Early life nutrition impacts durably several physiological and metabolic functions and is a risk factor for the development of metabolic disease in adults (obesity, type 2 diabetes, hypertension, …). This theory of nutritional imprinting or Developmental Origin of Health and Disease established by Barker in the late 80’s (1) has been reinforced by experimental data on organs and tissues directly involved in the pathophysiology of the metabolic syndrome (liver, adipose tissue, pancreas…) (2). The gut has got little attention in this context so far. Yet, evidences for a role of the gut in the pathophysiology of metabolic diseases in adults, especially with gut microbiota and barrier function maladaptation to a high fat diet, have emerged (3-4). The structure of the gut microbiota is established and the mucosal immune system programed in early life. This post-natal development is not hard-wired and is influenced by environmental and nutritional factors. Man can hypothesize that this flexibility in acquisition of the microbiota and education of the gut immune system in early life would be long-lasting and induce distinct response to a high fat diet later in life. There are already several evidences that early life environmental factors including stress such as maternal deprivation or chemical contaminants such as bisphenol A dramatically impact adult response to gut inflammation or visceral painful stimuli in models of inflammatory bowel disease and irritable bowel syndrome. Recently, evidences have also emerged that nutritional factors, including energy, fat and fatty acids, protein, and micronutrients imbalances during early life have remnant effects of gut function in adults with alterations in microbiota, intestinal barrier function and/or defense systems. Examples of such long-term effects on the gut will be provided, focusing on piglet model and adaptation to a high fat diet. Those emerging data challenges neonatal nutrition which, apart from its traditional role as a supplier of building blocks for growth, may play another, yet potentially crucial role in shaping the individual’s future life, impinging on the risk of disease decades later on.