Microbiota Diversification and Crash Induced by Dietary Oxalate in the Mammalian Herbivore Neotoma albigula

The bacteria associated with mammalian hosts exhibit extensive interactions with overall host physiology and contribute significantly to the health of the host. Bacteria are vital to the mitigation of the toxic effects of oxalate specifically as mammals do not possess the enzymes to degrade this compound, which is present in the majority of kidney stones. Contrary to the body of literature on a few oxalate-degrading specialists, our work illustrates that oxalate stimulates a broad but cohesive microbial network in a dose-dependent manner. The unique characteristics of the N. albigula microbiota make it an excellent source for the development of bacteriotherapies to inhibit kidney stone formation. Furthermore, this work successfully demonstrates methods to identify microbial networks responsive to specific toxins, their limits, and important elements such as microbial network cohesivity and architecture. These are necessary steps in the development of targeted bacteriotherapies. ABSTRACT Oxalate, broadly found in both dietary and endogenous sources, is a primary constituent in 80% of kidney stones, an affliction that has tripled in prevalence over the last 40 years. Oxalate-degrading bacteria within the gut microbiota can mitigate the effects of oxalate and are negatively correlated with kidney stone formation, but bacteriotherapies involving oxalate-degrading bacteria have met with mixed results. To inform the development of more effective and consistent bacteriotherapies, we sought to quantify the interactions and limits between oxalate and an oxalate-adapted microbiota from the wild mammalian herbivore Neotoma albigula (woodrat), which consumes a high-oxalate diet in the wild. We tracked the microbiota over a variable-oxalate diet ranging from 0.2% to 12%, with the upper limit approximating 10× the level of human consumption. The N. albigula microbiota was capable of degrading ~100% of dietary oxalate regardless of the amount consumed. However, the microbiota exhibited significant changes in diversity dynamically at the operational taxonomic unit (OTU), family, and community levels in accordance with oxalate input. Furthermore, a cohesive microbial network was stimulated by the consumption of oxalate and exhibited some resistance to the effects of prolonged exposure. This study demonstrates that the oxalate-adapted microbiota of N. albigula exhibits a very high level of degradation and tolerance for oxalate. IMPORTANCE The bacteria associated with mammalian hosts exhibit extensive interactions with overall host physiology and contribute significantly to the health of the host. Bacteria are vital to the mitigation of the toxic effects of oxalate specifically as mammals do not possess the enzymes to degrade this compound, which is present in the majority of kidney stones. Contrary to the body of literature on a few oxalate-degrading specialists, our work illustrates that oxalate stimulates a broad but cohesive microbial network in a dose-dependent manner. The unique characteristics of the N. albigula microbiota make it an excellent source for the development of bacteriotherapies to inhibit kidney stone formation. Furthermore, this work successfully demonstrates methods to identify microbial networks responsive to specific toxins, their limits, and important elements such as microbial network cohesivity and architecture. These are necessary steps in the development of targeted bacteriotherapies.