From observable fermentation data to hidden cell states: A modeling study of a mixotrophic Clostridium coculture under perfusion mode.

Hybrid modeling reveals hidden dormant cell states and metabolic interactions in a Clostridium coculture under perfusion mode, with significant biological reaction insights.

• Why it matters: Understanding internal physiological states in microbial cocultures is crucial for optimizing bioprocesses, yet these states are often unobservable with standard measurements, limiting interpretability.
• What they did: A combined structured population-state reconstruction and sparse identification (SINDy) approach was applied to a C. acetobutylicum-C. ljungdahlii coculture, estimating biomass trajectories, reconstructing dormant populations, and identifying extracellular metabolite dynamics from biomass and activity data.
• The result: The model accurately captured biomass and metabolite trajectories, highlighting acid-related state transitions and metabolic exchanges, thus enabling better interpretation of complex microbial interactions and dormant cell roles.