The microbiota-gut-brain axis is currently being explored in many types of rodent models, including models of behavioral, neurodegenerative and metabolic disorders. Our laboratory is interested in determining the mechanisms and consequences of activation of vagal afferent neurons that lead to activation of parasympathetic reflexes and changes in feeding behavior in the context of obesity. Obesity is associated with microbial dysbiosis, decreased intestinal barrier function, gut inflammation, metabolic endotoxemia, chronic low-grade systemic inflammation and desensitization of vagal afferent nerves. This review will present the evidence that altered gut microbiota together with decreased gut barrier function allows the passage of bacterial components or metabolites in obese individuals, leading to the disruption of vagal afferent signaling and consequently resulting in an increase in body weight. We first review the most recent descriptions of gut microbial dysbiosis due to a high fat diet and describe changes in the gut barrier and the evidence of increased intestinal permeability in obesity. We then will review the evidence to show how manipulating the gut microbiota via pre and probiotics can restore gut barrier function and prevent weight gain. Lastly, we present possible mechanisms by which the microbe-gut-brain axis may have a role in obesity. The studies mentioned in this review have provided new targets to treat and prevent obesity and have highlighted how the microbiota-gut-brain axis is involved.