Do gut microbes convert choline and carnitine into TMA, which the liver converts into TMAO?

The claimed pathway is well established in humans: dietary choline and carnitine can be metabolized by gut microbes to trimethylamine (TMA), then oxidized in the liver to trimethylamine N-oxide (TMAO).

Microbial production of TMA

• Choline: Under anaerobic conditions, microbial choline TMA-lyase CutC, activated by CutD, cleaves choline into TMA and acetaldehyde. Human phosphatidylcholine/egg challenge responses were abolished or markedly reduced after antibiotic microbiota suppression, supporting a necessary microbial role. Human-gut isolates including Clostridium, Proteus, Providencia, and Escherichia can carry out this conversion.
• Carnitine: The predominant colonic route is usually sequential: microbial metabolism converts carnitine to γ-butyrobetaine, followed by anaerobic γ-butyrobetaine-to-TMA conversion. The gbu/bbu pathway and Emergencia timonensis provide defined mechanistic support. Although CntA/CntB can directly convert carnitine to TMA under oxygen-dependent conditions, this is likely less important in the largely anaerobic colon.

Hepatic oxidation to TMAO

• In adult human liver, flavin-containing monooxygenase 3 (FMO3) is the dominant TMA N-oxygenating enzyme, accounting for an estimated ≥90% of hepatic TMA-oxidizing activity. FMO1 can oxidize TMA in vitro but is not the principal adult hepatic route.
• Human FMO3 loss-of-function variants provide strong confirmation: primary trimethylaminuria causes impaired TMA oxidation, TMA accumulation, and reduced TMAO relative to TMA in plasma or urine.

Clinical interpretation

• TMA/TMAO generation varies among individuals with microbial composition, pathway activity, habitual diet, renal clearance, and potentially liver physiology. Thus, circulating TMAO reflects the entire gut–liver–kidney pathway, not hepatic conversion alone.

Bottom line

• The claim is strongly supported: gut microbes convert choline and carnitine to TMA through characterized pathways, and hepatic FMO3 efficiently converts TMA to TMAO.