0113 The Gut Microbial Correlates of Strain-Specific Sleep Fragmentation in A Spaceflight Analog

Abstract

Introduction: The mammalian gastrointestinal microbiota interacts with the functions of the central nervous system, including sleep. Spaceflight is associated with disrupted sleep in astronauts, and our previous work has found altered gut microbiota during spaceflight in both humans and mice. To understand the role of the gut microbiota in disrupted sleep and the associated physiological changes under simulated spaceflight-like conditions, we studied mice in a spaceflight analog, hindlimb unloading (HLU), which models a non-load-bearing status in the hindlimbs, cephalic fluid shifts, as well as situational and confinement stress. Methods: We developed a method and the required apparatus that allowed us to perform HLU while simultaneously recording sleep using EEG/EMG. Female C57BL/6J (B6) and C3H/HeJ (C3H) mice were subjected to HLU for 4 weeks. Fecal samples were collected at multiple time points prior to and during HLU. Microbial DNA was isolated from fecal materials and used to profile gut microbiota structure using 16S rRNA gene amplicon sequencing. Results: B6 and C3H mice responded to HLU with striking differences. HLU led to ∼3 times more fragmented sleep in B6 mice but not C3H mice. This strain difference in sleep responses to HLU was associated with a large strain difference in the gut microbial composition between B6 and C3H mice, which persisted throughout the HLU period. Furthermore, in B6 mice, a difference in the microbial composition between HLU and control mice was observed at 1 week after the start of HLU but diminished after 3 weeks of HLU. The microbial composition in C3H mice remained unchanged. Conclusion: These findings demonstrate a strong host genetic basis for responses to HLU, with a concordant disparate community structure of the gut microbiota, raising questions about the underlying mechanisms leading to previous observation on physiological changes associated with HLU, and perhaps spaceflight itself. Findings from this study indicate the possibility that countermeasures based on modulating the gut microbiota could lead to better sleep adaptation during spaceflight, a key area that requires further research.