Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii , studied in twins

Abstract

The human gut microbiota harbors three main groups of H 2 -consuming microbes: methanogens including the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the gut is important for understanding how hydrogen metabolism affects the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic (MZ) and 28 dizygotic (DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. The concordance rate for methanogen carriage was significantly higher for MZ versus DZ twin pairs. Co-occurrence analysis revealed 22 bacterial specieslevel taxa positively correlated with methanogens: all but two were members of the Clostridiales, with several being, or related to, known hydrogen-producing and -consuming bacteria. The M. smithii pan-genome contains 987 genes conserved in all strains, and 1,860 variably represented genes. Strains from MZ and DZ twin pairs had a similar degree of shared genes and SNPs, and were significantly more similar than strains isolated from mothers or members of other families. The 101 adhesin-like proteins (ALPs) in the pan-genome (45 ± 6 per strain) exhibit strain-specific differences in expression and responsiveness to formate. We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches, by allowing them to establish syntrophic relationships with bacterial partners with differing metabolic capabilities and patterns of co-occurrence.hydrogen-consuming microbes | metagenomics | microbial genome evolution | horizontal gene tranfer H uman microbiome projects seek to determine how microbial communities are assembled, maintained, and operate within our various body habitats as a function of our different cultural and socioeconomic conditions, family structures, stages of life, genotypes, and physiologies. Culture-independent metagenomic surveys have revealed that microbial communities cluster according to body habitat but with considerable interpersonal variation in bacterial species content (1), although differences are smaller within rather than between families (2). The gut harbors our largest collection of microbes, spanning all three domains of life. Bacteria dominate, specifically members of the phyla Bacteroidetes and Firmicutes (2-5).Monozygotic (MZ) and dizygotic (DZ) twin pairs provide an attractive study paradigm for dissecting the relative contributions of host genotype and environmental exposures to shaping the microbial and viral landscape of our gut microbiota (2, 6). To date, bacterial 16S rRNA datasets indicate that adult MZ co-twins share no more similarity in their fecal bacterial communities than DZ ...

Identifying strains that contribute to complex diseases through the study of microbial inheritance

“…Well-controlled quantitative trait loci mapping studies in mice indicate that microbiota composition is affected by host genetic factors, including those involved in immune responses, as well as by environmental exposures (18,19). Although studies of dizygotic and monozygotic twins suggest that the representation of members of the gut community is impacted by genotype (11,20), genomewide surveys are needed to address the important question of the contributions of host genetics versus environment on microbiota structure and function. In our simplified model, we assume the probability that the (gut) microbiota of any individual is colonized with strain i (i.e., P(colonized i ) has the following form…”

“…1 and 2). For example, comparison of draft genomes of strains of (i) a prominent saccharolytic bacterium in the human gut microbiota, Bacteroides thetaiotaomicron (10), and (ii) the principal human gut archaeon, Methanobrevibacter smithii, isolated from the fecal microbiota of several families (11) disclosed that the same strains were shared between a majority of adult family members. Viewed in this light, microbial inheritance, where a proportion of our microbial inhabitants and their genes are passed between family members and once acquired are retained throughout life, parallels to a degree the inheritance of our human genes.…”

“…These studies have highlighted the variation in microbial diversity between body habitats in a given individual and intrapersonal variation in community membership within a given habitat over time, as well as substantial interpersonal differences. They have also revealed how a given species-level phylogenetic group in a given body habitat's microbial community (microbiota) can be composed of multiple strains of that species, each harboring a set of shared genes, as well as genes that are variably represented across strains (10)(11)(12). This variation in a species "pan-genome" has yet to be systematically characterized for a large number of taxa recovered from different habitats of a given individual, or between large numbers of individuals.…”

Methane yield phenotypes linked to differential gene expression in the sheep rumen microbiome

“…The SRMR2 group includes new mrtA genes within both Methanobrevibacter spp. (encompassing the Methanobrevibacter ruminantium [Leahy et al 2010] and M. gottschalkii clades [Hansen et al 2011]) and Methanosphaera spp. Fig.…”

Functional diversity within the simple gut microbiota of the honey bee

“…Variants of a given species may colonize different microenvironmental niches in the gut or potentially, may compete among each other, even at host expense. Alternatively, as in other microbial gut communities (19,20), this diversity might confer fitness benefits to bees when facing environmental challenges such as exposure to pathogens, varying food sources, or toxic compounds.…”