title: Skin wound healing is accelerated and scarless in the absence of commensal microbiota.
abstract: The commensal microbiota has a high impact on health and disease by modulating the development and homeostasis of host immune system. Immune cells are involved in virtually every aspect of the wound repair process; however, the impact of commensal microbiota on skin wound healing is largely unknown. In this study, we evaluated the influence of commensal microbiota on tissue repair of excisional skin wounds by using germ-free (GF) Swiss mice. We observed that macroscopic wound closure rate is accelerated in the absence of commensal microbiota. Accordantly, histologically assessed wound epithelization was accelerated in GF in comparison with conventional (CV) Swiss mice. The wounds of GF mice presented a significant decrease in neutrophil accumulation and an increase in mast cell and macrophage infiltration into wounds. Interestingly, alternatively activated healing macrophage-related genes were highly expressed in the wound tissue of GF mice. Moreover, levels of the anti-inflammatory cytokine IL-10, the angiogenic growth factor VEGF and angiogenesis were higher in the wound tissue of those mice. Conversely, scarring and levels of the profibrogenic factor TGF-β1 were greatly reduced in GF mice wounded skin when compared with CV mice. Of note, conventionalization of GF mice with CV microbiota restored wound closure rate, neutrophil and macrophage accumulation, cytokine production, and scarring to the same extent as CV mice. Overall, our findings suggest that, in the absence of any contact with microbiota, skin wound healing is accelerated and scarless, partially because of reduced accumulation of neutrophils, increased accumulation of alternatively activated healing macrophages, and better angiogenesis at wound sites.
authors.affiliation: Departamento de Fisiologia e Biofísica, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Maria C C
authors.initials: MC
authors.lastname: Canesso
authors.affiliation: Departamento de Microbiologia, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Angélica T
authors.initials: AT
authors.lastname: Vieira
authors.affiliation: Departamento de Fisiologia e Biofísica, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Tiago B R
authors.initials: TB
authors.lastname: Castro
authors.affiliation: Departamento de Fisiologia e Biofísica, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Brígida G A
authors.initials: BG
authors.lastname: Schirmer
authors.affiliation: Departamento de Microbiologia, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Daniel
authors.initials: D
authors.lastname: Cisalpino
authors.affiliation: Departamento de Microbiologia, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Flaviano S
authors.initials: FS
authors.lastname: Martins
authors.affiliation: Departamento de Patologia Geral, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil; and.
authors.forename: Milene A
authors.initials: MA
authors.lastname: Rachid
authors.affiliation: Departamento de Microbiologia, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil;
authors.forename: Jacques R
authors.initials: JR
authors.lastname: Nicoli
authors.affiliation: Departamento de Bioquímica e Imunologia, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Departamento de Fisiologia e Biofísica, Grupo de Imunofarmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil; luciolasbarcelos@gmail.com.
authors.forename: Lucíola S
authors.initials: LS
authors.lastname: Barcelos
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002921:Cicatrix / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D005856:Germ-Free Life / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D051379:Mice; D064307:Microbiota / Q000276:immunology; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D062326:Re-Epithelialization / Q000502:physiology*; D012867:Skin / Q000098:blood supply / Q000276:immunology* / Q000293:injuries / Q000382:microbiology; D013559:Symbiosis / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
chemical_list: C556062:IL10 protein, mouse; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10