Numerical simulation of biological methanation in bubble column reactors is challenging due to strong coupling between hydrodynamics, mass transfer and bioreaction. A satisfactory prediction of the mass transfer coefficient and the gas solubility is crucial to couple hydrodynamics and biokinetics. A comprehensive 1D multispecies multiple-way coupled gas-liquid model is developed. The hydrodynamics of the model is validated using experimental gas loading data at very low gas holdup. The local mass transfer is validated using literature data on CO2 mass transfer in the large-scale. The local gas holdup and interfacial CO2 mass transfer flux are correctly described thanks to a two-way coupling between hydrodynamics and mass transfer, including changes in bubble diameter and pressure effects. When a mixture of H-2, CO2 and CH4 is used, highly non-linear mass transfer profiles due to differences in solubilities are observed. An original flux-based metabolic model is proposed to simulate an industrial biological methanation process. This allows smooth transition between biologically and physically controlled regimes as the culture reaches a steady-state. The comprehensive model enlightens that the biological methanation performances are governed by the H-2 mass transfer limitation balanced by growth in the transient state and biological maintenance in the steady-state.