Patient genetics is linked to chronic wound microbiome composition and healing
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ABSTRACT:
PROVIDER: PRJNA627947 | ENA |
REPOSITORIES: ENA
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Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
2020-04-25 | GSE149314 | GEO
Project description:The clinical importance of microbiomes to the chronicity of wounds is widely appreciated, yet little is understood about patient-specific processes shaping wound microbiome composition. Here, a two-cohort microbiome-genome wide association study is presented through which patient genomic loci associated with chronic wound microbiome diversity were identified. Further investigation revealed that alternative TLN2 and ZNF521 genotypes explained significant inter-patient variation in relative abundance of two key pathogens, Pseudomonas aeruginosa and Staphylococcus epidermidis. Wound diversity was lowest in Pseudomonas aeruginosa infected wounds, and decreasing wound diversity had a significant negative linear relationship with healing rate. In addition to microbiome characteristics, age, diabetic status, and genetic ancestry all significantly influenced healing. Using structural equation modeling to identify common variance among SNPs, six loci were sufficient to explain 53% of variation in wound microbiome diversity, which was a 10% increase over traditional multiple regression. Focusing on TLN2, genotype at rs8031916 explained expression differences of alternative transcripts that differ in inclusion of important focal adhesion binding domains. Such differences are hypothesized to relate to wound microbiomes and healing through effects on bacterial exploitation of focal adhesions and/or cellular migration. Related, other associated loci were functionally enriched, often with roles in cytoskeletal dynamics. This study, being the first to identify patient genetic determinants for wound microbiomes and healing, implicates genetic variation determining cellular adhesion phenotypes as important drivers of infection type. The identification of predictive biomarkers for chronic wound microbiomes may serve as risk factors and guide treatment by informing patient-specific tendencies of infection.
| S-EPMC7302439 | biostudies-literature
Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.
2024-07-02 | MTBLS3315 | MetaboLights
Project description:We generated a genomic and phenotypic resource comprising genetically outbred mice in which we measured (i) quantitative differences in wound healing indicated as ear area (ii) bone marrow derived macrophage (BMDM) mRNA expression by RNA-sequencing (RNA-seq), (iii) genome-wide SNPs genotyping by low-coverage sequencing.We performed gene co-expression network analysis and we identified a network in macrophages enriched in cholesterol genes which is genetically controlled by Runx2 gene. In vivo pharmacological blockage of Fasn with cerulenin showed delayed wound healing in rats and increased macrophage recruitment to the wound.
2019-01-11 | GSE112171 | GEO
Project description:The aim of this study was to identify the genes differentially expressed between timepoints in the week following tympanic membrane perforation in rats. Tissue from 240 individual rats was used in this study following random allocation into timepoint groups to be sacrificed over 7 days. An Agilent one color microarray technique was performed and the results were analyzed using Genespring GX9 software. A total of 3262 genes were identified as significant (p<0.05) and differentially expressed above a two-fold threshold between the timepoints. This study provides a complete genetic review of rat tympanic membrane wound healing over 7 days. The results can be used as a model for other wound healing in other mammals and in different parts of the body. The information on differential gene expression can be used in research towards developing chronic tympanic membrane perforations and also in research to treat acute and chronic tympanic membrane perforations. The microarray was performed on animals in a disease free environment and the genetic information can be compared to future research in disease states of the TM including Otitis media, cholesteatoma, chronic perforation and tympanosclerosis. Rats were randomly selected as either controls or in the perforation group. Perforations were created unilaterally (left ear) in the upper outer quadrant of the pars tensa of ratsâ tympanic membranes using sterile 23 gauge needles . Rats were then randomly allocated into timepoint groups to be sacrificed at either 12, 24, 36, day 2, 3, 4, 5, 6, 7. At the point of microarray, there were 18 rats per timepoint group and 18 controls.
2010-08-18 | E-GEOD-17698 | biostudies-arrayexpress
Project description:The aim of this study was to identify the genes differentially expressed between timepoints in the week following tympanic membrane perforation in rats. Tissue from 240 individual rats was used in this study following random allocation into timepoint groups to be sacrificed over 7 days. An Agilent one color microarray technique was performed and the results were analyzed using Genespring GX9 software. A total of 3262 genes were identified as significant (p<0.05) and differentially expressed above a two-fold threshold between the timepoints. This study provides a complete genetic review of rat tympanic membrane wound healing over 7 days. The results can be used as a model for other wound healing in other mammals and in different parts of the body. The information on differential gene expression can be used in research towards developing chronic tympanic membrane perforations and also in research to treat acute and chronic tympanic membrane perforations. The microarray was performed on animals in a disease free environment and the genetic information can be compared to future research in disease states of the TM including Otitis media, cholesteatoma, chronic perforation and tympanosclerosis.
2009-08-19 | GSE17698 | GEO
Project description:The process of wound healing in humans is poorly understood. To identify spatiotemporal gene expression patterns during human wound healing, we performed single cell and spatial transcriptomics profiling of human in vivo wound samples.
2024-09-04 | GSE241132 | GEO
Project description:Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing
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Project description:Urinary bladder wound healing is today pooorly chracterized. MicroRNAs are small non-coding RNA molecules with regulatory functions. In this study we aimed at identifying microRNAs expressed during bladder wound healing. We performed Affymetrix microRNA profiling of the rodent urinary bladder during healing of a surgically created wound.
2021-12-01 | GSE176515 | GEO