An exclusive metabolic niche enables strain engraftment in the gut microbiota

The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are largely stable over time. In contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, largely unpredictable, and greatly influenced by the background microbiota. Therefore, investigation into factors governing strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here, we generate an exclusive metabolic niche via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harboring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of an exogenous strain at predictable abundances in mice harboring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain, and enables strain replacement. We demonstrate transfer of the 60kb porphyran utilization locus into a naïve strain of Bacteroides, and show finely tuned control of strain abundance in the gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.