The composition of the gut microbiome is hypothesized to be an environmental factor that contributes to obesity. Results of several human studies suggest that obesity is associated with differences in the gut microbiota composition, reduced bacterial diversity, and altered representation of bacterial metabolic pathways. The obese phenotype is associated with increased microbial fermentation and energy extraction from non-digestible food components; however, until recently it was not clear how relatively small increases in energy extraction could contribute to the large and rapid weight gain observed in the animal studies. Mechanisms by which the gut microbiome may influence metabolism and energy homeostasis include regulation of energy uptake from diet, interaction with signaling molecules involved in host metabolism, modification of gut permeability, release of gut hormones, and low-grade, chronic inflammation, the latter being a hallmark of obesity-related diseases.