Brain–gut–microbiome interactions in obesity and food addiction

Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis. Food addiction is an eating behaviour that reflects alterations in brain–gut–microbiome (BGM) interactions and a shift towards hedonic mechanisms. This Review summarizes the physiology of food addiction in obesity as it relates to BGM interactions and provides insights into treatment targets for food addiction aimed at each level of the BGM axis. Key points Food addiction refers to maladaptive ingestive behaviours resulting from a shift from primarily homeostatic to hedonic regulatory mechanisms of food intake; this shift reflects alterations at all levels of the brain–gut–microbiome (BGM) axis. Normal ingestive behaviour is the result of the tightly regulated interplay between orexigenic and anorexigenic gut hormones, leptin signalling from adipose tissue, hypothalamic nuclei, the dopaminergic reward system and prefrontal inhibitory influences. In food addiction, a disinhibition of reward and anorexigenic mechanisms at all levels of the BGM axis results in unrestrained craving for food. Several adverse early-life events, including nutrition, stress and antibiotic intake, can influence the development of BGM interactions and of ingestive behaviour. Lifelong dietary choices can modulate BGM interactions and ea