The Gansu zokor (Eospalax cansus), a typical subterranean rodent endemic to the Chinese Loess Plateau, spends almost its whole life in its self-constructed underground burrows and has strong adaptability to ambient
hypoxia. Energy adaptation is the key to supporting
hypoxia tolerance, and recent studies have shown that the intestinal microbiota has an evident effect on energy metabolism. However, how the gut microbiome of Gansu zokor will change in response to
hypoxia and the metabolic role played by the microbiome have not been reported. Thus, we exposed Gansu zokors to severe
hypoxia of 6.5% of O2 (6 or 44 h) or moderate
hypoxia of 10.5% of O2 (44 h or 4 weeks), and then analyzed
16S rRNA sequencing, metagenomic sequencing, metagenomic binning, liver
carbohydrate metabolites, and the related molecular levels. Our results showed that the
hypoxia altered the microbiota composition of Gansu zokor, and the relative contribution of Ileibacterium to carbohydrate metabolism became increased under
hypoxia, such as glycolysis and
fructose metabolism. Furthermore, Gansu zokor liver enhanced carbohydrate metabolism under the short-term (6 or 44 h)
hypoxia but it was suppressed under the long-term (4 weeks)
hypoxia. Interestingly, under all
hypoxia conditions, Gansu zokor liver exhibited enhanced
fructose-driven metabolism through increased expression of the GLUT5
fructose transporter,
ketohexokinase (KHK),
aldolase B (ALDOB), and
aldolase C (ALDOC), as well as increased KHK enzymatic activity and
fructose utilization. Overall, our results suggest that the altered gut microbiota mediates the
carbohydrate metabolic pattern under
hypoxia, possibly contributing to the hepatic metabolic flexibility in Gansu zokor, which leads to better adaptation to hypoxic environments.