title: Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible toPlasmodium yoelii.
abstract: C57BL/6 mice are widely used forin vivostudies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected withPlasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed ≥90% similarity in overall bacterial gene expression within vendors and ≤80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value < 0.05) relative to the mice purchased from Taconic. Included among these,fliC,ureABC, and six members of thenuogene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes includedbasigin, a cell surface receptor required forP. falciparuminvasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism.
authors.affiliation: Department of Microbiology, University of Tennessee Knoxville, TN, USA.
authors.forename: Joshua M A
authors.initials: JM
authors.lastname: Stough
authors.affiliation: Department of Chemistry, University of Tennessee Knoxville, TN, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Dearth
authors.affiliation: Department of Microbiology and Immunology, University of Louisville Louisville, KY, USA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Denny
authors.affiliation: Department of Microbiology, University of Tennessee Knoxville, TN, USA.
authors.forename: Gary R
authors.initials: GR
authors.lastname: LeCleir
authors.affiliation: Department of Microbiology and Immunology, University of Louisville Louisville, KY, USA.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Schmidt
authors.affiliation: Department of Chemistry, University of Tennessee Knoxville, TN, USA.
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Campagna
authors.affiliation: Department of Microbiology, University of Tennessee Knoxville, TN, USA.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Wilhelm
keywords: C57BL/6N lineage; malaria; metabolome; metatranscriptome; microbiome