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

Abstract

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.

Keywords: diet; fats; heavy metals; microbiota; physiology; polyphenols; protein.

FIG 1

Nutrient landscape of the gut as shaped by host and microbial processes. Gut microbial absolute and relative abundances are expected to be sensitive to the nutrients available within the gut lumen. Nutrient composition in the gut lumen is, in turn, dependent on (i) dietary intake of macronutrients, micronutrients, and phytochemicals; (ii) the bioavailability of those nutrients within the small intestine, which alters the fraction of ingested nutrients reaching the densest microbial communities in the colon; (iii) endogenous secretions such as bile acids and digestive enzymes that alter competitive dynamics among gut microbial taxa and/or modulate bioavailability; and (iv) microbial metabolism of nutrients, producing metabolites that may have downstream effects on competitive dynamics within the gut microbiota.

FIG 2

Many resources relevant to microbial growth and function are naturally sourced from the typical human diet. Identifying what specific resources drive microbial differences in humans whose diets vary is a complicated endeavor, however. Here, we show how the USDA MyPlate-recommended diet components include various microbially relevant resources such that changing diet broadly may not allow researchers to ascribe causality to microbial changes. Further theory on limiting resources and controlled experiments isolating individual aspects of diet are necessary to develop a dynamic range of manipulations and to understand the degree to which host physiology modulates microbial responses to diet.