Bioinformatic exploration of trimethylamine N-oxide metabolism in human gut bacteria

Abstract

Trimethylamine N-oxide (TMAO) is a microbial metabolite that has been shown to have protective effects on the blood–brain barrier, while elevated serum levels of TMAO and its precursors have been linked to cardiometabolic diseases in Western populations. Previous work examined the prevalence of TorA to determine which groups of bacteria were responsible for the metabolism of TMAO in the human gut. This study examined 6 TMAO metabolism pathways to provide a more in-depth analysis of bacterial TMAO metabolism. These results were then filtered for hits with >90% coverage and >70% identity. Results showed that Tor proteins were largely limited to members of the Enterobacteriaceae, mostly appearing in Escherichia coli and Citrobacter spp. >1% of 9898 Klebsiella spp. genomes examined encode any Tor proteins, despite previous work highlighting Klebsiella spp. as one of the prevalent genera encoding TorA. Dms proteins were much more prevalent than TorA in other genera of bacteria, along with MsrP and BisC. 118 of the HGRGs were found to encode for at least 1 TMAO metabolism protein. Overall, this work highlights the need for more comprehensive methods to be used to examine large genomic and metagenomic datasets and the need for in vitro work to be done alongside in silico analyses to improve functional annotations and our understanding of the roles of gut bacteria.