Project description:Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study. A factor-based integrative approach identified coordinated variation, revealing that the interferon response was amongst the most variable immune features in healthy participants. Microbiome composition, pathways, and stool metabolites varied concomitantly with interferon response pathways. Longitudinal data spanning more than a year indicated the significant stability of these parameters within individuals over time. Our study provides extensive data to examine the relationship between the immune states and microbiomes of healthy individuals at steady state, which paves the way for delineating inter-individual differences relevant for disease susceptibility and responses to therapy.
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:Human immune systems are highly variable, with most variation attributable to non-genetic sources. The gut microbiome crucially shapes the immune system; however, its relationship with the baseline immune states of healthy humans remains incompletely understood. Therefore, we performed multi-omic profiling of 110 healthy participants through the ImmunoMicrobiome study. A factor-based integrative approach identified coordinated variation, revealing that the interferon response was amongst the most variable immune features in healthy participants. Microbiome composition, pathways, and stool metabolites varied concomitantly with interferon response pathways. Longitudinal data spanning more than a year indicated the significant stability of these parameters within individuals over time. Our study provides extensive data to examine the relationship between the immune states and microbiomes of healthy individuals at steady state, which paves the way for delineating inter-individual differences relevant for disease susceptibility and responses to therapy.
Project description:The role of domestic and peridomestic animals in vector-borne diseases is very important as they share a common environment with people having the potential to extend the network of pathogen transmission to humans. The most significant vector-borne infectious diseases that are shared by man, domestic and peridomestic animals are leishmaniosis, borreliosis, bartonellosis, ehrlichiosis, rickettsiosis and anaplasmosis with fleas acting as main vectors in the transmission of some of these diseases. Flea-borne diseases which are relevant in Europe include plague (caused by Yersinia pestis), murine typhus (caused by Rickettsia typhi), flea-borne spotted fever (Rickettsia felis), and cat scratch disease (Bartonella henselae). In the present study, mNGS was applied to detect and understand the composition of the microbial communities of five different species of fleas (Archaeopsylla erinacei, Ctenocephalides felis, Spilopsyllus cuniculi, Pulex irritans and Ctenocephalides canis) collected on dogs, cats and hedgehogs from Andalusia (Spain) to know the prevalence of pathogenic bacteria among synanthropic fleas. Based on our results, we could conclude that Pulicidae family encompassed those flea species with a close contact with humans and therefore more involved in the potential transmission of infectious diseases. The higher relative abundance of the Phylum Pseudomanadota was mainly due to the presence of the endosymbiont Wolbachia, as well as to notice a high relative abundance of both genera Rickettsia and Bartonella in all flea species. For the first time, we detected Babesia sp. in all species tested, especially with higher abundance in S. cuniculi collected from cats emphasizing the need for further investigation into its potential implications as vectors. Our results also demonstrate that the microbiota composition of fleas is largely influenced by the host they parasitize. Lastly, statistical analyses of microbiota allowed for the ecological separation of flea species, with individuals from these five species clustering distinctly each other.
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:Search for SNPs associated with the pharmacogenomic profile of Benzidazole adverse reactions in Chagas Disease Homo sapiens patients.
Project description:Gene expression profiles in T. cruzi strains isolated from individuals presenting the indeterminate and cardiac forms of Chagas disease. Genetic markers differentially expressed may be of potential use in diagnostic/prognostic tests and could assist the understanding of pathogenesis of Chagas disease Keywords: other