Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model

Authors

Shivdeep S. Hayer, University of Nebraska at Omaha
Mackenzie Conrin, University of Nebraska at OmahaFollow
Jeffrey French, University of Nebraska at OmahaFollow
Andrew K. Benson, University of Nebraska - LincolnFollow
Sophie Alvarez, University of Nebraska-LincolnFollow
Kathryn Dempsey, University of Nebraska at OmahaFollow
Anne Fischer, University of Nebraska-Lincoln
Zahraa Wajih Alsafwani, University of Nebraska Medical CenterFollow
William Gasper, University of Nebraska at Omaha
Mallory J. Suhr Van Haute, University of Nebraska-Lincoln and University of Nebraska at OmahaFollow
Haley R. Hassenstab, University of Nebraska Medical CenterFollow
Shayda Azadmanesh, University of Nebraska at OmahaFollow
Missy Briardy, University of Nebraska at Omaha
Skyler Gerbers, University of Nebraska at Omaha
Aliyah Jabenis, University of Nebraska at Omaha
Jennifer L. Thompson, University of Nebraska at Omaha
Jonathan B. Clayton, University of Nebraska at Omaha and University of Nebraska-LincolnFollow

Date of this Version

1-10-2024

Document Type

Article

Citation

GUT MICROBES 2024, VOL. 16, NO. 1, 2305476 https://doi.org/10.1080/19490976.2024.2305476

Comments

Open access.

Abstract

Emerging evidence indicates that antibiotic-induced dysbiosis can play an etiological role in the pathogenesis of neuropsychiatric disorders. However, most of this evidence comes from rodent models. The objective of this study was to evaluate if antibiotic-induced gut dysbiosis can elicit changes in gut metabolites and behavior indicative of gut-brain axis disruption in common marmosets (Callithrix jacchus) – a nonhuman primate model often used to study sociability and stress. We were able to successfully induce dysbiosis in marmosets using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days. This gut dysbiosis altered gut metabolite profiles, behavior, and stress reactivity. Increase in gut Fusobacterium spp. post-antibiotic administration was a novel dysbiotic response and has not been observed in any rodent or human studies to date. There were significant changes in concentrations of several gut metabolites which are either neurotransmitters (e.g., GABA and serotonin) or have been found to be moderators of gut-brain axis communication in rodent models (e.g., short-chain fatty acids and bile acids). There was an increase in affiliative behavior and sociability in antibioticadministered marmosets, which might be a coping mechanism in response to gut dysbiosisinduced stress. Increase in urinary cortisol levels after multiple stressors provides more definitive proof that this model of dysbiosis may cause disrupted communication between gut and brain in common marmosets. This study is a first attempt to establish common marmosets as a novel model to study the impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.