LAUSR

It has become clear that the gut microbiota plays a key role in all aspects of health including mental health. The concept of the microbiota-gut-brain axis focuses on the ability of the microbiota to influence CNS function and modulate brain development and behaviour [1]. Microbiota composition can be affected by many different environmental factors such as stress, diet, exercise, illness and antibiotic treatment. Recent hypothesis suggests that neurodevelopment runs in parallel with establishment of an adult microbial profile and that disturbance or the lack thereof influences behaviour and brain function in adulthood [2]. Many different strategies can be utilized to investigate the role of the intestinal microbiota in host brain and behaviour. Here, we aimed to investigate whether exposure to antibiotic treatment or suboptimal diet both of which significantly affect microbiota composition resulted in long lasting effects on behaviour. Methods Male C57BL/6 mice were either exposed to high fat, a cafeteria diet or antibiotic treatment [3] for 21 days during the adolescence. We next assessed whether exposure to these known microbial interventions resulted in long lasting changes in gene expression and a variety of behaviours, in adulthood. Mice were tested for -like behaviour in the elevated plus maze and open field, memory in the novel object recognition task and fear in the fear conditioning paradigm. A T-test was used to compare antibiotic treatment with controls and ANOVA to compare controls and duet intervention, repeated measures were used when applicable. Results Both, diet and antibiotic treatment resulted in specific behavioural alterations. Antibiotic treatment alone resulted in increased anxiety-like behaviour in the elevated plus maze for the % time spend in the open arm (unpaired t-test, control M=17.64 SEM=±2.78 , antibiotic M=7.90 SEM=±1.99; t(17)=2.79 p=0.013), the % of entries into the open arm (unpaired t-test, control M=30.61 SEM=±2.95, antibiotic M=20.17 SEM=±2.86; t(17)=2.53 p=0.022) and head dips (unpaired t-test with Welch’s correction, control M=10.30 SEM=±1.76, antibiotic M=4.67 SEM=±0.80; t(12)=2.91 p=0.013), high fat diet induced increased contextual fear memory (two-way repeated measure ANOVA F(4, 54)=1.23, followed by Newman-Keuls multiple comparison test p Conclusion We demonstrate that short term exposure to known microbial altering factors during the adolescent period, a critical window of neurodevelopment, can induce long lasting changes on brain and behaviour. Further research needs to be done to investigate the mechanisms underlying the effects of altered microbiota on behaviour and brain circuits during this critical period.