Examining the Role of Microbiota in Emotional Behavior: Antibiotic Treatment Exacerbates Anxiety in High Anxiety-Prone Male Rats

Authors

M E. Glover, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Electronic address: meglover@vt.edu.
J L. Cohen, Department of Psychiatry, University of California, San Francisco, CA, USA.
J R. Singer, MD/PhD Medical Scientist Training Program, University of Alabama-Birmingham, Birmingham, AL, USA.
M N. Sabbagh, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.Follow
J R. Rainville, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
M T. Hyland, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
C D. Morrow, Department of Cell, Developmental, and Integrative Biology, University of Alabama-Birmingham, Birmingham, AL, USA.
C T. Weaver, Department of Pathology, University of Alabama-Birmingham, Birmingham, AL, USA.
G E. Hodes, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Ilan A. Kerman, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA; Behavioral Health Service Line, Veterans Affairs Pittsburgh Health System, Pittsburgh, PA, USA.
S M. Clinton, School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.

Document Type

Article

Abstract

Intestinal microbiota are essential for healthy gastrointestinal function and also broadly influence brain function and behavior, in part, through changes in immune function. Gastrointestinal disorders are highly comorbid with psychiatric disorders, although biological mechanisms linking these disorders are poorly understood. The present study utilized rats bred for distinct emotional behavior phenotypes to examine relationships between emotionality, the microbiome, and immune markers. Prior work showed that Low Novelty Responder (LR) rats exhibit high levels of anxiety- and depression-related behaviors as well as myriad neurobiological differences compared to High Novelty Responders (HRs). Here, we hypothesized that the divergent HR/LR phenotypes are accompanied by changes in fecal microbiome composition. We used next-generation sequencing to assess the HR/LR microbiomes and then treated adult HR/LR males with an antibiotic cocktail to test whether it altered behavior. Given known connections between the microbiome and immune system, we also analyzed circulating cytokines and metabolic factors to determine relationships between peripheral immune markers, gut microbiome components, and behavioral measures. There were no baseline HR/LR microbiome differences, and antibiotic treatment disrupted the microbiome in both HR and LR rats. Antibiotic treatment exacerbated aspects of HR/LR behavior, increasing LRs' already high levels of anxiety-like behavior while reducing passive stress coping in both strains. Our results highlight the importance of an individual's phenotype to their response to antibiotics, contributing to the understanding of the complex interplay between gut microbes, immune function, and an individual's emotional phenotype.

Medical Subject Headings

Animals; Anti-Bacterial Agents; Anxiety; Behavior, Animal; Emotions; Exploratory Behavior; Male; Microbiota; Rats

Publication Date

4-1-2021

Publication Title

Neuroscience

E-ISSN

1873-7544

Volume

459

First Page

179

Last Page

197

PubMed ID

33540050

Digital Object Identifier (DOI)

10.1016/j.neuroscience.2021.01.030

Recommended Citation

Glover, M E.; Cohen, J L.; Singer, J R.; Sabbagh, M N.; Rainville, J R.; Hyland, M T.; Morrow, C D.; Weaver, C T.; Hodes, G E.; Kerman, Ilan A.; and Clinton, S M., "Examining the Role of Microbiota in Emotional Behavior: Antibiotic Treatment Exacerbates Anxiety in High Anxiety-Prone Male Rats" (2021). Neurology. 876.
https://scholar.barrowneuro.org/neurology/876