The human gut microbiome is a dense and dynamic ecosystem in which only a fraction of organisms can be readily cultured or structurally analysed. Among these organisms, acetogens represent a numerically small but functionally influential group. Despite forming only a minor fraction of the microbiome, they contribute substantially to metabolic balance through the production of acetate and other fermentation products. Their diverse physiology ranges from autotrophic CO₂ fixation via the Wood–Ljungdahl pathway to mixotrophic growth on complex sugars, and includes the use of specialised bacterial microcompartments.
To address long-standing gaps in our understanding of these microorganisms, this project applies an interdisciplinary, scale-bridging strategy that combines cryo-electron tomography with complementary imaging and biochemical analyses. This approach enables direct visualisation of the unperturbed cellular landscape and reveals previously unrecognised structural complexity, including enzyme-decorated nanowires, filamentous enzymatic assemblies and metabolically specialised microcompartments. These features offer insights into how acetogens organise and channel metabolic flux in the gut.
The project aims to define the architecture and dynamics of these structures, determine how they remodel under different nutrient regimes and assess their role in mixotrophic growth and interactions with a minimal defined microbial community. By linking molecular architecture to metabolic function, this work provides a framework for understanding how acetogens contribute to gut ecosystem stability and, ultimately, to human health.