Mouse models with defined flora clarify relationships between gut microbiota, immune gene expression, and serum metabolites

To systematically evaluate the impact of gut microbiome without the use of antibiotics or fecal transfer, we analyzed C57BL/6 mice with defined flora created through mouse embryo transfer. Metagenomics, metabolomics, transcriptomics, and full-spectrum immunophenotyping reveal clear associations between microbiome perturbation, gene expression and serum metabolites. Insights include clarification of microbiome-dependent and microbiome-depleted metabolites, and a universal transcriptional response of the mTOR signaling pathway to the presence of live bacteria. In contrast, varying microbiome composition did not alter immune cell types, or the number and function of innate immune cells previously thought to be controlled by segmented filamentous bacteria. Essential regression revealed hidden variables underlying changes in metabolites and gene expression, and illustrate the benchmark utility of the data sets for the development of new analytic tools.