Syntrophy via Interspecies H(2) Transfer between Christensenella and Methanobrevibacter Underlies Their Global Cooccurrence in the Human Gut

Across human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae cooccur and are enriched in individuals with a lean, compared to an obese, body mass index (BMI). Whether these association patterns reflect interactions between metabolic partners, as well as whether these associations play a role in the lean host phenotype with which they associate, remains to be ascertained. Here, we validated previously reported cooccurrence patterns of the two families and their association with a lean BMI with a meta-analysis of 1,821 metagenomes derived from 10 independent studies. Furthermore, we report positive associations at the genus and species levels between Christensenella spp. and Methanobrevibacter smithii, the most abundant methanogen of the human gut. By coculturing three Christensenella spp. with M. smithii, we show that Christensenella spp. efficiently support the metabolism of M. smithii via H(2) production far better than Bacteroides thetaiotaomicron does. Christensenella minuta forms flocs colonized by M. smithii even when H(2) is in excess. In culture with C. minuta, H(2) consumption by M. smithii shifts the metabolic output of C. minuta’s fermentation toward acetate rather than butyrate. Together, these results indicate that the widespread cooccurrence of these microorganisms is underpinned by both physical and metabolic interactions. Their combined metabolic activity may provide insights into their association with a lean host BMI.