Abstract:[Background] Individuals adjust their nutrition absorption and energy metabolism when exposing to hypobaric hypoxia. Gut microbiota performs essential functions for host physiology, including digestive, metabolic, and immune mechanisms. However, little is known about the dynamic composition of gut microbiota as well as metabolic function during host acclimatized to hypobaric hypoxia. [Objective] To characterize and compare the gut microbiota of SD rats during 1, 7, 14, 21 and 28 days after being exposed to a simulated altitude of 4 500 m (hypobaric chamber) with control groups (43.5 m). [Methods] We studied fecal samples by Illumina HiSeq platform targeting the V3?V4 region of the 16S rRNA gene. Sequences were processed using the QIIME software package, UPARSE pipeline. LEfSe analysis was used to determine the different species between groups. The functional profiles of microbial communities were predicted by using PICRUSt. [Results] Fecal microbiota analysis revealed that the hypoxic exposure caused distinctive gut microbiota in rats, compared to the control groups. We detected the overrepresentation of Bacteroidetes, Bacteroidales, Bacteroidaceae, Prevotellaceae, Prevotella, copri and underrepresentation of Ruminococcaceae, Ruminococcus, Clostridia and Clostridiales in hypoxic exposure rats’feces. PICRUSt analysis revealed that Genetic Information Processing and metabolic related pathways were enriched in the hypoxic exposure groups than those in the control groups. [Conclusion] Hypoxic exposure caused dramatic changes of the structure, diversity and predicted function of gut microbiota in rats. The relative abundance of gut microbiota with complex glycan depolymerisation were enriched after hypoxic exposure. Those may involve in host adjustment of metabolism, and could be beneficial for host acclimatized to hypobaric hypoxia.