Exploring the impact of time-restricted feeding on circadian rhythm and the gut microbiome in a mouse model of Huntington's disease
OA Version
Citation
Abstract
Many individuals suffering from Huntington’s Disease (HD) and other neurodegenerative disorders exhibit disruptions in their circadian system. Many researchers in this area have suggested that there is a bidirectional relationship between circadian disruption and HD pathogenesis although this remains to be established. This suggested feedback loop asserts HD pathology disrupts the circadian rhythmicity of the microbiome--thus leading to worsening of cognitive, motor, and psychiatric symptoms via gut dysbiosis. Time-restricted feeding (TRF) is an experimental diet that takes advantage of the influence that the daily feed/fast cycle exerts on the central and peripheral circadian clocks by confining the eating window to a six-hour window during the murine active phase for this experiment. Using mouse models of HD, we have demonstrated that time-restricted feeding (TRF) improves activity rhythms, sleep architecture and motor performance. These benefits raise questions about the underlying mechanisms. Prior work has established that the species abundance of the microbiome is rhythmic and can be modulated by scheduled feeding. HD patients and mouse models have been shown to exhibit dysbiosis but rhythms in the microbiome have not been studied nor has the impact of TRF on the microbiome been investigated in the context of HD. As a first step, we sought to measure the composition of the gut microbiome in BACHD mice compared to WT mice just before the disrupted circadian phenotype emerges (3 months of age) using fecal samples. We found that alpha and beta diversity were largely intact in the HD model although changes in the species abundance of operational taxonomic units (OTUs) were noted. Next, we examined the impact of TRF on the microbiome. While these experiments are ongoing, preliminary observations again suggest an impact of TRF on the beta diversity of both species as well as changes in the OTU species abundance. Future studies will look at the impact of time of day but perhaps more importantly determining whether these commensal gut bacteria are necessary for the TRF-driven improvements in BACHD mice.
Description
2024