Community-Scale Metabolic Modelling Reveals Coral-Derived Betaine Drives Stress-Associated Microbiome Restructuring

Stress-induced changes in host metabolism may shape microbiome assembly, however this mechanism remains poorly understood in coral holobionts. Here, we investigated this process by focusing on betaine, a stress-associated coral metabolite, and reconstructing genome-scale metabolic models of bacteria associated with fire corals (Millepora spp.). Community-scale constraint-based simulations showed that increasing betaine availability reshaped microbial composition, metabolic activity and ecological interactions. Elevated betaine acted as a selective metabolic filter, favouring betaine-utilizing Alphaproteobacteria while reducing putatively beneficial lineages, including Endozoicomonadaceae. This response was nonlinear and was accompanied by reorganization of microbial interaction networks and reduced community-level metabolic output. These patterns suggest that increased betaine availability does not simply weaken holobiont metabolic support, but instead shifts the microbiome toward a more specialized state characterized by reduced taxonomic breadth and strengthened positive associations among Alphaproteobacteria-associated lineages. Our findings identify coral-derived betaine as a plausible metabolic mediator of stress-associated microbiome reorganization and provide a mechanistic framework for understanding how stress-induced changes in host metabolism can influence microbiome restructuring across host-associated systems.