The vertebrate gut microbiota evolved in an environment typified by periodic fluctuations in nutrient availability, yet little is known about its responses to host feeding and fasting. As many model species (for example, mice) are adapted to lifestyles of frequent small meals, we turned to the Burmese python, a sit-and-wait foraging snake that consumes large prey at long intervals (>1 month), to examine the effects of a dynamic nutrient milieu on the gut microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities harvested from the intestines of fasted and digesting snakes, and from their rodent meal. In this unprecedented survey of a reptilian host, we found that Bacteroidetes and Firmicutes numerically dominated the python gut. In the large intestine, fasting was associated with increased abundances of the genera Bacteroides, Rikenella, Synergistes and Akkermansia, and with reduced overall diversity. A marked postprandial shift in bacterial community configuration occurred. Between 12 h and 3 days after feeding, Firmicutes, including the taxa Clostridium, Lactobacillus and Peptostreptococcaceae, gradually outnumbered the fasting-dominant Bacteroidetes, and overall 'species'-level diversity increased significantly. Most lineages seemed to be indigenous to the python rather than ingested with the meal, but a dietary source of Lactobacillus could not be ruled out. Thus, the observed large-scale alterations of the gut microbiota that accompany the Burmese python's own dramatic physiological and morphological changes during feeding and fasting emphasize the need to consider both microbial and host cellular responses to nutrient flux. The Burmese python may provide a unique model for dissecting these interrelationships.