Objective To investigate the effect of different physical exercise interventions on the cognitive function in mice with circadian rhythm disorders, and to explore the correlation between gut microbiota and metabolism and cognitive function.

Methods A circadian rhythm disorder model was established by a reversed light cycle exposure, and the model mice were divided into three groups: quiet group (DC), MICT exercise group (DM) and HIIT exercise group (DH), and another control group (CC), with 15 mice in each group. After 6 weeks of exercise intervention, the colon tissue was observed by HE staining; cognitive function was detected by Morris water maze and 16S rRNA high-throughput sequencing for detection of gut microbiota and LC-MS to detect fecal metabolites.

Results ① The degree of glandular destruction was reduced in the DM and DH groups. ② Platform latency and initial arrival time at the platform were significantly shorter, swimming distance was reduced, and the number of crossing stations and percentage of swimming time in the target quadrant were significantly increased in the DM and DH groups. ③ The groups with higher abundance in the DC group were the phylum Tenericutes and Mollicutes; the DM group was the family Ruminococcaceae; the DH group was the genus Lutispora, etc. ④ Metabolite levels of creatine, butyric acid and methionine were significantly higher in the DM group than in the DC group, and metabolite levels of arachidonic acid were significantly higher in the DH group than in the DC group. ⑤ The correlation between Treponema spp. and Lactobacillus spp. in the intestinal flora and cognitive function was significant, so was the correlation between curcumin and oleic acid in metabolites and cognitive function.

Conclusion MICT and HIIT modulate the structure and abundance of intestinal flora and improve cognitive function in mice with circadian rhythm disorders; related gut microbiota and metabolites are involved in the regulation of exercise to improve cognitive function in mice with circadian rhythm disorders.