RÉSUMÉ
Hypertrophic scarring is a fibro-proliferative disorder caused by abnormal cutaneous wound healing. Circulating metabolites and the gut microbiome may be involved in the formation of these scars, but high-quality evidence of causality is lacking. To assess whether circulating metabolites and the gut microbiome contain genetically predicted modifiable risk factors for hypertrophic scar formation. Two-sample Mendelian randomization (MR) was performed using MR-Egger, inverse-variance weighting (IVW), Mendelian Randomization Pleiotropy RESidual Sum and Outlier, maximum likelihood, and weighted median methods. Based on the genome-wide significance level, genetically predicted uridine (P = 0.015, odds ratio [OR] = 1903.514, 95% confidence interval [CI] 4.280-846,616.433) and isovalerylcarnitine (P = 0.039, OR = 7.765, 95% CI 1.106-54.512) were positively correlated with hypertrophic scar risk, while N-acetylalanine (P = 0.013, OR = 7.98E-10, 95% CI 5.19E-17-0.012) and glycochenodeoxycholate (P = 0.021, OR = 0.021 95% CI 0.003-0.628) were negatively correlated. Gastranaerophilales and two unknown gut microbe species (P = 0.031, OR = 0.378, 95% CI 0.156-0.914) were associated with an decreased risk of hypertrophic scarring. Circulating metabolites and gut microbiome components may have either positive or negative causal effects on hypertrophic scar formation. The study provides new insights into strategies for diagnosing and limiting hypertrophic scarring.
Sujet(s)
Cicatrice hypertrophique , Microbiome gastro-intestinal , Analyse de randomisation mendélienne , Humains , Microbiome gastro-intestinal/physiologie , Cicatrice hypertrophique/microbiologie , Cicatrice hypertrophique/sang , Cicatrice hypertrophique/étiologie , Facteurs de risque , Étude d'association pangénomique , Polymorphisme de nucléotide simpleSujet(s)
Antifongiques/usage thérapeutique , Cicatrice hypertrophique/traitement médicamenteux , Mycoses cutanées/traitement médicamenteux , Itraconazole/usage thérapeutique , Chéloïde/traitement médicamenteux , Inhibiteurs de l'angiogenèse/effets indésirables , Inhibiteurs de l'angiogenèse/usage thérapeutique , Antifongiques/effets indésirables , Division cellulaire/effets des médicaments et des substances chimiques , Cicatrice hypertrophique/microbiologie , Cicatrice hypertrophique/anatomopathologie , Mycoses cutanées/microbiologie , Mycoses cutanées/anatomopathologie , Fibroblastes/effets des médicaments et des substances chimiques , Fibroblastes/anatomopathologie , Humains , Itraconazole/effets indésirables , Chéloïde/anatomopathologie , Peau/vascularisation , Peau/effets des médicaments et des substances chimiques , Peau/anatomopathologieSujet(s)
Cicatrice hypertrophique/microbiologie , Chéloïde/microbiologie , Mycoses/complications , Adulte , Antifongiques/usage thérapeutique , Cicatrice hypertrophique/traitement médicamenteux , Femelle , Humains , Itraconazole/usage thérapeutique , Chéloïde/traitement médicamenteux , Mâle , Adulte d'âge moyen , Mycoses/traitement médicamenteuxRÉSUMÉ
Although the association between hypertrophic burn scarring and infection is well described, an association with colonization has not been established. This retrospective study sought to determine whether a significant association between hypertrophic scarring and bacterial colonization exists. Details from the case notes of all patients seen in our institution's burns unit over a two-year period were recorded and the incidence of hypertrophic scarring and burn bacterial colonization was noted. A total of 127 scars were recorded, and of these, 51 were hypertrophic and 76 nonhypertrophic. The incidence of bacterial colonization in the hypertrophic scar group was 88%, an association that achieved significance (P < .05) in comparison with nonhypertrophic scars (27%). This association holds true for individual organisms such as Staphylococcus aureus and Escherichia coli and for all burn depths and healing times. This study suggests that burn wound bacterial colonization may be more important than previously believed and perhaps suggests that striving toward an aseptic burn wound environment may reduce the incidence of hypertrophic scarring.