Effects of Spaceflight on Gastrointestinal Microbiota in Mice: Mechanisms and Impact on Multi-System Physiology

This proposal in response to NNH14ZTT002N NRA “Research Opportunities for Flight Experiments in Space Biology” is intended to examine the potential role(s) of disruption of microbial communities in the gut (dysbiosis) in mammalian adjustment to the space environment. Many challenges to mammalian physiological homeostasis present in the space environment are known to create dysbiosis. Similarly, immune or inflammatory changes, including metabolic changes observed with time in spaceflight may be attributable in part to dysbiosis. A series of experiments in mice will be carried out to define changes in microbiota as a function of time in space, diet, and host genotype; relate these changes to gene expression (by RNA-seq) and physiological changes in serum, colon, ileum, spleen, liver, and fat as well as sleep/wake and feeding behavioral changes. Extensive use of ground based studies will be used to support the analysis and interpretation of spaceflight data. Five projects at three institutions will focus on different aspects. Project 1 (University of Illinois at Chicago, PI: SJ Green) will carry out metagenomic sequencing of microbiota from fecal samples and cecal contents (including from the tissue sharing opportunity); Projects 2 and 3 (Rush University Medical Center, PIs: A Keshavarzian and C Forsyth) will use gene expression, physiological and histologic measures of gastrointestinal and immune function respectively; while Projects 4 and 5 (Northwestern University, PIs: FW Turek and MH Vitaterna) will focus on metabolism and circadian behavioral organization respectively. Dr. Turek (Northwestern) will provide Principal PI oversight. These studies are in alignment with NRA Research Emphases 1)“Spaceflight Omics Studies” and 3)“Understanding How Complex Organisms Adapt to Spaceflight”.