The authors used an advanced intercross line (AIL) mouse model to investigate the environmental and genetic factors that shape the composition of the gut microbiota. In the AIL mice, increased recombination has resulted in a genetic background that is easier to analyse than that of standard mouse models. Faecal microbiota of 654 AIL mice were phenotyped by pyrosequencing of 16S ribosomal DNA, revealing the presence of 420 genera, 143 families, 53 orders, 24 classes and 16 phyla across the AIL population. Of the genera identified, a few were found in most or all AIL mice, leading the authors to define a conserved core measurable microbiota (CMM) that accounted for >90% of all the sequence reads and contained 19 genera and 64 taxonomic groups.
Benson et al. looked for co-segregation of the relative proportions of each CMM taxon with 530 single nucleotide polymorphisms in the mouse genome to identify quantitative trait loci (QTL) through which the host genotype influences variation in the microbiota composition. They found that 26 of the 64 CMM taxa showed an association with 13 significant QTL (and with five other suggestive QTL), indicating that the presence of a particular allele in the host genome can lead to a greater or lesser abundance of a particular species in the gut microbiota. The association between QTL and species was spread across the entire microbiota, with at least one taxon from each major phylum associating with at least one genomic locus. Host gene influence was exerted mostly at the tips of the phylogenetic tree — that is, QTL were mostly associated with variation at the genus and family levels, with only a few associations affecting variation at the phylum or class level. Finally, some QTL exhibited pleiotropic effects on multiple taxa, both closely and distantly related. One of the outcomes of this pleiotropy is that disparate groups of gut microorganisms (such as taxa in the Firmicutes and Actinobacteria) persistently occur together.
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