Role of the Microbiota in Skin Neoplasms: New Therapeutic Horizons

Abstract

The skin and the gut are regularly colonized by a variety of microorganisms capable of interacting with the immune system through their metabolites and influencing the balance between immune tolerance and inflammation. Alterations in the composition and diversity of the skin microbiota have been described in various cutaneous diseases, including skin cancer, and the actual function of the human microbiota in skin carcinogenesis, such as in progression and metastasis, is currently an active area of research. The role of Human Papilloma Virus (HPV) in the pathogenesis of squamous cell carcinoma is well consolidated, especially in chronically immunosuppressed patients. Furthermore, an imbalance between Staphylococcus spp., such as Staphylococcus epidermidis and aureus, has been found to be strongly related to the progression from actinic keratosis to squamous cell carcinoma and differently associated with various stages of the diseases in cutaneous T-cell lymphoma patients. Also, in melanoma patients, differences in microbiota have been related to dissimilar disease course and prognosis and may affect the effectiveness and tolerability of immune checkpoint inhibitors, which currently represent one of the best chances of a cure. From this point of view, acting on microbiota can be considered a possible therapeutic option for patients with advanced skin cancers, even if several issues are still open.

Keywords: cutaneous carcinogenesis; gut–skin axis; melanoma; microbiota; skin cancer.

Figure 1

Epithelial barriers: from skin to gut. Common and specific traits of the skin (A), oral cavity (B), small (C) and large intestine (D). Image created with BioRender.com.

Figure 2

Gut–skin axis (GSA). The GSA is bidirectional: it is involved in the host’s homeostasis through immunological and neuroendocrine pathways. Gut and skin microbiota eubiosis is affected by several factors, generally recognized as the exposome. Image created with BioRender.com.

Figure 3

Skin and gut microbiota composition. The skin and gut are mainly colonized by Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes, with a peculiar composition for each single niche. Moist sites are colonized mainly by Firmicutes and Actinobacteria, oily ones by Actinobacteria, while dry areas by diverse microbial populations. Gut microbiota differs between the small and large intestines. Firmicutes and Proteobacteria are the most dominant phyla in the small intestine, while Bacteroidetes dominate the anaerobic environment of the large intestine. Image created with BioRender.com.