Inflammation-associated enterotypes, host genotype, cage and inter-individual effects drive gut microbiota variation in common laboratory mice.
BACKGROUND
Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing.


RESULTS
We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calprotectin levels, a marker for intestinal inflammation. After enterotype stratification, we find that genetic, caging and inter-individual variation contribute on average 19%, 31.7% and 45.5%, respectively, to the variance in the murine gut microbiota composition. Genetic distance correlates positively to microbiota distance, so that genetically similar strains have more similar microbiota than genetically distant ones. Specific mouse strains are enriched for specific operational taxonomic units and taxonomic groups, while the 'cage effect' can occur across mouse strain boundaries and is mainly driven by Helicobacter infections.


CONCLUSIONS
The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals. Furthermore, the observed environmental and genetic effects have important consequences for experimental design in mouse microbiome research.
Falk
F
Hildebrand
Thi Loan Anh
TL
Nguyen
Brigitta
B
Brinkman
Roberto Garcia
RG
Yunta
Benedicte
B
Cauwe
Peter
P
Vandenabeele
Adrian
A
Liston
Jeroen
J
Raes
D000818:Animals; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D016998:Helicobacter / Q000302:isolation & purification; D007249:Inflammation / Q000235:genetics / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000382:microbiology*; D064307:Microbiota; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013045:Species Specificity
D039841:Leukocyte L1 Antigen Complex; D012336:RNA, Ribosomal, 16S