Thinking Outside the Cereal Box: Noncarbohydrate Routes for Dietary Manipulation of the Gut Microbiota

The gut microbiota is a diverse and dynamic ecological community that is increasingly recognized to play important roles in host metabolic, immunological, and behavioral functioning. As such, identifying new routes for manipulating the microbiota may provide valuable additional methods for improving host health. Dietary manipulations and prebiotic supplementation are active targets of research for altering the microbiota, but to date, this work has disproportionately focused on carbohydrates. However, many other resources can limit or shape microbial growth. Here, we provide a brief overview of the resource landscape in the mammalian gut and review relevant literature documenting associations between noncarbohydrate nutrients and the composition of the gut microbiota. To spur future work and accelerate translational applications, we propose that researchers take new approaches for studying the effects of diet on gut microbial communities, including more-careful consideration of media for in vitro experiments, measurement of absolute as well as relative abundances, concerted efforts to articulate how physiology may differ between humans and the animal models used in translational studies, and leveraging natural variation for additional insights. Finally, we close with a discussion of how to determine when or where to employ these potential dietary levers for manipulating the microbiota.