Ileal Dysbiosis Is Associated with Increased Acoustic Startle in the 22q11.2 Microdeletion Mouse Model of Schizophrenia

Abstract

Recent studies involving transplantation of feces from schizophrenia (SCZ) patients and their healthy controls into germ-free mice have demonstrated that the gut microbiome plays a critical role in mediating SCZ-linked physiology and behavior. To date, only one animal model (a metabotropic glutamate receptor 5 knockout) of SCZ has been reported to recapitulate SCZ-linked gut dysbiosis. Since human 22q11.2 microdeletion syndrome is associated with increased risk of SCZ, we investigated whether the 22q11.2 microdeletion (“Q22”) mouse model of SCZ exhibits both SCZ-linked behaviors and intestinal dysbiosis. We demonstrated that Q22 mice display increased acoustic startle response and ileal (but not colonic) dysbiosis, which may be due to the role of the ileum as an intestinal region with high immune and neuroimmune activity. We additionally identified a negative correlation between the abundance of a Streptococcus species in the ilea of Q22 mice and their acoustic startle response, providing early evidence of a gut–brain relationship in these mice. Given the translational relevance of this mouse model, our work suggests that Q22 mice could have considerable utility in preclinical research probing the relationship between gut dysbiosis and the gut–brain axis in the pathogenesis of SCZ.

Keywords

• microbiome
• schizophrenia
• gut–brain axis
• DiGeorge
• 22q11.2
• microdeletion