Riboswitch Distribution in the Human Gut Microbiome Reveals Common Metabolite Pathways

Riboswitches are widely distributed, conserved RNAs which
regulate
metabolite levels in bacterial cells through direct, noncovalent binding
of their cognate metabolite. Various riboswitch families are highly
enriched in gut bacteria, suggestive of a symbiotic relationship between
the host and bacteria. Previous studies of the distribution of riboswitches
have examined bacterial taxa broadly. Thus, the distribution of riboswitches
associated with bacteria inhabiting the intestines of healthy individuals
is not well understood. To address these questions, we survey the
gut microbiome for riboswitches by including an international database
of prokaryotic genomes from the gut samples. Using Infernal, a program
that uses RNA-specific sequence and structural features, we survey
this data set using existing riboswitch models. We identify 22 classes
of riboswitches with vitamin cofactors making up the majority of riboswitch-associated
pathways. Our finding is reproducible in other representative databases
from the oral as well as the marine microbiomes, underscoring the
importance of thiamine pyrophosphate, cobalamin, and flavin mononucleotide
in gene regulation. Interestingly, riboswitches do not vary significantly
across microbiome representatives from around the world despite major
taxonomic differences; this suggests an underlying conservation. Further
studies elucidating the role of bacterial riboswitches in the host
metabolome are needed to illuminate the consequences of our finding.