Abstract
Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). A reduction in TMA formation has shown cardioprotective effects, and some phytochemicals may reduce TMA formation. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study the inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20% fecal slurry (1:10 in PBS), 100 µM choline, and 12 h fermentation. Additionally, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50% reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80–90% TMA production inhibition), with IC50 around 5 mM. Neither DMB nor gallic acid or chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA-lyase activity or expression.
Highlights
The World Health Organization (WHO) reports that cardiovascular disease (CVD) is the leading cause of death worldwide (31% of all deaths), with an estimate of 17.3 million deaths a year [1]
To monitor the presence of endogenous TMA and TMA-containing substrates, TMA, choline, L-carnitine, betaine, γ-butyrobetaine and trimethylamine N-oxide (TMAO) levels were quantified in fecal slurry 1:10 in PBS 1X and a 20% dilution of this mixture in fermentation background (Table 1)
We evaluated the % inhibition of gallic acid and chlorogenic acid in choline use
Summary
The World Health Organization (WHO) reports that cardiovascular disease (CVD) is the leading cause of death worldwide (31% of all deaths), with an estimate of 17.3 million deaths a year [1]. Atherosclerosis is a relevant factor contributing to CVD development [2], and several factors can contribute to its development (i.e., endothelial dysfunction) [3]. Strategies to prevent atherosclerosis and CVD could be greatly beneficial for the general population. The gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has emerged as a pro-atherogenic molecule associated with higher cardiovascular risk [4,5,6]. TMAO is formed due to consecutive gut bacterial and host metabolism of substrates such as choline and L-carnitine. The first metabolic step occurs in the gut, where bacteria oxidize these substrates into trimethylamine (TMA) through TMA-lyase enzymes
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