Poster (15W223)

Depletion of Gut Microbiota during adulthood in rats: Implications for brain and behavior

Author(s)

Hoban AE1,2, Moloney RD1, Dinan TG1,3, Clarke G1,3, Cryan JF1,2

Department(s)/Institutions

1APC Microbiome Institute, University College Cork. 2Department of Anatomy and Neuroscience, University College Cork 3Department of Psychiatry and Neurobehavioural Science, University College Cork

Introduction

There is growing appreciation for the importance of the gut microbiota in shaping brain function and behavior. Proof-ofprinciple studies in germ-free (GF) animals have played an important role in revealing the alterations in stress-related behaviors and neurochemistry.

Aims/Background

However, the maturation of multiple aspects of host physiology is contingent on normal patterns of gut microbiome assembly in early life. In order to more precisely parse the role of the gut microbiota outside of this critical time window, we set out to establish a rat model of microbiota depletion via chronic administration of antibiotics in adulthood.

Method

Adult Sprague Dawley rats (n=10/group) were treated with vehicle or a combination of antibiotics for 6 weeks in adulthood and throughout behavioral testing. Behavioral tests commenced after the 6 week antibiotic treatment period. HPLC and qRT-PCR was used to assess changes in key gut-brain axis neuromodulators in adulthood.

Results

Antibiotic treatment reduced visceral sensitivity with decreased glucocorticoid receptor (GR) and corticotrophin releasing hormone receptor 1 (CRHR1) in the amygdala. Moreover, antibiotic-treatment induced a depressive-like phenotype and induced cognitive deficits in parallel with altered tryptophan metabolism and serotonin synthesis (5-HT) in the hippocampus.

Conclusions

Microbiota depletion in adulthood by means of chronic treatment with antibiotics impacts visceral sensitivity and depressive and cognitive behaviors as well as key neuromodulators in a manner that is similar to that reported in GF animals. This model may represent an additional strategy for the assessment of the continuous role of the gut microbiota in the modulation of brain and behavior.