Antibiotic-induced gut dysbiosis elicits gut-brain axis relevant multi-omic signatures and behavioral and neuroendocrine changes in a nonhuman primate model
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 (a nonhuman primate model often used to study sociability and stress). We were able to successfully induce dysbiosis using a custom antibiotic cocktail (vancomycin, enrofloxacin and neomycin) administered orally for 28 days in common marmosets. 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 impact of severe gut dysbiosis on gut-brain axis cross-talk and behavior.