Microbial communities in the intestinal tract exhibit complex metabolic interactions critical for their stability and function. However, the mechanisms underlying these interactions, particularly cross-feeding, remain poorly understood. This project investigates the metabolic interdependencies within the simplified SIHUMIx gut microbiome model, consisting of eight bacterial species extended by the bacterial species Eggerthella lenta, to elucidate the relevance and flexibility of cross-feeding interactions. Using the innovative Species-Specific Partitioned Co-Cultivation (S-PECOC) system, we aim to track metabolite exchanges at a species-specific level under controlled conditions. Coupled with innovative metabolic modeling approaches, we will systematically analyze the dependence of community members on cross-feeding, the rewiring of metabolic networks following species loss, and the extent of metabolite exchange in complex ecosystems. Experimental and computational insights will be integrated to reconstruct a comprehensive cross-feeding network, shedding light on metabolic pathways that sustain community stability and resilience. This research will enhance our mechanistic understanding of microbial metabolic cooperation, providing a foundation for microbiome-based therapies and ecological engineering applications.

The trillions of microbes living in our gut form a community that depends on sharing and exchanging nutrients to stay stable and healthy. One important way they do this is through cross-feeding—when one microbe produces a substance that another microbe needs. Yet, we still know little about how these exchanges really work. In this project, we study these nutrient-sharing relationships using a simplified gut community made up of nine well-known bacterial species. To follow who gives what to whom, we use a new system that allows us to track nutrient exchanges at the level of individual species under controlled conditions. Together with advanced computer models, this approach will help us understand how microbes depend on each other, what happens when certain species disappear, and how flexible their networks of cooperation are. By combining experiments and simulations, we will build a detailed “map” of nutrient sharing in the gut. This will not only deepen our understanding of how gut microbes keep their community stable and resilient, but also open up new possibilities for designing microbiome-based treatments and sustainable ecological applications.