The Acute Influence of Acid Suppression with Esomeprazole on Gastrointestinal Microbiota and Brain Gene Expression Profiles in a Murine Model of Restraint Stress

•Stress and acid suppression independently and additively alter stomach microbiota.•Stress with acid suppression induces differential hippocampal gene expression.•Hippocampal gene expression is related to the distribution of gastric bacteria.•These altered expression of these genes may contribute to acute brain dysfunction. The central nervous system (CNS) and gastrointestinal tract (GIT) are linked through neuro-endocrine and humoral pathways. Critically ill patients suffer severe physical and emotional stress and frequently receive acid suppressants; however, stress and acid suppression may alter GIT microbiota. This study evaluated the effects of acid suppression on the GIT microbiota and genome-wide expression of brain-specific genes in a murine model of restraint stress. Twenty-four male C57BL/6J mice were randomly assigned to three days of restraint stress by hypothermic immobilization or control environment for three hours daily and either esomeprazole 2 mg/kg or saline by intraperitoneal injection daily. Bacterial communities associated with the stomach, ileum, cecum, and mid-colon were determined by broad-range 16S rRNA gene sequencing, while RNA-sequencing assessed mRNA expression in the hippocampus. Both stress (p