A Natural History of Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Microbiomes

Abstract

Actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) are two of the most common dermatologic conditions in Western countries and cause substantial morbidity worldwide. The role of human papillomaviruses under these conditions has been well studied yet remains inconclusive. One PCR-based study has investigated bacteria in the etiology of these conditions; however, no study has investigated the microbiomes of AK and SCC more broadly. We longitudinally profiled the microbiomes of 112 AK lesions, profiled cross sections of 32 spontaneously arising SCC lesions, and compared these to matching nonlesional photodamaged control skin sites. We identified commonly occurring strains of Propionibacterium and Malassezia at higher relative abundances on nonlesional skin than in AK and SCC lesions, and strains of Staphylococcus aureus were relatively more abundant in lesional than nonlesional skin. These findings may aid in the prevention of SCC.

Molecular Profiling of Keratinocyte Skin Tumors Links Staphylococcus aureus Overabundance and Increased Human β-Defensin-2 Expression to Growth Promotion of Squamous Cell Carcinoma

“…The reason for the increase of S. aureus (in relation to the resident microbiota) in cutaneous SCCs is so far unknown but may be due to several reasons. Notably, our findings support two recent publications identifying increased S. aureus in cutaneous SCCs [33,34]. Microscopically we identified abundant cocci often in areas of hyper-or parakeratosis.…”

“…This might inhibit commensals like Propionibacterium, which are dependent on lipids derived from sebum [7,44], and potentially opens niches for S. aureus to proliferate. Interestingly, we found evidence for competitive exclusion between S. aureus and P. acnes in SCCs and AKs which was also suggested recently [34]. In addition, S. epidermidis, a known competitor of S. aureus, was also found to be reduced in tumors, and this bacterium was recently shown to protect against skin cancer [8,16,45].…”

“…Finally, it could be that a changed metabolism of the neoplastic cells might favor S. aureus growth. AKs and SCCs are supposed to be impaired in sebum production [34]. This might inhibit commensals like Propionibacterium, which are dependent on lipids derived from sebum [7,44], and potentially opens niches for S. aureus to proliferate.…”

“…Consequently, skin fungi might also be involved, since we detected at least histologically increased fungal structures in certain AK samples. Interestingly, fungi could also potentially protect from pathogenic bacteria, as the yeast Malassezia, which is supposed to compete against S. aureus and which was shown to be reduced in cutaneous SCCs [34]. Together this knowledge might open the avenue for the development of biotherapeutics for out-competition of skin pathogens such as S. aureus.…”

Skin microbiome transplantation and manipulation: Current state of the art

“…Even skin cancers, such as squamous cell carcinoma, and its predecessor condition actinic keratosis are associated with dysbiosis of the skin microbiome [60] . As noted with other lesional skin diseases, an increase in S. aureus is observed in combination with a decrease in skin commensals, such as C. acnes .…”