Project description:Host-microbiome-dietary interactions play crucial roles in regulating human health, yet direct functional assessment of their interplays, cross-regulations and downstream disease impacts remains challenging. We adopted metagenome-informed metaproteomics (MIM), in both mice and humans, to simultaneously explore host, dietary, and species-level microbiome interactions across diverse scenarios, including commensal and pathogen colonization, nutritional modifications, and antibiotic-induced perturbations. Implementation of MIM in murine auto-inflammation and in human IBD characterized a ‘compositional dysbiosis’ and a concomitant, species-specific ‘functional dysbiosis’ driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutrient assessment enabled determination of IBD-related consumption patterns, dietary treatment compliance and small-intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology, while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.
Project description:Purpose:To help identify molecular regulatory mechanisms of developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, microRNA profiles in red drum larvae exposed to different DWH oils (source/mass and artificially weathered oil) were evaluated using High Throughput Sequencing (HTS). Methods:Total microRNA profiles of 48 hpf red drum larvae after source oil (0.135%, 0.27%, and 0.54%) and slick oil (1.25%, 2.5% and 5%) exposure were generated by deep sequencing, in triplicate, using Illumina NextSeq 500. Results: Source and slick oil significantly dysregulated the expression of miR-18a, miR-27b, and miR-203a across all exposure concentrations. The target genes of these miRNAs were predominantly involved in the neuro-cardio system development processes and associated key signaling pathways such as axonal guidance signaling, CREB signaling in neurons, synaptic long-term potentiation pathway, calcium signaling and role of NFAT in cardiac hypertrophy.
Project description:In this study we characterize the gill transcriptome changes in Gulf killifish (Fundulus grandis) that coincide with controlled laboratory-based exposure to various concentrations of experimentally-weathered south Louisiana crude oil. Gill transcription was contrasted between doses and across timepoints following dosing.
Project description:In this study we characterize the liver transcriptome changes in Gulf killifish (Fundulus grandis) that coincide with controlled laboratory-based exposure to various concentrations of experimentally-weathered south Louisiana crude oil. Liver transcription was contrasted between doses and across timepoints following dosing.
Project description:On going efforts are directed at understanding the mutualism between the gut microbiota and the host in breast-fed versus formula-fed infants. Due to the lack of tissue biopsies, no investigators have performed a global transcriptional (gene expression) analysis of the developing human intestine in healthy infants. As a result, the crosstalk between the microbiome and the host transcriptome in the developing mucosal-commensal environment has not been determined. In this study, we examined the host intestinal mRNA gene expression and microbial DNA profiles in full term 3 month-old infants exclusively formula fed (FF) (n=6) or breast fed (BF) (n=6) from birth to 3 months. Host mRNA microarray measurements were performed using isolated intact sloughed epithelial cells in stool samples collected at 3 months. Microbial composition from the same stool samples was assessed by metagenomic pyrosequencing. Both the host mRNA expression and bacterial microbiome phylogenetic profiles provided strong feature sets that clearly classified the two groups of babies (FF and BF). To determine the relationship between host epithelial cell gene expression and the bacterial colony profiles, the host transcriptome and functionally profiled microbiome data were analyzed in a multivariate manner. From a functional perspective, analysis of the gut microbiota's metagenome revealed that characteristics associated with virulence differed between the FF and BF babies. Using canonical correlation analysis, evidence of multivariate structure relating eleven host immunity / mucosal defense-related genes and microbiome virulence characteristics was observed. These results, for the first time, provide insight into the integrated responses of the host and microbiome to dietary substrates in the early neonatal period. Our data suggest that systems biology and computational modeling approaches that integrate “-omic” information from the host and the microbiome can identify important mechanistic pathways of intestinal development affecting the gut microbiome in the first few months of life. KEYWORDS: infant, breast-feeding, infant formula, exfoliated cells, transcriptome, metagenome, multivariate analysis, canonical correlation analysis 12 samples, 2 groups
Project description:Purpose: To help identify molecular regulatory mechanisms of developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, microRNA profiles in mahi-mahi (Coryphaena hippurus) larvae exposed to different DWH oils (source/mass and artificially weathered oil) were evaluated using High Throughput Sequencing (HTS). Methods: Total microRNA profiles of 48 hpf mahi-mah larvae after slick (0.5%, 1%, and 2%) and source/mass oil (0.125%, 0.25% and 5%) exposure were generated by deep sequencing, in triplicate, using Illumina NextSEQ v2. Results: Among over 100 significant DE miRNAs, DE miRNAs that were inversely correlated with target mRNAs after slick and source oil exposure were identfied. miR-34b, miR-181b, miR-23b, and miR-203a responsive to both slick and source oil exposure were further filtered to predict downstream biological functions. The target genes of these four miRNAs were involved AhR signaling, Cardiac β-adrenergic signaling, nNOS signaling in neurons, xenobiotic metabolism signaling, p53 signaling, cell cycle regulation, etc., as well as potential diseases including cardiovascular disease, neurological disease, developmental disorder, ophthalmic disease, metabolism disease, etc.