A286 MICROBIOTA DEPLETION IN ADULTHOOD ALTERS MOUSE BEHAVIOR WITH POTENTIAL INVOLVEMENT OF MICROBIAL-METABOLITE SENSOR IN THE BRAIN

The gut microbiota is a complex community of microorganisms that dwell in the gastrointestinal (GI) tract in a mutualistic fashion with its host. Essential for normal homeostasis, the microbiota plays a defined role in the human gut. Interestingly, the GI tract exhibits a bidirectional communication with the central nervous system (CNS), which recently has been described to be influenced by the gut microbiota – usually referred as the microbiota-gut-brain axis. Although many have shown gut microbiota influences over the CNS, mechanism(s) of how this modulation occurs have yet to be completely elucidated. Byproducts generated by the microbiota are found in the bloodstream and they are altered in accordance with microbial changes, such as in antibiotic-treated and germ-free mice. Therefore, we hypothesized that gut microbiota influences brain activity and host behavior, signaling via bacterial byproducts acting at distinct receptors directly in the brain. To test that, we assessed the expression of potential microbial-metabolite sensors in the brain of C57Bl/6 male mice. Moreover, broad-spectrum antibiotic cocktail was offered to mice for 2 weeks to deplete their intestinal microbiota. Following treatment, behavior was assessed by stablished behavior tests, such as the elevated plus maze, the open field test, the 3 chamber test, and the tail suspension test. Efficacy of antibiotic administration was verified through quantification of the bacterial load in the cecal matter after treatment. Mice treated with antibiotics had reduced bacterial load in the cecal matter, without presenting body weight alterations. No changes were observed in anxiety-like behavior and social preference. Interestingly, antibiotic-treated mice presented with a reduction in the depressive-like behavior. Measurement of microbial-metabolite sensors (e.g. aryl hydrocarbon receptor, AHR) in the brain were performed aiming to correlate their expression with the phenotypic behavior found. The brain regions selected for analyzes were the hippocampus, amygdala, and hypothalamus, chosen due to their close influence in anxiety and depressive behaviors. The mRNA of AHR was highly expressed on the three different regions of the brain. Moreover, after antibiotic treatment, AHR expression only in hippocampus was reduced, with no alterationsin the amygdala and hypothalamus. These data suggest that changes in the intestinal microbiota, manifesting behavior alterations, may be driven, in part, by alterations in the expression and activity of microbial-metabolite sensing receptors in the brain. Further work is required to determine if AHR activity directly modulates brain regions responsible for depression-like behavior. CIHR Brazilian National Council for Scientific and Technological Development

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