Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits

Autumn M. McKnite, Maria Elisa Perez-Munoz, Lu Lu, Evan G. Williams, Simon Brewer, Pénélope A. Andreux, John W.M. Bastiaansen, Xusheng Wang, Stephen D. Kachman, Johan Auwerx, Robert W. Williams, Andrew K. Benson, Daniel A. Peterson, Daniel C. Ciobanu

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic factors and is associated with several polygenic diseases. In this study we combined next-generation sequencing, genetic mapping, and a set of physiological traits of the BXD mouse population to explore genetic factors that explain differences in gut microbiota and its impact on metabolic traits. Molecular profiling of the gut microbiota revealed important quantitative differences in microbial composition among BXD strains. These differences in gut microbial composition are influenced by host-genetics, which is complex and involves many loci. Linkage analysis defined Quantitative Trait Loci (QTLs) restricted to a particular taxon, branch or that influenced the variation of taxa across phyla. Gene expression within the gastrointestinal tract and sequence analysis of the parental genomes in the QTL regions uncovered candidate genes with potential to alter gut immunological profiles and impact the balance between gut microbial communities. A QTL region on Chr 4 that overlaps several interferon genes modulates the population of Bacteroides, and potentially Bacteroidetes and Firmicutes-the predominant BXD gut phyla. Irak4, a signaling molecule in the Toll-like receptor pathways is a candidate for the QTL on Chr15 that modulates Rikenellaceae, whereas Tgfb3, a cytokine modulating the barrier function of the intestine and tolerance to commensal bacteria, overlaps a QTL on Chr 12 that influence Prevotellaceae. Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation.

Original languageEnglish (US)
Article numbere39191
JournalPloS one
Volume7
Issue number6
DOIs
StatePublished - Jun 18 2012

Fingerprint

Quantitative Trait Loci
intestinal microorganisms
quantitative trait loci
Genes
mice
Toll-Like Receptors
gastrointestinal system
Gastrointestinal Tract
Ports and harbors
Chemical analysis
Metabolism
Gene expression
digestive system
Interferons
Bacteroidetes
Bacteria
Bacteroides
Firmicutes
Cytokines
Microbiota

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

McKnite, A. M., Perez-Munoz, M. E., Lu, L., Williams, E. G., Brewer, S., Andreux, P. A., ... Ciobanu, D. C. (2012). Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PloS one, 7(6), [e39191]. https://doi.org/10.1371/journal.pone.0039191

Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. / McKnite, Autumn M.; Perez-Munoz, Maria Elisa; Lu, Lu; Williams, Evan G.; Brewer, Simon; Andreux, Pénélope A.; Bastiaansen, John W.M.; Wang, Xusheng; Kachman, Stephen D.; Auwerx, Johan; Williams, Robert W.; Benson, Andrew K.; Peterson, Daniel A.; Ciobanu, Daniel C.

In: PloS one, Vol. 7, No. 6, e39191, 18.06.2012.

Research output: Contribution to journalArticle

McKnite, AM, Perez-Munoz, ME, Lu, L, Williams, EG, Brewer, S, Andreux, PA, Bastiaansen, JWM, Wang, X, Kachman, SD, Auwerx, J, Williams, RW, Benson, AK, Peterson, DA & Ciobanu, DC 2012, 'Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits', PloS one, vol. 7, no. 6, e39191. https://doi.org/10.1371/journal.pone.0039191
McKnite AM, Perez-Munoz ME, Lu L, Williams EG, Brewer S, Andreux PA et al. Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PloS one. 2012 Jun 18;7(6). e39191. https://doi.org/10.1371/journal.pone.0039191
McKnite, Autumn M. ; Perez-Munoz, Maria Elisa ; Lu, Lu ; Williams, Evan G. ; Brewer, Simon ; Andreux, Pénélope A. ; Bastiaansen, John W.M. ; Wang, Xusheng ; Kachman, Stephen D. ; Auwerx, Johan ; Williams, Robert W. ; Benson, Andrew K. ; Peterson, Daniel A. ; Ciobanu, Daniel C. / Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. In: PloS one. 2012 ; Vol. 7, No. 6.
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