Evolving approaches to profiling the microbiome in skin disease

Abstract

Despite its harsh and dry environment, human skin is home to diverse microbes, including bacteria, fungi, viruses, and microscopic mites. These microbes form communities that may exist at the skin surface, deeper skin layers, and within microhabitats such as the hair follicle and sweat glands, allowing complex interactions with the host immune system. Imbalances in the skin microbiome, known as dysbiosis, have been linked to various inflammatory skin disorders, including atopic dermatitis, acne, and psoriasis. The roles of abundant commensal bacteria belonging to Staphylococcus and Cutibacterium taxa and the fungi Malassezia, where particular species or strains can benefit the host or cause disease, are increasingly appreciated in skin disorders. Furthermore, recent research suggests that the interactions between microorganisms and the host’s immune system on the skin can have distant and systemic effects on the body, such as on the gut and brain, known as the “skin-gut” or “skin-brain” axes. Studies on the microbiome in skin disease have typically relied on 16S rRNA gene sequencing methods, which cannot provide accurate information about species or strains of microorganisms on the skin. However, advancing technologies, including metagenomics and other functional ‘omic’ approaches, have great potential to provide more comprehensive and detailed information about the skin microbiome in health and disease. Additionally, inter-species and multi-kingdom interactions can cause cascading shifts towards dysbiosis and are crucial but yet-to-be-explored aspects of many skin disorders. Better understanding these complex dynamics will require meta-omic studies complemented with experiments and clinical trials to confirm function. Evolving how we profile the skin microbiome alongside technological advances is essential to exploring such relationships. This review presents the current and emerging methods and their findings for profiling skin microbes to advance our understanding of the microbiome in skin disease.

Characterization of the skin microbiome in normal and cutaneous squamous cell carcinoma affected cats and dogs

“…Skin has extremely low microbial biomass due to its dry and nutrient-poor conditions ( 26 ); it has ~1/100th the biomass of stool samples ( 27 ). Low microbial biomass makes obtaining high read depth from amplicon sequencing challenging.…”

Scientific Rationale and Clinical Basis for Clindamycin Use in the Treatment of Dermatologic Disease

“…The development of inflammatory acne lesions may result from a change from skin homeostasis to a state of inflammation [ 87 ], a process which is thought to involve: (i) excess sebum production, (ii) increased C. acnes presence and metabolic activity, leading to cytotoxic metabolite release in the pilosebaceous unit, (iii) pro-inflammatory cytokine release, (iv) recruitment of immune cells to the acne lesion locale, (v) incessant C. acnes pathogenic activity marked by biofilm formation and immune cell involvement, and (vi) an overall alteration to and dysbiosis of the skin flora in acne patients [ 14 , 15 , 87 , 92 , 93 ]. The succession of events outlined above remains a debated topic; for example, immune cells may first initiate hyperkeratinization and comedone formation [ 61 , 87 , 94 ].…”

“…C. acnes is a known commensal bacterium on human skin, yet its involvement in the pathogenesis of acne has not been fully elucidated. Certain virulent and acne-causing strains of C. acnes are thought to be promoters of inflammation [ 10 , 14 , 15 , 92 ]. Building upon the idea that C. acnes activity within the pilosebaceous unit is central to inflammation in acne [ 90 ], it has been reported that the pilosebaceous unit is a hostile, oxygen-poor environment [ 92 ], but that C. acnes thrives in this environment by feeding on sebaceous lipids; thus, sebum quantity is likely directly related to C. acnes colonization on the skin and acne severity [ 61 ].…”

“…Certain virulent and acne-causing strains of C. acnes are thought to be promoters of inflammation [ 10 , 14 , 15 , 92 ]. Building upon the idea that C. acnes activity within the pilosebaceous unit is central to inflammation in acne [ 90 ], it has been reported that the pilosebaceous unit is a hostile, oxygen-poor environment [ 92 ], but that C. acnes thrives in this environment by feeding on sebaceous lipids; thus, sebum quantity is likely directly related to C. acnes colonization on the skin and acne severity [ 61 ]. Also, sebaceous glands are inherently key players in the innate immune system and have endocrine system-responsive properties; while they contribute to the production of sebum, they also secrete AMPs [ 61 ].…”

Temporal dynamics of skin microbiota and immune correlates in psoriasis patients receiving systemic treatment

“…Lastly, we recognized the challenges of low biomass even on skin lesions and attempted to sequence cDNA sequences of 16S amplicons instead of the corresponding DNA sequences directly. How this unique approach could have resulted in biased representations of certain Phyla has not been well characterized [41]. Future studies that collect detailed information on serial medications, may provide novel insights on the long-term trajectories of therapeutic effects on the lesional microbiota.…”