Spatiotemporal Dynamics during Niche Remodeling By Super-Colonizing Bacteria in the Mammalian Gut

Fecal Microbiota Transplantation (FMT) has gained traction as a therapy for restoring healthy gut ecosystems within dysbiotic individuals yet has provided mixed results, with outcomes affected by interpersonal variation in microbiome composition. While recent high-profile studies have discovered preliminary markers for successful therapy the specific mechanisms determining the success of microbial transplantation via FMT remain undefined. Here, we used a mouse gut colonization model that leverages natural inter-individual variation in gut microbiomes to explore the spatiotemporal dynamics of colonizing microbes following FMT. We show that microbiomes of C57BL/6 mice acquired from different vendors exhibit variable outcomes when subject to inter-vendor FMT and identified a “super-colonizing” microbiota consortium capable of robustly engrafting in diverse recipients. We then characterized the dynamics of super-colonizers in FMT recipients through a series of longitudinal and spatial metagenomic assays to identify predictors and mechanisms of successful FMT. Finally, we used Metagenomic Plot Sampling by Sequencing (MaPS-Seq) to study the micron-scale spatial arrangement of microbes in intact biological samples. By performing MaPS-Seq on FMT communities, we discovered that microbial species form spatially associating communities in the gut that retain their structure after FMT. Furthermore, we found that super-colonization is facilitated by cooperative metabolic activities to exploit unused nutrient niches within the recipient gut. Overall, this study revolutionizes our understanding of microbial dynamics during FMT, revealing previously unknown mechanisms underlying FMT success. These findings have the potential to inform and guide the selection of both donors and recipients, unlocking new approaches to personalized therapeutics.