Biology subjects

Horwinski, J.

Publications and source records attributed to Horwinski, J..

3 recordsLinked to original sources

bioRxiv2020

Commensal Microbiota Regulates Skin Barrier Function And Repair Via Signaling Through The Aryl Hydrocarbon Receptor

The epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while sensing and integrating environmental signals. The tightly orchestrated cellular changes required for the proper formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germ free mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier. These effects were mediated by the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Murine skin lacking keratinocyte AHR was more susceptible to barrier damage and infection, during steady state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, with far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.

microbiology↗

bioRxiv2018

The microbial basis of impaired wound healing: differential roles for pathogens, \"bystanders\", and strain-level diversification in clinical outcomes

Chronic, non-healing wounds are a major complication of diabetes associated with high morbidity and health care expenditures estimated at $9-13 billion annually in the US. Though microbial infection and critical colonization is hypothesized to impair healing and contribute to severe outcomes such as amputation, antimicrobial therapy is inefficacious and the role of microbes in tissue repair, regeneration, and healing remains unclear. Here, in a longitudinal prospective cohort study of 100 subjects with non-infected neuropathic diabetic foot ulcer (DFU), we performed metagenomic shotgun sequencing to elucidate microbial temporal dynamics at strain-level resolution, to investigate pathogenicity and virulence of the DFU microbiome with respect to outcomes, and to determine the influence of therapeutic intervention on the DFU microbiota. Slow healing DFUs were associated with signatures of biofilm formation, host invasion, and virulence. Though antibiotic resistance was widespread at the genetic level, debridement, rather than antibiotic treatment, significantly shifted the DFU microbiome in patients with more favorable outcomes. Primary clinical isolates of S. aureus, C. striatum, and A. faecalis induced differential biological responses in keratinocytes and in a murine model of diabetic wound healing, with the S. aureus strain associated with non-healing wounds eliciting the most severe phenotype. Together these findings implicate strain-level diversification of the wound pathogen S. aureus in chronic wound outcomes, while revealing potential contributions from skin commensals and other previously underappreciated constituents of the wound microbiota.

genomics↗

bioRxiv2017

ANTISEPTIC AGENTS ELICIT SHORT-TERM, PERSONALIZED AND BODY SITE-SPECIFIC SHIFTS IN RESIDENT SKIN BACTERIAL COMMUNITIES

Despite critical functions in cutaneous health and disease, it is unclear how resident skin microbial communities are altered by topical antimicrobial interventions commonly used in personal and clinical settings. Here we show that acute exposure to antiseptic treatments elicits rapid but short-term depletion of microbial community diversity and membership. Thirteen subjects were enrolled in a longitudinal treatment study to analyze the effects of topical treatments (ethanol, povidone-iodine, chlorhexidine, water) on the skin microbiome at two skin sites of disparate microenvironment: forearm and back. Treatment effects were highly dependent on personalized and body site-specific colonization signatures, which concealed community dynamics at the population level when not accounted for in this analysis. The magnitude of disruption was influenced by the identity and abundance of particular bacterial inhabitants. Lowly abundant members of the skin microbiota were more likely to be displaced, and subsequently replaced by the most abundant taxa prior to treatment. Members of the skin commensal family Propionibactericeae were particularly resilient to treatment, suggesting a distinct competitive advantage in the face of disturbance. These results provide insight into the stability and resilience of the skin microbiome, while establishing the impact of topical antiseptic treatment on skin bacterial dynamics and community ecology.

microbiology↗