A humanized gnotobiotic mouse model of host–archaeal–bacterial mutualism

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Abstract
Our colons harbor trillions of microbes including a prominent archaeon,Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice withBacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or withoutM. smithiior the sulfate-reducing bacteriumDesulfovibrio piger. Whole-genome transcriptional profiling ofB. thetaiotaomicron, combined with mass spectrometry, revealed that, unlikeD. piger,M. smithiidirectsB. thetaiotaomicronto focus on fermentation of dietary fructans to acetate, whereasB. thetaiotaomicron-derived formate is used byM. smithiifor methanogenesis.B. thetaiotaomicron–M. smithiicocolonization produces a significant increase in host adiposity compared with monoassociated, orB. thetaiotaomicron–D. pigerbiassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance.