Challenges and Future Directions in Microbiome Engineering

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The skin is a complex ecosystem teeming with microorganisms, including bacteria, fungi, viruses, and archaea. This diverse community, known as the skin microbiome, is integral to skin health, playing a crucial role in barrier protection, immune regulation, wound repair, and defense against pathogens.¹ Disruptions in the delicate balance of the skin microbiome have been closely linked to the development and exacerbation of numerous skin disorders, such as acne, eczema, and psoriasis.² This highlights the potential of microbiome engineering as a therapeutic strategy.

The Skin Microbiome’s Role in Health and Disease

A recent review found that epidermal Staphylococcus, a common skin commensal, can secrete sphingomyelinases that, while providing essential nutrients for itself, produce ceramides utilized by host cells to enhance the integrity and permeability of the skin barrier.³ The skin microbiome is integral to skin health, influencing the skin barrier's function, defense against pathogens, and interaction with the immune system. Commensal bacteria like Staphylococcus and Cutibacterium contribute to the skin barrier by producing substances that maintain its integrity and regulate pH, while the microbiome also prevents pathogen colonization through various mechanisms, including the production of antimicrobial substances. Furthermore, the skin microbiome modulates both innate and adaptive immune responses, influencing cytokine production and establishing immune tolerance. 

Microbiome Engineering: A New Therapeutic Frontier

The review highlights that disruptions in the skin microbiome's balance are closely associated with the development and exacerbation of various skin disorders. This connection indicates the potential of microbiome engineering as a therapeutic approach for skin diseases.

The authors discuss various strategies for microbiome engineering, categorizing them into nontargeted and targeted approaches. Nontargeted approaches, such as probiotics and skin microbiome transplantation, aim to reshape the overall microbial community. Targeted approaches, including phage therapy and engineered bacteria, precisely modulate microbial populations or influence the skin environment.

The review emphasizes the importance of the skin microbiome in maintaining the skin's physicochemical properties. Skin microorganisms secrete enzymes that regulate epidermal cell differentiation and maturation. They also influence the production of sebum and ceramides, which are essential for the skin barrier's integrity and permeability. Additionally, the skin microbiome can modify the spatial structure of the skin barrier by regulating the attachment of sebaceous and sweat glands.

Furthermore, the review discusses the skin microbiome's role in preventing pathogen colonization. It highlights that a reduced abundance of commensal bacteria in certain skin diseases can increase susceptibility to pathogenic microorganisms. Skin commensals can also produce antimicrobial substances, such as bacteriocins and short-chain fatty acids, to combat pathogens.

Continuing, the review explores the intricate relationship between the skin microbiome and the immune system. The skin microbiome regulates both innate and adaptive immune responses. It influences the production of cytokines, which are crucial for immune cell signaling and coordination. Additionally, the skin microbiome is involved in establishing immune tolerance in early life by interacting with dendritic cells and inducing the formation of regulatory T cells. The review also discusses the association between specific skin microorganisms and various skin diseases.

For instance, Cutaneous warts are caused by the Human Papillomavirus. Herpes zoster is highly associated with the Varicella-zoster virus. Tinea infections are mostly caused by fungi of the genus Trichophyton, Microsporum, and Epidermophyton. Atopic dermatitis involves an overgrowth of S. aureus and an imbalance of other commensal microorganisms. Acne is associated with the dysbiosis of the skin microbiome, particularly the overgrowth and imbalance of C. acnes subtypes. Seborrheic dermatitis is characterized by the abundant colonization of Malassezia fungi. Psoriasis involves changes in the structure and function of the skin microbiome and decreased alpha and beta diversity. Lupus erythematosus is associated with decreased alpha and beta diversity in the skin microbiome and an increase in the relative abundance of S. aureus.

Challenges and Future Directions

While the potential of microbiome engineering in dermatology is exciting, researchers note several challenges remain. Safety, standardization, regulatory approval, and long-term ecological stability must be addressed to ensure the efficacy and reproducibility of microbiome-based therapies in clinical settings.

References

1. Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16(3):143-155. doi:10.1038/nrmicro.2017.157
2. Cundell AM. Microbial Ecology of the Human Skin. Microb Ecol. 2018;76(1):113-120. doi:10.1007/s00248-016-0789-6
3. Lyu Y, Shen J, Che Y, Dai L. Skin microbiome engineering: Challenges and opportunities in skin diseases treatment. iMetaOmics e70012. 2025. doi:10.1002/imo2.70012