Genome-scale metabolic models predict diet- and lifestyle-driven shifts of ecological interactions in the gut microbiome.

Microbiomes and their host environments form complex, interconnected ecosystems. The microbial species within a microbiome, on the one hand, compete for resources, while on the other hand, they exchange vital metabolites to support their survival. These interactions are influenced by the microbial genetic repertoire, environmental conditions, and availability of nutrients. We developed EcoGS (http://www.github.com/KaletaLab/EcoGS), a metabolic modeling tool designed to predict the ecological interactions between pairs of microbes. Applying EcoGS to the microbiomes of two distinct human cohorts revealed a shift from collaborative to exploitative ecological interactions associated with increased dietary intake of simple sugars (glucose and fructose) in diabetic individuals and those living industrialized lifestyles. On the other hand, the consumption of cobalamin (vitamin B12), phylloquinone (vitamin K1), and biotin (vitamin B7), among other compounds, was associated with increased collaboration in the gut microbiome. We conclude that the abundance of simple sugars as an energy source reduces the necessity for microbes to cooperate, thereby increasing competition and hostility among microbiome members. Moreover, our study proposes multiple compounds, such as urate, deoxyadenosine, deoxyguanosine, and hypoxanthine, for in vitro validation tests as dietary interventions that have the potential to restore the ecological balance within the community. EcoGS serves as a valuable tool for exploring microbiome dynamics and their connections to environmental changes and disease.