Converging evidence shows that obesity-related microbiota dysregulations, which play a critical role in induction of peripheral and brain inflammation (Bruce-Keller et al., 2015), impact mood and cognitive functions (Cryan and Dinan, 2012), although the nature of the biological pathways (neuronal, hormonal and/or immune) underlying this effect is still elusive (Cryan and Dinan, 2012).
Interestingly, it has been recently reported that transplantation of gut microbiota from DIO mice to lean mice is sufficient to induce both brain microglial activation and neurobehavioral changes in the absence of obesity (Bruce-Keller et al., 2015).
This elegant study supports the notion that obesity-related gut microbiota alterations may modulate gut-to-brain communication pathways, leading to the development of neuropsychiatric comorbidities associated with neuroinflammation.
Akin with this assumption, the use of compounds which beneficially alter the microbiota (e.g., prebiotics or probiotics) appears as a promising way to improve neuropsychiatric comorbidities in obese patients (Cryan and Dinan, 2012). More generally, nutritional interventions based on factors with immunomodulatory properties and known impact on behavior and mood, in particular omega-3 polyunsaturated fatty acids and antioxidants (see Gomez-Pinilla and Nguyen, 2012; Bazinet and Layé, 2014 for review), are tractable strategies for developing novel therapeutics for obesity-related neuropsychiatric disorders.
Lastly, based on the key role of the kynurenine pathway in altering mood and cognition (Dantzer et al., 2008), the opportunity of directly targeting this pathway, as promisingly tested in the context of cancer (Platten et al., 2015), should likely represent another interesting therapeutic approach.