BioModelsWilliam ScottNon-curatedotherL3V1https://www.ebi.ac.uk/biomodels/MODEL2602030001falseBioModelsSBMLModelsMetabolic modeling unveils potential probiotic roles of Flavonifractor plautii in reshaping the Western gut microbiota landscape2026MODEL2602030001William T Scott, Enden Dea Nataya, Clara Belzer, Peter J SchaapWilliam T Scott10.1101/2025.04.16.649128, Flavonifractor plautii , a prevalent gut commensal, uniquely combines flavonoid degradation with the capacity to produce health-promoting short-chain fatty acids (SCFAs), notably butyrate and propionate. However, its metabolic pathways, ecological roles, and health impacts remain poorly characterized. To explore its probiotic potential and ecological functions, we developed a genome-scale metabolic model (GEM), iFP655 , using automated reconstruction, deep-learning-based gap-filling, thermodynamic constraints, and transcriptomics. The iFP655 model substantially improved the predictions of growth rates and SCFA profiles compared to previous models. Simulations identified acetyl-CoA pathways as the preferred route for butyrate production, whereas the energetically costly lysine pathway remained inactive despite robust gene expression. Propionate synthesis occurred primarily via the methylmalonyl-CoA pathway. Community metabolic modeling with representative species of a Western minimal gut microbiota highlighted F. plautii ‘s contributions to enhanced SCFA production, especially butyrate, amino acid metabolism, and syntrophic interactions driven by dietary substrates. Our findings indicate that diet-driven syntrophy significantly shapes microbial community structure and function, underscoring the ecological importance of F. plautii in gut microbial interactions and highlighting its potential as a probiotic candidate to beneficially modulate gut microbiota through dietary interventions.. , . Agricultural & Biological Engineering Purdue University Systems and Synthetic Biology, UNLOCK Wageningen University & Researchwilliam.scott@wur.nl10.1101/2025.04.16.649128Wageningen University & ResearchfalseMetabolic modeling unveils potential probiotic roles of Flavonifractor plautii in reshaping the Western gut microbiota landscapeFlavonifractor plautii, a prevalent gut commensal, uniquely combines flavonoid degradation with the capacity to produce health-promoting short-chain fatty acids (SCFAs), notably butyrate and propionate. However, its metabolic pathways, ecological roles, and health impacts remain poorly characterized. To explore its probiotic potential and ecological functions, we developed a genome-scale metabolic model (GEM), iFP655, using automated reconstruction, deep-learning-based gap-filling, thermodynamic constraints, and transcriptomics. The iFP655 model substantially improved the predictions of growth rates and SCFA profiles compared to previous models. Simulations identified acetyl-CoA pathways as the preferred route for butyrate production, whereas the energetically costly lysine pathway remained inactive despite robust gene expression. Propionate synthesis occurred primarily via the methylmalonyl-CoA pathway. Community metabolic modeling with with representative species of a Western minimal gut microbiota highlighted F. plautii ‘s contributions to enhanced SCFA production, especially butyrate, amino acid metabolism, and syntrophic interactions driven by dietary substrates. Our findings indicate that diet-driven syntrophy significantly shapes microbial community structure and function, underscoring the ecological importance of F. plautii in gut microbial interactions and highlighting its potential as a probiotic candidate to beneficially modulate gut microbiota through dietary 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