Transplantation of the NLRP3 KO gut microbiota inhibited the increased expression of circHIPK2 in CUS mice. a–e The correlation of the relative abundances of phyla (Bacteroidetes and Firmicutes) and families (S24-7, Ruminococcaceae and Lachnospiraceae) with circHIPK2 levels in the plasma of CUS-treated mice. f circHIPK2 levels in plasma and hippocampi were significantly increased by CUS treatment. N = 9–12 mice/group. *p < 0.05 and ***p < 0.001 vs. the control group using Student’s t test. g, h circHIPK2 levels in the plasma (g) and hippocampi (h) of the WT microbiota recipient mice were significantly increased by CUS treatment, and these levels were significantly inhibited in the NLRP3 KO microbiota recipient mice. N = 6–8 mice/group. *p < 0.05 and **p < 0.01 vs. the FMT-WT control group. #p < 0.05, and ##p < 0.01 vs. the CUS-treated FMT-WT group using one-way ANOVA followed by the Holm-Sidak test. i Illustration of lentivirus microinjection and the experimental procedure. Mice were microinjected with the GFP-labeled circCon or circHIPK2 siRNA lentivirus for 2 weeks, followed by CUS treatment for another 4 weeks. Behavioral tests were performed before the mice were sacrificed. j circHIPK2 levels decreased in circHIPK2 siRNA-injected mice compared with those in circ siRNA control-injected mice in both the control and CUS-treated groups. k circHIPK2 siRNA microinjection significantly attenuated the CUS-induced decrease in sucrose preference. l, m circHIPK2 siRNA microinjection significantly inhibited the CUS-induced increase in immobility time in the FST (l) and TST (m). N = 7–15 mice/group. *p < 0.05, **p < 0.01 and ***p < 0.001 vs. the circCon control group. #p < 0.05 and ##p < 0.01 vs. the CUS-treated circCon group using one-way ANOVA followed by the Holm-Sidak test.