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.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome. The results were used to demonstarte the usefulness of applying HuMiChip to human microbiome studies.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome.
Project description:HuMiChip2 was applied to analyze perform both strain-level identification and the functional profiling of human gut microbiomes from alcoholic cirrhosis patients and healthy individuals with alcohol abuse.
Project description:RNA was extracted from the meninges of mice from either Specific pathogen free or Germ free facilities or from the offspring of mice reconstituted with different human microbiomes.
Project description:We developed an approach named Rapid Assay of Individual Microbiome (RapidAIM) to screen xenobiotics against individual microbiomes, and conducted a proof-of-concept (POC) study on the use of RapidAIM. We tested 43 compounds against five individual microbiomes. The individual microbiomes are cultured in 96-well plates for 24 hours and the samples are then analyzed using a metaproteomics-based analytical approach to gain functional insight into the individual microbiomes responses following drug treatments.The tested compounds significantly affected overall microbiome abundance, microbiome composition and functional pathways at multiple taxonomic levels. The microbiome responses to berberine, metformin, diclofenac, fructooligosaccharide and most antibiotics were consistent among most individual microbiomes. Interestingly, most of our tested NSAIDs, statins, and histamine-2 blockers induced individually distinct responses. Our workflow offers an effective solution to systematically study the effects of many different compounds on individual microbiomes.
Project description:There is mounting evidence for the role of epigenetic processes in the regulation of plant responses to a wide range of external stimuli. Despite their importance, the significance of epigenetic processes in plant-pathogen interactions remain poorly understood. So far, the role of histone modifications has not been investigated at genome wide level in plant-nematode interactions, although their expression levels are altered in nematode-induced galls. In this study, we first applied chemical inhibitors of histone modifying enzymes on rice plants. Despite theirdistinct effects on histone modifications, application of different concentrations of Niconinamide, sulfamethazine and fumaric acid lead to reduced susceptibility to nematode infection. Similarly, two overexpression lines of histone lysine methyltransferases and one histone deacetylase were analyzed in an infection assay with nematodes, showing contrasting results in susceptibility. These data indicate that histone modifications can affect plant defence against nematodes in rice. To further investigate their effect, the genome-wide level of three histone marks namely H3K9ac, H3K9me2 and H3K27me3 was studied by chromatin-immunoprecipitation (ChIP)-sequencing on nematode-induced galls in comparison with control root tips.