Obesity and the gut microbiota: implications of neuroendocrine and immune signaling

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity. An unhealthy diet impairs the symbiotic relationship between the gut microbiota and the host, contributing to obesity. At the intestinal level, identification of host-microbe events essential for proper neuroendocrine/immune signaling is key to the development of microbiome-based strategies to promote metabolic health in obesity (probiotics, biotherapeutic products, and fecal microbiota transplantation). These strategies may help restore food sensing and so, eating behavior, and confer protection against intestinal and systemic inflammation. image