PT - JOURNAL ARTICLE AU - Amy C Reichelt AU - Amy Loughman AU - Ashton Bernard AU - Mukesh Raipuria AU - Kirsten N Abott AU - James Dachtler AU - Thi Thu Hao Van AU - Robert J Moore TI - An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats AID - 10.1101/328294 DP - 2018 Jan 01 TA - bioRxiv PG - 328294 4099 - http://biorxiv.org/content/early/2018/05/22/328294.short 4100 - http://biorxiv.org/content/early/2018/05/22/328294.full AB - Excessive consumption of high fat and high sugar (HFHS) diets are known to alter reward processing and aspects of behaviour, and change microbiota profiles. Studies in gnotobiotic mice also provide evidence that gut microorganisms influence social behaviour. To further investigate these interactions, the impact of intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition was examined. Rats were permitted intermittent daily access (2h / day) to a palatable HFHS diet for 28 days across the adolescent period. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. Reduced social interaction behaviours, and impaired social memory and novel object recognition were observed in HFHS diet rats. Reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA were observed in the PFC of HFHS diet rats. The relative abundance of a number of specific taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria, which also predicted social behaviours, novel object recognition performance and Maoa expression. This is the first study to show that limited daily access to HFHS diet alters social behaviour and cognition in rats. Furthermore, behavioural changes are associated with alterations to cortical gene expression of enzymes involved in monoamine synthesis and neuroplasticity, and microbiota profiles predicted diet-induced changes to behaviour and gene expression.