A microbiome and metabolomic signature of phases of cutaneous healing identified by profiling sequential acute wounds of human skin: An exploratory study

Abstract

Profiling skin microbiome and metabolome has been utilised to gain further insight into wound healing processes. The aims of this multi-part temporal study in 11 volunteers were to analytically profile the dynamic wound tissue and headspace metabolome and sequence microbial communities in acute wound healing at days 0, 7, 14, 21 and 28, and to investigate their relationship to wound healing, using non-invasive quantitative devices. Metabolites were obtained using tissue extraction, sorbent and polydimethylsiloxane patches and analysed using GCMS. PCA of wound tissue metabolome clearly separated time points with 10 metabolites of 346 being involved in separation. Analysis of variance-simultaneous component analysis identified a statistical difference between the wound headspace metabolome, sites (P = 0.0024) and time points (P<0.0001), with 10 out of the 129 metabolites measured involved with this separation between sites and time points. A reciprocal relationship between Staphylococcus spp. and Propionibacterium spp. was observed at day 21 (P<0.05) with a statistical correlation between collagen and Propionibacterium (r = 0.417; P = 0.038) and Staphylococcus (r = -0.434; P = 0.03). Procrustes analysis showed a statistically significant similarity between wound headspace and tissue metabolome with non-invasive wound devices. This exploratory study demonstrates the temporal and dynamic nature of acute wound metabolome and microbiome presenting a novel class of biomarkers that correspond to wound healing, with further confirmatory studies now necessary.

Valsartan nano‐filaments alter mitochondrial energetics and promote faster healing in diabetic rat wounds

“…Fumarate has known anti‐inflammatory properties and has been used for the treatment of psoriasis 28 . In addition, L‐glutamine is a metabolite that is significantly increased in wounds after 21 days of healing and measuring its intensity in wounds can help discriminate between early‐ and late‐stage wound healing 29 . Our work demonstrates increased levels of L‐aspartate, fumarate and L‐glutamine in val‐filament treated wounds, suggesting that RAS blockade via valsartan may lessen dysregulation to these metabolites observed in diabetic wounds.…”

New Advances in Tissue Metabolomics: A Review

“…However, the characterization of dynamic changes in skin tissue following an acute injury has been unexplored. For the first time, Ashrafi et al [ 132 ] reported the wound metabolome following skin tissue biopsies performed on four spots on the inner arm of volunteers in conjunction with skin microbiome analyses. Non-invasive headspace sampling was also performed using polydimethylsiloxane patches positioned at the wound site at three time points following a 28 day period of healing.…”

“…As expected, fewer features (129 versus 346) were detected in headspace wound sampling as compared to direct tissue biopsy analyses when using GC-MS. Temporal changes in metabolite levels were identified after a false discovery adjustment, where specific volatile organics from headspace sampling were associated with skin healing processes (e.g., blood flow), such as isobutyl-2,2,4-trimethyl-3-hydroxypentanoate. However, no changes in bacterial genera abundances were evident since they remain largely stable on the skin when normal healing processes occur after an acute injury [ 132 ]. Nevertheless, further validation of this study is warranted in a larger cohort with standardized sampling collection procedures to enable reliable quantification of metabolites from skin tissues/wounds, whereas MS/MS is needed for the identification of a large fraction of unknown volatile organic compounds.…”

Enhanced Access to the Health-Related Skin Metabolome by Fast, Reproducible and Non-Invasive WET PREP Sampling

“…These pathogenic strains have a role in the development of skin disease, and consequently a diseased skin can be identified by changes in the metabolome, as reviewed in Yan et al, 2017 [ 7 ]. Metabolites can furthermore indicate the progression of wound healing in the skin, where linolenic acid is initially increased followed by an increase in adenosine [ 8 ]. In summary, taken the recent literature, the skin metabolome gives insights into the physiology of wound healing, topical diseases and their link to systemic comorbidities, and cosmetic aspects and aging related topics.…”