Project description:The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-b-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.
Project description:Investigation of the overall in vitro response of Bacteroides thetaiotaomicron to human milk oligosaccharides. Comparison with response to MM-lactose and MM-galactose (Analysis performed using as a baseline datasets GSM301635 and GSM301637 corresponding to Bacteroides thetaiotaomicron response in MM-Glucose)
Project description:We report next generation sequencing RNA-seq data of human gut commensal Bacteroides thetaiotaomicron strains deficient in inositol lipid synthesis, including dBT_1522 (phosphoinositol dihydroceramide synthase knockout) and its wild-type background strain, and iSPTdBT_1526 (myo-inositol-phosphate synthase) knockout with its background strain ("iSPT," inducible serine palmitoyltransferase).
Project description:Investigation of the overall in vitro response of Bacteroides thetaiotaomicron to human milk oligosaccharides. Comparison with response to MM-lactose and MM-galactose (Analysis performed using as a baseline datasets GSM301635 and GSM301637 corresponding to Bacteroides thetaiotaomicron response in MM-Glucose) In vitro transcriptional profiles of Bacteroides thetaiotaomicron obtained from biological duplicate cultures taken: (i) at middle log phase in minimal media galactose (MM-Gal) and minimal media lactose (MM-L) and (ii) at two timepoints during log phase in minimal media human milk oligosaccharides (MM-HMO).
Project description:Bacteroidaceae are common gut microbiota members in all warm-blooded animals. However, if Bacteroidaceae are to be used as probiotics, the species selected for different hosts should reflect the natural distribution. In this study, we therefore evaluated host adaptation of bacterial species belonging to the family Bacteroidaceae. B. dorei, B. uniformis, B. xylanisolvens, B. ovatus, B. clarus, B. thetaiotaomicron and B. vulgatus represented human-adapted species while B. gallinaceum, B. caecigallinarum, B. mediterraneensis, B. caecicola, M. massiliensis, B. plebeius and B. coprocola were commonly detected in chicken but not human gut microbiota. There were 29 genes which were present in all human-adapted Bacteroides but absent from the genomes of all chicken isolates and these included genes required for the pentose cycle, and glutamate or histidine metabolism. These genes were expressed during an in vitro competitive assay, in which human-adapted Bacteroides species overgrew the chicken adapted isolates. Not a single gene specific for the chicken-adapted species was found. Instead, chicken adapted species exhibited signs of frequent horizontal gene transfer, of KUP, linA and sugE genes in particular. The differences in host adaptation should be considered when the new generation of probiotics for humans or chickens is designed.
Project description:The goal of this project was to sequence the transcriptome of wild type Bacteroides thetaiotaomicron VPI-5482 grown in minimal media with either glucose or bovine alpha 1 acid glycoprotein (AAGP) as the sole carbon source. Using these data we could then compare relative gene expression levels under each condition and identify genes specifically upregulated during growth on AAGP. Analysis of the spent media indicated that only the N-glycan component of the AAGP had been used by the cells to support growth.
Project description:Purpose: Examining the transcriptome of Bacteroides thetaiotaomicron VPI-5482 challenged with Bacteroides phage to assess surface molecule expression changes Methods: Bacteroides thetaiotaomicron was grown in BPRM in vitro or Germ-Free mice were monocolonized with Bacteroides thetaiotaomicron and gavaged with ARB25 phage. Fold change was calculated as live phage versus heat-killed phage treated samples with n=3 biological replicates. Once cells reached an optical density corresponding to mid-log phase growth (absorbance between 0.4-0.5), RNA was isolated and rRNA depleted. Samples were multiplexed for sequencing on the Illumina HiSeq platform at the University of Michigan Sequencing Core. Data was analyzed using Arraystar software (DNASTAR, Inc.) using DEseq2 normalization with default parameters. Genes with significant up- or down-regulation were determined by the following criteria: genes with an average fold-change >5-fold and with at least 2/3 biological replicates with a normalized expression level >1% of the overall average, and a p-value < 0.05 (t test with Benjamini-Hochberg correction) Results: Specific capsule expression was increased in wild-type B. thetaiotaomicron during phage infection in vitro and in vivo. Many corresponding in vivo genes were upregulated as well as other surface layer proteins.