A294 ROLE OF MACROPHAGE IN GUT MICROBIOTA-BRAIN SIGNALING

Gut microbiota shapes host’s immune system, which plays an important role in host’s behavior and brain development. Peripheral macrophages have been implicated in sickness-like behavior induced by endotoxin and recent studies have highlighted the existence of a novel axis between the immune system and the brain involving monocytes trafficking to the brain, regulating mood and behaviour. However, the role of macrophages in microbiota-gut-brain signaling has not yet been investigated. To investigate the role of macrophages in altered behaviour in a murine model of antibiotic-induced dysbiosis. Specific pathogen–free (SPF) BALB/c mice (6–8 weeks old) received i.p. injection of clodronate encapsulated liposomes to deplete macrophages or phosphate buffered saline (PBS). Two days later the mice received a mixture of non-absorbable antimicrobials (ATM) in drinking water or placebo for 7 days. Behavioural profiles (the light preference and the step-down test) were assessed, and the mice were sacrificed thereafter. F4/80 positive cells were evaluated in colonic tissues and gut microbiota composition was analyzed by 16S rRNA gene sequencing with Illumina technique. Statistical analyses were performed using un-paired t test (Mann-Whitney U test) or Kruskal–Wallis test followed by Dunn post-test as appropriate. ATM administration induced anxiolytic behavior and increased exploratory behavior during the light preference test in all mice regardless of clodronate liposomes injections. Interestingly, only antibiotic treated mice that did not receive clodronate’s injections showed a reduced latency to step down in comparison to age matched controls. As expected, clodronate liposomes’s injections induced a depletion significantly the number of F4/80 positive cells in colonic lamina propria. Antibiotic treatment alone did not alter the number of F4/80 positive cells in colonic lamina propria. Our preliminary data suggest that macrophages might be involved in the modulation of mouse behaviour induced by intestinal dysbiosis and that antibiotic treatment alone did not alter the number of macrophages in colonic lamina propria. Further studies are needed to understand the exact role of macrophages in microbiota-gut-brain signaling. CIHR