l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans.
Level 3 - non-randomized controlled study
Non-randomized controlled metabolic tracer and cohort study with interventional antibiotic and supplementation arms
PubMed 30530985 · doi:10.1172/JCI94601
What was done
Omnivores (n = 40) and vegans/vegetarians (n = 32) ingested deuterium-labeled l-carnitine (d3-l-carnitine) or deuterium-labeled gamma-butyrobetaine (d9-gBB). Plasma metabolites and fecal polymicrobial conversions were evaluated at baseline, following oral antibiotic administration, and after chronic (>=2 months) oral l-carnitine supplementation. Culturing of human fecal commensals was performed under anaerobic conditions to identify specific bacterial species responsible for each step of the metabolic pathway.
What was found
Antibiotic suppression confirmed that the transformation of l-carnitine to gBB and subsequently to trimethylamine (TMA) requires gut microbiota. Oral d3-l-carnitine administration produced a greater than 20-fold increase in d3-TMAO generation in omnivores compared to vegans/vegetarians (P = 0.001), despite similar baseline fasting endogenous plasma levels of l-carnitine and gBB in both groups (n = 32 vegans/vegetarians vs n = 40 omnivores). Both dietary groups converted l-carnitine to gBB rapidly, but conversion of gBB to TMA was inducible by chronic l-carnitine supplementation and omnivorous dietary patterns. Anaerobic isolation identified multiple taxa converting l-carnitine to gBB, but only one commensal bacterium (Emergencia timonensis, order Clostridiales) that converted gBB to TMA.
Why it matters
This study defines the sequential microbial pathway (l-carnitine to gBB to TMA to TMAO) in humans and demonstrates that habitual diet selects for specific gut commensals that enable the downstream production of pro-atherogenic TMAO.
Limits
The abstract reports on a total cohort of 72 participants, but does not detail sample sizes for the antibiotic or chronic supplementation subgroups. Clinical cardiovascular endpoints were not measured; findings are limited to intermediate circulating metabolites and ex vivo microbial metabolism.
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