The gut's trillions of bacteria are not a uniform soup—individual cells differ wildly in how active they are, and this project will map that metabolic activity one bacterium at a time. Current methods average bacterial activity across entire populations, missing the crucial detail of which individual microbes are actually working, reproducing, or interacting with the host. This gap makes it impossible to understand why some bacteria thrive during health while others drive inflammation. The researchers will use advanced single-cell analysis to track metabolic activity in real time, both in lab cultures and in living animals, and examine how antibodies from the immune system shape which bacteria become active. If successful, this work will reveal the hidden ecological rules governing the gut microbiome—which bacteria occupy which nutritional niches, and how the immune system patrols them. This is fundamental science; it will not produce a therapy tomorrow. But understanding these single-cell dynamics could eventually allow researchers to design immune-based interventions that selectively encourage beneficial bacteria to colonise, offering a precision tool for managing chronic inflammatory conditions.
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Metabolic activity of bacteria is linked with increased functionality, e.g. proliferation, production of host- and microbial community-relevant metabolites. We hypothesise that metabolically active bacteria are spatially stratified and interact more actively with the host to maintain homeostasis or when perturbed contribute to disease. Host-secreted compounds and nutrient gradients contribute to differences in microbial community composition and activity in different locations. This project aims at a functional understanding of the metabolic activity landscape of the intestinal microbiome in situ at an unprecedented resolution, i.e. on the single cell level. It addresses how metabolic activity of individual microbiota shapes the microbiota as a whole and its interaction with the host and its immune system during steady state and when disturbed, for instance due to inflammation. We will use in vitro and in vivo models of immune system-microbiota interaction to decipher how the adaptive immune system via production of mucosal antibodies affects metabolic activity of distinct commensal strains and vice versa. Thus, this project will help resolve the ecological and functional interactions within the microbial community, in potentially dedicated nutritional niches and with the host in the context of homeostasis and when perturbed in chronic inflammation. This interdisciplinary proposal brings together a team and collaborators with complementary expertise in microbial single-cell analyses techniques optimally suited to address this aim. Created knowledge will unveil new possibilities to manipulate the microbiome to support health, for instance by designing immune system-targeted interventions to enhance colonisation of beneficial commensals.
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