SOCIAL BEHAVIOR CHANGES ASSOCIATED WITH DIETARY TMAO-INDUCED INFLAMMATION

Social behavior is sensitive to increasing inflammatory signals in the central and peripheral nervous system. When the sources of this inflammation involve metabolic variables, they are most often related to obesity where multisystemic action prevents determining the relevance of the factors individually. Yet it is still unknown if metabolic variables associated with a diet unbalanced by an excess of animal-based foods could change social behavior without changing body weight.
Here, using a dietary source to raise the brain levels of TMAO (Trimethylamine N-oxide) with no weight variation, we characterize behavioral, neurogenic and physiological changes.
First, we showed that dietary TMAO reaches the mouse brain and is distributed heterogeneously in structures that control social behavior and female mice have higher levels than males, despite a reduced intake, suggesting a more efficient TMA into TMAO conversion or a more permeable blood brain barrier. We evidenced that social novelty and social interaction was reduced in the presence of high TMAO. Under these circumstances, we reported higher levels of TNFα, IL-6, IFN-ɣ and IL1β in different social behavior controlling areas and altered neurogenesis in the subventricular zone with functional olfactory consequences. Finally, we counteracted most of the behavioral and inflammatory effect of TMAO with the TMA-lyase inhibitor iodomethylcholine.
All together our results indicated a crucial role of the dietary metabolite TMAO in inflammatory modulation of social behaviors.