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

Abstract

23Across human populations, 16S rRNA gene-based surveys of gut microbiomes 24 have revealed that the bacterial family Christensenellaceae and the archaeal family 25Methanobacteriaceae co-occur and are enriched in individuals with a lean, compared to 26 an obese, BMI. Whether these association patterns reflect interactions between 27 metabolic partners remains to be ascertained, as well as whether these associations 28 play a role in the lean host phenotype with which they associate. Here, we validated 29 previously reported co-occurrence patterns of the two families, and their association 30 with a lean BMI, with a meta-analysis of 1,821 metagenomes derived from 10 31 independent studies. Furthermore, we report positive associations at the genus and 32 species level between Christensenella spp. and Methanobrevibacter smithii, the most 33 abundant methanogen of the human gut. By co-culturing three Christensenella spp. with 34 M. smithii, we show that Christensenella spp. efficiently support the metabolism of M. 35 smithii via H 2 production, far better than Bacteroides thetaiotaomicron. C. minuta forms 36 flocs colonized by M. smithii even when H 2 is in excess. In culture with C. minuta, H 2 37 consumption by M. smithii shifts the metabolic output of C. minuta's fermentation 38 towards acetate rather than butyrate. Together, these results indicate that the 39 widespread co-occurrence of these microbiota is underpinned by both physical and 40 metabolic interactions. Their combined metabolic activity may provide insights into their 41 association with a lean host BMI. 42 43 44 45 Importance 46 The human gut microbiome is made of trillions of microbial cells, most of which 47 are Bacteria, with a subset of Archaea. The bacterial family Christensenellaceae and 48 the archaeal family Methanobacteriaceae are widespread in human guts. They correlate 49with each other and with a lean body type. Whether species of these two families 50 interact, and how they affect the body type, are unanswered questions. Here, we 51 showed that species within these families correlate with each other across people. We 52 also demonstrated that particular species of these two families grow together in dense 53 flocs, wherein the bacteria provide hydrogen gas to the archaea, which then make 54 methane. When the archaea are present, the ratio of bacterial products (which are 55 nutrients for humans) is changed. These observations indicate when these species 56 grow together, their products have the potential to affect the physiology of their human 57 host. 58 the human gut microbiome, the family Christensenellaceae was described relatively 65 recently, when the type strain Christensenella minuta was reported in 2012 (16). Prior to 66 the description of C. minuta, 16S rRNA sequences from this genus escaped notice in 67 the gut microbiome, though these sequences accumulated steadily in SSU rRNA gene 68 databases. A positive association between a lean host BMI and the relative abundance 69 in the gut of Christensenellaceae 16S rRNA genes was fi...