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

AbstractAcross human populations, 16S rRNA gene-based surveys of gut microbiomes have revealed that the bacterial familyChristensenellaceae and the archaeal familyMethanobacteriaceaeco-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 betweenChristensenellaspp. andMethanobrevibacter smithii,the most abundant methanogen of the human gut. By co-culturing threeChristensenellaspp. WithM. smithii,we show thatChristensenellaspp. efficiently support the ofM. smithiivia H2production, far better thanBacteroides thetaiotaomicron.C. minutaforms flocs colonized byM. smithiieven when H2is in excess. In culture withC. minuta, H2consumption byM. smithiishifts the metabolic output ofC. 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.ImportanceThe human gut microbiome is made of trillions of microbial cells, most of which areBacteria, with a subset ofArchaea. The bacterial familyChristensenellaceaeand the archaeal familyMethanobacteriaceaeare 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.