Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. This study examines factors affecting microbiota composition in a large mouse advanced intercross line (n = 645) derived from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota identified a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals. Although some variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways: some control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases. The study used a large murine intercross model to investigate the combination of environmental and host genetic factors that shape gut microbiota composition. The CMM, defined as 19 genera and 64 taxonomic groups, was found to be influenced by host genetics. Litter and cohort effects were significant, but host genotype also played a role. QTL analysis identified 18 significant QTL and 5 suggestive QTL that control variability in the abundances of different taxa. These QTL affect microbiota composition in three ways: some control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. The study also found that some QTL have pleiotropic effects on multiple taxa, with effects divided into three groups. The results suggest that host genetic control is exerted across the entire phylogenetic space of the gut microbiota, with at least one taxon from each of the four major phyla mapping to a significant QTL. The study highlights the importance of host genetic control in shaping individual microbiome diversity in mammals and provides insights into the factors that govern the assemblages of gut microbiota associated with complex diseases. The findings suggest that host genetic factors can influence the composition of the gut microbiota, which in turn may contribute to the development of complex diseases. The study also demonstrates that the gut microbiota can be viewed as an environmental factor that is itself controlled in part by host genetic factors and potentially by interactions between host and microbial genomes. This view implies that genetic predisposition to complex diseases may be manifested in part by a predisposition to aberrant patterns of microbial colonization,Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. This study examines factors affecting microbiota composition in a large mouse advanced intercross line (n = 645) derived from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota identified a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals. Although some variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways: some control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases. The study used a large murine intercross model to investigate the combination of environmental and host genetic factors that shape gut microbiota composition. The CMM, defined as 19 genera and 64 taxonomic groups, was found to be influenced by host genetics. Litter and cohort effects were significant, but host genotype also played a role. QTL analysis identified 18 significant QTL and 5 suggestive QTL that control variability in the abundances of different taxa. These QTL affect microbiota composition in three ways: some control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. The study also found that some QTL have pleiotropic effects on multiple taxa, with effects divided into three groups. The results suggest that host genetic control is exerted across the entire phylogenetic space of the gut microbiota, with at least one taxon from each of the four major phyla mapping to a significant QTL. The study highlights the importance of host genetic control in shaping individual microbiome diversity in mammals and provides insights into the factors that govern the assemblages of gut microbiota associated with complex diseases. The findings suggest that host genetic factors can influence the composition of the gut microbiota, which in turn may contribute to the development of complex diseases. The study also demonstrates that the gut microbiota can be viewed as an environmental factor that is itself controlled in part by host genetic factors and potentially by interactions between host and microbial genomes. This view implies that genetic predisposition to complex diseases may be manifested in part by a predisposition to aberrant patterns of microbial colonization,