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 CO 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.