title: Metabolomic Modeling To Monitor Host Responsiveness to Gut Microbiota Manipulation in the BTBR(T+tf/j) Mouse.
abstract: The microbiota, the entirety of microorganisms residing in the gut, is increasingly recognized as an environmental factor in the maintenance of health and the development of disease. The objective of this analysis was to model in vivo interactions between gut microbiota and both serum and liver metabolites. Different genotypic models (C57BL/6 and BTBR(T+tf/j) mice) were studied in combination with significant dietary manipulations (chow vs ketogenic diets) to perturb the gut microbiota. Diet rather than genotype was the primary driver of microbial changes, with the ketogenic diet diminishing total bacterial levels. Fecal but not cecal microbiota profiles were associated with the serum and liver metabolomes. Modeling metabolome-microbiota interactions showed fecal Clostridium leptum to have the greatest impact on host metabolism, significantly correlating with 10 circulating metabolites, including 5 metabolites that did not correlate with any other microbes. C. leptum correlated negatively with serum ketones and positively with glucose and glutamine. Interestingly, microbial groups most strongly correlated with host metabolism were those modulating gut barrier function, the primary site of microbe-host interactions. These results show very robust relationships and provide a basis for future work wherein the compositional and functional associations of the microbiome can be modeled in the context of the metabolome.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Klein
authors.forename: Christopher
authors.initials: C
authors.lastname: Newell
authors.forename: Marc R
authors.initials: MR
authors.lastname: Bomhof
authors.forename: Raylene A
authors.initials: RA
authors.lastname: Reimer
authors.forename: Dustin S
authors.initials: DS
authors.lastname: Hittel
authors.affiliation: Departments of Paediatrics & Clinical Neurosciences, Alberta Children's Hospital Research Institute, University of Calgary , Calgary, Alberta T2N 2T9, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000302:isolation & purification / Q000378:metabolism; D001644:Bifidobacterium / Q000302:isolation & purification / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002432:Cecum / Q000382:microbiology; D003013:Clostridium / Q000302:isolation & purification / Q000378:metabolism; D055423:Diet, Ketogenic; D004755:Enterobacteriaceae / Q000302:isolation & purification / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D005973:Glutamine / Q000097:blood; D007659:Ketones / Q000097:blood; D007778:Lactobacillus / Q000302:isolation & purification / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007659:Ketones; D005973:Glutamine
keywords: Metabolome; communication; ketogenic diet; metabolomics; microbiota; modeling; mouse