The Car1 Knockout Mice Exhibit Antidepressant-like Behaviors Accompanied with Gut Microbiota Disturbance

Major depressive disorder (MDD) is a severe mental disorder with largely unknown mechanisms. Carbonic anhydrases convert CO₂ to carbonates and protons, playing roles in various brain functions. Carbonic anhydrase 1 (Car1) is particularly abundant and may be linked to microbiota at interstitial sites. We developed Car1-deficient mice to explore the relationship between depression-like behaviors and gut microbiota. Behavioral tests confirmed depression-like behavior in Car1^−/− mice. Fecal samples from Car1^−/− and WT mice were collected, and 16S rRNA gene sequencing identified distinct microbiota components between the groups. Car1^−/− mice exhibited significantly increased immobility in the tail suspension test (TST) compared to WT mice. The gut microbiota composition differed at the phylum level in p_Bacteroidetes, p_Verrucomicrobia, p_Firmicutes, and p_Tenericutes. At the family level, Car1^−/− mice had significantly different abundances in eight microbiota groups compared to WT mice. Car1 deficiency is associated with depressive-like behavior and gut microbiota dysbiosis, potentially linked to depressive-like phenotypes.