The importance of a well-balanced skin microbiota in the healing process

Skin-specific microbiota, established during birth and stabilized after the first year of life, contributes to the cutaneous homeostasis and controls diverse aspects of tissue physiology.^1,2,3
Over 1000 bacterial species have been identified within the most superficial level of skin.⁴

Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host innate and adaptive immune system, and protection from invading pathogenic microorganisms.^1,2,3

Damaged skin: changes in skin microbiota composition

As other various stressors, injuries modify the diversity and abundance of the cutaneous microbiota, which profile is then considerably disturbed up to day 14.^2,5

The presence and abundance of microbes in skin wounds depend on wound type.²

• In chronic wounds:
  • The microbiota is less diverse than that of healthy skin.⁶
  • Polymicrobial biofilms, which are highly abundant in chronic wounds, foster pathogenic microbial growth.⁴
• Acute wounds (i.e. burns, blunt or penetrating traumas, open fracture) exhibit changes in skin microbial composition and significant differences in diversity.²

Wound type

• Chronic wounds (diabetic foot ulcers, decubitus ulcers, venous leg ulcers and post-surgical wounds)
• Burns
• Open fracture

Main microbiota changes

• Predominance of Staphylococcus, notably S. aureus and S. epidermidis⁴
  Increase of Pseudomonas aeruginosa and Streptococcus^4,6,7
• Increase of thermophile microbes such as Aeribacillus, Caldalkalibacilus, and Nesterenkonia⁴
  Decreased of Corynebacterium⁴
• Predominance of Staphylococcus, Corynebacterium, Streptococcus, Acinetobacter, Anaerococcus, Finegoldia, and Pseudomonas⁴

Unbalanced microbiota: a proven impact on the healing process

Both in-vivo and in-vitro studies of the cutaneous microbiome have supported a general consensus that the microbial composition of skin wounds impacts wound healing.⁴

• More inflammation: in the presence of tissue injury, loss of microbial diversity results in prolonged inflammation, due to the increased abundance of proteases, reactive oxygen species, and other bioactive substances.⁴
  Prolonged and dysregulated production of inflammatory cytokines leads to excessive neutrophil influx, resulting in sustained inflammatory responses and delayed healing.⁸
• A higher infection risk: under normal conditions, resident and transient bacteria will increase the resistance of the skin against pathogens through immunomodulation. But, the breach of the skin barrier impairs the immune defenses and creates changed environments in which commensal bacteria may become opportunistic pathogens and microorganisms with heightened inflammatory potential may proliferate.^3,7,9,10

The beneficial role of a normal skin microbiota

Commensal skin bacteria have been shown to both reduce inflammation during wound healing and activate innate immunity and inflammatory cytokines.⁶

Inflammation controlled: the normal skin microflora includes staphylococcal species, some of which products inhibit skin inflammation.⁸ As seen in healthy microbial colonization, high diversity of skin commensals is involved in both the benign induction of the immune system and the attenuation of the immune response. Among them, S. epidermidis is particularly involved in inflammation control.⁴

Going further

How does S. epidermidis promote wound healing^1,4,10>

Skin commensals influence a variety of cell signaling and homeostatic processes including keratinocyte proliferation, epithelial differentiation, and epidermal blood vessel growth. In particular, S. epidermidis- induced CD8+ T cells promote rapid keratinocyte progression via upregulation of toll-like receptors (TLR) and downstream modulation of TNF-α. Their impact is detectable during the proliferation phase of wound healing, perhaps through an effect on keratinocyte proliferation, as they express high levels of amphiregulin, a molecule described for its mitogenic role on keratinocytes through binding the epidermal growth factor receptor (EGFR). In addition, S. epidermidis’ production of lipoteichoic acid decreases cutaneous inflammation via Toll-like receptor (TLR) 2 signaling. The ability of S. epidermidis to modulate the innate immune response in non-infectious skin wounds coincides with its ability to accelerate wound healing in various skin models, and highlights the ability for bacterial products to reduce cutaneous inflammation.

Infection risk decreased: It is now well known that the normal skin microbiota supports and modulates the innate immune host response to prevent colonization of potentially pathogenic microorganisms.² In particular, both S. epidermidis and the typically low-abundant S. aureus, induce expression of AMPs in human keratinocytes, ultimately benefiting skin by providing host protection from invasion of other pathogenic microorganisms.⁴

Microbiota induce a form of adaptive immunity that couples antimicrobial function with tissue repair¹
VegF, Fgf, Pdgf, Areg, Mmp: pleiotropic factors involved in various aspects of wound healing
MHCI: major histocompatibility complex class I

Counterbalance the skin microbiota to improve wound healing: current perspectives

Finding alternative ways to modulate the microbiota in hopes of improving wound healing is of the utmost importance. Clinical applications targeting the microbiota to improve wound healing have already been demonstrated in the treatment of atopic dermatitis (probiotics, Vitreoscilla filiformis, short chain fatty acids (SCFAs), etc).⁴
In the other hand, moisturizers and emollients, seen as the cornerstone of AD treatment, help restore and maintain skin barrier integrity, combat xerosis and enhance treatment efficacy. And certain emollients having shown, in clinical studies, their ability to increase microbiota diversity in atopic skin could be considered to improve wound healing.¹¹