口服益生菌治疗皮肤疾病的作用机制与应用进展

doi:10.35541/cjd.20240514

Abstract

Abstract: 【Abstract】 The gut microbiota is closely associated with skin health, and probiotic supplementation contributes to regulating the gut microbiota and maintaining gut homeostasis. Studies have shown that probiotics, such as Lactobacillus and Bifidobacterium, exert beneficial effects in the treatment of skin diseases through various mechanisms, including modulation of immune responses mediated by metabolites such as short-chain fatty acids, regulation of neuroendocrine functions, and enhancement of barrier structures. This review summarizes the mechanisms by which oral probiotics improve skin health and discusses the advances in their application in the treatment of specific skin diseases, including atopic dermatitis, psoriasis, and acne vulgaris.

Key words: Skin diseases, Gastrointestinal microbiome, Probiotics, Short-chain fatty acids, Gut-skin axis, Dermatitis, atopic, Psoriasis, Acne vulgaris

Ying-Ying DAI Lian Wang XIAN JIANG. Oral probiotics in the treatment of skin diseases: mechanisms of action and advances in their application[J]. Chinese Journal of Dermatology,2026,e20240514. doi:10.35541/cjd.20240514

References ［66］

［1］	Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing［J］. Nature, 2010,464（7285）:59⁃65. DOI: 10.1038/nature08821.
［2］	Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease［J］. Nat Rev Microbiol, 2021,19（1）:55⁃71. DOI: 10. 1038/s41579⁃020⁃0433⁃9.
［3］	Park YM, Lee SY, Kang MJ, et al. Imbalance of gut Streptococcus, Clostridium, and Akkermansia determines the natural course of atopic dermatitis in infant［J］. Allergy Asthma Immunol Res, 2020,12（2）:322⁃337. DOI: 10.4168/aair. 2020.12.2.322.
［4］	Zhao H, Shang L, Zhang Y, et al. IL⁃17A inhibitors alleviate psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function［J］. Front Immunol, 2024,15:1344963. DOI: 10.3389/fimmu.2024.1344963.
［5］	Deng Y, Wang H, Zhou J, et al. Patients with acne vulgaris have a distinct gut microbiota in comparison with healthy controls［J］. Acta Derm Venereol, 2018,98（8）:783⁃790. DOI: 10. 2340/00015555⁃2968.
［6］	Mahmud MR, Akter S, Tamanna SK, et al. Impact of gut microbiome on skin health: gut⁃skin axis observed through the lenses of therapeutics and skin diseases［J］. Gut Microbes, 2022,14（1）:2096995. DOI: 10.1080/19490976.2022.2096995.
［7］	Hill C, Guarner F, Reid G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic［J］. Nat Rev Gastroenterol Hepatol, 2014,11（8）:506⁃514. DOI: 10.1038/nrgastro.2014.66.
［8］	Varela⁃Trinidad GU, Domínguez⁃Díaz C, Solórzano⁃Castanedo K, et al. Probiotics: protecting our health from the gut［J］. Microorganisms, 2022, 10（7）:1428. DOI: 10.3390/microorganisms 10071428.
［9］	Aburto MR, Cryan JF. Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota⁃gut⁃brain axis［J］. Nat Rev Gastroenterol Hepatol, 2024,21（4）:222⁃247. DOI: 10.1038/s41575⁃023⁃00890⁃0.
［10］	Stec A, Sikora M, Maciejewska M, et al. Bacterial Metabolites: a link between gut microbiota and dermatological diseases［J］. Int J Mol Sci, 2023, 24（4）:3494. DOI: 10.3390/ijms24043494.
［11］	Xie L, Alam MJ, Marques FZ, et al. A major mechanism for immunomodulation: dietary fibres and acid metabolites［J］. Semin Immunol, 2023,66:101737. DOI: 10.1016/j.smim.2023. 101737.
［12］	Barman M, Gio⁃Batta M, Andrieux L, et al. Short⁃chain fatty acids （SCFA） in infants' plasma and corresponding mother's milk and plasma in relation to subsequent sensitisation and atopic disease［J］. EBioMedicine, 2024,101:104999. DOI: 10. 1016/j.ebiom.2024.104999.
［13］	Li D, Luo ZB, Zhu J, et al. Ginsenoside F2⁃mediated intestinal microbiota and its metabolite propionic acid positively impact the gut⁃skin axis in atopic dermatitis mice［J］. J Agric Food Chem, 2024,72（1）:339⁃350. DOI: 10.1021/acs.jafc.3c06015.
［14］	Zhu L, Jian X, Zhou B, et al. Gut microbiota facilitate chronic spontaneous urticaria［J］. Nat Commun, 2024,15（1）:112. DOI: 10.1038/s41467⁃023⁃44373⁃x.
［15］	Sanchez HN, Moroney JB, Gan H, et al. B cell⁃intrinsic epigenetic modulation of antibody responses by dietary fiber⁃derived short⁃chain fatty acids［J］. Nat Commun, 2020,11（1）:60. DOI: 10.1038/s41467⁃019⁃13603⁃6.
［16］	Lu W, Deng Y, Fang Z, et al. Potential role of probiotics in ameliorating psoriasis by modulating gut microbiota in imiquimod⁃induced psoriasis⁃like mice［J］. Nutrients, 2021, 13（6）:2010. DOI: 10.3390/nu13062010.
［17］	Schwarz A, Bruhs A, Schwarz T. The short⁃chain fatty acid sodium butyrate functions as a regulator of the skin immune system［J］. J Invest Dermatol, 2017,137（4）:855⁃864. DOI: 10. 1016/j.jid.2016.11.014.
［18］	Schwarz A, Philippsen R, Schwarz T. Induction of regulatory T cells and correction of cytokine disbalance by short⁃chain fatty acids: implications for psoriasis therapy［J］. J Invest Dermatol, 2021,141（1）:95⁃104.e2. DOI: 10.1016/j.jid.2020. 04.031.
［19］	Szelest M, Walczak K, Plech T. A new insight into the potential role of tryptophan⁃derived AhR ligands in skin physiological and pathological processes［J］. Int J Mol Sci, 2021, 22（3）:1104. DOI: 10.3390/ijms22031104.
［20］	Brown J, Robusto B, Morel L. Intestinal dysbiosis and tryptophan metabolism in autoimmunity［J］. Front Immunol, 2020,11:1741. DOI: 10.3389/fimmu.2020.01741.
［21］	Ferreira Branquinho MS, Silva M, Castilho GA, et al. Kynurenine inhibits melanogenesis in human melanocyte⁃keratinocyte co⁃cultures and in a reconstructed 3D skin model［J］. Exp Dermatol, 2022,31（3）:427⁃432. DOI: 10.1111/exd.14486.
［22］	Fang Z, Pan T, Li L, et al. Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut⁃skin axis［J］. Gut Microbes, 2022,14（1）:2044723. DOI: 10.1080/19490976.2022.2044723.
［23］	Yang L, Li D, Sun S, et al. Dupilumab therapy improves gut microbiome dysbiosis and tryptophan metabolism in Chinese patients with atopic dermatitis［J］. Int Immunopharmacol, 2024,131:111867. DOI: 10.1016/j.intimp.2024.111867.
［24］	Collins SL, Stine JG, Bisanz JE, et al. Bile acids and the gut microbiota: metabolic interactions and impacts on disease［J］. Nat Rev Microbiol, 2023,21（4）:236⁃247. DOI: 10.1038/s41579⁃022⁃00805⁃x.
［25］	王凯丽. 从次级胆汁酸调控Th17/Treg免疫平衡探讨解毒祛瘀滋阴方治疗SLE的作用机制［D］. 杭州: 浙江中医药大学, 2023. DOI: 10.27465/d.cnki.gzzyc.2023.000212.
［26］	Chen X, Chen Y, Stanton C, et al. Dose⁃response efficacy and mechanisms of orally administered bifidobacterium breve CCFM683 on IMQ⁃induced psoriasis in mice［J］. Nutrients, 2023, 15（8）:1952. DOI: 10.3390/nu15081952.
［27］	Xiao W, Chen M, Peng Q, et al. Lithocholic acid promotes rosacea⁃like skin inflammation via G protein⁃coupled bile acid receptor 1［J］. Biochim Biophys Acta Mol Basis Dis, 2022,1868（12）:166563. DOI: 10.1016/j.bbadis.2022.166563.
［28］	Pessôa R, Clissa PB, Sanabani SS. The interaction between the host genome, epigenome, and the gut⁃skin axis microbiome in atopic dermatitis［J］. Int J Mol Sci, 2023, 24（18）:14322. DOI: 10.3390/ijms241814322.
［29］	Sikora M, Kiss N, Stec A, et al. Trimethylamine N⁃oxide, a gut microbiota⁃derived metabolite, is associated with cardiovascular risk in psoriasis: a cross⁃sectional pilot study［J］. Dermatol Ther （Heidelb）, 2021,11（4）:1277⁃1289. DOI: 10.1007/s13555⁃021⁃00547⁃3.
［30］	Barrea L, Muscogiuri G, Pugliese G, et al. Association of trimethylamine N⁃oxide （TMAO） with the clinical severity of hidradenitis suppurativa （acne inversa）［J］. Nutrients, 2021, 13（6）:1997. DOI: 10.3390/nu13061997.
［31］	Li Y, Liang L, Deng X, et al. Lipidomic and metabolomic profiling reveals novel candidate biomarkers in active systemic lupus erythematosus［J］. Int J Clin Exp Pathol, 2019,12（3）:857⁃866.
［32］	Verde L, Frias⁃Toral E, Cacciapuoti S, et al. Very low⁃calorie ketogenic diet （VLCKD）: a therapeutic nutritional tool for acne?［J］. J Transl Med, 2024,22（1）:322. DOI: 10.1186/s12967⁃024⁃05119⁃5.
［33］	Verde L, Cacciapuoti S, Caiazzo G, et al. Very low⁃calorie ketogenic diet （VLCKD） in the management of hidradenitis suppurativa （acne inversa）: an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study［J］. J Transl Med, 2024,22（1）:149. DOI: 10.1186/s12967⁃024⁃04853⁃0.
［34］	Chen G, Chen ZM, Fan XY, et al. Gut⁃Brain⁃skin axis in psoriasis: a review［J］. Dermatol Ther （Heidelb）, 2021,11（1）:25⁃38. DOI: 10.1007/s13555⁃020⁃00466⁃9.
［35］	Ralvenius WT, Neumann E, Pagani M, et al. Itch suppression in mice and dogs by modulation of spinal α2 and α3GABAA receptors［J］. Nat Commun, 2018,9（1）:3230. DOI: 10.1038/s41467⁃018⁃05709⁃0.
［36］	Thirion F, Guilly S, Fromentin S, et al. Changes in gut microbiota of patients with atopic dermatitis during balneotherapy［J］. Clin Cosmet Investig Dermatol, 2022,15:163⁃176. DOI: 10.2147/CCID. S342104.
［37］	Uehara E, Hokazono H, Sasaki T, et al. Effects of GABA on the expression of type I collagen gene in normal human dermal fibroblasts［J］. Biosci Biotechnol Biochem, 2017,81（2）:376⁃379. DOI: 10.1080/09168451.2016.1238296.
［38］	Wang X, Su Y, Cai Z, et al. γ⁃Aminobutyric acid promotes the inhibition of hair growth induced by chronic restraint stress［J］. Life Sci, 2023,317:121439. DOI: 10.1016/j.lfs.2023.121439.
［39］	Wardhana M, Windari M, Puspasari N, et al. Role of serotonin and dopamine in psoriasis: a case⁃control study［J］. Open Access Maced J Med Sci, 2019,7（7）:1138⁃1142. DOI: 10.3889/oamjms. 2019.267.
［40］	Keren A, Gilhar A, Ullmann Y, et al. Instantaneous depolarization of T cells via dopamine receptors, and inhibition of activated T cells of psoriasis patients and inflamed human skin, by D1⁃like receptor agonist: fenoldopam［J］. Immunology, 2019,158（3）:171⁃193. DOI: 10.1111/imm.13109.
［41］	Vijay A, Kouraki A, Gohir S, et al. The anti⁃inflammatory effect of bacterial short chain fatty acids is partially mediated by endocannabinoids［J］. Gut Microbes, 2021,13（1）:1997559. DOI: 10.1080/19490976.2021.1997559.
［42］	Varian BJ, Poutahidis T, DiBenedictis BT, et al. Microbial lysate upregulates host oxytocin［J］. Brain Behav Immun, 2017,61:36⁃49. DOI: 10.1016/j.bbi.2016.11.002.
［43］	Woo YR, Kim HS. Interaction between the microbiota and the skin barrier in aging skin: a comprehensive review［J］. Front Physiol, 2024,15:1322205. DOI: 10.3389/fphys.2024.1322205.
［44］	Tang X. Probiotic Roles of Clostridium butyricum in piglets: considering aspects of intestinal barrier function［J］. Animals （Basel）, 2024, 14（7）:1069. DOI: 10.3390/ani14071069.
［45］	Polak K, Bergler⁃Czop B, Szczepanek M, et al. Psoriasis and gut microbiome⁃current state of art［J］. Int J Mol Sci, 2021, 22（9）:4529. DOI: 10.3390/ijms22094529.
［46］	Drago F, De Col E, Agnoletti AF, et al. The role of small intestinal bacterial overgrowth in rosacea: a 3⁃year follow⁃up［J］. J Am Acad Dermatol, 2016,75（3）:e113⁃e115. DOI: 10.1016/j.jaad.2016.01.059.
［47］	Woo YR, Han YJ, Kim HS, et al. Updates on the risk of neuropsychiatric and gastrointestinal comorbidities in rosacea and its possible relationship with the gut⁃brain⁃skin axis［J］. Int J Mol Sci, 2020, 21（22）:8427. DOI: 10.3390/ijms21228427.
［48］	Yang Z, Zhou Y, Han Z, et al. The effects of probiotics supplementation on Helicobacter pylori standard treatment: an umbrella review of systematic reviews with meta⁃analyses［J］. Sci Rep, 2024,14（1）:10069. DOI: 10.1038/s41598⁃024⁃59399⁃4.
［49］	Liang B, Yuan Y, Peng XJ, et al. Current and future perspectives for Helicobacter pylori treatment and management: from antibiotics to probiotics［J］. Front Cell Infect Microbiol, 2022,12:1042070. DOI: 10.3389/fcimb.2022.1042070.
［50］	Wiese⁃Szadkowska M, Helmin⁃Basa A, Eljaszewicz A, et al. Selected commensal bacteria change profiles of Helicobacter pylori⁃induced T cells via dendritic cell modulation［J］. Helicobacter, 2019,24（6）:e12614. DOI: 10.1111/hel.12614.
［51］	Boyanova L, Gergova G, Markovska R, et al. Bacteriocin⁃like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains［J］. Lett Appl Microbiol, 2017,65（6）:469⁃474. DOI: 10.1111/lam.12807.
［52］	Augusto de Oliveira MF, Agne DB, Bastos L, et al. Atopic dermatitis pediatric patients show high rates of nasal and intestinal colonization by methicillin⁃resistant Staphylococcus aureus and coagulase⁃negative staphylococci［J］. BMC Microbiol, 2024,24（1）:42. DOI: 10.1186/s12866⁃023⁃03165⁃5.
［53］	Piewngam P, Zheng Y, Nguyen TH, et al. Pathogen elimination by probiotic Bacillus via signalling interference［J］. Nature, 2018,562（7728）:532⁃537. DOI: 10.1038/s41586⁃018⁃0616⁃y.
［54］	Trompette A, Pernot J, Perdijk O, et al. Gut⁃derived short⁃chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation［J］. Mucosal Immunol, 2022,15（5）:908⁃926. DOI: 10.1038/s41385⁃022⁃00524⁃9.
［55］	Li W, Wang Z, Cao J, et al. Melatonin improves skin barrier damage caused by sleep restriction through gut microbiota［J］. J Pineal Res, 2023,75（1）:e12874. DOI: 10.1111/jpi.12874.
［56］	Lee K, Kim HJ, Kim SA, et al. Exopolysaccharide from Lactobacillus plantarum HY7714 protects against skin aging through skin⁃gut axis communication［J］. Mol Basel Switz, 2021, 26（6）:1651. DOI: 10.3390/molecules26061651.
［57］	Seo E, Song HH, Kim H, et al. Oral administration of mixed probiotics improves photoaging by modulating the cecal microbiome and MAPK pathway in UVB⁃irradiated hairless mice［J］. Mol Nutr Food Res, 2023,67（12）:e2200841. DOI: 10.1002/mnfr.202200841.
［58］	Ai J, Ma W, Pan Z, et al. Ameliorative effect of Lactobacillus plantarum CCFM8661 on oleic acid⁃induced acne: integrated gut microbiota link to acne pathogenesis［J］. J Sci Food Agric, 2024,104（1）:328⁃339. DOI: 10.1002/jsfa.12921.
［59］	Rybak I, Haas KN, Dhaliwal SK, et al. Prospective placebo⁃controlled assessment of spore⁃based probiotic supplementation on sebum production, skin barrier function, and acne［J］. J Clin Med, 2023, 12（3）:895. DOI: 10.3390/jcm12030895.
［60］	Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and prebiotic galacto⁃oligosaccharides in the prevention of allergic diseases: a randomized, double⁃blind, placebo⁃controlled trial［J］. J Allergy Clin Immunol, 2007, 119（1）:192⁃198. DOI: 10. 1016/j.jaci.2006.09.009.
［61］	Voigt J, Lele M. Lactobacillus rhamnosus used in the perinatal period for the prevention of atopic dermatitis in infants: a systematic review and meta⁃analysis of randomized trials［J］. Am J Clin Dermatol, 2022,23（6）:801⁃811. DOI: 10.1007/s40257⁃022⁃00723⁃x.
［62］	Navarro⁃López V, Martínez⁃Andrés A, Ramírez⁃Boscá A, et al. Efficacy and safety of oral administration of a mixture of probiotic strains in patients with psoriasis: a randomized controlled clinical trial［J］. Acta Derm Venereol, 2019,99（12）:1078⁃1084. DOI: 10.2340/00015555⁃3305.
［63］	Atefi N, Mohammadi M, Bodaghabadi M, et al. Evaluating the effectiveness of probiotic supplementation in combination with doxycycline for the treatment of moderate acne: a randomized double⁃blind controlled clinical trial［J］. J Cosmet Dermatol, 2025,24（1）:e16614. DOI: 10.1111/jocd.16614.
［64］	Yu J, Duan Y, Zhang M, et al. Effect of combined probiotics and doxycycline therapy on the gut⁃skin axis in rosacea［J］. mSystems, 2024,9（11）:e0120124. DOI: 10.1128/msystems.01201⁃24.
［65］	张红燕, 李丽, 王明霞, 等. 益生菌在痤疮治疗中的应用进展［J］. 中华皮肤科杂志, 2023,56（3）:283⁃285. DOI: 10.35541/cjd.20200657.
［66］	Gao YW, Yao X, Yang XY. Application of bioengineered bacteria in allergic diseases［J］. Int J Dermatol Venereol, 2023, 6（1）:43. DOI: 10.1097/JD9.0000000000000242.

[1]	China Dermatologist Association, Chinese Society of Dermatology, Dermatology Branch of China International Exchange and Promotive Association for Medical and Health Care, Dermatology Branch of China Alliance for Rare Diseases. Expert consensus on the long-term management of plaque psoriasis with biologic agents （2026 edition） [J]. Chinese Journal of Dermatology, 2026, 59(9): 827-843.
[2]	Ma Jing, Luan Chao, Chen Kun. Lipid metabolism-related proteins in psoriasis [J]. Chinese Journal of Dermatology, 2026, 59(9): 915-918.
[3]	Chen Xingyu, Yao Xu. Role of neutrophils in inflammatory dermatoses [J]. Chinese Journal of Dermatology, 2026, 59(9): 905-910.
[4]	Zhang Hanmei, Feng Suying. Gut, skin, and oral microbiota in autoimmune bullous diseases [J]. Chinese Journal of Dermatology, 2026, 59(9): 902-905.
[5]	Huang Jinjin, Li Zhuqing, Lu Juanjuan, Li Shuhua, Cao Zhe, Xu Donghua, Wang Guoying, . Role of nucleotide-binding oligomerization domain-like receptor protein 3 in the pathogenesis of androgenetic alopecia and therapeutic advances [J]. Chinese Journal of Dermatology, 2026, 59(8): 802-805.
[6]	Shi Rongcan¹, ², Yu Zengyang², ³, Luo Qingqiong², Ma Rui¹, ², Jiang Xingyu¹, ², Wang Yuanyuan¹, ², Cai Jiangluyi¹, ², Shi Yuling¹, ². Palmitoyl-proteomic profiles of psoriatic lesions and their role in inflammatory responses: a preliminary study [J]. Chinese Journal of Dermatology, 2026, 59(8): 738-749.
[7]	Writing Committee Expert Group on “Diagnosis and treatment of pustular psoriasis: a Chinese expert consensus statement （ edition）”. Diagnosis and treatment of pustular psoriasis: a Chinese expert consensus statement （2026 edition） [J]. Chinese Journal of Dermatology, 2026, 59(8): 717-727.
[8]	Wei Jin¹, Yan Huiwen¹, Zhang Jianzhong², Lun Wenhui¹. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis complicated by HIV infection: a clinical observation of 10 cases [J]. Chinese Journal of Dermatology, 2026, 59(7): 671-674.
[9]	Yuwen Tianyi¹, Zhou Zizhen¹, Tian Jingyu¹, Chen Sihan², Li Min², Zhang Fengyuan¹, Gu Heng, ², Chen Xu, ². Expression of the glutaminase 1/ammonia metabolism axis in keratinocytes in ultraviolet B-induced acute skin injury and psoriatic skin inflammation [J]. Chinese Journal of Dermatology, 2026, 59(7): 654-661.
[10]	Zhang Xiaoxu, Luo Suju. Efficacy and safety of upadacitinib in the treatment of six cases of palmoplantar pustulosis [J]. Chinese Journal of Dermatology, 2026, 59(5): 459-463.
[11]	Xu Zhuohong, Zhou Huan, Hu Yu, Gu Heng. Balneotherapy in skin diseases [J]. Chinese Journal of Dermatology, 2026, 59(5): 482-485.
[12]	Chen Tingnan, Liang Jingyao, Deng Shilin, Shu Zhirong, Zhang Xibao. Immunophenotypic switching between psoriasis and atopic dermatitis after biologic therapy: a systematic review of clinical features, mechanisms and management strategies [J]. Chinese Journal of Dermatology, 2026, 59(5): 474-481.
[13]	Chinese Association of Rehabilitation Dermatology, Combination of Traditional and Western Medicine Dermatology. Expert consensus on the diagnosis, treatment and rehabilitation of psoriasis in the elderly （2026 edition） [J]. Chinese Journal of Dermatology, 2026, 59(5): 407-418.
[14]	Chinese Society of Dermatology, China Dermatologist Association, Dermatology Branch of China International Exchange and Promotive Association for Medical and Health Care, Dermatology Branch of China Alliance for Rare Diseases. Expert consensus on fecal microbiota transplantation in the treatment of psoriasis （2026 edition） [J]. Chinese Journal of Dermatology, 2026, 59(5): 427-435.
[15]	Yang Jianqiu, Liu Qiannan, Zhou Shengru, Li Min, . Pyogenic arthritis, pyoderma gangrenosum and acne syndrome: a case report and literature review [J]. Chinese Journal of Dermatology, 2026, 59(4): 366-369.

Oral probiotics in the treatment of skin diseases: mechanisms of action and advances in their application

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［66］

Related Articles 15

Metrics

Comments

Recommended 0