Syntrophy via interspecies H2transfer betweenChristensenellaandMethanobrevibacterunderlies their global co-occurrence in the human gut

Across human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial family Christensenellacea e and the archaeal family Methanobacteriaceae co-occur and are enriched in individuals with a lean, compared to an obese, BMI. Whether these association patterns reflect interactions between metabolic partners remains to be ascertained, as well as whether these associations play a role in the lean host phenotype with which they associate. Here, we validated previously reported co-occurrence 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 level between Christensenella spp. and Methanobrevibacter smithii, the most abundant methanogen of the human gut. By co-culturing three Christensenella spp. With M. smithii, we show that Christensenella spp. efficiently support the of M. smithii via H 2 production, far better than Bacteroides thetaiotaomicron . C. 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 towards acetate rather than butyrate. Together, these results indicate that the widespread co-occurrence of these microbiota is underpinned by both physical and metabolic interactions. Their combined metabolic activity may provide insights into their association with a lean host BMI. Importance The human gut microbiome is made of trillions of microbial cells, most of which are Bacteria , with a subset of Archaea . The bacterial family Christensenellaceae and the archaeal family Methanobacteriaceae are widespread in human guts. They correlate with each other and with a lean body type. Whether species of these two families interact, and how they affect the body type, are unanswered questions. Here, we showed that species within these families correlate with each other across people. We also demonstrated that particular species of these two families grow together in dense flocs, wherein the bacteria provide hydrogen gas to the archaea, which then make methane. When the archaea are present, the ratio of bacterial products (which are nutrients for humans) is changed. These observations indicate when these species grow together, their products have the potential to affect the physiology of their human host.