bioRxiv2020
Archaea of the order Methanomassiliicoccales use methylated-amines such as trimethylamine as a substrate for methane production. They form two large phylogenetic clades and reside in diverse environments, from soil to the human gut. Two genera, one from each clade, inhabit the human gut: Methanomassiliicoccus, which has one cultured representative, and "candidatus Methanomethylophilus", which has none. Questions remain regarding their distribution across different biomes and human populations, their association with other taxa in the human gut, and whether host genetics correlate with their abundance. To gain insight into the Methanomassiliicoccales, and the human-associated members in particular, we performed a genomic comparison of 72 Methanomassiliicoccales genomes and assessed their presence in metagenomes derived from the human gut (n=4472 representing 25 populations), nonhuman animal gut (n=145) and nonhost environments (n=160). Our analyses showed that all taxa are generalists: they were detected in animal gut and environmental samples. We confirmed two large clades, one enriched in the gut, the other enriched in the environment, with notable exceptions. Genomic adaptations to the gut include genome reduction, a set of adhesion factors distinct from that of environmental taxa, and genes involved in the shikimate pathway and bile resistance. Genomic adaptations differed by clade, not habitat preference, indicating convergent evolution between the clades. In the human gut, the relative abundance of Methanomassiliicoccales correlated with trimethylamine-producing bacteria and was unrelated to host genotype. Our results shed light on the microbial ecology of this group may help guide Methanomassiliicoccales-based strategies for trimethylamine mitigation in cardiovascular disease. ImportanceMethanomassiliicoccales are a lesser known component of the human gut microbiota. This archaeal order is composed of methane producers that use methylated amines, such as trimethylamine, in methane production. This group has only one cultured representative; how they adapted to inhabit the mammalian gut and how they interact with other microbes is largely unknown. Using bioinformatics methods applied to DNA from a wide range of samples, we profiled the relative abundances of these archaea in environmental and host-associated microbial communities. We observed two groups of Methanomassiliicoccales, one largely host-associated and one largely found in environmental samples, with some exceptions. When host-associated, these archaea have a distinct set of genes related to adhesion and possess genes related to bile resistance. We did not detect Methanomassiliicoccales in all human populations tested but when present, they are correlated with Bacteria known to produce trimethylamine. Since trimethylamine is linked to cardiovascular disease risk, these intriguing Archaea may also be involved.