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GRK 1482 Jahrbuch 2011-2014

Publications [1] Kaiyala KJ, et al. Direct animal calorimetry, the under- used gold standard for quantifying the fire of life. Comp BiochemPhysiolAMolIntegrPhysiol.2011,158:252-264. [2] Tremaroli V, et al. Functional interactions between the gut microbiota and host metabolism. Nature. 2012, 489: 242-249. [3] Turnbaugh PJ, et al. An obesity-associated gut micro- biome with increased capacity for energy harvest. Nature. 2006, 444: 1027-1031. Outlook Animal studies will test the hypothesis that germfree mice are protected against DIO. Moreover, colonization of germ-free C57BL/6J mice with the microbiota from either an AKR/J or a SWR/J donor mouse will verify whether the gut microbiota di- rectly contributes to DIO susceptibility or resistance. 16S rRNA sequencing of gut samples will be used to detect dif- ferences in microbial diversity and composition between phe- notypes. Further analysis of metabolites as well as host gene and protein expression will provide a better understanding on how the gut bacteria and the host energy metabolism communicate. Interestingly, metabolite clusters occurred due to cohousing. For this reason, a controlled cohousing experiment with wild- type and mutant mice is currently in process to investigate genotype-driven effects on metabolite clusters. ASSOCIATED FELLOWS GRK Progress Report 2011-2014 | Page 75 Aim The working hypothesis of this project is that the gut microbiota affect host energy metabolism. We aim at i) investigating the impact of the gut microbiota on key parameters of energy ba- lance (e.g. energy expenditure, energy assimilation), ii) compa- ring the role of the gut microbiota in three inbred mouse strains either prone or resistant to DIO, and iii) identifying associations between the microbiota-derived metabolic profiles and the obesity propensity in genetically obese mice. Methods and Results Mice are phenotyped continuously by monitoring body mass and composition as well as rectal temperature. At defined expe- rimental endpoints, energy expenditure and energy assimilation are determined by indirect calorimetry and bomb calorimetry, respectively. Fecal as well as gut samples are collected to characterize the microbiota by i) viable and total cell count determination via cultivation or using a counting chamber, and ii) by 16S rRNA gene diversity and composition analysis via high-throughput sequencing. The first trial was performed on three mouse strains chosen by their different susceptibility to DIO (SWR/J