Project description:Under steady state conditions, the immune system is poised to sense and respond to the microbiota. As such, immunity to the microbiota, including T cell responses, is expected to precede any inflammatory trigger. How this pool of preformed microbiota-specific T cells contributes to tissue pathologies remains unclear. Here, using an experimental model of psoriasis, we show that recall responses to commensal skin fungi can significantly aggravate tissue inflammation. Enhanced pathology caused by fungi pre-exposure depends on Th17 responses and neutrophil extracellular traps and recapitulates features of the transcriptional landscape of human lesional psoriatic skin. Together, our results propose that recall responses directed to skin fungi can directly promote skin inflammation and that exploration of tissue inflammation should be assessed in the context of recall responses to the microbiota.
Project description:<p>Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.</p>
Project description:The resident skin microbiota plays a fundamental role in the control of skin physiology and growing evidence support the idea that, at this barrier site, both immunity and inflammatory processes are controlled by skin resident microbiota. However, how defined skin microbes influence the skin immune system under both steady state conditions and inflammatory settings remains poorly understood. Obesity has been linked to increased prevalence of skin inflammatory disorders. We used microarray analysis to investigate how Corynebacterium spp., dominant members of the skin microbiota of mice and humans, influence gene expression in the skin in mice under normal diet or a high-fat diet regimen.
Project description:D-galactose orally intake ameliorate DNCB-induced atopic dermatitis by modulating microbiota composition and quorum sensing. The increased abundance of bacteroidetes and decreased abundance of firmicutes was confirmed. By D-galactose treatment, Bacteroides population was increased and prevotella, ruminococcus was decreased which is related to atopic dermatitis.