Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model
Shivdeep S. Hayer,
Mackenzie Conrin,
Jeffrey A. French,
Andrew K. Benson,
Sophie Alvarez,
Kathryn Cooper,
Anne Fischer,
Zahraa Wajih Alsafwani,
William Gasper,
Mallory J. Suhr Van Haute,
Haley R. Hassenstab,
Shayda Azadmanesh,
Missy Briardy,
Skyler Gerbers,
Aliyah Jabenis,
Jennifer L. Thompson,
Jonathan B. Clayton
Affiliations
Shivdeep S. Hayer
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Mackenzie Conrin
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Jeffrey A. French
Callitrichid Research Center, University of Nebraska at Omaha, Omaha, NE, USA
Andrew K. Benson
Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
Sophie Alvarez
Proteomics and Metabolomics Facility, Nebraska Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA
Kathryn Cooper
School of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA
Anne Fischer
Proteomics and Metabolomics Facility, Nebraska Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA
Zahraa Wajih Alsafwani
School of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA
William Gasper
School of Interdisciplinary Informatics, College of Information Science and Technology, University of Nebraska at Omaha, Omaha, NE, USA
Mallory J. Suhr Van Haute
Nebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA
Haley R. Hassenstab
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Shayda Azadmanesh
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Missy Briardy
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Skyler Gerbers
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Aliyah Jabenis
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Jennifer L. Thompson
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
Jonathan B. Clayton
Department of Biology, University of Nebraska at Omaha, Omaha, NE, USA
ABSTRACTEmerging 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 antibiotic-administered marmosets, which might be a coping mechanism in response to gut dysbiosis-induced 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.
