Syntrophy via Interspecies H Transfer between and 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 and the archaeal family 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 spp. and , the most abundant methanogen of the human gut. By coculturing three spp. with , we show that spp. efficiently support the metabolism of via H production far better than does. forms flocs colonized by even when H is in excess. In culture with , H consumption by shifts the metabolic output of '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. The human gut microbiome is made of trillions of microbial cells, most of which are , with a subset of The bacterial family and the archaeal family 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 show that species within these families correlate with each other across people. We also demonstrate 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 that when these species grow together, their products have the potential to affect the physiology of their human host.