位皮肤的差异对菌群结构的影响大于其他因素，如年龄、性别等ADDINEN.CITEADDINEN.CITE.DATA[38]。然而，随着年龄的增长，同一个体皮肤菌群状态也发生变化，如在65岁以上的人群中，奇异变形杆菌（

Proteusmirabilis）和铜绿假单胞菌（Pseudomonasaeruginosa）的皮肤定殖率比年轻人增加了约25%（LaubeS.Skininfectionsandageing）。皮肤酸碱度也是影响菌群结构的因素之一。H.Lambers等ADDINEN.CITE<EndNote><Cite><Author>Lambers</Author><Year>2006</Year><RecNum>125</RecNum><DisplayText><styleface="superscript">[39]</style></DisplayText><record><rec-number>125</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614253432">125</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lambers,H.</author><author>Piessens,S.</author><author>Bloem,A.</author><author>Pronk,H.</author><author>Finkel,P.</author></authors></contributors><auth-address>SaraLeeHouseholdandBodyCareResearch,Fruitweg,TheHague,TheNetherlands.</auth-address><titles><title>NaturalskinsurfacepHisonaveragebelow5,whichisbeneficialforitsresidentflora</title><secondary-title>IntJCosmetSci</secondary-title><alt-title>Internationaljournalofcosmeticscience</alt-title></titles><periodical><full-title>IntJCosmetSci</full-title><abbr-1>Internationaljournalofcosmeticscience</abbr-1></periodical><alt-periodical><full-title>IntJCosmetSci</full-title><abbr-1>Internationaljournalofcosmeticscience</abbr-1></alt-periodical><pages>359-70</pages><volume>28</volume><number>5</number><edition>2008/05/21</edition><dates><year>2006</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>0142-5463</isbn><accession-num>18489300</accession-num><urls></urls><electronic-resource-num>10.1111/j.1467-2494.2006.00344.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[39]研究发现皮肤的pH值一般在5.0以下，金黄色葡萄球菌（Staphylococcusaureus，S.aureus）会随着pH值的增加逐渐成为优势菌种。总之，皮肤菌群结构是相对稳定的，同时也会随解剖部位、个体生理状态的差异而展现出不同的结构特性。1.2.1皮肤菌群与疾病皮肤菌群与皮肤疾病之间的关系仍处于探索阶段。鉴于皮肤生理环境的复杂性，二者之间的作用可能是相互的ADDINEN.CITE<EndNote><Cite><Author>Grice</Author><Year>2011</Year><RecNum>201</RecNum><DisplayText><styleface="superscript">[40]</style></DisplayText><record><rec-number>201</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1616155029">201</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Grice,E.A.</author><author>Segre,J.A.</author></authors></contributors><auth-address>GeneticsandMolecularBiologyBranch,NationalHumanGenomeResearchInstitute,NationalInstitutesofHealth,Bethesda,Maryland20892-4442,USA.</auth-address><titles><title>Theskinmicrobiome</title><secondary-title>NatRevMicrobiol</secondary-title><alt-title>Naturereviews.Microbiology</alt-title></titles><periodical><full-title>NatRevMicrobiol</full-title><abbr-1>Naturereviews.Microbiology</abbr-1></periodical><alt-periodical><full-title>NatRevMicrobiol</full-title><abbr-1>Naturereviews.Microbiology</abbr-1></alt-periodical><pages>244-53</pages><volume>9</volume><number>4</number><edition>2011/03/17</edition><keywords><keyword>AdaptiveImmunity</keyword><keyword>Humans</keyword><keyword>Immunity,Innate</keyword><keyword>*Metagenome</keyword><keyword>Skin/anatomy&histology/immunology/*microbiology</keyword><keyword>SkinDiseases,Infectious/immunology/microbiology</keyword></keywords><dates><year>2011</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1740-1526(Print) 1740-1526</isbn><accession-num>21407241</accession-num><urls></urls><custom2>PMC3535073</custom2><custom6>NIHMS424100</custom6><electronic-resource-num>10.1038/nrmicro2537</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[40]。皮肤生理状态的变化诱发皮肤菌群结构改变；皮肤菌群结构的变化又影响到皮肤生理状态，如经皮失水率、皮脂分泌量等。皮肤的附属器也会对皮肤菌群结构产生重要的影响。皮肤的小汗腺和皮脂腺可为皮肤菌群提供营养成分ADDINEN.CITE<EndNote><Cite><Author>Sanford</Author><Year>2013</Year><RecNum>126</RecNum><DisplayText><styleface="superscript">[35]</style></DisplayText><record><rec-number>126</rec-number><foreign-keys><keyapp="EN"db-id="ew90evvzx5zdf8erppyxzepptzf5arx0dw5w"timestamp="1614253577">126</key></foreign-k