Figure 1. Model of brain–gut–microbiome interactions in ingestive behavior.

In the periphery, gut-generated and vagally transmitted orexogenic and anorexogenic signals interact with specific nuclei in the hypothalamus in the homeostatic regulation of food intake. Food-related factors interact with gut microorganisms and gut microbial metabolites modulate the release of orexogenic and anorexogenic peptides from enteroendocrine cells in the distal small intestine, shifting the balance between anorexogenic and orexogenic signaling in the hypothalamus. In addition, gut microorganisms can signal to the brain via inflammatory mediators (such as lipopolysaccharides) and neuroactive metabolites (such as tryptophan metabolites). Centrally, interactions between several brain networks, including the prefrontal cortex, the dopaminergic reward system and the sensorimotor system underlie the hedonic regulation of food intake. Several environmental influences such as food advertisements, food cues engage the extended reward system which can override the homeostatic control mechanisms. Exposure to visual and sensory cues, as well as psychosocial stress play important role in this process. Blue boxes on the left represent different parts of the BGM axis. Light green boxes in the center show mechanisms involved in altered BGM interactions in food addiction. Upward arrows show upregulation, downward arrows show downregulation. Modified with permission from Volkow et al. Biological Psychiatry 2013 EM: DONE