Fecal bbu genes predict L-carnitine-mediated TMAO production

Gut microbial metabolism of L-carnitine, leading to TMAO production, offers a plausible explanation for the association between red meat consumption and cardiovascular diseases. However, the specific gut microbes and the relevant genes involved in L-carnitine-mediated TMAO production are not fully understood. In this study, we performed an integrated analysis of 292 oral carnitine challenge tests and shotgun metagenome sequencing of fecal samples. We identified that the microbial bbu gene cluster is likely the primary contributor to TMAO formation resulting from L-carnitine consumption. Furthermore, we detected novel anaerobes, such as the Oscillospiraceae bacterium Marseille-Q3528, which possess the bbu gene cluster and are significantly correlated with TMAO production from L-carnitine. We isolated these bacteria and validated their TMA/TMAO-producing capability both in vitro and in vivo. Lastly, we developed a qPCR-based method to quantify fecal bbuB and verified its correlation with TMAO levels resulting from L-carnitine. Our findings pave the way for advances in precision nutrition.