A small, polyphyletic group of Firmicutes synthesizes trimethylamine from l‐carnitine

Impact statement Gut microbiota‐derived trimethylamine (TMA) is associated with cardiometabolic disorders and exemplifies a microbial involvement in the etiology of emerging, noncommunicable diseases, the leading causes of death worldwide. Three biochemical pathways taking dietary compounds as intake have been described with distinct taxa involved that are all present at low relative abundances. A recently discovered pathway is now considered to be the main route for TMA synthesis from l ‐carnitine involving γ‐butyrobetaine as an intermediate product. By comprehensive (meta) genomic screening of publicly available data, namely, genomes of the UHGG catalog ( n > 200,000) and 10 metagenomic (transcriptomic) data sets, we revealed bacteria synthesizing TMA via this pathway and specified their ecophysiology. Results will contribute to stratification of individuals based on their gut microbiota's potential to synthesize TMA and might aid in the development of strategies restricting TMA formation.