Identification of sleep fragmentation-induced gut microbiota alteration and prediction of functional impact in Sprague Dawley rats harboring microbiome derived from multiple human donors

OBJECTIVES: Poor quality sleep, including sleep fragmentation (SF), can result in severe health consequences. Gut microbiota symbiotically coexist with the host, making essential contributions to overall well-being. In this study, the effects of both acute (6-day) and chronic (6-week) SF in a humanized rat model were examined to evaluate the impact of SF on this symbiotic relationship. MATERIAL AND METHODS: Human fecal material was transplanted into antibiotic-treated, microbially depleted, Sprague Dawley rats. Animals were subjected to either acute or chronic SF and shifts to gut microbiota were investigated using 16S rRNA sequencing and predictive functional profiles were constructed with PICRUSt. We also investigated SF-induced intestinal microbial adhesion and penetration or increased microbial invasion of selected tissues and organs; as well as changes in crypt/villi architecture. RESULTS: Microbiota profiling indicated that chronic, but not acute, SF significantly decreased the richness of alpha-diversity of distal ileum microbiota, and altered cecum and distal ileum beta-diversity; although both acute and chronic SF significantly changed select populations of microbiota in all three regions. Neither acute nor chronic SF induced changes to microbial adhesion, penetration, or invasion into intestinal tissues or nearby organs. Additionally, we found that chronic SF caused a reduction in villus height in the proximal colon. DISCUSSION: Our study suggests that acute SF alters the gut microbiota in this humanized rat model, while chronic SF produces more pronounced changes to microbiota populations. This study identified potential microbiota targets for the prevention and/or intervention of the adverse effects of S F.