Diet is one of the primary drivers that sculpts the form and function of the mammalian gut microbiota. However, the enormous taxonomic and metabolic diversity held within the gut microbiota makes it difficult to isolate specific diet-microbe interactions. The objective of the current study was to elucidate interactions between the gut microbiota of the mammalian herbivore Neotoma albigula and dietary oxalate, a plant secondary compound (PSC) degraded exclusively by the gut microbiota. We quantified oxalate degradation in N. albigula fed increasing amounts of oxalate over time and tracked the response of the fecal microbiota using high-throughput sequencing. The amount of oxalate degraded in vivo was linearly correlated with the amount of oxalate consumed. The addition of dietary oxalate was found to impact microbial species diversity by increasing the representation of certain taxa, some of which are known to be capable of degrading oxalate (e.g., Oxalobacter spp.). Furthermore, the relative abundances of 117 operational taxonomic units (OTU) exhibited a significant correlation with oxalate consumption. The results of this study indicate that dietary oxalate induces complex interactions within the gut microbiota that include an increase in the relative abundance of a community of bacteria that may contribute either directly or indirectly to oxalate degradation in mammalian herbivores.
Mammals live in a complex and largely symbiotic relationship with their gut microbiota. This microbiota harbors 150 times more genes than the host and exhibits complex interactions with the host's diet (1-3). In mammalian herbivores, diverse intestinal bacteria ferment a diet high in recalcitrant cellulose and in turn synthesize nutrients from the diet in a form more amenable to absorption by the host (4). Furthermore, mammalian herbivores harbor greater microbial diversity in their gut than either omnivores or carnivores (1). Despite the progress of research into the interactions between the mammalian gut microbiota and diet, the isolation of specific diet-microbe interactions in such a complex system has proven to be difficult (5, 6).In addition to having a role in fermentation, microbes play an important role in the biotransformation of dietary toxins in mammalian herbivores (4, 7-10). For some toxins, such as oxalate or 3,4-dihydroxypyridine (DHP), a single species of bacteria is capable of biotransforming the toxin, and this function can be transferred to other mammals through microbial transplants (7,8,11,12). For other toxins, such as creosote resin, whole microbial community transplantation into other mammals can increase tolerance (10).Oxalate, a widely produced and ingested plant secondary compound (PSC), serves as an excellent model to study diet-microbe interactions (13). It is the simplest organic acid and is toxic to mammals (14-16). Oxalate can bind to free calcium ions in the blood and aggregate in the kidneys to form kidney stones (17). In fact, oxalate is a constituent in 80% of kidney stones in humans (17). Oxala...