ASMT determines gut microbiota and increases neurobehavioral adaptability to exercise in female mice

N-acetylserotonin O-methyltransferase (ASMT) is responsible for melatonin biosynthesis. The Asmt gene is located on the X chromosome, and its genetic polymorphism is associated with depression in humans. However, the underlying mechanism remains unclear. Here, we use CRISPR/Cas9 to delete 20 bp of exon 2 of Asmt, and construct C57BL/6J mouse strain with Asmt frameshift mutation (Asmt ^ft/ft). We show that female Asmt ^ft/ft mice exhibit anxiety- and depression-like behaviors, accompanied by an obvious structural remodeling of gut microbiota. These behavioral abnormalities are not observed in male. Moreover, female Asmt ^ft/ft mice show a lower neurobehavioral adaptability to exercise, while wild-type shows a “higher resilience”. Cross-sectional and longitudinal analysis indicates that the structure of gut microbiota in Asmt ^ft/ft mice is less affected by exercise. These results suggests that Asmt maintains the plasticity of gut microbiota in female, thereby enhancing the neurobehavioral adaptability to exercise.