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Abstract

The skin microbiota is crucial in defending against toxic, solar, and pathogenic assaults, yet it can also precipitate dermatosis when its equilibrium is disrupted. The composition and distribution of various microorganisms within the skin maintain a dynamic balance, modulating the barrier function and the immune system, thereby constituting the skin microbiota. This microbiota not only offers new insights into pathological microbe-host interactions and associated dermatoses but also inspires innovative therapeutic strategies that promise high efficacy and reduced symptomatology. In this review, we synthesize recent advancements in the field of skin microbiota, focusing on its relationship with dermatosis and the application of microbiota-based therapies in skin diseases. Our aim is to scrutinize the current understanding of the skin microbiota’s role, ranging from a protective barrier to a causative agent of dermatosis.

Keywords

clinical trial dermatosis microbial therapy probiotic skin microbiota

Introduction

The skin, the human body’s largest organ, covers an area of 1.2–2 m² and constitutes approximately 16% of total body mass. Its thickness ranges from 0.5 to 4 mm, with a layered structure that includes the subcutaneous tissue, dermis, and epidermis, progressing from the deepest to the outermost layer. In addition, accessory organs such as hair follicles, sebaceous glands, and sweat glands offer a diverse array of environments for surface microorganisms.¹ The skin’s microbiota is the second most abundant in the body, after the gut, housing around 40 trillion microorganisms—accounting for 16% of the total symbiotic microorganisms within the human body.² These microorganisms primarily reside in the epidermis, sebum membrane, hair follicles, glands, and even the subcutaneous fat.³ Skin microorganisms can be categorized based on their duration of residence into resident and transient bacteria, and by their effects on the host, into pathogenic and non-pathogenic bacteria.⁴ The diversity of the skin microbiota is influenced by the skin’s moisture levels and structural variations.⁴ In this article, we aim to provide an overview of the structure of the skin microbiota and discuss the diseases and treatment strategies associated with it.

Overview of skin microbiota

Distribution and dynamic changes of skin microbiota

The skin provides a multitude of niches where diverse microbial communities are subjected to various ecological pressures. These pressures include the sebum-rich environment, temperature fluctuations, humidity levels, the presence of wrinkles, and the composition of antimicrobial peptides and lipids. Consequently, the distribution of these microbial communities varies across different regions of the skin⁵ (Figure 1). The facial skin, often characterized by its oily nature, provides an ideal environment for the growth and reproduction of lipophilic Propionibacterium species. In contrast, moist regions such as the axilla are preferentially colonized by Corynebacterium and Staphylococcus species. The feet exhibit a remarkable diversity of microbial colonization, including fungi such as Aspergillus, Rhodotorula, Cryptococcus, and Epicoccum.⁵ Sweat glands secrete sweat, which is rich in antimicrobial molecules and can lead to skin acidification. This acidic environment is not conducive to the growth and colonization of many microorganisms. In contrast, sebaceous glands secrete sebum, a lipid-rich substance that fosters the colonization of lipophilic bacteria, such as Propionibacterium. Furthermore, regions with high temperature and humidity are particularly favorable for the proliferation of Corynebacterium and Staphylococcus aureus.¹

Figure 1.

Variations in skin microbiota composition across different body sites. (a) Relative abundance of skin microbiota communities at various body sites.⁴ (b) Nonmetric multidimensional scaling ordination illustrating the similarity in bacterial composition among different body sites, with color coding to indicate the specific site.⁶ (c) Stacked bar plot depicting the relative abundance of the top ten most abundant bacterial families across five distinct body sites. The “Others” category encompasses less prevalent taxa.⁶

The microbiome within a single niche of the human body exhibits significant heterogeneity due to a variety of intrinsic and environmental factors. For instance, the microbial communities on the feet are influenced by factors such as skin thickness, anatomical features, the distribution of sweat glands, skin pH, and oxygen availability.⁷ The human foot is characterized by a variety of anatomical features, including fossa, pouches, and skin folds, which create distinct microenvironments that influence microbial colonization. The plantar heel, with its thicker epidermis and relatively drier conditions, is predominantly populated by Staphylococcaceae, while the presence of Proteobacteria and Bacteroidetes is less abundant and is comparatively sparse. In contrast, the interdigital web spaces between the toes, which are characterized by thinner epidermal layers and a moist, warm environment, are commonly and abundantly inhabited by Actinobacteria and Firmicutes.⁸ The soles and toe clefts of the feet are known to be colonized by strains of Methylobacterium. Significant quantitative variations in microbial counts have been observed across different sites on the foot. For instance, the mean total counts in the fourth toe cleft reach 1.04 × 10⁷ colony-forming units (cfu) per square centimeter of skin, whereas the counts on the sole and dorsal surface of the feet are 4.08 × 10⁵ cfu/cm² and 1.21 × 10³ cfu/cm², respectively.⁹ Furthermore, conditions such as diabetes mellitus, chronic venous insufficiency, medication use, and skin injuries can also significantly impact the distribution of the microbiome.

Aging is indeed a critical factor in the variation of the skin microbiome.⁹ As individuals age, several skin characteristics change, including the development of spots and wrinkles, an increase in epidermal thickness, and a decline in collagen and elastin fibers. During the first 8 years of human growth and development, microbial diversity on the skin surface increases with age, which correlates with a decrease in the dominance of lactobacilli on the skin. By the age of 14, the skin microbiota has matured, and its diversity is quite similar to that of adults.¹⁰ On the skin of older individuals, the proportion of Corynebacterium increased on the cheek and forehead, while the proportion of Acinetobacter increased on the scalp.⁹ The variation of Malassezia species changes with age.¹¹ On the trunk skin of children, Malassezia furfur is predominant; in individuals aged 21–35, Malassezia restricta was characteristic; in subjects aged 36–50, Malasseiza was the predominant species, whereas M. sympodial was more prominent in older individuals.

The differences in daily lifestyles will gradually lead to differences in the types of skin microbiota among individuals. When deodorants or antiperspirants are stopped, the bacterial density on the skin surface increases, approaching the bacterial density of individuals without using any products. However, when they use deodorants or antiperspirants again, the bacterial density drops sharply.¹² 16S rRNA sequencing showed that individuals who habitually use antiperspirants or deodorants have a predominantly Staphylococcus armpit bacterial community, while individuals who do not use such products have a predominantly Corynebacterium armpit bacterial community. Furthermore, the application of makeup has been shown to significantly enhance the diversity of the microbial community on the forehead. This finding has spurred the development of numerous skincare products designed to stabilize and enrich the skin’s microbiota.

Microecology regulation and protection mechanism

The skin microbiota achieves stability and performs its functions through a complex network of interactions that serve both internal regulation and external feedback mechanisms. These interactions primarily encompass three types: microbiota-microbiota interactions, microbiota-host interactions, and environment-microbiota interactions. The commensal skin microbiota plays a crucial role in protecting the skin from infections by outcompeting pathogenic organisms and contributes to immune homeostasis by modulating host immune responses in a manner that can be both detrimental and beneficial.^13,14

The interaction between the skin microbiota and its host is indeed reciprocal. Antimicrobial peptides, released by epithelial and immune cells within the skin, play a critical role in controlling microbial colonization. These peptides help to regulate which microbes can inhabit the skin’s surface. In addition, bacteriocins produced by Gram-positive bacteria, such as Lactococcus, Streptomyces spp., and Streptococcus, inhibit the growth of competing bacterial strains. This competition for nutrients and other resources is a key aspect of the microbiota’s dynamic balance.¹⁵ On the nasal cavity surface, colonization by S. aureus is curbed in individuals harboring specific strains of S. epidermidis.¹⁶ The protease secreted by S. epidermidis dismantles the biofilms established by S. aureus, and a thiolactone-containing peptide from S. epidermidis disrupts the S. aureus agr quorum sensing system, which governs the expression of various virulence factors.

Furthermore, it has been established that skin microbial colonization plays a crucial role in triggering effective T-cell responses and in mounting protective immunity against infections, such as those caused by the parasite Leishmania. major.^17,18 Notably, the immune deficiency observed in germ-free animals, which are unable to develop protective T-cell immunity to L. major, can be remedied through the introduction of skin microbiota. The commensal bacterium S. epidermidis, when colonizing the skin of these mice, modulates interleukin (IL)-1-dependent inflammatory responses, which is sufficient to restore effective T-cell immunity against L. major. We are confident that a deeper understanding of the role of skin commensals can be achieved through collaborative efforts across various disciplines, potentially leading to significant contributions to human health.

Dysfunctional skin microecology and dermatosis

Conversely, an imbalance in the skin’s microecology can lead to dermatosis. In recent years, the extensive use of antibacterial drugs has led to an increase in pathogenic bacterial resistance, and in some cases, the emergence of “superbugs.” As research continues to unfold, it has become evident that a variety of dermatoses are associated with the skin microbiota (Figure 2). To better understand the mechanisms underlying skin immune homeostasis and the development of dermatosis, further investigation into the dialogue between the microbiota and the host is essential (Table 1).

Figure 2.

The distribution of skin microbiota and related dermatosis. (a) Distribution of various microorganisms (middle circle) across different skin regions (inner circle) and related skin diseases (outer circle). (b) Atopic dermatitis flares are marked by significant shifts in the relative abundance of several bacterial species.¹⁹ Compared to healthy skin (left), there is a notable increase in the proportion of Staphylococcaceae (right). (c) The relative abundance of Cutibacterium acnes strain in the nose pilosebaceous unit varies between acne patients (middle, right) and healthy individuals (left). In contrast to healthy individuals (left), the relative abundance of C. acnes strains RT3 and RT6 is reduced, while strains RT4, RT5, RT7, RT8, RT9, and RT10 are increased in acne-induced dysbiosis (middle). The chronic nature of acne vulgaris and its partial response to antibiotic treatment may be attributed to biofilm-forming C. acnes strains that reside in various skin appendages, including the skin surface, sebaceous glands, hair follicles, and pores themselves (right).

Table 1.

Dermatosis and related microorganisms.

Skin diseases	Related microorganisms changes	Possible mechanisms	References
SCC	Staphylococcus aureus increased	Increased expression of hBD-2	Madhusudhan et al.²⁰
	Malassezia decreased	Skin barrier disruption	Li et al.²¹
Melanoma	Corynebacterium increased in stage III/IV patients	Induce the upregulating IL-6 and its signal activator and transducer of transcription 3 via IL-17	Mizuhashi et al.²²
AD	S. aureus increased	Cause an imbalance of Th1 and Th2	Kong et al.²³
	S. epidermidis decreased	Induced the release of IL-10 from skin dendritic cells	Laborel-Préneron et al.²⁴
Acne	Colonization of S. epidermis and Cutibacterium acnes	Causes activation of Toll like receptor 2 (TLR2) in monocytes leads to the production of pro-inflammatory cytokines IL-8 and IL-12	Graham et al.²⁵
Psoriasis	Corynebacterium, Staphylococcus, Propionibacterium, and Streptococcus increased	Activating a systemic pro-inflammatory status	Alekseyenko et al.²⁶
	Streptococcus increased, but Streptococcus and Propionibacterium decreased	The interplay between bacteria and immune cells	Fahlén et al.²⁷
	Propionibacterium decreased	Disordered ecological niches	Gao et al.²⁸
	Firmicutes decreased, but Proteobacteria increased	Altering the T-cell response	Zákostelská et al.²⁹
Diabetic foot ulcer	Induced expression of USA300 virulence factors Panton-Valentine leukocidin and α-hemolysin	Wound reepithelialization was significantly delayed by mixed-species biofilms through suppression of keratinocyte growth factor 1	Pastar et al.³⁰
	The abundance of Actinobacteria was higher, but the abundance of Staphylococcus species was lower	Disorgdered bacterial diversity	Redel et al.³¹
	S. aureus became the most common species, commensal bacteria including Corynebacterium and Propionibacterium species were highly prevalent	Undefined mechanism	Wolcott et al.³²
	High microbial diversity, anaerobic bacteria, and Gram-negative Proteobacteria increased in those of long duration, while Staphylococcus, mainly S. aureus was found in superficial ulcers and those of short duration	Dynamic wound microbiome is indicative of clinical outcomes	Loesche et al.³³
	Two clinical S. aureus isolates were found to be associated with nonhealing wounds, SA10757 and SA7372, Alcaligenes faecalis associated with high levels of IL-8 and other cytokines that enhance wound healing	Functional level differences between microbiota species, or even strains may determine the clinical outcomes of chronic wounds	Kalan et al.³⁴

hBD-2, human beta defensin-2; IL, interleukin.

Tumors

Commensal bacteria have been shown to directly influence tumor development, progression, and response to therapies.³⁵ Three primary mechanisms have been identified as potential modes of crosstalk between skin microbes and tumorigenesis: direct facilitation of tumor development through increased mutagenesis, modulation of oncogenes and related signaling pathways, and regulation of the host immune system.^36–40 In comparison to normal tissues, S. aureus colonization is higher in squamous cell carcinoma (SCC) tissues and has been linked to an increased expression of human beta defensin-2 (hBD-2), which directly accelerates SCC proliferation.^20,41 Conversely, a decrease in the colonization of Malassezia in SCC skin compared to non-lesional healthy skin has been observed.²¹ As a lipophilic resident commensal, the reduced colonization of Malassezia is attributed to skin barrier disruption and decreased sebum availability. These findings suggest that tumor development can influence the distribution of microbes on the skin.

Within malignant melanoma tissues, the presence of the bacterial genus Corynebacterium correlates more significantly with patients in stages III/IV compared to those in stages I/II.²² Patients with a positive Corynebacterium profile exhibit a higher level of IL-17 positive cells, which may stimulate melanoma growth by upregulating IL-6 and the signal transducer and activator of transcription 3 (STAT3) pathway.⁴² This upregulation suggests a potential role for skin microbes in tumorigenesis, highlighting the possibility of developing microorganism-based therapeutic strategies.⁴³

Atopic dermatitis

Atopic dermatitis (AD) is a chronic skin condition characterized by a propensity for recurrence.⁴⁴ Linked to a disrupted microbiome, S. aureus emerges as the predominant colonizer and pathogen.⁴⁵ Studies have identified a temporal shift in the AD microbiome, with a loss of community diversity preceding flares and subsequent dominance of S. aureus dominant.^23,46 While the exact mechanisms linking AD to a disordered microbiome are not fully understood, early life colonization with non-S. aureus commensal bacteria has been shown to decrease the risk of AD, whereas early colonization with S. aureus can precipitate its development.^47,48 S. aureus may disrupt the balance of Th1 and Th2 cells in the skin of AD patients, elevate pro-inflammatory cytokine IL-4 levels, increase serum immunoglobulin E, and suppress the growth of regulatory T-cells, thereby contributing to inflammation.^24,49 However, symbiotic bacteria like S. epidermidis can mitigate these pro-inflammatory effects by stimulating the release of IL-10 from skin dendritic cells.²⁴

Acne

Acne is one of the most prevalent skin conditions, characterized by a complex etiology. The interplay between the host and the microbiome, which regulates both innate and adaptive immune homeostasis, appears to be a critical factor in its pathogenesis.⁵⁰ In acne, S. epidermis and Cutibacterium acnes are key microbial inhabitants that, while implicated in the development of acne, also play a role in maintaining skin health by suppressing the growth and proliferation of potential pathogens. The balance of the acne microbiota is disrupted, leading to alterations in both composition and activity. C. acnes, in particular, displays TLR2 ligands that are thought to trigger inflammation by stimulating the release of IL-1α and granulocyte macrophage colony stimulating factor (GM-CSF).²⁵ In addition, the presence of C. acnes leads to the activation of TLR2 in monocytes, which in turn promotes the production of pro-inflammatory cytokines such as IL-8 and IL-1β.⁵¹ Certain host antimicrobial peptides, including hBD-2 and hBD-3, are upregulated in acne lesions and may be induced by components of C. acnes culture supernatants. These peptides are believed to contribute to the pathogenesis of acne.^52–54 C. acnes exhibits substantial genomic and functional heterogeneity, which can influence its role in both health and disease.⁵⁵ For instance, studies have shown that different subspecies and strains of C. acnes can have distinct effects on skin health. In acne vulgaris, certain phylotypes of C. acnes are associated with increased expression of virulence factors that exacerbate inflammation. These phylotypes are characterized by higher production of pro-inflammatory molecules and toxins, which contribute to the development of acne lesions. Moreover, the relative abundance and diversity of C. acnes phylotypes can vary between healthy skin and diseased skin. Metagenomic analyses have revealed that acne lesions often show a decrease in C. acnes diversity compared to healthy skin, with specific pathogenic strains becoming more dominant. This suggests that the balance of different C. acnes subspecies may be crucial in maintaining skin homeostasis and preventing disease. In addition to acne, C. acnes has also been implicated in other skin conditions, such as AD. However, its role in these conditions appears to be more complex, with some studies indicating that certain strains of C. acnes may have protective effects by modulating the skin’s immune response.

Psoriasis

Psoriasis lesions can be triggered by a multitude of factors, including infections, stress, certain painkillers, and antibiotics. Recent studies have linked the disease to the composition of the skin microbiota.⁵⁶ The microbiota implicated in psoriasis includes bacteria such as S. pyogenes and S. aureus, viruses such as endogenous retroviruses and human papillomavirus, and fungi including Candida albicans and Malassezia. This microbial diversity is not limited to lesional skin but is also present on skin that appears unaffected, carrying a strong diagnostic signal for psoriasis.²⁶ A decrease in Propionibacterium and C. acnes has been observed in psoriasis lesions, indicating a disrupted ecological balance.²⁷ This inhospitable environment for these microorganisms may contribute to the pathogenesis of psoriasis.²⁸ Recent studies have highlighted the importance of the gut-skin axis in the pathogenesis of psoriasis. For instance, a Mendelian randomization study identified potential causal relationships between specific gut microbiota taxa and the risk of psoriasis. This study found that certain bacterial taxa, such as Lactococcus and Eubacterium (coprostanoligenes group), may be linked to psoriasis risk, suggesting that gut microbiota dysbiosis could trigger or exacerbate psoriasis through various pathways.

Chronic wounds

Chronic wounds are defined as wounds where the healing process is impeded and the skin’s functional integrity is not restored within 4 weeks. This category includes conditions such as diabetic foot ulcers, venous leg ulcers, pressure ulcers, and nonhealing surgical wounds.⁵⁷ Wounds offer microorganisms an opportunity to invade underlying tissues from the skin surface and find conducive conditions for colonization and proliferation.⁵⁸ In comparison to uninfected wounds or those with single-species biofilms, mixed-species biofilms exhibit interactions that enhance the virulence of pathogens such as methicillin resistant, leading to a delayed wound healing process.³⁰ These findings suggest that the interactions among bacterial species within mixed-species biofilms contribute to the severity of chronic wound healing by introducing virulence factors.

Microorganism-based therapy for dermatosis

To enhance therapeutic outcomes, antibacterial agents, including antibiotics, are extensively employed in the treatment of skin diseases. However, antibiotic use not only fosters resistance in pathogenic bacteria but also disrupts the balance of the skin’s microecology by harming beneficial bacteria. This can lead to an imbalance in the microbiota. While hormones and biological agents offer swift anti-inflammatory and antibacterial effects by targeting skin cells, they fail to address the underlying issues of probiotic depletion and pathogenic bacterial infections within the microecology, which can result in disease recurrence.

Recently, microorganism-based therapies, such as microbiota transplantation and bacteriophage therapy, have emerged as treatments for skin diseases. These approaches aim to maintain microecological balance, alleviate symptoms, minimize adverse reactions, and reduce the likelihood of disease recurrence.⁵⁹ In conditions closely associated with the skin microbiota, such as AD, acne, and malignant melanoma (MM), numerous clinical trials have explored the potential of microecological treatments (Table 2).

Table 2.

Clinical trials of microbial therapies for skin diseases.

Agent	Type	Indications	Sponsors	Stage of clinical trial	Registration number
OH2	Recombinant oncolytic type II herpes simplex virus	Stage III inoperable/stage IV melanoma	Wuxi PharmaTech Company	Phase III	2018L02743
Roseomonas mucosa	Symbiotic bacteria	AD with the active involvement of the antecubital fossa	NIAID, NIH, Bethesda, MD, USA	Phase I/II	NCT03018275
ShA9	Staphylococcus hominis A9	Moderate-to-severe atopic dermatitis	NIAID, NIH, Bethesda, MD, USA	Phase I	NCT03151148
SIM03	Oral microbiome formula	Eczema in 1–5 years old children	GenieBiome Limited	Phase I	NCT05607511
Moisturizer plus bacteria	Autologous microbiome transplant	Adult patients with AD	University of California, San Diego	Phase I	NCT01959113
NB01	The live strain of C. acnes	Adults with moderate acne	Naked Biome, Inc., Dermatology Research Institute, QST Consultations	Phase I	NCT03450369
Topical propionate application	Microbial metabolite	Adult patients with mild to moderate AD	National Natural Science Foundation of China	Phase I	ChiCTR2100043963
Bths-08	Probiotics	Patients with acne	Bionou Research, S.L.	Phase I	NCT04570319

AD, atopic dermatitis; NIAID, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases.

Microbial metabolite

In patients with AD, skin dysbiosis is characterized by an increased abundance of Staphylococcus and a reduction in microbial diversity. Qiu et al. observed a decreased level of sebum and propionate—a microbial metabolite—on the skin surface of AD patients.⁶⁰ The topical application of propionate has been shown to inhibit IL-33 production in keratinocytes, thereby mitigating skin inflammation through the regulation of histone deacetylase (HDAC) inhibition and the aryl hydrocarbon receptor (AhR) signaling pathway.⁶⁰ Moreover, a proof-of-concept clinical trial (ChiCTR2100043963) demonstrated the positive therapeutic effects of topical propionate application for AD patients. Yu et al. identified major microbial metabolites of tryptophan (Trp) on the skin surfaces of healthy subjects, whereas the level of indole-3-aldehyde (IAId), a derivative of Trp catabolism, was significantly lower in AD patients.⁶¹ IAId has been found to inhibit the expression of thymic stromal lymphopoietin in keratinocytes, negatively regulating skin inflammation in AD patients, and showing potential as a therapeutic agent for the treatment of AD. Natural products have also garnered attention for their potential therapeutic effects on skin conditions. For example, carnosic acid (CA), a phenolic diterpene found in rosemary, has been shown to exhibit anti-inflammatory, antioxidant, and anti-angiogenic properties. In a recent study, CA was identified as a promising therapeutic agent for skin inflammation by targeting STAT1, a key signaling molecule involved in psoriasis. This finding underscores the potential of natural products as effective and sustainable treatments for chronic inflammatory skin conditions.

Bacteriophage

Bacteriophage therapy, a non-antibiotic treatment for bacterial infections, has recently gained significant attention.⁶² The employment of specialized and personalized phage cocktails has risen as a compelling alternative for tackling multidrug-resistant (MDR) bacterial infections.^63,64 Mycobacterium chelonae, a rapidly growing nontuberculous mycobacterium, is known to induce chronic infections in immunocompromised individuals.⁶⁵ The MDR nature of M. chelonae poses a considerable therapeutic challenge, with extended courses of antimicrobials leading to substantial toxicities and the potential for further antimicrobial resistance. However, the combination of a single bacteriophage named Muddy with antimicrobial therapy has shown remarkable clinical responses in practice.⁶⁶ In the context of diabetic wound infections, Fish et al. successfully employed the anti-staphylococcal bacteriophage Sb-1, achieving effective treatment across a range of patients.⁶⁷ These findings suggest that bacteriophage therapy is an auspicious treatment option for MDR infections, warranting accelerated progress toward comprehensive clinical trials.

Probiotic

Probiotics, which are live microorganisms, confer a range of health benefits when ingested or applied topically.⁶⁸ They have been widely used in the treatment of various skin conditions, including AD, acne, and eczema.^69–71 Kang et al. documented the positive effects of a lotion containing Enterococcus faecalis SL-5 on C. acnes.⁷² Lactobacillus species, extracted from human feces, have shown significant impacts on Gram-positive bacteria, particularly C. acnes. In a phase III clinical trial, participants treated with the SL-5 lotion experienced a notable decrease in inflammatory lesions and inhibition of C. acnes. In addition, Lactobacillus plantarum has been reported to enhance skin barrier recovery and diminish acne lesions in another phase III trial.⁷³ The application of a formulation containing 5% L. plantarum led to a significant reduction in lesion size and erythema.

Microecology environment regulation

The skin’s microecology is influenced by a variety of endogenous factors, such as pH, skin moisture, and sebum.^74,75 In addition, exogenous factors, including the application of cosmetic products, occlusive dressings, and detergents, can significantly impact the skin’s microbial community.^76,77 Selecting appropriate skincare products tailored to individual skin types can foster a healthy microecological environment.⁷⁸ Recently, the use of biomaterials in the adjuvant treatment of skin diseases has gained considerable attention due to their high safety, excellent biocompatibility, and superior therapeutic effects.^79,80 These advanced biomaterials offer innovative approaches to regulate and reprogram the skin’s microecology, presenting exciting opportunities to engineer or rebuild the skin microbiota for the treatment of skin diseases.^81,82

Conclusion

The skin’s surface, replete with wrinkles and patterns, offers an ideal environment for the colonization of a diverse array of microorganisms, thereby establishing a unique microecological system. The various components occupying different ecological niches on the skin maintain a dynamic balance with the host, contributing to the overall health of the skin microbiota. However, our understanding of the skin microbiota remains limited. The widespread use of antibacterial products, such as antibiotics, in the treatment of skin diseases has often overlooked the importance of maintaining this microbiota. Consequently, this has led to the development of antibiotic resistance among pathogenic bacteria and an increased risk of disease recurrence. From a microecological perspective, microbial therapies not only alleviate symptoms but also reduce the likelihood of disease relapse by preserving the balance of the skin’s microbial community.

As our understanding deepens, we are increasingly recognizing the significance of the skin microbiota and its role in shaping our health. Gaining a more profound comprehension of the mechanisms by which the microbiota contributes to skin diseases is essential, as it could offer valuable insights into the diverse functions of tissue-specific microbiota in the initiation, progression and treatment of dermatological conditions. Future advancements in in situ monitoring of skin microbiota and the identification of pathogenic strains that disrupt microecological balance are expected to provide critical information for the treatment of skin diseases.⁸³ The development of more precise treatment strategies, such as the engineering of microbiota with tailored characteristics, personalized microbial therapies, and biomaterials that interact with macroecology, will pave the way for clinical applications.

Footnotes

Acknowledgements

None.

Declarations

ORCID iD

Xianghui Li

References

Huttenhower

Gevers

Knight

, et al. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486(7402): 207–214.

Harris-Tryon

Grice

EA.

Microbiota and maintenance of skin barrier function. Science 2022; 376(6596): 940–945.

Schommer

Gallo

RL.

Structure and function of the human skin microbiome. Trends Microbiol 2013; 21(12): 660–668.

Byrd

Belkaid

Segre

JA.

The human skin microbiome. Nat Rev Microbiol 2018; 16(3): 143–155.

Lange-Asschenfeldt

Marenbach

Lang

, et al. Distribution of bacteria in the epidermal layers and hair follicles of the human skin. Skin Pharmacol Physiol 2011; 24(6): 305–311.

Dimitriu

Iker

Malik

, et al. New insights into the intrinsic and extrinsic factors that shape the human skin microbiome. mBio 2019; 10(4): e00839-19.

Adamczyk

Garncarczyk

Antończak

, et al. The foot microbiome. J Cosmet Dermatol 2020; 19(5): 1039–1043.

Anesti

Vohra

Goonetilleka

, et al. Molecular detection and isolation of facultatively methylotrophic bacteria, including Methylobacterium podarium sp. nov., from the human foot microflora. Environ Microbiol 2004; 6(8): 820–830.

Marshall

Leeming

Holland

KT.

The cutaneous microbiology of normal human feet. J Appl Bacteriol 1987; 62(2): 139–146.

10.

Lehtimäki

Karkman

Laatikainen

, et al. Patterns in the skin microbiota differ in children and teenagers between rural and urban environments. Sci Rep 2017; 7(1): 45651.

11.

Prohic

Simic

Sadikovic

, et al. Distribution of Malassezia species on healthy human skin in Bosnia and Herzegovina: correlation with body part, age and gender. Iran J Microbiol 2014; 6(4): 253–262.

12.

Urban

Fergus

Savage

, et al. The effect of habitual and experimental antiperspirant and deodorant product use on the armpit microbiome. PeerJ 2016; 4: e1605.

13.

Pasparakis

Haase

Nestle

FO.

Mechanisms regulating skin immunity and inflammation. Nat Rev Immunol 2014; 14(5): 289–301.

14.

Gallo

Hooper

LV.

Epithelial antimicrobial defence of the skin and intestine. Nat Rev Immunol 2012; 12(7): 503–516.

15.

Iwase

Uehara

Shinji

, et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 2010; 465(7296): 346–349.

16.

Otto

Süßmuth

Vuong

, et al. Inhibition of virulence factor expression in Staphylococcus aureus by the Staphylococcus epidermidis agr pheromone and derivatives. FEBS Lett 1999; 450(3): 257–262.

17.

Naik

Bouladoux

Wilhelm

, et al. Compartmentalized control of skin immunity by resident commensals. Science 2012; 337(6098): 1115–1120.

18.

Scholz

Badgley

Sadowsky

, et al. Immune mediated shaping of microflora community composition depends on barrier site. PLoS One 2014; 9(1): e84019.

19.

Brandwein

Steinberg

Meshner

Microbial biofilms and the human skin microbiome. NPJ Biofilms Microbiomes 2016; 2(1): 3.

20.

Madhusudhan

Pausan

Halwachs

, et al. Molecular profiling of keratinocyte skin tumors links staphylococcus aureus overabundance and increased human β-defensin-2 expression to growth promotion of squamous cell carcinoma. Cancers (Basel) 2020; 12(3): 541.

21.

Goh

Teh

, et al. Skin commensal Malassezia globosa secreted protease attenuates Staphylococcus aureus biofilm formation. J Invest Dermatol 2018; 138(5): 1137–1145.

22.

Mizuhashi

Kajihara

Sawamura

, et al. Skin microbiome in acral melanoma: Corynebacterium is associated with advanced melanoma. J Dermatol 2021; 48(1): e15–e16.

23.

Kong

Deming

, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res 2012; 22(5): 850–859.

24.

Laborel-Préneron

Bianchi

Boralevi

, et al. Effects of the Staphylococcus aureus and Staphylococcus epidermidis secretomes isolated from the skin microbiota of atopic children on CD4+ T cell activation. PLoS One 2015; 10(10): e0141067.

25.

Graham

Farrar

Cruse-Sawyer

, et al. Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol 2004; 150(3): 421–428.

26.

Alekseyenko

Perez-Perez

De Souza

, et al. Community differentiation of the cutaneous microbiota in psoriasis. Microbiome 2013; 1(1): 31.

27.

Fahlén

Engstrand

Baker

, et al. Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res 2012; 304(1): 15–22.

28.

Gao

Tseng

Strober

, et al. Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One 2008; 3(7): e2719.

29.

Zákostelská

Málková

Klimešová

, et al. Intestinal microbiota promotes psoriasis-like skin inflammation by enhancing Th17 response. PLoS One 2016; 11(7): e0159539.

30.

Pastar

Nusbaum

Gil

, et al. Interactions of methicillin resistant Staphylococcus aureus USA300 and Pseudomonas aeruginosa in polymicrobial wound infection. PLoS One 2013; 8(2): e56846.

31.

Redel

Gao

, et al. Quantitation and composition of cutaneous microbiota in diabetic and nondiabetic men. J Infect Dis 2013; 207(7): 1105–1114.

32.

Wolcott

Hanson

Rees

, et al. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound Repair Regen 2016; 24(1): 163–174.

33.

Loesche

Gardner

Kalan

, et al. Temporal stability in chronic wound microbiota is associated with poor healing. J Invest Dermatol 2017; 137(1): 237–244.

34.

Kalan

Meisel

Loesche

, et al. Strain- and species-level variation in the microbiome of diabetic wounds is associated with clinical outcomes and therapeutic efficacy. Cell Host Microbe 2019; 25(5): 641–655.e5.

35.

Wong-Rolle

Wei

Zhao

, et al. Unexpected guests in the tumor microenvironment: microbiome in cancer. Protein Cell 2021; 12(5): 426–435.

36.

Garrett

WS.

Cancer and the microbiota. Science 2015; 348(6230): 80–86.

37.

Dzutsev

Badger

Perez-Chanona

, et al. Microbes and cancer. Annu Rev Immunol 2017; 35: 199–228.

38.

Ramírez-Labrada

Isla

Artal

, et al. The influence of lung microbiota on lung carcinogenesis, immunity, and immunotherapy. Trends Cancer 2020; 6(2): 86–97.

39.

Duya

Chen

Bai

, et al. Nature products of traditional Chinese medicine provide new ideas in γδT cell for tumor immunotherapy. Acupunct Herb Med 2022; 2(2): 78–83.

40.

Wang

Chen

, et al. Novel emerging nano-assisted anti-cancer strategies based on the sting pathway. Acta Mater Medica 2023; 2(3): 323–341.

41.

Wood

DLA

Lachner

Tan

J-M

, et al. A history of actinic keratosis and cutaneous squamous cell carcinoma microbiomes. mBio 2018; 9(5): e01432-18.

42.

Wang

Kortylewski

, et al. IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009; 206(7): 1457–1464.

43.

Ridaura

Bouladoux

Claesen

, et al. Contextual control of skin immunity and inflammation by Corynebacterium. J Exp Med 2018; 215(3): 785–799.

44.

Rieder

Mukherjee

PK.

Skin microbiome in atopic dermatitis: New insights from clinical trials. J Eur Acad Dermatol Venereol 2023; 37(4): 649–650.

45.

Langan

Irvine

Weidinger

Atopic dermatitis. Lancet 2020; 396(10247): 345–360.

46.

Totté

JEE

van der Feltz

Hennekam

, et al. Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol 2016; 175(4): 687–695.

47.

Kennedy

Connolly

Hourihane

JOB

, et al. Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J Allergy Clin Immunol 2017; 139(1): 166–172.

48.

Meylan

Lang

Mermoud

, et al. Skin colonization by Staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy. J Invest Dermatol 2017; 137(12): 2497–2504.

49.

Byrd

Deming

Cassidy

SKB

, et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med 2017; 9(397): S229–S230.

50.

O’Neill

Gallo

RL.

Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris. Microbiome 2018; 6(1): 177.

51.

Takeuchi

Hoshino

Kawai

, et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components to participate in the antibacterial host defense but not in the antifungal response, indicating that particular pathogens induce specific. Technol Japan Sci 1999; 11: 443–451.

52.

Trivedi

Gilliland

Zhao

, et al. Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol 2006; 126(5): 1071–1079.

53.

Beom

, et al. Expression and modulation of LL-37 in normal human keratinocytes, HaCaT cells, and inflammatory skin diseases. J Korean Med Sci 2005; 20(4): 649–654.

54.

Lee

Yamasaki

Rudsil

, et al. Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes. J Invest Dermatol 2008; 128(7): 1863–1866.

55.

Liu

, et al. Multi-omics signatures reveal genomic and functional heterogeneity of Cutibacterium acnes in normal and diseased skin. Cell Host Microbe 2024; 32(7): 1129–1146.e8.

56.

Gupta

Weinberg

Yamauchi

, et al. Psoriasis: embarking a dynamic shift in the skin microbiota. J Cosmet Dermatol 2022; 21(4): 1402–1406.

57.

Tomic-Canic

Burgess

O’Neill

, et al. Skin microbiota and its interplay with wound healing. Am J Clin Dermatol 2020; 21: 36–43.

58.

Zeeuwen

PLJM

Boekhorst

van den Bogaard

, et al. Microbiome dynamics of human epidermis following skin barrier disruption. Genome Biol 2012; 13(11): R101.

59.

Zhao

Luo

, et al. Advances in microbial decorations and its applications in drug delivery. Acta Mater Med 2023; 2(4): 466–479.

60.

Qiu

Zhu

Liu

, et al. A dysregulated sebum–microbial metabolite–IL-33 axis initiates skin inflammation in atopic dermatitis. J Exp Med 2022; 219(10): e20212397.

61.

Luo

Zhu

, et al. A tryptophan metabolite of the skin microbiota attenuates inflammation in patients with atopic dermatitis through the aryl hydrocarbon receptor. J Allergy Clin Immunol 2019; 143(6): 2108–2119.e12.

62.

Spellberg

Guidos

Gilbert

, et al. The epidemic of antibiotic-resistant infections: a call to action for the medical community from the infectious diseases society of America. Clin Infect Dis 2008; 46(2): 155–164.

63.

Plumet

Ahmad-Mansour

Dunyach-Remy

, et al. Bacteriophage therapy for Staphylococcus aureus infections: a review of animal models, treatments, and clinical trials. Front Cell Infect Microbiol 2022; 12: 907314.

64.

Metsemakers

Onsea

Moriarty

, et al. Bacteriophage therapy for human musculoskeletal and skin/soft tissue infections. Clin Microbiol Infect 2023; 29: 695–701.

65.

Dousa

Babiker

Van Aartsen

, et al. Ibrutinib therapy and Mycobacterium chelonae skin and soft tissue infection. Open Forum Infect Dis 2018; 5(7): ofy168.

66.

Little

Dedrick

Freeman

, et al. Bacteriophage treatment of disseminated cutaneous Mycobacterium chelonae infection. Nat Commun 2022; 13(1): 2313.

67.

Fish

Kutter

Wheat

, et al. In: Azeredo

Sillankorva

(eds) Bacteriophage therapy, Compassionate Use of Bacteriophage Therapy for Foot Ulcer Treatment as an Effective Step for Moving Toward Clinical Trials, vol 1693. Springer New York. 2018.

68.

Goodarzi

Mozafarpoor

Bodaghabadi

, et al. The potential of probiotics for treating acne vulgaris: a review of literature on acne and microbiota. Dermatol Ther 2020; 33(3): e13279.

69.

Lee

Maarouf

Hendricks

, et al. Topical probiotics: the unknowns behind their rising popularity. Dermatol Online J 2019; 25(5): 5.

70.

Fuchs-Tarlovsky

Marquez-Barba

Sriram

Probiotics in dermatologic practice. Nutrition 2016; 32(3): 289–295.

71.

Yang

Mijakovic

, et al. Advances in the human skin microbiota and its roles in cutaneous diseases. Microb Cell Fact 2022; 21(1): 176.

72.

Kang

Seo

Lee

, et al. Antimicrobial activity of enterocins from Enterococcus faecalis SL-5 against Propionibacterium acnes, the causative agent in acne vulgaris, and its therapeutic effect. J Microbiol 2009; 47(1): 101–109.

73.

Muizzuddin

Maher

Sullivan

, et al. Physiological effect of a probiotic on skin. J Cosmet Sci 2012; 63(6): 385–395.

74.

Schmid-Wendtner

Korting

HC.

The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol 2006; 19(6): 296–302.

75.

Aiello

Coulborn

Perez

, et al. Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis. Am J Public Health 2008; 98(8): 1372–1381.

76.

Wang

Yang

Chai

, et al. Tea as a natural gift for discovering antiviral candidates. Acupunct Herb Med 2022; 2(4): 211–220.

77.

Zhao

Wang

Jiang

, et al. The application of skin care product in acne treatment. Dermatol Ther 2020; 33(6): e14287.

78.

Meckfessel

Brandt

The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products. J Am Acad Dermatol 2014; 71(1): 177–184.

79.

Zhu

Jin

Zhao

, et al. Reactive oxygen species scavenging sutures for enhanced wound sealing and repair. Small Struct 2021; 2: 2100002.

80.

Zhang

Yang

, et al. Injectable self-healing adhesive pH-responsive hydrogels accelerate gastric hemostasis and wound healing. Nanomicro Lett 2021;13(1): 80.

81.

Wang

, et al. Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy. Biomater Res 2022; 26(1): 47.

82.

Chen

Cheng

Tian

, et al. Dissolved oxygen from microalgae-gel patch promotes chronic wound healing in diabetes. Sci Adv 2020; 6(20): eaba4311.

83.

Cao

Khader

JA.

Rhinofacial entomophthoromycosis. N Engl J Med 2018; 378(9): e13.

The role and prospects of skin microbiota in dermatosis

Abstract

Keywords

Introduction

Overview of skin microbiota

Distribution and dynamic changes of skin microbiota

Microecology regulation and protection mechanism

Dysfunctional skin microecology and dermatosis

Tumors

Atopic dermatitis

Acne

Psoriasis

Chronic wounds

Microorganism-based therapy for dermatosis

Microbial metabolite

Bacteriophage

Probiotic

Microecology environment regulation

Conclusion

Footnotes

Acknowledgements

Declarations

ORCID iD

References