微生物学报

Skin problems	Strains	Key mechanism	Literature
Skin cancer	Staphylococcus epidermidis MO34	Produces 6-N-hydroxyaminopurine (6-HAP), selectively inhibiting the proliferation of skin tumor cells	A commensal strain of Staphylococcus epidermidis protects against skin neoplasia^[48]
	Lacticaseibacillus rhamnosus LGG LTA	Enhances immune surveillance in skin tissue and relieves immunosuppression caused by ultraviolet rays	Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective agent against UV-induced carcinogenesis^[49]
	Genetically engineered Staphylococcus epidermidis	Activates CD8⁺ T cells, reaches melanoma, exerts cytotoxic effects and directly kills tumors	Engineered skin bacteria induce antitumor T cell responses against melanoma^[50]
	Lactiplantibacillus plantarum L-14 extract	Inhibits the survival and migration of melanoma A375 cells, induces endogenous apoptosis while reducing the expression of tumor migration-related genes	Anti-cancer effects of Lactiplantibacillus plantarum L-14 cell-free extract on human malignant melanoma A375 cells^[51]
	Lactiplantibacillus plantarum WLPL09	Induces apoptosis of B16F10 melanoma cells, inhibit tumor angiogenesis and regulate the composition of intestinal flora in vivo	Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota^[52]
Skin inflammation	A probiotic mixture of Bifidobacterium longum RAPO and Lactiplantibacillus plantarum LRCC5264 (1:1)	Up-regulates the anti-inflammatory factor IL-6, down-regulate the pro-inflammatory factor IL-9 in RAW 264.7 cells, and significantly reduce the dermatitis score, plasma IgE, TEWL, and the expression of skin ceramidase mRNA	Probiotic consumption alleviates atopic dermatitis-related immune responses in association with gut microbial changes: in vitro and mouse model studies^[53]
	Bifidobacterium longum CCFM1029	Up-regulates tryptophan metabolism and produce indole-3-formaldehyde, and activate the aromatic hydrocarbon receptor signaling pathway	Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis^[54]
	Lactiplantibacillus plantarum SM5-2	It efficiently degrades histamine in the intestines, blood and skin tissues, alleviating inflammation in the skin of mice	Lactiplantibacillus plantarum SM5-2 with high histamine-degrading ability for alleviating atopic dermatitis and its application^[55]
	Lactobacillus casei DN-114001	Reduces the recruitment of CD8⁺ T cells from the peripheral blood of patients with atopic dermatitis to the skin, and increase the proportion of FoxP3⁺ regulatory T cells (Treg) in the skin and promote their production of IL-10	Oral probiotic controls skin inflammation by acting on both effector and regulatory T cells^[56]
	Limosilactobacillus fermentum SLAM 216	It significantly reduces skin inflammatory responses and alleviates symptoms such as skin erythema, desquamation, dryness, and scratching	Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism^[47]
Skin photoaging	Lactiplantibacillus plantarum HY7714	Inhibits the JNK/AP-1 signaling pathway to down-regulate the expression of MMP-1, the activities of MMP-2 and MMP-9 induced by ultraviolet rays, reduce the decrease in procollagen expression caused by UVB irradiation, and thereby relieve oxidative stress caused by UVA	Oral administration of Lactiplantibacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging^[57]
	Bifidobacterium breve B-3	It inhibits the skin water loss and epidermal thickening caused by chronic UVB irradiation, reduces the damage of chronic UVB irradiation to the tight junction structure and basement membrane of the skin, and simultaneously inhibits the production of skin interleukin-1 β (IL-1β) induced by ultraviolet rays	Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice^[58]
	Lactiplantibacillus plantarum CGMCC8198	Significantly eliminate ABTS and DPPH free radicals and significantly reduce the production of melanin in B16F10 cells	Lactiplantibacillus plantarum CGMCC 8198 cell-free supernatant inhibits melanogenesis^[59]
	Limosilactobacillus fermentum XJC60	Stabilizes the NAD⁺/NADH level of the skin after ultraviolet damage, restore mitochondrial membrane potential, reduce ROS and inhibit collagen degradation	Limosilactobacillus fermentum XJC60 with high nicotinamide biosynthesis capacity for anti-photoaging and its application^[60]
	Limosilactobacillus fermentum XJC48	Regulating the IGF-1/Akt/FOXO pathway prolongs the lifespan of dermal fibroblasts and assists in resisting ultraviolet oxidative damage	Limosilactobacillus fermentum XJC48 with dermal fibroblast lifespan extension and anti-skin aging properties and its application^[11]
	Lactobacillus rhamnosus HK-9	Effectively eliminate DPPH free radicals and up-regulate the expression of antioxidant-related genes such as superoxide dismutase (SOD) and glutathione (GSH)	Enhancement of skin antioxidant and anti-inflammatory potentials of Agastache rugosa leaf extract by probiotic bacterial fermentation in human epidermal keratinocytes^[61]
	Lactobacillus buchneri	Significantly increase the expression of type I collagen induced by UVB, reduce collagenase activity and the mRNA level of MMPs, and simultaneously promote the expression of moisturizing factors and antioxidant enzymes	Anti-photoaging effect of plant extract fermented with Lactobacillus buchneri on CCD-986sk fibroblasts and HaCaT keratinocytes^[62]

Skin problems	Strains	Key mechanism	Literature
Skin cancer	Staphylococcus epidermidis MO34	Produces 6-N-hydroxyaminopurine (6-HAP), selectively inhibiting the proliferation of skin tumor cells	A commensal strain of Staphylococcus epidermidis protects against skin neoplasia^[48]
	Lacticaseibacillus rhamnosus LGG LTA	Enhances immune surveillance in skin tissue and relieves immunosuppression caused by ultraviolet rays	Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective agent against UV-induced carcinogenesis^[49]
	Genetically engineered Staphylococcus epidermidis	Activates CD8⁺ T cells, reaches melanoma, exerts cytotoxic effects and directly kills tumors	Engineered skin bacteria induce antitumor T cell responses against melanoma^[50]
	Lactiplantibacillus plantarum L-14 extract	Inhibits the survival and migration of melanoma A375 cells, induces endogenous apoptosis while reducing the expression of tumor migration-related genes	Anti-cancer effects of Lactiplantibacillus plantarum L-14 cell-free extract on human malignant melanoma A375 cells^[51]
	Lactiplantibacillus plantarum WLPL09	Induces apoptosis of B16F10 melanoma cells, inhibit tumor angiogenesis and regulate the composition of intestinal flora in vivo	Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota^[52]
Skin inflammation	A probiotic mixture of Bifidobacterium longum RAPO and Lactiplantibacillus plantarum LRCC5264 (1:1)	Up-regulates the anti-inflammatory factor IL-6, down-regulate the pro-inflammatory factor IL-9 in RAW 264.7 cells, and significantly reduce the dermatitis score, plasma IgE, TEWL, and the expression of skin ceramidase mRNA	Probiotic consumption alleviates atopic dermatitis-related immune responses in association with gut microbial changes: in vitro and mouse model studies^[53]
	Bifidobacterium longum CCFM1029	Up-regulates tryptophan metabolism and produce indole-3-formaldehyde, and activate the aromatic hydrocarbon receptor signaling pathway	Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis^[54]
	Lactiplantibacillus plantarum SM5-2	It efficiently degrades histamine in the intestines, blood and skin tissues, alleviating inflammation in the skin of mice	Lactiplantibacillus plantarum SM5-2 with high histamine-degrading ability for alleviating atopic dermatitis and its application^[55]
	Lactobacillus casei DN-114001	Reduces the recruitment of CD8⁺ T cells from the peripheral blood of patients with atopic dermatitis to the skin, and increase the proportion of FoxP3⁺ regulatory T cells (Treg) in the skin and promote their production of IL-10	Oral probiotic controls skin inflammation by acting on both effector and regulatory T cells^[56]
	Limosilactobacillus fermentum SLAM 216	It significantly reduces skin inflammatory responses and alleviates symptoms such as skin erythema, desquamation, dryness, and scratching	Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism^[47]
Skin photoaging	Lactiplantibacillus plantarum HY7714	Inhibits the JNK/AP-1 signaling pathway to down-regulate the expression of MMP-1, the activities of MMP-2 and MMP-9 induced by ultraviolet rays, reduce the decrease in procollagen expression caused by UVB irradiation, and thereby relieve oxidative stress caused by UVA	Oral administration of Lactiplantibacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging^[57]
	Bifidobacterium breve B-3	It inhibits the skin water loss and epidermal thickening caused by chronic UVB irradiation, reduces the damage of chronic UVB irradiation to the tight junction structure and basement membrane of the skin, and simultaneously inhibits the production of skin interleukin-1 β (IL-1β) induced by ultraviolet rays	Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice^[58]
	Lactiplantibacillus plantarum CGMCC8198	Significantly eliminate ABTS and DPPH free radicals and significantly reduce the production of melanin in B16F10 cells	Lactiplantibacillus plantarum CGMCC 8198 cell-free supernatant inhibits melanogenesis^[59]
	Limosilactobacillus fermentum XJC60	Stabilizes the NAD⁺/NADH level of the skin after ultraviolet damage, restore mitochondrial membrane potential, reduce ROS and inhibit collagen degradation	Limosilactobacillus fermentum XJC60 with high nicotinamide biosynthesis capacity for anti-photoaging and its application^[60]
	Limosilactobacillus fermentum XJC48	Regulating the IGF-1/Akt/FOXO pathway prolongs the lifespan of dermal fibroblasts and assists in resisting ultraviolet oxidative damage	Limosilactobacillus fermentum XJC48 with dermal fibroblast lifespan extension and anti-skin aging properties and its application^[11]
	Lactobacillus rhamnosus HK-9	Effectively eliminate DPPH free radicals and up-regulate the expression of antioxidant-related genes such as superoxide dismutase (SOD) and glutathione (GSH)	Enhancement of skin antioxidant and anti-inflammatory potentials of Agastache rugosa leaf extract by probiotic bacterial fermentation in human epidermal keratinocytes^[61]
	Lactobacillus buchneri	Significantly increase the expression of type I collagen induced by UVB, reduce collagenase activity and the mRNA level of MMPs, and simultaneously promote the expression of moisturizing factors and antioxidant enzymes	Anti-photoaging effect of plant extract fermented with Lactobacillus buchneri on CCD-986sk fibroblasts and HaCaT keratinocytes^[62]

皮肤微生态调控皮肤健康的作用机制研究进展

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谢小利 ¹^,² , 吴清平 ¹^,² , 陈玲 ²^,³ , 李滢 ²^,³^,^* , 吴毓薇 ⁴^,^*

微生物学报 | 综述 2026,66(10): 4733-4748

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微生物学报 |综述 2026 , 66 (10) : 4733 -4748

皮肤微生态调控皮肤健康的作用机制研究进展

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谢小利¹^,², 吴清平¹^,², 陈玲²^,³, 李滢²^,³^,^*, 吴毓薇⁴^,^*

作者信息

^1.陕西科技大学食品科学与工程学院，陕西西安

^2.广东省科学院微生物研究所，华南应用微生物国家重点实验室，广东省微生物安全与健康重点实验室，国家卫健委微生物食品营养与安全科技创新平台，国家市场监管重点实验室(食品微生物安全大数据技术)，广东广州

^3.广东省微生物分析检测中心，食品药品实验室，广东广州

^4.广东科环生物科技有限公司，广东广州

通讯作者:

李滢, 吴毓薇

作者简介:

作者贡献声明

谢小利：文献检索与筛选，论文内容梳理与撰写、修改；吴清平：论文内容优化与细节修改；陈玲：参与论文讨论；李滢：论文逻辑框架构思，内容逻辑优化与细节修改；吴毓薇：参与论文讨论、内容优化及细节修改。

Research progress on the mechanisms of skin microecology regulating skin health

Xiaoli XIE¹^,², Qingping WU¹^,², Ling CHEN²^,³, Ying LI²^,³^,^*, Yuwei WU⁴^,^*

Affiliations

^1.School of Food Science and Engineering, Shaanxi University of Science and Technology, Xi’an, Shaanxi, China

^2.State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Safety and Health, National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Foods, Key Laboratory of Big Data Technologies for Food Microbiological Safety, State Administration for Market Regulation, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China

^3.Food and Drug Laboratory, Guangdong Detection Center of Microbiology, Guangzhou, Guangdong, China

^4.Guangdong Kehuan Biotechnology Co. , Ltd. , Guangzhou, Guangdong, China

Corresponding Author:

^*E-mail: LI Ying, liying@gdim.cn

WU Yuwei, 13503036950@163.com

出版时间: 2026-10-04 doi: 10.13343/j.cnki.wsxb.20260196

文章导航

摘要

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皮肤微生物组是由定植于皮肤表面的多种微生物构成的复杂生态系统，其通过与宿主相互作用共同维持皮肤健康。研究表明，皮肤微生态失衡可通过诱导皮肤细胞DNA损伤、促进促炎因子分泌等多种途径引发各类皮肤健康问题。近年来，多项研究证实益生菌在改善皮肤健康方面具有重要作用，其机制涵盖抗氧化、免疫调节及增强皮肤屏障功能等。本文全面综述了皮肤微生态的组成及其维持皮肤正常功能的作用，以及微生态失衡诱发皮肤问题的病理机制研究进展；在此基础上，系统总结了微生态治疗尤其是益生菌在改善皮肤恶性肿瘤、皮肤炎症及光老化等方面的作用机制与研究进展，旨在为益生菌提升皮肤健康的机制探索与应用研究提供理论依据。

关键词

皮肤健康 / 微生态 / 癌症 / 炎症 / 光老化 / 益生菌

Abstract

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The skin microbiota refers to a complex ecosystem composed of diverse microorganisms that colonize the skin, which contributes to the maintenance of skin health through interactions with the host. Studies have demonstrated that an imbalanced skin microecology can cause various skin health problems through multiple pathways, such as the induction of DNA damage in skin cells and the promotion of pro-inflammatory factor secretion. In recent years, numerous studies have confirmed that probiotics play a significant role in improving skin health, with mechanisms including antioxidation, immunomodulation, and enhancement of skin barrier function. This review comprehensively summarized the composition of the skin microecology, its role in maintaining normal skin functions, and the research progress on the pathological mechanisms of skin problems induced by microecological imbalance. Based on this, this review systematically summarized the mechanisms and research progress of microecological therapy, particularly probiotics, in improving various skin health problems, especially skin cancer, skin inflammation and photoaging, aiming to provide a theoretical basis for the exploration of the mechanisms and application of probiotics in improving skin health.

Key words

skin health / microecology / cancer / inflammation / photoaging / probiotics

引用本文

谢小利, 吴清平, 陈玲, 李滢, 吴毓薇. 皮肤微生态调控皮肤健康的作用机制研究进展. 微生物学报, 2026 , 66 (10) : 4733 -4748 . DOI: 10.13343/j.cnki.wsxb.20260196

Xiaoli XIE, Qingping WU, Ling CHEN, Ying LI, Yuwei WU. Research progress on the mechanisms of skin microecology regulating skin health[J]. Acta Microbiologica Sinica, 2026 , 66 (10) : 4733 -4748 . DOI: 10.13343/j.cnki.wsxb.20260196

正文

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作为人体最大的上皮器官，皮肤是连接人体与外界环境的重要纽带，由皮下组织、真皮和表皮组成。皮肤上定植着数以万亿计的细菌、真菌、病毒及古细菌，它们共同构成了皮肤微生物组^[1]。皮肤微生物组、皮肤细胞及细胞分泌物等共同构成了皮肤微生态，其与宿主之间建立起的平衡有利于维持皮肤的健康稳态。然而，日常生活中存在多种环境及遗传因素，如紫外线、环境污染、衰老等均可导致皮肤微生态的组成和功能发生改变。目前多项研究已证实，当微生态发生严重失调时可引发各类皮肤疾病，包括皮肤癌、皮肤炎症、老化等^[2-3] (图1)。

益生菌(probiotics)是一类当摄入适当数量时即可对宿主健康产生有益作用的活性微生物^[4]。前期研究已建成库存量超过20 000株的健康功能微生物菌种资源库，通过对这些菌种资源进行靶向功能挖掘，证实了不同益生菌株在降糖、降脂、抗氧化等方面具有显著功能^[5-7]。值得注意的是，肠道与皮肤作为机体最大的2个界面器官，其微生态稳态之间存在密切的功能对话。在局部微生态方面，已有研究表明健康菌群能够有效降解毒素、减轻内毒素对皮肤的负面影响，因此具有预防痤疮等皮肤问题的作用^[8]；在系统调控方面，益生菌还可通过调节肠道菌群及其介导的“肠道-皮肤轴” (gut-skin axis)实现肠道与皮肤的远程调控，从而改善皮肤健康^[9]；此外，前期研究还发现益生菌能修复毛发炎症性损伤^[10]，并可抵抗紫外线诱导的细胞损伤^[11-12]。上述多样化的保护效应可共同增强机体免疫功能，帮助抵御外界病原体侵害，维持皮肤的健康状态。其显著的抗炎作用也有助于减轻皮肤炎症反应，缓解皮肤过敏、红肿等症状^[13-14]。

为解决皮肤健康领域微生态调控手段不足、益生菌在皮肤健康调控中的应用机制不明等问题，本综述系统总结皮肤微生态与健康相互作用的机制，以及益生菌改善皮肤健康的研究现状，重点阐述皮肤微生态、皮肤健康和益生菌三者关系的最新研究进展，旨在为开发基于益生菌的皮肤健康产品提供理论依据和参考。

1 皮肤微生态与健康的关系

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皮肤微生物组是由细菌、真菌、病毒及古细菌组成的动态平衡系统，与皮肤健康密切相关。在健康状态下，该系统中的群落结构相对稳定，有益菌群占优势^[15]。研究指出，皮肤中的有益菌可抑制病原微生物的生长繁殖，形成微生物屏障，有效抵御外界有害微生物的入侵，同时协助维持皮肤的正常生理功能，如调节皮肤pH值等^[16]。此外，这些菌群还能参与皮肤细胞代谢过程，维持皮肤水合作用及油脂分泌等生理功能的正常运行。然而，当宿主免疫状态、皮肤理化性质发生变化，或受到外界病原体入侵时，微生物组的多样性可能下降，有益菌的优势地位被削弱，继而引发痤疮、湿疹、银屑病等多种皮肤问题，影响皮肤的外观和功能^[17]。因此，维持皮肤微生态的平衡对于保障皮肤健康、增强其防御能力至关重要。

1.1 正常皮肤微生态的结构与功能

近年来，研究者通过高通量测序发现，正常皮肤微生态由多种微生物共同组成，包括真菌[如马拉色菌属(Malassezia)]、细菌[如葡萄球菌属(Staphylococcus)和表皮杆状菌属(Cutibacterium)]、病毒[如人乳头瘤病毒(human papillomavirus, HPV)]等；这些微生物覆盖了人体皮肤高达90%的表面，形成了一个复杂的生态系统，影响着皮肤的健康状态^[18]。Lange-Asschenfeldt等^[19]研究发现，85%的细菌存在于前2-6层角质细胞中，约25%的皮肤细菌则定植于毛囊内。与此同时，由于皮脂含量、温度、湿度、皮肤褶皱等因素存在差异，不同部位的皮肤微生物群在组成和分布上有所不同。例如，潮湿的腋窝通常以棒杆菌(Corynebacterium)和葡萄球菌的定植为主；而干燥的皮肤区域(如肢体屈侧)则以变形杆菌(Variimorphobacter)、黄杆菌(Flavobacterium)和马拉色菌的混合种群定植为主^[20]。在此基础上，Li等^[18]基于皮肤微生物组的特征将皮肤分为2种亚型：C型(C-cutotype)和M型(M-cutotype)；其中C型皮肤常见于青少年，通常具有更高的水合状态和油脂含量，但微生物多样性较低，以疮疱表皮杆状菌(Cutibacterium acnes)为优势种属；M型皮肤常见于老年人群，以奥斯陆莫拉氏菌(Moraxella osloensis)为优势种属，该亚型皮肤水分和油脂含量较低，较为干燥，但物种丰富度和生物多样性较高。

基于宏基因组学划分的皮肤亚型，动态反映了微生物群落与宿主皮肤之间的相互作用。具体而言，皮肤微生物通过3个层面的机制发挥对宿主皮肤的保护作用。在物理防御层面，皮肤微生物可通过生物、物理、化学和免疫等多个层次完善皮肤屏障功能，帮助抵御外界病原体的入侵。Cogen等^[21]研究发现，表皮葡萄球菌(Staphylococcus epidermidis)能够分泌2种酚溶性调控蛋白(phenol-soluble modulins, PSMs)，即PSM γ和PSM δ，这2种蛋白在一定浓度下可有效抑制金黄色葡萄球菌(Staphylococcus aureus)的生长，具有增强皮肤防御屏障的能力。在免疫调节层面，皮肤微生物能够与宿主免疫细胞相互作用，调节免疫应答和免疫耐受。Linehan等^[22]发现，共生菌Staphylococcus epidermidis通过非经典主要组织相容性复合体(major histocompatibility complex, MHC) I类分子被免疫系统识别，进而诱导产生兼具抗菌防御和组织修复功能的特异性T细胞；并且在皮肤活检实验中发现，提前定植Staphylococcus epidermidis的小鼠伤口处组织修复更为明显，表明共生菌通过非经典免疫途径加速伤口愈合并减少炎症。在代谢互作层面，皮肤微生物还参与了皮肤的pH调节、脂质代谢等生理过程。Holland等^[23]发现Cutibacterium acnes可通过分泌三酰甘油脂肪酶将皮脂三酰甘油酯分解为甘油和游离脂肪酸。健康皮肤的生理pH在4.1-5.8之间，丙酸有助于维持皮肤表面的酸性环境，而酸性pH可抑制病原菌的定植^[24-25]。然而，当微生物群落与宿主皮肤之间动态的相互作用模式受到破坏时上述功能将丧失，进而引发银屑病、特应性皮炎(atopic dermatitis, AD)、痤疮等各类皮肤疾病。

1.2 皮肤癌症与微生态

皮肤癌症是指由于皮肤细胞发生异常增殖所形成的恶性肿瘤^[26]。既往认为，引发皮肤癌症的因素主要是紫外线辐射和电离辐射。然而，近期研究证实，皮肤微生态的改变也可参与皮肤癌症的发生发展，尤其是病毒感染及菌群失衡。在病毒感染层面，Feltkamp等^[27]通过对荷兰540例感染人乳头瘤病毒患者进行临床观察性研究，发现感染8型及38型HPV的患者其皮肤癌发生率相较于阴性者分别提升了14.7倍和3.0倍；尤其在免疫抑制患者(如器官移植受者)中患癌风险更是增加100倍。在细菌群落层面，多项研究揭示了黑色素瘤(malignant melanoma, MM)及皮肤癌患者中的特征性菌群失调模式。Mrázek等^[28]利用16S rRNA基因测序比较了黑色素瘤动物模型中正常皮肤与黑色素瘤组织间皮肤微生物的组成差异，结果显示，与正常皮肤相比，黑色素瘤组织中梭杆菌属和梭状杆菌属的丰度显著增加。此外，Voigt等^[29]对健康人群、光化性角化病(皮肤癌前病变)及鳞状细胞癌患者的皮肤微生物组进行宏基因组分析，发现鳞状细胞癌患者皮肤中致病性金黄色葡萄球菌的相对丰度增加，而共生的疮疱表皮杆状菌丰度明显减少。

深入研究发现，皮肤中的异常微生物可能通过多种机制促进皮肤癌症的发生及发展，包括诱导皮肤细胞异常增殖、积累活性氧(reactive oxygen species, ROS)、造成细胞DNA损伤等。在病毒致癌机制方面，HPV的E6蛋白通过泛素-蛋白酶体途径促进肿瘤抑制蛋白p53的降解，抑制细胞凋亡并促进细胞增殖；E7蛋白则通过结合并降解视网膜母细胞瘤蛋白(retinoblastoma protein, pRb)，解除对细胞周期的抑制，促进细胞异常增殖，从而驱动癌症的发生^[30]。除病毒外，皮肤异常定植的细菌也可通过炎症与氧化应激通路发挥促癌作用。Madhusudhan等^[31]发现，S. aureus可通过Toll样受体2/4 (Toll like receptors 2/4, TLR2/4)激活核因子κB (nuclear factor kappa-B, NF-κB)信号通路，引起人β防御素-2 (human β-defensin-2, HBD-2)表达增加，进而加速皮肤肿瘤的生长。另外，Krueger等^[32]从光化性角化病和鳞状细胞癌患者皮肤中分离出不同的金黄色葡萄球菌临床菌株，通过转录组和蛋白组分析这些菌株分泌的代谢产物，结果发现部分S. aureus可通过分泌α-毒素等细胞溶解毒素和蛋白酶诱导角质形成细胞产生白细胞介素(interleukin, IL)-6等促肿瘤炎症因子。然而，这些研究多为体外实验或小样本观察性研究，存在“因果倒置”的风险。此外，目前仍缺乏前瞻性队列研究及因果干预实验的确证。

综上所述，皮肤微生物群落在皮肤癌的发生和发展中起重要作用。然而，关于皮肤癌与微生态的研究仍存在不足：缺乏皮肤微生物群与皮肤癌症之间因果关系的研究；同时，针对皮肤中真菌和病毒的致癌机制研究相对较少。造成这一空白的原因主要在于：皮肤真菌组和病毒组的检测深度要求远高于细菌16S rRNA基因测序；缺乏标准化的低生物量样本DNA、RNA提取方案；此外，真菌培养条件复杂且皮肤病毒多为潜伏感染，缺乏稳定的体外复制体系。在未来的研究中可利用荧光标记真菌迁移追踪、补体级联阻断等手段，明确皮肤真菌是否经相同通路促进皮肤癌症的发生；建立真菌-细菌跨界互作体系；应用多组学技术构建病毒-免疫-菌群互作网络，全面解析皮肤微生态与皮肤癌之间的复杂关系。

1.3 皮肤炎症与微生态

多种皮肤炎症(如特应性皮炎、银屑病、痤疮等)已被证实与皮肤微生态失调紧密相关。研究指出，健康皮肤的微生物群落通常具有较高的多样性，而炎症状态下皮肤微生态多样性急剧减少，特定致病菌或条件致病菌成为主要的皮肤定植菌^[18]。这种菌群组成的变化不仅是炎症的结果，更是推动炎症进展的主动因素。微生态失衡会破坏皮肤屏障功能，导致免疫失调和炎症反应加剧，某些微生物代谢产物也会促进炎症介质释放，进而加重皮肤炎症。Li等^[33]通过皮肤16S rRNA基因测序分析发现，真皮层微生物群落失衡会加重甲沟炎患者的炎症，导致皮肤核心微生物由需氧菌转变为厌氧菌，这些厌氧微生物可产生大量促炎物质，诱发真皮层尤其是甲沟部位的炎症加重。然而，该研究无法区分活菌与死菌，且缺乏功能性验证实验，有待进一步验证。此外，Heng等^[34]对100例面部脂溢性皮炎患者和42例正常对照进行了研究，发现糠秕马拉色菌(Malassezia furfur)密度与脂溢性皮炎的严重程度存在相关性。类似地，在痤疮机制研究中，Fitz-Gibbon等^[35]利用16S rRNA基因测序方法分析了痤疮患者和健康人群鼻部皮肤的微生物群落构成，发现特定种群的Cutibacterium acnes菌株(如RT4、RT5)在痤疮患者中显著富集，与痤疮显著相关，而RT6则与健康皮肤相关。因此，恢复皮肤微生态平衡可能是治疗炎症性皮肤病的重要策略，其中靶向特定菌群的精准干预方案仍需前瞻性随机对照试验加以验证。

进一步研究菌群失调驱动炎症的因果机制，发现皮肤微生物主要通过产生各类致炎性代谢产物诱发皮肤炎症。在细菌代谢产物方面，Deng等^[36]研究发现，金黄色葡萄球菌分泌的丝氨酸蛋白酶V8 (glutamyl endopeptidase I, GluV8)能够裂解皮肤感觉神经元细胞的蛋白酶激活受体1 (protease activated receptor 1, PAR1)，引发皮肤瘙痒和损伤。此外，van Dalen等^[37]发现，在特应性皮炎中S. aureus通过细胞壁磷壁酸上的β-N-乙酰葡萄糖胺(N-acetyl-β-glucosamine, β-GlcNAc)被皮肤朗格汉斯细胞(Langerhans cell, LC)特有的受体langerin识别，这种相互作用使LC能够区分S. aureus与其他葡萄球菌，并启动促炎反应。除金黄色葡萄球菌外，马拉色菌及其代谢产物也是引起皮肤炎症的重要原因。Wolf等^[38]发现马拉色菌通过其细胞壁甘露聚糖(mannan, Man)和β-葡聚糖(β-glucan, β-Glc)被宿主细胞凝集素受体识别，触发Syk-CARD9信号通路并激活含吡啶结构域的NOD样受体家族蛋白3 (NOD-like receptor family pyrin domain containing 3, NLRP3)炎症小体，促进IL-1β、IL-18等促炎细胞因子的成熟与释放。此外，Jia等^[39]研究发现，球形马拉色菌(Malassezia globosa)通过β-glucan与角质形成细胞表面的Dectin-1受体结合，诱导角质形成细胞分泌IL-23；分泌的IL-23进一步促进初始T细胞向致病性辅助性T细胞17 (T helper 17 cell, Th17)分化，Th17细胞继而产生IL-17A、IL-22等促炎细胞因子，加剧皮肤炎症反应。然而，上述马拉色菌相关研究多为体外实验或小样本观察性研究，菌群失调究竟是炎症的原因还是结果尚不明确，临床转化价值仍需评估。

综上所述，皮肤炎症与微生态的相关研究已取得进展，但皮肤中关键诱发炎症微生物的作用机制尚未被完全阐明。例如，以疮疱表皮杆状菌IA1型(RT4/5)为主的菌株表现出强大的毒力特性，这类菌株在富脂微环境中产生毒性与促炎效应，但疮疱表皮杆状菌在健康皮肤中又具有维持皮肤稳态的作用^[40]。后续可应用单细胞测序与空间转录组技术解析疮疱表皮杆状菌在不同微环境下的代谢表型转换及毒力因子调控网络，明确“健康共生-致病转化”的分子开关。此外，皮肤炎症的发生与个体差异、环境因素关系密切，尤其是环境暴露[如紫外线(ultraviolet, UV)、污染物]可能改变皮肤pH值或氧化应激状态，进而影响菌群-免疫互作^[41-42]，但目前对上述现象的机制探索仍较为匮乏。未来可通过建立标准化环境暴露模拟体系，结合宏16S rRNA基因/宏基因组与宿主转录组时序分析，量化环境应激通过改变皮肤pH值、氧化应激状态进而重塑菌群-免疫互作的因果链条。总之，针对皮肤微生态与炎症机制的研究亟需超越“相关性”范畴，向“因果性”及“精准调控”方向深入，为新型抗炎策略的开发提供理论指导。

1.4 光老化与微生态

光老化(photoaging)是一种由长期暴露于紫外线所导致的皮肤衰老现象，表现为皮肤皱纹增多、色素沉着、弹性下降及屏障功能受损^[43]。目前研究已发现皮肤微生态在光老化进程中扮演重要角色：紫外线照射后可导致皮肤微生态多样性降低，削弱微生物群落的稳定性和对外界刺激的抵抗力。同时，光老化过程中表皮葡萄球菌及乳杆菌丰度显著下降，而潜在致病菌(如金黄色葡萄球菌)的相对丰度呈增加趋势，这些变化可能导致皮肤老化进一步加剧^[44]。

陈慧贞^[45]前期研究发现，微生物源抗氧化物质的减少是皮肤光老化过程中的重要特征之一。长期接受单侧光照的公交司机面部皮肤存在微生态结构差异，光照导致皮肤中依可多因、烟酰胺单核苷酸转运蛋白等微生物源抗氧化代谢物显著减少，皮肤修复光损伤的能力下降。同时，光老化过程中微生物群落功能异常，使皮肤微生物群产生的短链脂肪酸(short-chain fatty acids, SCFAs)、超氧化物歧化酶(superoxide dismutase, SOD)等抗氧化物质合成减少，且无法有效清除ROS，导致细胞内ROS积累，激活丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)、NF-κB等信号通路，促进炎症反应和细胞外基质降解，加速皮肤光老化进程^[46]。尽管已有研究揭示了光老化与皮肤微生物群落变化之间的关联，但这些微生物群落变化如何具体影响皮肤细胞的抗氧化能力、炎症反应和胶原蛋白降解等机制仍不完全清楚。另外，目前大多数研究集中在短期或急性光老化模型上，对于长期紫外线暴露下皮肤微生态的动态变化及其对光老化的长期影响研究较少。因此，后续研究可通过建立慢性UV暴露动物模型模拟人类长期光老化，结合宏基因组与皮肤转录组、代谢组及蛋白质组的多组学整合分析，追踪关键菌属与相关抗氧化通路，全面解析皮肤微生态在光老化中的作用机制。

综上所述，皮肤微生态作为皮肤健康的重要调控者，其平衡与皮肤屏障功能、免疫调节及抗衰老等生理过程密切相关。通过科学的干预措施可有效改善皮肤微生态，增强皮肤的天然防御机制，从而促进皮肤健康。近年研究表明，干预皮肤微生态的治疗手段可从多方面、多机制地改善皮肤健康：通过调节皮肤微生物群落促进有益菌生长，能增强皮肤表面脂质膜形成，减少经表皮水分流失，抵御外界刺激。总之，科学地干预皮肤微生态，为改善皮肤健康、解决多种皮肤问题提供了新途径，在皮肤护理与皮肤病防治领域极具应用潜力。

2 益生菌改善皮肤健康的研究进展

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随着研究者对皮肤微生态与健康之间关联认识的深入，干预微生态已成为改善皮肤健康的新手段。近年来，益生菌在改善皮肤健康方面的研究取得了显著进展。研究表明，益生菌可通过多种机制对皮肤健康产生积极影响：一方面，益生菌通过“肠道-皮肤轴”或直接作用于皮肤微生态，增强皮肤屏障及免疫功能，进而改善皮肤癌症、痤疮等疾病^[9]；另一方面，益生菌的代谢产物也可通过调节皮肤微生态提升皮肤修复能力，进而延缓皮肤炎症及光老化进程^[46-47]。总体而言，益生菌在皮肤护理和皮肤疾病治疗方面潜力巨大，而个性化益生菌疗法和微生态调控或将成为皮肤健康管理的新方向(表1)。

2.1 益生菌在改善皮肤癌症中的作用

大量研究证实，益生菌可通过抑制肿瘤细胞生长、调节肿瘤微环境和提升系统免疫作用3种途径影响皮肤癌症的治疗效果。Nakatsuji等^[48]发现，表皮葡萄球菌MO34可产生6-N-羟氨基嘌呤(6-N-hydroxyaminopurine, 6-HAP)，选择性抑制皮肤肿瘤细胞的增殖；同时，6-HAP不损伤正常皮肤细胞，具有良好的应用安全性；在体内实验中，经小鼠尾静脉注射6-HAP可有效抑制B16F10黑色素瘤的生长，且注射后不会引发小鼠肝肾损伤；该结果提示，益生菌及其有益代谢产物可直接抑制肿瘤生长。Weill等^[49]通过对紫外线辐射诱导的皮肤癌小鼠口服鼠李糖乳酪杆菌(Lacticaseibacillus rhamnosus) LGG脂磷壁酸(lipoteichoic acid, LTA)，发现LTA能够调节肠道相关淋巴组织、恢复UV诱导的免疫抑制，还可通过“肠道-皮肤轴”延迟UV诱导的皮肤肿瘤出现。此外，还有研究者通过设计多种工程化益生菌进行抗皮肤癌症治疗。例如，Chen等^[50]通过基因工程改造表皮葡萄球菌，使其表面表达肿瘤抗原，经动物实验证实该改造可显著减缓黑色素瘤的进展；口服改造菌株后，小鼠体内肿瘤特异性CD8⁺ T细胞被激活，并经血液循环抵达原发和转移的黑色素瘤中，进而发挥细胞毒性作用、直接杀伤肿瘤。上述结果均证实，益生菌具有被开发为新一代抗皮肤癌症生物制剂的巨大潜力。

针对益生菌改善皮肤癌症的机制研究发现，益生菌可通过多个途径抑制皮肤肿瘤生长，包括菌体互作、分泌代谢产物、诱导肿瘤细胞凋亡及激活免疫系统等。Park等^[51]在人黑色素瘤细胞株A375培养过程中加入植物乳植杆菌(Lactiplantibacillus plantarum) L-14提取液，发现L-14提取液可有效抑制A375细胞的存活和迁移，降低肿瘤迁移相关基因的表达，同时诱导细胞内源性凋亡。Wang等^[52]研究发现，植物乳植杆菌WLPL09的胞外多糖(exopolysaccharides-09, EPS-09)可诱导B16F10黑色素瘤细胞凋亡、抑制肿瘤血管生成，并在体内调节肠道菌群组成，在抗黑色素瘤过程中发挥积极作用。上述发现证实，益生菌及其代谢产物具有直接抗肿瘤活性，可通过多靶点协同发挥抗肿瘤功效。

基于上述研究发现，益生菌可通过多种方式改善皮肤癌，直接借助自身或其代谢产物抑制皮肤肿瘤细胞增殖，调节免疫功能、解除紫外线导致的免疫抑制。这些研究进展彰显了益生菌在癌症治疗中的潜力。随着后续研究的深入，益生菌及其相关产物有望被开发为安全有效的新型生物制剂，为皮肤癌治疗提供更多温和、精准的新选择。此外，针对目前皮肤中真菌和病毒致癌机制研究相对较少的现状，益生菌可通过竞争排斥、产生抗菌肽等方式直接抑制皮肤真菌过度增殖和病毒复制，为开发“抗真菌/抗病毒型益生菌”提供新策略。未来应建立益生菌-真菌-病毒三元共培养体系，结合单细胞测序明确跨界互作网络，推动皮肤微生态致癌机制研究从“细菌中心”向“多界整合”转变。

2.2 益生菌在抑制皮肤炎症中的作用

目前研究已证实，益生菌可通过调节皮肤微生态、增强皮肤屏障功能、调控免疫反应等途径在皮肤炎症的预防和治疗中显示出显著效果。Kang等^[53]发现，长双歧杆菌(Bifidobacterium longum) RAPO与植物乳植杆菌LRCC5264的混合益生菌(1:1，1×10⁶ CFU/mL)可上调RAW 264.7细胞抗炎因子IL-6，下调促炎因子IL-9；在2,4-二硝基氯苯(2,4-dinitrochlorobenzene, DNCB)诱导的AD小鼠模型中，混合益生菌显著降低皮炎评分、血浆IgE、TEWL及皮肤神经酰胺酶mRNA表达，表明其通过抑制IL-9介导的信号通路并修复皮肤屏障发挥治疗作用。

对于过敏性炎症，Fang等^[54]研究发现，长双歧杆菌CCFM1029通过上调色氨酸代谢产生吲哚-3-甲醛(indole-3-carboxaldehyde, I3CA)，继而激活芳香烃受体(aryl hydrocarbon receptor, AhR)信号通路，从而改善特应性皮炎的皮肤炎症水平。此外，吴毓薇等^[55]发现，植物乳植杆菌SM5-2可通过高效降解肠道、血液及皮肤组织中的组胺缓解小鼠皮肤炎症。Hacini-Rachinel等^[56]发现，口服干酪乳酪杆菌(Lacticaseibacillus casei) DN-114001可显著减少接触性超敏反应(contact hypersensitivity, CHS)诱发性(即症状期)患者外周血中CD8⁺ T细胞向皮肤的募集，同时增加皮肤中FoxP3⁺调节性T细胞(regulatory T cell, Treg)的比例并促进其产生IL-10；皮肤中的IL-10具有减轻角质细胞凋亡及局部过敏性炎症的作用，可改善皮肤过敏症状。此外，Choi等^[47]从发酵黏液乳杆菌(Limosilactobacillus fermentum) SLAM 216中分离并鉴定了胞外囊泡(extracellular vesicles, EVs) LF216-EV，在特应性皮炎小鼠模型发现LF216-EV显著减轻了皮肤炎症反应，缓解了皮肤红斑、脱屑、干燥和抓挠等症状。

综上所述，益生菌影响皮肤炎症的作用机制多样，其在产品开发上的应用也在不断扩展，从口服补充剂到外用化妆品，益生菌为皮肤炎症的治疗提供了新思路。随着研究的深入，基于益生菌的外用制剂有望成为治疗皮肤炎症、促进伤口愈合的新策略，益生菌护肤品的开发也将为皮肤健康管理提供新方向。

2.3 益生菌在预防和修复光老化中的作用

近年来，益生菌在预防和修复皮肤光老化方面的研究取得了长足进展。研究指出，益生菌可通过多种机制发挥抗氧化作用，帮助皮肤抵御光老化。例如，益生菌通过减少基质金属蛋白酶(matrix metalloproteinase, MMPs)的表达延缓光老化进程：植物乳植杆菌HY7714通过抑制JNK/c-Jun信号通路减少MMP-1表达，恢复中波紫外线(ultraviolet B, UVB)照射损伤的前胶原表达；并在无毛小鼠模型中显著抑制UVB诱导的皱纹形成、表皮增厚及真皮MMP-2、MMP-9、MMP-13活性^[57]。此外，短双歧杆菌(Bifidobacterium breve) B-3能明显抑制UVB慢性照射引起的皮肤水分丢失及表皮增厚，同时减轻UVB慢性照射对皮肤紧密连接结构和基底膜的损伤，并抑制紫外线诱导的皮肤白细胞介素-1β (interleukin-1β, IL-1β)产生，预防慢性紫外线照射引起的光老化^[58]。除此之外，益生菌还可通过清除自由基、抑制黑色素形成发挥抗氧化作用。张彩姣等^[59]检测了植物乳植杆菌CGMCC 8198破碎上清液(lysis supernatant, LAS)的抗氧化和抑制黑色素生成活性，发现LAS能显著清除2,2′-联氮-双(3-乙基苯并噻唑啉-6-磺酸) [(2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS]和2,2-二苯基-1-苦基肼(2,2-diphenyl-1-picrylhydrazyl, DPPH)，并显著降低B16F10细胞内黑色素的生成，表现出良好的抗氧化能力。

研究发现，益生菌还可直接抵抗紫外线对细胞的损伤。吴清平等^[60]通过体外细胞实验和动物模型发现发酵黏液乳杆菌XJC60具有抗光老化潜力，进一步通过基因组挖掘和代谢组学验证发现其关键抗光老化代谢产物主要为烟酰胺，但该研究尚未经人体临床试验验证，且菌株活性成分的稳定性及安全性仍需进一步评估。此外，吴清平等^[11]还发现一株具有缓解光老化损伤后真皮细胞凋亡作用的发酵黏液乳杆菌XJC48，其可通过调节胰岛素样生长因子1 (insulin-like growth factor 1, IGF-1)/Akt丝氨酸(Akt serine, Akt)/叉头框蛋白O (forkhead box O, FOXO)通路延长真皮成纤维细胞寿命，协助抵抗紫外线氧化损伤。

除直接抗光老化作用外，益生菌还可通过发酵天然植物成分增强其抗氧化特性，提升抗光老化效果^[11]。例如，经鼠李糖乳酪杆菌HK-9发酵后的广藿香叶提取物相较于未发酵提取物具有更强的皮肤抗氧化和抗炎性能^[61]。布氏慢生乳杆菌(Lentilactobacillus buchneri)发酵的植物提取物可显著增加UVB诱导的I型胶原蛋白表达，降低胶原酶活性和MMPs的mRNA水平，同时促进保湿因子和抗氧化酶的表达，具有显著的抗光老化效果^[62]。

综上所述，益生菌可通过减少MMPs表达、抵抗紫外线损伤等多种机制发挥良好的抗皮肤光老化作用。随着研究的不断深入，益生菌有望成为一种新型皮肤健康保护剂，为预防和治疗皮肤光老化提供新策略。尽管益生菌在皮肤光老化中的作用机制已得到初步揭示，但其最佳应用方式(口服或外用)、活菌与灭活菌的效果差异，以及如何确保益生菌在皮肤上的长期定植等问题仍需进一步研究^[46]。未来可通过开展口服与外用益生菌的对照试验，结合药代动力学研究明确给药途径及抗光老化效果差异；开发荧光标记益生菌结合皮肤拭子时序采样与16S rRNA基因定量PCR，追踪外用益生菌在不同皮肤微环境中的定植动力学，并整合宏基因组功能预测与皮肤代谢组学，为开发具有明确作用机制、标准化活性组分及可控定植能力的下一代益生菌制剂提供理论依据。

3 总结与展望

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皮肤微生态在维持皮肤健康方面发挥着重要作用，包括增强免疫力、提供营养、调节皮肤表面酸碱平衡以及抑制有害微生物生长等。然而，当皮肤微生态失衡时可导致痤疮、特应性皮炎、皮肤癌症等多种皮肤疾病的发生。因此，深入了解皮肤微生态的作用机制对于揭示疾病发生机理和寻找新的治疗靶点具有重要意义。同时，研究已发现通过调节皮肤微生态可有效维持皮肤健康。其中，益生菌作为一类有益微生物，在皮肤健康领域已被广泛研究并应用于多种皮肤疾病的治疗。目前，益生菌已被证实可通过多种机制发挥作用：通过调节皮肤微生态平衡、抑制有害微生物生长，从而减少皮肤炎症和感染风险；通过“肠-脑-皮肤轴”间接改善皮肤健康、降低疾病复发率；通过调节免疫系统、减轻皮肤炎症反应，从而对痤疮等疾病起到治疗作用(图2)。

将上述机制发现转化为临床实践，关键在于建立有效的干预策略。目前改善皮肤微生态的给药方式主要分为口服和外用两大路径，二者协同但作用层面不同。口服给药的核心在于通过“肠道-皮肤轴”发挥系统性调节作用，益生菌经消化后能够重塑肠道菌群平衡，降低全身性炎症，并通过短链脂肪酸等代谢产物经血液循环远程调控皮肤的免疫状态和屏障功能。外用给药则为局部直接干预，将益生菌及其活性代谢产物以精华、乳液、喷雾等形式直接作用于皮肤，快速补充有益菌或营养物质，竞争性抑制病原菌，加固皮肤物理屏障，并调节局部免疫反应。理想状态下，口服调节系统性内环境与外用强化局部微生态防御相结合，可实现从内到外、标本兼治的协同增效，是维护和修复皮肤微生态健康的前沿策略。因此，在现有研究基础上还需进一步探索皮肤微生态、皮肤健康与益生菌三者之间更深层次的关系，以更好地理解皮肤疾病的发生机制，为开发新的治疗方法提供更多理论依据(图3)。

尽管益生菌的内外协同策略展现出广阔前景，但其在实际应用中仍面临严峻的安全性质疑。Wang等^[63]从7种市售益生菌产品中分离到10株细菌，通过全基因组分析发现其中3株含有毒力因子基因、3株携带耐药基因(其中2株显示潜在多药耐药性)，提示益生菌菌株筛选需遵循严格标准。对于长期应用的安全性，Hradicka等^[64]对长期补充复合益生菌(乳酸杆菌混合物)的健康Wistar大鼠进行多维度评估，发现长期益生菌补充导致系统性促炎反应，血清炎症细胞因子显著升高，与胃肠道炎症促进相关的细菌科(如肠杆菌科)丰度增加，提示需关注长期使用益生菌可能产生的副作用。因此，未来研究需建立标准化的菌株筛选流程，并整合基因组学、动物模型及长期临床监测等多种手段，以确保益生菌应用的安全性。

综上所述，皮肤微生态是维系皮肤健康的核心要素，其稳态失衡易诱发痤疮、特应性皮炎等多种皮肤疾病，而益生菌可通过调节微生态平衡、介导“肠-脑-皮肤轴”及调控免疫系统等多重机制改善皮肤健康，口服与外用相结合的协同给药策略更是实现皮肤微生态从内到外修复的前沿路径。然而，益生菌的实际应用仍面临菌株安全性存疑、长期使用潜在副作用等问题，未来需建立标准化的菌株筛选体系，结合基因组学、动物实验及长期临床监测等多手段开展研究，为其临床转化与安全应用提供坚实保障。

基金

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国家重点研发计划(2023YFF1104100)
广东省重点研发专项(2022B1111070006)
广东省科学院项目(2022GDASZH-2022010101)

参考文献

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2026年第66卷第10期

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doi: 10.13343/j.cnki.wsxb.20260196

接收时间：2026-03-10
首发时间：2026-10-13
出版时间：2026-10-04

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收稿日期：2026-03-10
录用日期：2026-04-25

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National Key Research and Development Program of China(2023YFF1104100)

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Guangdong Provincial Key Research and Development Project(2022B1111070006)

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^1.陕西科技大学食品科学与工程学院，陕西西安

^3.广东省微生物分析检测中心，食品药品实验室，广东广州

^4.广东科环生物科技有限公司，广东广州

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Skin problems	Strains	Key mechanism	Literature
Skin cancer	Staphylococcus epidermidis MO34	Produces 6-N-hydroxyaminopurine (6-HAP), selectively inhibiting the proliferation of skin tumor cells	A commensal strain of Staphylococcus epidermidis protects against skin neoplasia^[48]
	Lacticaseibacillus rhamnosus LGG LTA	Enhances immune surveillance in skin tissue and relieves immunosuppression caused by ultraviolet rays	Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective agent against UV-induced carcinogenesis^[49]
	Genetically engineered Staphylococcus epidermidis	Activates CD8⁺ T cells, reaches melanoma, exerts cytotoxic effects and directly kills tumors	Engineered skin bacteria induce antitumor T cell responses against melanoma^[50]
	Lactiplantibacillus plantarum L-14 extract	Inhibits the survival and migration of melanoma A375 cells, induces endogenous apoptosis while reducing the expression of tumor migration-related genes	Anti-cancer effects of Lactiplantibacillus plantarum L-14 cell-free extract on human malignant melanoma A375 cells^[51]
	Lactiplantibacillus plantarum WLPL09	Induces apoptosis of B16F10 melanoma cells, inhibit tumor angiogenesis and regulate the composition of intestinal flora in vivo	Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota^[52]
Skin inflammation	A probiotic mixture of Bifidobacterium longum RAPO and Lactiplantibacillus plantarum LRCC5264 (1:1)	Up-regulates the anti-inflammatory factor IL-6, down-regulate the pro-inflammatory factor IL-9 in RAW 264.7 cells, and significantly reduce the dermatitis score, plasma IgE, TEWL, and the expression of skin ceramidase mRNA	Probiotic consumption alleviates atopic dermatitis-related immune responses in association with gut microbial changes: in vitro and mouse model studies^[53]
	Bifidobacterium longum CCFM1029	Up-regulates tryptophan metabolism and produce indole-3-formaldehyde, and activate the aromatic hydrocarbon receptor signaling pathway	Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis^[54]
	Lactiplantibacillus plantarum SM5-2	It efficiently degrades histamine in the intestines, blood and skin tissues, alleviating inflammation in the skin of mice	Lactiplantibacillus plantarum SM5-2 with high histamine-degrading ability for alleviating atopic dermatitis and its application^[55]
	Lactobacillus casei DN-114001	Reduces the recruitment of CD8⁺ T cells from the peripheral blood of patients with atopic dermatitis to the skin, and increase the proportion of FoxP3⁺ regulatory T cells (Treg) in the skin and promote their production of IL-10	Oral probiotic controls skin inflammation by acting on both effector and regulatory T cells^[56]
	Limosilactobacillus fermentum SLAM 216	It significantly reduces skin inflammatory responses and alleviates symptoms such as skin erythema, desquamation, dryness, and scratching	Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism^[47]
Skin photoaging	Lactiplantibacillus plantarum HY7714	Inhibits the JNK/AP-1 signaling pathway to down-regulate the expression of MMP-1, the activities of MMP-2 and MMP-9 induced by ultraviolet rays, reduce the decrease in procollagen expression caused by UVB irradiation, and thereby relieve oxidative stress caused by UVA	Oral administration of Lactiplantibacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging^[57]
	Bifidobacterium breve B-3	It inhibits the skin water loss and epidermal thickening caused by chronic UVB irradiation, reduces the damage of chronic UVB irradiation to the tight junction structure and basement membrane of the skin, and simultaneously inhibits the production of skin interleukin-1 β (IL-1β) induced by ultraviolet rays	Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice^[58]
	Lactiplantibacillus plantarum CGMCC8198	Significantly eliminate ABTS and DPPH free radicals and significantly reduce the production of melanin in B16F10 cells	Lactiplantibacillus plantarum CGMCC 8198 cell-free supernatant inhibits melanogenesis^[59]
	Limosilactobacillus fermentum XJC60	Stabilizes the NAD⁺/NADH level of the skin after ultraviolet damage, restore mitochondrial membrane potential, reduce ROS and inhibit collagen degradation	Limosilactobacillus fermentum XJC60 with high nicotinamide biosynthesis capacity for anti-photoaging and its application^[60]
	Limosilactobacillus fermentum XJC48	Regulating the IGF-1/Akt/FOXO pathway prolongs the lifespan of dermal fibroblasts and assists in resisting ultraviolet oxidative damage	Limosilactobacillus fermentum XJC48 with dermal fibroblast lifespan extension and anti-skin aging properties and its application^[11]
	Lactobacillus rhamnosus HK-9	Effectively eliminate DPPH free radicals and up-regulate the expression of antioxidant-related genes such as superoxide dismutase (SOD) and glutathione (GSH)	Enhancement of skin antioxidant and anti-inflammatory potentials of Agastache rugosa leaf extract by probiotic bacterial fermentation in human epidermal keratinocytes^[61]
	Lactobacillus buchneri	Significantly increase the expression of type I collagen induced by UVB, reduce collagenase activity and the mRNA level of MMPs, and simultaneously promote the expression of moisturizing factors and antioxidant enzymes	Anti-photoaging effect of plant extract fermented with Lactobacillus buchneri on CCD-986sk fibroblasts and HaCaT keratinocytes^[62]

Skin problems

Strains

Key mechanism

Literature

Skin cancer

Staphylococcus epidermidis MO34

Produces 6-N-hydroxyaminopurine

(6-HAP), selectively inhibiting the proliferation of skin tumor cells

A commensal strain of Staphylococcus epidermidis protects against skin neoplasia^[48]

Lacticaseibacillus rhamnosus LGG LTA

Enhances immune surveillance in skin tissue and relieves immunosuppression caused by ultraviolet rays

Lipoteichoic acid from Lactobacillus rhamnosus GG as an oral photoprotective agent against UV-induced carcinogenesis^[49]

Genetically engineered Staphylococcus epidermidis

Activates CD8⁺ T cells, reaches melanoma, exerts cytotoxic effects and directly kills tumors

Engineered skin bacteria induce antitumor T cell responses against melanoma^[50]

Lactiplantibacillus plantarum L-14 extract

Inhibits the survival and migration of melanoma A375 cells, induces endogenous apoptosis while reducing the expression of tumor migration-related genes

Anti-cancer effects of Lactiplantibacillus plantarum L-14 cell-free extract on human malignant melanoma A375 cells^[51]

Lactiplantibacillus plantarum WLPL09

Induces apoptosis of B16F10 melanoma cells, inhibit tumor angiogenesis and regulate the composition of intestinal flora in vivo

Antitumor effect of exopolysaccharide from Lactiplantibacillus plantarum WLPL09 on melanoma mice via regulating immunity and gut microbiota^[52]

Skin inflammation

A probiotic mixture of Bifidobacterium longum RAPO and Lactiplantibacillus plantarum LRCC5264 (1:1)

Up-regulates the anti-inflammatory factor IL-6, down-regulate the pro-inflammatory factor IL-9 in RAW 264.7 cells, and significantly reduce the dermatitis score, plasma IgE, TEWL, and the expression of skin ceramidase mRNA

Probiotic consumption alleviates atopic dermatitis-related immune responses in association with gut microbial changes: in vitro and mouse model studies^[53]

Bifidobacterium longum CCFM1029

Up-regulates tryptophan metabolism and produce indole-3-formaldehyde, and activate the aromatic hydrocarbon receptor signaling pathway

Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis^[54]

Lactiplantibacillus plantarum SM5-2

It efficiently degrades histamine in the intestines, blood and skin tissues, alleviating inflammation in the skin of mice

Lactiplantibacillus plantarum SM5-2 with high histamine-degrading ability for alleviating atopic dermatitis and its application^[55]

Lactobacillus casei DN-114001

Reduces the recruitment of CD8⁺ T cells from the peripheral blood of patients with atopic dermatitis to the skin, and increase the proportion of FoxP3⁺ regulatory T cells (Treg) in the skin and promote their production of IL-10

Oral probiotic controls skin inflammation by acting on both effector and regulatory T cells^[56]

Limosilactobacillus fermentum SLAM 216

It significantly reduces skin inflammatory responses and alleviates symptoms such as skin erythema, desquamation, dryness, and scratching

Extracellular vesicles of Limosilactobacillus fermentum SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism^[47]

Skin photoaging

Lactiplantibacillus plantarum HY7714

Inhibits the JNK/AP-1 signaling pathway to down-regulate the expression of MMP-1, the activities of MMP-2 and MMP-9 induced by ultraviolet rays, reduce the decrease in procollagen expression caused by UVB irradiation, and thereby relieve oxidative stress caused by UVA

Oral administration of Lactiplantibacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging^[57]

Bifidobacterium breve B-3

It inhibits the skin water loss and epidermal thickening caused by chronic UVB irradiation, reduces the damage of chronic UVB irradiation to the tight junction structure and basement membrane of the skin, and simultaneously inhibits the production of skin interleukin-1 β (IL-1β) induced by ultraviolet rays

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice^[58]

Lactiplantibacillus plantarum CGMCC8198

Significantly eliminate ABTS and DPPH free radicals and significantly reduce the production of melanin in B16F10 cells

Lactiplantibacillus plantarum CGMCC 8198 cell-free supernatant inhibits melanogenesis^[59]

Limosilactobacillus fermentum XJC60

Stabilizes the NAD⁺/NADH level of the skin after ultraviolet damage, restore mitochondrial membrane potential, reduce ROS and inhibit collagen degradation

Limosilactobacillus fermentum XJC60 with high nicotinamide biosynthesis capacity for anti-photoaging and its application^[60]

Limosilactobacillus fermentum XJC48

Regulating the IGF-1/Akt/FOXO pathway prolongs the lifespan of dermal fibroblasts and assists in resisting ultraviolet oxidative damage

Limosilactobacillus fermentum XJC48 with dermal fibroblast lifespan extension and anti-skin aging properties and its application^[11]

Lactobacillus rhamnosus HK-9

Effectively eliminate DPPH free radicals and up-regulate the expression of antioxidant-related genes such as superoxide dismutase (SOD) and glutathione (GSH)

Enhancement of skin antioxidant and anti-inflammatory potentials of Agastache rugosa leaf extract by probiotic bacterial fermentation in human epidermal keratinocytes^[61]

Lactobacillus buchneri

Significantly increase the expression of type I collagen induced by UVB, reduce collagenase activity and the mRNA level of MMPs, and simultaneously promote the expression of moisturizing factors and antioxidant enzymes

Anti-photoaging effect of plant extract fermented with Lactobacillus buchneri on CCD-986sk fibroblasts and HaCaT keratinocytes^[62]