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This review will examine the recent scientific literature surrounding high-fat-diet (HFD)-induced alterations in gut microbiota and subsequent development of obesity and chronic disease risk.Excessive consumption of HFDs has undoubtedly contributed to the obesity epidemic. The mechanisms responsible for this relationship are, however, likely to be more complex than the simple concept of energy balance. In fact, emerging literature has implicated HFD-induced alterations in gut microbiota in the obesity epidemic. HFD consumption generally leads to a decrease in Bacteroidetes and an increase in Firmicutes, alterations that have been associated with obesity and subsequent development of chronic diseases. Potential mechanisms for this effect include an improved capacity for energy harvest and storage, and enhanced gut permeability and inflammation. We highlight the most important recent advances linking HFD-induced dysbiosis to obesity, explore the possible mechanisms for this effect, examine the implications for disease development, and evaluate the possibility of therapeutic targeting of the gut microbiome to reduce obesity.A better understanding of the mechanisms linking HFD to alterations in gut microbiota is necessary to allow for the regulation of dysbiosis and ensuing promotion of antiobesity effects.