216. Gut Microbiota Indole Production and Depressive-Like Symptoms: A Fecal Transplantation Study in Mice
Résumé
Background:Recently, our group has shown that over-production of a bacterial metabolite, indole, triggered anxietyand depressive-like behaviors in rats and mice. Therefore, we investigated whether differences in indole production existbetween adolescents with and without major depressive dis-order (MDD) and whether this difference could play a role in theemergence of symptoms, in an animal model.
Methods:The amount of indole was assessed in fecal sam-ples from a cohort of 15 to 20 year-old adolescents, 2/3 ofwhom had MDD. Next, fecal samples from participants withMDD having high (n¼4, HI) and low indole-producing potential(n¼4, LI) were used to inoculate germ-free mice. Six weekslater, HI (n¼21) and LI (n¼17) mice underwent depression-relevant behavioral tasks: nesting, splash, sucrose, tail sus-pension and forced swim tests.
Results:The amount of fecal indole varies in the cohort(n¼194) from 28 to 877 nmol/g. Fecal indole concentration washigher in HI vs LI mice 2- and 6-weeks post inoculation(p<0.001). The analysis of cecal SCFA shown that their totalproduction is higher in HI vs LI mice (P<0.001). No significantdifferences were observed between HI and LI mice in thebehavioral tests. However, in a memory test, the HI miceperformed better at distinguishing a new from an old object.Conclusions:This study demonstrates the feasibility oftransferring indole production, a bacteria-dependent function,from humans to mice. Future studies should test whetheralternative paradigms, such as unpredictable chronic mildstress, are better suited to examine the role indole plays in theemergence of depressive-like symptoms.
Supported By:R01MH090072; BBRF