Nav1.8-expressing neurons control daily oscillations of food intake, body weight and gut microbiota in mice

Vagal afferents transmit gastrointestinal cues to the brain to control food intake and energy metabolism. Their dysregulation, due to high-energy-dense foods, contributes to metabolic diseases. Nevertheless, the function of specific populations of sensory vagal neurons on the gut-brain axis is still understudied. Using diphtheria toxin-assisted ablation we generated a mouse model lacking Nav1.8 expressing neurons to assess their impact on the gut microbiota-brain axis under control or high fat high sugar diets with ad-libitum and time-restricted feeding regimens. We demonstrated that Nav1.8+ neurons are required to control food intake and daily body weight variations, not only because of their role as drivers of the gut-to brain communication, but also because of their critical function in maintaining physiological enteroendocrine responses, intestinal immune homeostasis, and the rhythmicity of prandial microbiota oscillations. Thus, strategies targeting Nav1.8+ neurons could be explored to restore the energy balance in metabolic-related diseases.