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Neuroscience. 2019 Feb 1;398:206-217. doi: 10.1016/j.neuroscience.2018.11.048. Epub 2018 Dec 15.

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

Author information

1
Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, C238, 12850 East Montview Blvd, Aurora, CO 80045, USA. Electronic address: rob.maclaren@ucdenver.edu.
2
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, C238, 12850 East Montview Blvd, Aurora, CO 80045, USA. Electronic address: Richard.radcliffe@ucdenver.edu.
3
College of Pharmacy, Department of Clinical Pharmacy and Translational Science, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: Edward.vanmatre@uthsc.edu.
4
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, B168 12700 East 19th Avenue, Aurora, CO 80045, USA. Electronic address: charles.robertson@ucdenver.edu.
5
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, B168 12700 East 19th Avenue, Aurora, CO 80045, USA. Electronic address: diana.ir@ucdenver.edu.
6
Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, B168 12700 East 19th Avenue, Aurora, CO 80045, USA. Electronic address: daniel.frrank@ucdenver.edu.

Abstract

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 < 0.001) and esomeprazole (p = 0.006) had significant, independent effects on the composition of stomach microbiota. Stress had no impact on the hippocampus but the addition of esomeprazole induced differential expression of 124 genes, many of which are involved in cognitive and behavior pathways. Gene expression was correlated with the abundances of multiple microbial families. Acute stress has region-specific effects on the distribution of GIT commensal bacteria which is heightened with acid suppression. Several key biological processes in the hippocampus that are needed for neurocognition are affected by dysbiosis caused by acid suppression during stress. Further studies should evaluate associations between microbiota, host gene expression, the abundance of CNS neurocognitive modulators, and their impact on cognition and behavior.

KEYWORDS:

gene; hippocampus; microbiome; neurocognition; proton pump inhibitor; stress ulcer

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