Project description:In this study, we conducted an integrated analysis of skin measurements, clinical BSTI surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical association. By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups based on their age distribution. We established strong connections between 15 core genera and the four KSC types within the three aging groups, revealing three prominent clusters of the facial skin microbiome. Together with skin microbiome variations, skin tone/elasticity distinguishes aging groups while oiliness/hydration distinguishes individual differences within aging groups. Our study provides prospective reality data for customized skin care based on the microbiome environment of each skin type.
Project description:The skin Microbiome stratifies Patients with CTCL into two subgroups. One subgroup has a balanced microbiome, while the other subgroups has a skin dybiosis with S. aureus outgrow. This is accompanied by impaired TCR repertoir and poor clinical outcome.
Project description:The skin Microbiome stratifies Patients with CTCL into two subgroups. One subgroup has a balanced microbiome, while the other subgroups has a skin dybiosis with S. aureus outgrowth. This is accompanied by impaired TCR repertoire and poor clinical outcome.
2023-12-01 | GSE218874 | GEO
Project description:Skin microbiome project/ mock community study
Project description:Squalene makes up 12 % of human skin surface lipids, however little is known about its affects on the host skin microbiome. Here we tested the effect of squalene on genetic regulation of staphylococci, showing that it profoundly affects expression virulence or colonisation determinants, and of iron uptake systems.
Project description:Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. In this study, we discovered that epithelium-derived antimicrobial peptides defensins activate orphan GPCRs Mrgpra2a/b on neutrophils. This signaling axis is required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated two mutant mouse lines, Defensin conditional knockout (Def cKO, K14-cre; Def fl/fl) in which the entire Def gene cluster is conditionally deleted from keratinocytes, and Mrgpra2 double knockout (Mrgpra2 dKO). We used high-throughput RNA sequencing to evaluate the whole transcriptomes of WT and mutant animals' skin under naive condition and 24 hours post-S. aureus infection. Disruption of defensin-Mrgpra2 signaling caused reduction of a network of pro-inflammatory and antibacterial gene expression. This study demonstrates the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.
Project description:Objectives: To understand the crosstalk between the immune system and keratinization in psoriatic skin, using a systems biology approach based on transcriptomics, proteomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesion and non-lesion skin of 13 patients with psoriasis (PsO), 15 patients with psoriatic arthritis (PsA), and healthy skin from 12 patients with ankylosing spondylitis (AS). We performed transcriptome sequencing and metagenomics profiling on the local skin sites to study the similarities and differences in the molecular profiles between the three conditions. To assess the systemic nature of the disease, we performed a high-throughput proteome profiling to study the profiles of proteins circulating in the serum of the same donors. Results: We found that lesion and non-lesional samples were remarkably different in terms of their transcriptome profiles. Functional annotation of differentially expressed genes (DEGs) showed a major enrichment in neutrophil activation. By using co-expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we extracted a “core” set of genes that were functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundance of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the “core network” of genes. We further identified 39 circulating proteins from the serum that were significantly correlated with the corresponding local skin gene expression, highlighting systemic aberrations due to skin disease. Integration of “core” genes identified from skin with circulating protein profiles revealed PI3 as a key biomarker for psoriasis. Conclusions: We identified a core network that regulates inflammation and hyper-keratinization in psoriatic skin, and is associated with local disease severity and microbiome composition. Multi-omics analysis identified PI3 as a psoriasis-specific biomarker for disease severity and potential target for treatment strategies.
Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.