Resource limitation is a fundamental factor governing the composition and function of ecological communities. The mammalian large intestine is typically considered a hospitable environment for microbes. At the same time, the host’s primary uptake of dietary proteins, fatty acids, and simple carbohydrates occurs in the small intestine. We therefore hypothesized that concentrations of essential elements are diminished, especially relative to demand, and become limiting for growth of the microbiota in the large intestine. Nitrogen is likely to be among the limiting nutrients for bacteria in the large intestine as it is for myriad free-living organisms in diverse environments worldwide. We used stoichiometric and stable-isotope tracing approaches in vitro and in vivo to ask whether nitrogen is limiting in the mammalian gut and how nitrogen availability is managed by the host.
We found that gut microbiota confront nitrogen limitation in the large intestines of mammal species, regardless of diet or digestive physiology. Colonic nitrogen limitation results from hosts’ absorption of dietary nutrients, producing a stoichiometric gradient with distal sections having higher C:N than the small intestine (P<0.05, Tukey’s HSD). We show that animals mitigate nitrogen limitation of gut microbes via internal secretions. These secretions are dynamic and diminish when bacterial loads are reduced by antibiotic treatment. This results in a near doubling of fecal C:N within 48 hours (P<0.001, Bonferroni-corrected Mann-Whitney U). Single-cell spectrometry suggests select members of the phylum Bacteroidetes are the primary foragers of nitrogen, and we find that these taxa, are depleted when secretions are reduced. Bacteroidaceae abundance is strongly negatively correlated with fecal C:N (rho=-0.58, P<0.001, Spearman correlation) indicating they are more abundant under high nitrogen availability. Together, our findings indicate that nitrogen limitation arises from preferential host utilization of dietary nutrients and subsequently enables hosts to selectively regulate microbial communities in the large intestine. Host control of nutrient availability presents a metabolic cost, but provides mammals with a mechanism for maintaining a mutualistic gut microbiota.