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The prevalence of obesity, insulin resistance and type 2 diabetes has steadily increased in the last decades. In addition to the genetic and environmental factors, gut microbiota may play an important role in the modulation of intermediary phenotypes leading to metabolic disease.Obesity and type 2 diabetes are associated with specific changes in gut microbiota composition. The mechanisms underlying the association of specific gut microbiota and metabolic disease include increasing energy harvest from the diet, changes in host gene expression, energy expenditure and storage, and alterations in gut permeability leading to metabolic endotoxemia, inflammation and insulin resistance. In some studies, the modifications of gut microbiota induced by antibiotics, prebiotics and probiotics led to improved inflammatory activity in parallel to amelioration of insulin sensitivity and decreased adiposity. However, these effects were mainly observed in animal models. Their extrapolation to humans awaits further studies.The fascinating role of gut microbiota on metabolic disease opens new avenues in the treatment of obesity, insulin resistance and type 2 diabetes. A co-evolutionary clue for microbiota and insulin resistance is suggested.