Project description:Atypical myopathy (AM) is a severe rhabdomyolysis syndrome that occurs in grazing horses. Despite the presence of toxins in their blood, all horses from the same pasture are not prone to display clinical signs of AM. The objective of this study was to compare the blood metabolomic profiles of horses with AM clinical signs with those of healthy co-grazing (Co-G) horses. To do so, plasma samples from 5 AM horses and 11 Co-G horses were investigated using untargeted metabolomics. Metabolomic data were evaluated using unsupervised, supervised, and pathway analyses. Unsupervised principal component analysis performed with all detected features separated AM and healthy Co-G horses. Supervised analyses had identified 1276 features showing differential expression between both groups. Among them, 46 metabolites, belonging predominantly to the fatty acid, fatty ester, and amino acid chemical classes, were identified by standard comparison. Fatty acids, unsaturated fatty acids, organic dicarboxylic acids, and fatty esters were detected with higher intensities in AM horses in link with the toxins' pathological mechanism. The main relevant pathways were lipid metabolism; valine, leucine, and isoleucine metabolism; and glycine metabolism. This study revealed characteristic metabolite changes in the plasma of clinically affected horses, which might ultimately help scientists and field veterinarians to detect and manage AM. The raw data of metabolomics are available in the MetaboLights database with the access number MTBLS2579.
Project description:Standardized muscular biopsies of the dorsal compartment of the gluteus medius muscle were performed in 7 horses suffering from equine polysaccharide storage myopathy (PSSM) and 6 sound Norman Cob horses . Gene expression analysis was performed using an equine oligonucleotide microarray which included 384 equine gene probes of the nuclear genome and all the mitochondrial genes.
Project description:Equine atypical myopathy (AM) is a severe environmental intoxication linked to the ingestion of protoxins contained in seeds and seedlings of the sycamore maple (Acer pseudoplatanus) in Europe. The toxic metabolites cause a frequently fatal rhabdomyolysis syndrome in grazing horses. Since toxic metabolites can also be present in co-grazing horses, it is still unclear as to why, in a similar environmental context, some horses show signs of AM whereas others remain clinically healthy. Label-free proteomics analyses on the serum of 26 diseased AM, 23 co-grazers and 11 control horses were performed to provide insights into biological processes and pathways. A total of 43 and 44 differentially expressed proteins between “AM vs co-grazing horses” and “AM vs control horses” were found. Disease-linked changes in the proteome of different groups were found to correlate with detected amounts of toxins and principal component analysis was performed to identify the 29 proteins with the greatest impact on the proteomic differences between groups. Among the pathway-specific changes the glycolysis/gluconeogenesis pathway, the coagulation/complement cascade, and the biosynthesis of amino acid were affected. Sycamore maple poisoning results in a combination of inflammation, oxidative stress, and high energy demand, which is trying to be met by enhanced glycolysis.
Project description:The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea-2nd study
Project description:Standardized muscular biopsies of the dorsal compartment of the gluteus medius muscle were performed in 7 horses suffering from equine polysaccharide storage myopathy (PSSM) and 6 sound Norman Cob horses . Gene expression analysis was performed using an equine oligonucleotide microarray which included 384 equine gene probes of the nuclear genome and all the mitochondrial genes. All the samples of PSSM muscles were hybridized against the reference control muscles. This reference was made by pooling together all the mRNA extracted after in vitro transcription from the 6 control muscles of the sound horses. Briefly, the hybridization protocol was adapted from Le Brigand et al. (2006). An open-access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes. Nucleic Acids Res. 2006 Jul 19;34(12).
Project description:Microbial RNAseq analysis of cecal and fecal samples collected from mice colonized with the microbiota of human twins discordant for obesity. Samples were colleted at the time of sacrifice, or 15 days after colonization from mice gavaged with uncultured or cultured fecal microbiota from the lean twins or their obese co-twins. Samples were sequenced using Illumina HiSeq technology, with 101 paired end chemistry. Comparisson of microbial gene expression between the microbiota of lean and obese twins fed a Low fat, rich in plant polysaccharide diet.
Project description:Significant gut microbiota heterogeneity exists amongst UC patients though the clinical implications of this variance are unknown. European and South Asian UC patients exhibit distinct disease risk alleles, many of which regulate immune function and relate to variation in gut microbiota β-diversity. We hypothesized ethnically distinct UC patients exhibit discrete gut microbiotas with unique luminal metabolic programming that influence adaptive immune responses and relate to clinical status. Using parallel bacterial 16S rRNA and fungal ITS2 sequencing of fecal samples (UC n=30; healthy n=13), we corroborated previous observations of UC-associated depletion of bacterial diversity and demonstrated significant gastrointestinal expansion of Saccharomycetales as a novel UC characteristic. We identified four distinct microbial community states (MCS 1-4), confirmed their existence using microbiota data from an independent UC cohort, and show they co-associate with patient ethnicity and degree of disease severity. Each MCS was predicted to be uniquely enriched for specific amino acid, carbohydrate, and lipid metabolism pathways and exhibited significant luminal enrichment of metabolic products from these pathways. Using a novel in vitro human DC/T-cell assay we show that DC exposure to patient fecal water led to MCS -specific changes in T-cell populations, particularly the Th1:Th2 ratio, and that patients with the most severe disease exhibited the greatest Th2 skewing. Thus, based on ethnicity, microbiome composition, and associated metabolic dysfunction, UC patients may be stratified in a clinically and immunologically meaningful manner, providing a platform for the development of FMC-focused therapy. Fecal microbiome was assessed with Affymetrix PhyloChip arrays from patients with ulcerative colitis and healthy controls.