Hydrogenotrophic methanogens of the mammalian gut: Functionally similar, thermodynamically different—A modelling approach

Methanogenic archaea occupy a functionally important niche in the gut microbial ecosystemof mammals. Our purpose was to quantitatively characterize the dynamics of methanogenesisby integrating microbiology, thermodynamics and mathematical modelling. For that, invitro growth experiments were performed with pure cultures of key methanogens from thehuman and ruminant gut, namely Methanobrevibacter smithii, Methanobrevibacter ruminantiumand Methanobacterium formicium. Microcalorimetric experiments were performed toquantify the methanogenesis heat flux. We constructed an energetic-based mathematicalmodel of methanogenesis. Our model captured efficiently the dynamics of methanogenesiswith average concordance correlation coefficients of 0.95 for CO2, 0.98 for H2 and 0.97 forCH4. Together, experimental data and model enabled us to quantify metabolism kineticsand energetic patterns that were specific and distinct for each species despite their use ofanalogous methane-producing pathways. Then, we tested in silico the interactions betweenthese methanogens under an in vivo simulation scenario using a theoretical modelling exercise.In silico simulations suggest that the classical competitive exclusion principle is inapplicableto gut ecosystems and that kinetic information alone cannot explain gut ecologicalaspects such as microbial coexistence. We suggest that ecological models of gut ecosystemsrequire the integration of microbial kinetics with nonlinear behaviours related to spatialand temporal variations taking place in mammalian guts. Our work provides novel informationon the thermodynamics and dynamics of methanogens. This understanding will beuseful to construct new gut models with enhanced prediction capabilities and could havepractical applications for promoting gut health in mammals and mitigating ruminant methaneemissions.